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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article" dtd-version="1.0" specific-use="sps-1.6" xml:lang="en">
  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">ijcs</journal-id>
      <journal-title-group>
        <journal-title>International Journal of Cardiovascular Sciences</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Int. J. Cardiovasc. Sci.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">2359-4802</issn>
      <issn pub-type="epub">2359-5647</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">Y4mBNrbrG5XcLGbW78vXZMH</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S2359-56472017000500373</article-id>
      <article-id pub-id-type="doi">10.5935/2359-4802.20170066</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Articles</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Chim&#243;, a Smokeless Tobacco Preparation, is Associated with a Lower Frequency of Hypertension in Subjects with Type 2 Diabetes</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Gonz&#225;lez-Rivas</surname>
            <given-names>Juan P.</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Santiago</surname>
            <given-names>Raul Jos&#233; Garc&#237;a</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mechanick</surname>
            <given-names>Jeffrey I.</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Nieto-Mart&#237;nez</surname>
            <given-names>Ramfis</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">3</xref>
          <xref ref-type="aff" rid="aff4">4</xref>
          <xref ref-type="aff" rid="aff5">5</xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgname">The Andes Clinic of Cardio-Metabolic Studies</institution>
        <addr-line>
          <named-content content-type="city">M&#233;rida</named-content>
        </addr-line>
        <country country="VE">Venezuela</country>
        <institution content-type="original">The Andes Clinic of Cardio-Metabolic Studies, M&#233;rida - Venezuela</institution>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution content-type="orgname">Icahn School of Medicine at Mount Sinai</institution>
        <institution content-type="orgdiv1">Division of Endocrinology, Diabetes and Bone Disease</institution>
        <addr-line>
          <named-content content-type="city">New York</named-content>
        </addr-line>
        <country country="US">EUA</country>
        <institution content-type="original">Division of Endocrinology, Diabetes and Bone Disease, Icahn School of Medicine at Mount Sinai, New York - EUA</institution>
        <institution content-type="normalized"> Icahn School of Medicine at Mount Sinai </institution>
      </aff>
      <aff id="aff3">
        <label>3</label>
        <institution content-type="orgname">Universidad Centro-Occidental "Lisandro Alvarado"</institution>
        <institution content-type="orgdiv1">School of Medicine</institution>
        <institution content-type="orgdiv2">Department of Physiology</institution>
        <country country="VE">Venezuela</country>
        <institution content-type="original">Department of Physiology, School of Medicine, Universidad Centro-Occidental "Lisandro Alvarado" (UCLA) and Cardio-Metabolic Unit 7</institution>
        <institution content-type="normalized">Universidad Centroccidental Lisandro Alvarado</institution>
      </aff>
      <aff id="aff4">
        <label>4</label>
        <institution content-type="orgname">Miami VA Healthcare System</institution>
        <institution content-type="orgdiv1">Geriatric Research, Education and Clinical Center</institution>
        <addr-line>
          <named-content content-type="city">Miami</named-content>
          <named-content content-type="state">FL</named-content>
        </addr-line>
        <country country="US">USA</country>
        <institution content-type="original"> Geriatric Research, Education and Clinical Center (GRECC), Miami VA Healthcare System, Miami, FL, USA</institution>
      </aff>
      <aff id="aff5">
        <label>5</label>
        <institution content-type="orgname">South Florida Veterans Affairs Foundation for Research &amp; Education</institution>
        <addr-line>
          <named-content content-type="city">Miami</named-content>
        </addr-line>
        <country country="US">USA</country>
        <institution content-type="original">South Florida Veterans Affairs Foundation for Research &amp; Education, Miami - USA</institution>
      </aff>
      <author-notes>
        <corresp id="c1"><bold>Mailing Address: Juan P. Gonz&#225;lez</bold> - Rivas The Andes Clinic of Cardio-Metabolic Studies. Av. Miranda, 3112, Sector Centre, Timotes, M&#233;rida - Venezuela. E-mail: <email>juanpgonzalezr@hotmail.com</email>; <email>juanpgonzalezr79@gmail.com</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Conception and design of the research: Gonz&#225;lez-Rivas JP, Santiago RJG. Acquisition of data: Gonz&#225;lez-Rivas JP. Analysis and interpretation of the data: Gonz&#225;lez-Rivas JP, Santiago RJG, Mechanick JI, Nieto-Mart&#237;nez R. Statistical analysis: Gonz&#225;lez-Rivas JP. Writing of the manuscript: Gonz&#225;lez-Rivas JP. Critical revision of the manuscript for intellectual content: Santiago RJG, Mechanick JI, Nieto-Mart&#237;nez R. Supervision / as the major investigador: Mechanick JI, Nieto-Mart&#237;nez R.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potential Conflict of Interest</bold>
          </p>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub-ppub">
        <season>Sep-Oct</season>
        <year>2017</year>
      </pub-date>
      <volume>30</volume>
      <issue>05</issue>
      <fpage>373</fpage>
      <lpage>379</lpage>
      <history>
        <date date-type="received">
          <day>28</day>
          <month>06</month>
          <year>2016</year>
        </date>
        <date date-type="rev-recd">
          <day>28</day>
          <month>12</month>
          <year>2016</year>
        </date>
        <date date-type="accepted">
          <day>05</day>
          <month>04</month>
          <year>2017</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
        </license>
      </permissions>
      <abstract>
        <title>Abstract</title>
        <sec>
          <title>Background:</title>
          <p>Tobacco use and hypertension are leading preventable causes of death globally. Tobacco is presented as smoked or smokeless tobacco (ST). ST use has been related to cardiovascular disease, type 2 diabetes (T2D), and cancer. In Venezuela, chim&#243; is the most common ST preparation, and its relationship with hypertension is unknown.</p>
        </sec>
        <sec>
          <title>Objective:</title>
          <p>To evaluate the relationship between chim&#243; use and hypertension in a population with a high prevalence of ST use in Venezuela.</p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p>From 2013-2014, a total of 1,938 consecutive subjects aged 20 years or older were evaluated in a medical center. Anthropometrics and blood pressure (BP) measurements, and responses to a standard questionnaire were obtained.</p>
        </sec>
        <sec>
          <title>Results:</title>
          <p>The participants had a mean age of 49.2 years, 59.5% were female, 38.9% had hypertension, 23.2% reported ST use, and 11.6% reported having T2D. One-third of the subjects with T2D were ST users, and this group showed lower heart rate, systolic BP, body mass index (BMI), and frequency of hypertension when compared with T2D subjects who were not ST users (p &lt; 0.05). In subjects with T2D who were 50 years or older, ST use was associated with a 69% lower frequency of hypertension when compared with subjects without ST use. On logistic regression adjusted by heart rate, age, occurrence of T2D, overweight/obesity, and family history of hypertension, ST use was associated with a 30% lower frequency of hypertension (odds ratio 0.70; 95% confidence interval 0.55 - 0.90).</p>
        </sec>
        <sec>
          <title>Conclusion:</title>
          <p>Chim&#243;, a ST frequently used in the Andes region of Venezuela, is associated with lower BP, heart rate, BMI, and frequency of hypertension in subjects with T2D older than 50 years. This counter-intuitive negative association of chim&#243; with some cardiometabolic risk factors highlights the complex nature of these relationships and the need for further studies.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords:</title>
        <kwd>Tobacco Use</kwd>
        <kwd>Tobacco Products</kwd>
        <kwd>Hypretension</kwd>
        <kwd>Coronary Artery Disease</kwd>
        <kwd>Venezuela</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>Tobacco use and hypertension are leading causes of disease burden worldwide. Together, they caused globally 15.4 million preventable deaths in 2012,<xref ref-type="bibr" rid="B1">1</xref> and 13.3% of disability-adjusted life years (DALY's) in 2010.<xref ref-type="bibr" rid="B2">2</xref> Tobacco use is defined as current use of any tobacco product in either smoked or smokeless form.<xref ref-type="bibr" rid="B3">3</xref> Many forms of smokeless tobacco (ST) products exist worldwide, and it has been reported that tobacco use increases the risk of coronary heart disease,<xref ref-type="bibr" rid="B4">4</xref> stroke,<xref ref-type="bibr" rid="B5">5</xref> metabolic syndrome,<xref ref-type="bibr" rid="B6">6</xref> type 2 diabetes (T2D),<xref ref-type="bibr" rid="B7">7</xref> and oropharyngeal cancer.<xref ref-type="bibr" rid="B8">8</xref>
			</p>
      <p>The prevalence of ST use ranges from 2% to 40% according to the region of the world.<xref ref-type="bibr" rid="B9">9</xref> A high prevalence of ST use (38%) has been described in the Andes region of Venezuela. The prevalence was higher in men than women (58% <italic>versus</italic> 18% respectively, p &lt; 0.0001), and increased with age.<xref ref-type="bibr" rid="B10">10</xref> Chim&#243; is the most common ST preparation in this region, and is composed of tobacco leaf, sodium bicarbonate, brown sugar, ashes from the mam&#243;n tree (<italic>Melicocca bijuga</italic>), and vanilla and anisette flavoring. The ingredients vary according to the region in Venezuela. A small amount of chim&#243; is placed between the lip or cheek and the gum and is left there for some time, usually 30 minutes. The mixture of chim&#243; and saliva is spit out.<xref ref-type="bibr" rid="B11">11</xref>
			</p>
      <p>The relationship between ST use and hypertension is not completely understood. In Sweden, the use of ST is not banned as in other European countries, and has an increased rate among men (27.2%).<xref ref-type="bibr" rid="B12">12</xref> In a prospective observational study, Hergens et al.<xref ref-type="bibr" rid="B5">5</xref> reported a 36% increased risk of hypertension among male Swedish users of snuff (made from ground or pulverized tobacco leaves) compared with non-users. In another cohort study using data from the Swedish Annual Level-of-Living Survey, Johansson et al.<xref ref-type="bibr" rid="B13">13</xref> found no difference in the age-adjusted incidence rates of hypertension between daily snuffers and non-tobacco users. Additionally, subjects with T2D are sensitive to nicotine via neuronal nicotinic acetylcholine receptors (nAChRs),<xref ref-type="bibr" rid="B14">14</xref>, <xref ref-type="bibr" rid="B15">15</xref> which can impair insulin action in the presence but not in the absence of T2D.<xref ref-type="bibr" rid="B16">16</xref>
			</p>
      <p>The prevalence of hypertension in the Andes region of Venezuela is elevated (25.0%)<xref ref-type="bibr" rid="B17">17</xref> and similar to that in the Barquisimeto city (24.7%),<xref ref-type="bibr" rid="B18">18</xref> located in the Western region of the country and identified as having the second highest prevalence of hypertension according to the Cardiovascular Risk Factor Multiple Evaluation in Latin America (CARMELA) study, almost duplicating the overall prevalence in Latin America (16.3%).<xref ref-type="bibr" rid="B18">18</xref> Given the global dimensions of hypertension and tobacco use, along with the elevated prevalence of hypertension and chim&#243; use in the Andes region of Venezuela, a critical goal of this study was to understand the relationships and interactions among hypertension, tobacco use, T2D, and other risk factors.</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <sec>
        <title>Population characteristics</title>
        <p>From 2013 to 2014, a total of 1,938 subjects aged 20 years or older consecutively attended a medical center located in Timotes in the Andes Region of Venezuela. Timotes is a mainly agricultural population in the Andean region of Venezuela, with 18,179 inhabitants, located at an altitude of 2,025 meters and with an average annual temperature of 16 &#176;C. The study participants completed a questionnaire. Information about age, gender, personal history of T2D, family and personal history of hypertension and tobacco use was obtained. The use of chim&#243; was questioned, with potential responses given in <xref ref-type="table" rid="t1">Table 1</xref>. Anthropometric measurements were also obtained. Weight was measured with the subjects wearing as few clothes as possible and no shoes, using a calibrated scale. Height was measured using a metric tape fixed on the wall. Body mass index (BMI; kg/m<xref ref-type="bibr" rid="B2">2</xref>) was calculated. Blood pressure (BP) was measured twice with an automated BP device (OMRON&#174; HEM-907XL; Omron Healthcare, Inc., 2007, Illinois, USA)<xref ref-type="bibr" rid="B19">19</xref> placed in the right arm at the heart level, with the individual in the sitting position and after 5 minutes of rest. All subjects signed an informed consent for participation.</p>
        <table-wrap id="t1">
          <label>Table 1</label>
          <caption>
            <title>Questionnaire of Smokeless Tobacco Use</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="50%"/>
              <col width="50%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left" style="background-color:#B2B2B2">Questions</th>
                <th align="center" style="background-color:#B2B2B2">Answers</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">Have you ever used smokeless tobacco, such as chim&#243;, chewing tobacco, or snus?</td>
                <td align="center">Yes, I currently use</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">Yes, but not within the past 12 months</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">No, I never used</td>
              </tr>
              <tr>
                <td align="left">Number of years of use</td>
                <td align="center">_________ years</td>
              </tr>
              <tr>
                <td align="left">Frequency of use</td>
                <td align="center">Daily</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">Weekly</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">Less than weekly</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
      </sec>
      <sec>
        <title>Variables definitions</title>
        <p>Hypertension was defined as a systolic BP &#8805; 140 mmHg, diastolic BP &#8805; 90 mmHg, or current use of antihypertensive medications.<xref ref-type="bibr" rid="B20">20</xref> ST use was defined as daily or weekly consumption of chim&#243; for the past 12 months. T2D was defined based on self-report.</p>
      </sec>
      <sec>
        <title>Statistical analysis</title>
        <p>All calculations were performed using the SPSS 20 program (IBM Corp., 2011, Armonk, NY, USA). Data for continuous variables are presented as mean &#177; standard deviation. After evaluation for normality, differences between mean values were assessed by unpaired Student's <italic>t</italic> test. Frequencies are presented as prevalence rates and 95% confidence intervals (95%CIs). The chi-square test was applied to compare different frequencies. Logistic regression was performed to estimate risk factors associated with hypertension. Statistical significance was considered at an alpha level of p &lt; 0.05.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <sec>
        <title>Subjects characteristics</title>
        <p>The study included 1,938 adults with a mean age of 49.2 years, 59.5% females, 38.9% with hypertension, 23.2% users of ST, and 11.6% with T2D. One-third of the subjects with T2D were ST users (<xref ref-type="table" rid="t2">Table 2</xref>). The subjects with T2D who were ST users showed lower values of heart rate, systolic BP, and BMI, as well as a lower frequency of hypertension when compared with those who were not ST users. In subjects without T2D, ST use was more frequent in men and older individuals. Also, among those without T2D, the heart rate was lower in ST users than in non-ST users.</p>
        <table-wrap id="t2">
          <label>Table 2</label>
          <caption>
            <title>Subject characteristics</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left" rowspan="3" style="background-color:#B2B2B2">
								</th>
                <th align="center" colspan="2" style="border-bottom-width:thin;border-bottom-style:solid;background-color:#B2B2B2">Type 2 diabetes</th>
                <th align="center" colspan="2" style="border-bottom-width:thin;border-bottom-style:solid;background-color:#B2B2B2">Without type 2 diabetes</th>
              </tr>
              <tr>
                <th align="center" colspan="2" style="border-bottom-width:thin;border-bottom-style:solid;background-color:#B2B2B2">
                  <bold>Smokeless Tobacco</bold>
                </th>
                <th align="center" colspan="2" style="border-bottom-width:thin;border-bottom-style:solid;background-color:#B2B2B2">
                  <bold>Smokeless Tobacco</bold>
                </th>
              </tr>
              <tr>
                <th align="center" style="background-color:#B2B2B2">
                  <bold>Users</bold>
                </th>
                <th align="center" style="background-color:#B2B2B2">
                  <bold>Non-users</bold>
                </th>
                <th align="center" style="background-color:#B2B2B2">
                  <bold>Users</bold>
                </th>
                <th align="center" style="background-color:#B2B2B2">
                  <bold>Non-users</bold>
                </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">Total: n</td>
                <td align="center">68</td>
                <td align="center">157</td>
                <td align="center">381</td>
                <td align="center">1332</td>
              </tr>
              <tr>
                <td align="left">Male (%)</td>
                <td align="center">51.5</td>
                <td align="center">40.1</td>
                <td align="center">55.6<xref ref-type="table-fn" rid="TFN4">**</xref>
								</td>
                <td align="center">35.7</td>
              </tr>
              <tr>
                <td align="left">Age (years)</td>
                <td align="center">61.9 &#177; 9.6</td>
                <td align="center">62.6 &#177; 13.8</td>
                <td align="center">50.0 &#177; 17.7<xref ref-type="table-fn" rid="TFN4">**</xref>
								</td>
                <td align="center">46.7 &#177; 16.9</td>
              </tr>
              <tr>
                <td align="left">Heart Rate</td>
                <td align="center">77.8 &#177; 11.7<xref ref-type="table-fn" rid="TFN3">*</xref>
								</td>
                <td align="center">82.2 &#177; 13.2</td>
                <td align="center">74.3 &#177; 13.9<xref ref-type="table-fn" rid="TFN3">*</xref>
								</td>
                <td align="center">78.6 &#177; 14.3</td>
              </tr>
              <tr>
                <td align="left">SBP (mmHg)</td>
                <td align="center">129.1 &#177; 22.8<xref ref-type="table-fn" rid="TFN3">*</xref>
								</td>
                <td align="center">136.6 &#177; 25.1</td>
                <td align="center">126.9 &#177; 20.6</td>
                <td align="center">126.3 &#177; 20.6</td>
              </tr>
              <tr>
                <td align="left">DBP (mmHg)</td>
                <td align="center">76.2 &#177; 12.2</td>
                <td align="center">78.7 &#177; 12.8</td>
                <td align="center">78.2 &#177; 12.4</td>
                <td align="center">79.0 &#177; 12.3</td>
              </tr>
              <tr>
                <td align="left">BMI (kg/m<sup>2</sup>)</td>
                <td align="center">25.8 &#177; 4.2<xref ref-type="table-fn" rid="TFN4">**</xref>
								</td>
                <td align="center">28.5 &#177; 4.8</td>
                <td align="center">27.5 &#177; 4.7</td>
                <td align="center">27.9 &#177; 5.1</td>
              </tr>
              <tr>
                <td align="left">Family Hypertension (%)</td>
                <td align="center">52.9 (41.04 - 64.76)</td>
                <td align="center">51.0 (43.18 - 58.82)</td>
                <td align="center">50.4 (45.38 - 55.42)</td>
                <td align="center">54.7 (52.03 - 57.37)</td>
              </tr>
              <tr>
                <td align="left">Overweight/Obesity (%)</td>
                <td align="center">61.8 (50.25 - 73.35)</td>
                <td align="center">74.5 (67.68 - 81.32)</td>
                <td align="center">69.8 (65.19 - 74.41)</td>
                <td align="center">70.2 (67.74 - 72.66)</td>
              </tr>
              <tr>
                <td align="left">Hypertension (%)</td>
                <td align="center">50.0 (38.12 - 61.88)<xref ref-type="table-fn" rid="TFN3">*</xref>
								</td>
                <td align="center">69.4 (62.19 - 76.61)</td>
                <td align="center">33.3 (28.57 - 38.03)</td>
                <td align="center">36.3 (33.72 - 38.88)</td>
              </tr>
              <tr>
                <td align="left">Current Cigarettes (%)</td>
                <td align="center">4.4 (0.47 - 9.27)</td>
                <td align="center">4.5 (1.26 - 7.74)</td>
                <td align="center">5.5 (3.21 - 7.79)</td>
                <td align="center">7.9 (6.45 - 9.35)</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN1">
              <p>Continuous variables are expressed as mean &#177; standard deviation (SD).</p>
            </fn>
            <fn id="TFN2">
              <p>Frequencies are expressed as percentages (95% confidence interval).</p>
            </fn>
            <fn id="TFN3">
              <label>*</label>
              <p>p &lt; 0.05;</p>
            </fn>
            <fn id="TFN4">
              <label>**</label>
              <p>p &lt; 0.0001 indicates differences between ST users and non-users using Student's t test for means and chi-square test for frequencies. SBP: Systolic blood pressure; DBP: Diastolic blood pressure; BMI: Body mass index. Overweight/Obesity: BMI &#8805; 25 kg/m<sup>2</sup>.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>Smokeless tobacco and hypertension</title>
        <p>The use of ST showed a significant relationship with hypertension in subjects with T2D who were older than 50 years (<xref ref-type="table" rid="t3">Table 3</xref>). In this group, ST users had a 69% lower frequency of hypertension compared with non-ST users. The association between ST use and lower frequency of hypertension remained significant after the variables were adjusted according to BMI (<xref ref-type="fig" rid="f1">Figure 1</xref>). Logistic regression adjusted by heart rate, age, T2D, overweight/obesity, and family history of hypertension showed that ST use was associated with a 30% lower frequency of hypertension (odds ratio = 0.70, 95%CI 0.55 - 0.90) (<xref ref-type="table" rid="t4">Table 4</xref>).</p>
        <table-wrap id="t3">
          <label>Table 3</label>
          <caption>
            <title>Relationship between ST use and hypertension in subjects with type 2 diabetes who were older than 50 years<xref ref-type="table-fn" rid="TFN5">*</xref>
						</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left" style="background-color:#B2B2B2">
								</th>
                <th align="center" style="background-color:#B2B2B2">
								</th>
                <th align="center" style="background-color:#B2B2B2">Hypertension</th>
                <th align="center" style="background-color:#B2B2B2">Normotension</th>
                <th align="center" style="background-color:#B2B2B2">OR (95% CI)</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">T2D</td>
                <td align="center">Smokeless Tobacco</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left" rowspan="2">Present</td>
                <td align="center">ST users</td>
                <td align="center">23.2 (15.80 - 30.60)</td>
                <td align="center">49.2 (36.85 - 61.55)</td>
                <td align="center" rowspan="2">0.31 (0.16 - 0.59)</td>
              </tr>
              <tr>
                <td align="center">ST non-users</td>
                <td align="center">76.8 (69.40 - 84.20)</td>
                <td align="center">50.8 (38.45 - 63.15)</td>
              </tr>
              <tr>
                <td align="left" rowspan="2">Absents</td>
                <td align="center">ST users</td>
                <td align="center">21.4 (17.34 - 25.46)</td>
                <td align="center">27.3 (22.46 - 32.14)</td>
                <td align="center" rowspan="2">0.72 (0.51 - 1.02)</td>
              </tr>
              <tr>
                <td align="center">ST non-users</td>
                <td align="center">78.6 (74.54 - 82.66)</td>
                <td align="center">72.7 (67.86 - 77.54)</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN5">
              <label>*</label>
              <p>Subjects younger than 50 years showed a non-significant relationship. Data are expressed as percentage (95% confidence interval [95%CI]).OR: Odds ratio; ST: Smokeless Tobacco; T2D: Type 2 diabetes.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>
          <fig id="f1">
            <label>Figure 1</label>
            <caption>
              <title>Frequency of hypertension according to nutritional status and smokeless tobacco use. Obesity: Body mass index (BMI) &#8805; 30 kg/m<sup>2</sup>; Overweight: BMI 25 to 29.9 kg/m2; Normal weight: BMI &lt; 25 kg/m<sup>2</sup>. p: differences between tobacco users and non-users by chi-square test.</title>
            </caption>
            <graphic xlink:href="2359-5647-ijcs-30-05-0373-70066-gf01.jpg"/></fig>
        </p>
        <table-wrap id="t4">
          <label>Table 4</label>
          <caption>
            <title>Risk factors associated with hypertension*</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="33%"/>
              <col width="33%"/>
              <col width="33%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left" style="background-color:#B2B2B2">
								</th>
                <th align="center" style="background-color:#B2B2B2">OR</th>
                <th align="center" style="background-color:#B2B2B2">95% CI</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">Smokeless tobacco (chim&#243;)</td>
                <td align="center">0.70</td>
                <td align="center">0.55 - 0.90</td>
              </tr>
              <tr>
                <td align="left">Heart rate</td>
                <td align="center">1.01</td>
                <td align="center">1.01 - 1.01</td>
              </tr>
              <tr>
                <td align="left">Age</td>
                <td align="center">1.06</td>
                <td align="center">1.05 - 1.06</td>
              </tr>
              <tr>
                <td align="left">Type 2 diabetes</td>
                <td align="center">1.62</td>
                <td align="center">1.17 - 2.22</td>
              </tr>
              <tr>
                <td align="left">Overweight/Obesity</td>
                <td align="center">1.65</td>
                <td align="center">1.30 - 2.09</td>
              </tr>
              <tr>
                <td align="left">Family hypertension</td>
                <td align="center">2.19</td>
                <td align="center">1.75 - 2.70</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">* Multiple logistic regression.</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN6">
              <p>OR: Odds ratio; 95%CI: Confidence Interval. Overweight/Obesity: BMI &#8805; 25 kg/m<sup>2</sup>.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>The use of chim&#243;, a form of ST frequently consumed in the Andes region of Venezuela, is associated with lower BP, heart rate, BMI, and hypertension in subjects with T2D older than 50 years. This is the first report associating chim&#243; and lower rates of hypertension, and the reason for this counter-intuitive association is unknown. This result fuels the controversy surrounding ST use and hypertension and may be due to one or more factors.</p>
      <p>India has a high prevalence of ST use.<xref ref-type="bibr" rid="B21">21</xref> In a cross-sectional study in that country evaluating 443 men older than 15 years of age in a rural setting, the prevalence of exclusive ST use (no smoked tobacco) was 21%.<xref ref-type="bibr" rid="B22">22</xref> The group that used only ST exhibited higher values of diastolic BP and a higher prevalence of diastolic hypertension compared with non-ST users, or with users of ST plus smoked tobacco.<xref ref-type="bibr" rid="B22">22</xref> The association between high BP and ST use can be related to nicotine levels and sodium concentrations in the ST composition. This result could be explained as some ST products contain large amounts of sodium, as part of the sodium bicarbonate, an alkaline buffer that is necessary to facilitate nicotine absorption. The sodium load (30 to 40 excess mEq sodium per day) could increase BP.<xref ref-type="bibr" rid="B23">23</xref> However, in 1,061 professional baseball players, ST use was not related to higher BP compared with non-ST users.<xref ref-type="bibr" rid="B24">24</xref> In that study, serum nicotine and cotinine (a major metabolite of nicotine) were measured. Participants who used snuff had higher serum levels of both cotinine and nicotine than those who used chewing tobacco. In participants with higher nicotine levels, higher diastolic BP was found.<xref ref-type="bibr" rid="B24">24</xref> Thus, the sodium content and the nicotine content and absorption can vary in different ST preparations potentially accounting for different BP effects.</p>
      <p>Another possible explanation for our result is the occurrence of masked hypertension in tobacco users. This effect has been previously reported in smokers, but not in ST users. Smokers tend to have a high daytime ambulatory BP (when they are more likely to be smoking) in comparison with their office BP (when they are less likely to be smoking).<xref ref-type="bibr" rid="B25">25</xref> The Second Australian National Blood Pressure Study also found that smoking predicted masked hypertension.<xref ref-type="bibr" rid="B26">26</xref>
			</p>
      <p>The effect of ST use on BP level observed in this report was only significant in T2D subjects. The sensitivity to nicotine in T2D has been evaluated comparing the effects of acute nicotine infusion in patients with and without diabetes.<xref ref-type="bibr" rid="B16">16</xref> Nicotine infusion did not affect the amount of insulin needed to maintain glucose levels in healthy volunteers, but higher levels of insulin were required in patients with diabetes, indicating that patients with T2D are more susceptible to a negative effect of nicotine on insulin sensitivity.<xref ref-type="bibr" rid="B16">16</xref>
			</p>
      <p>In smokers, nicotine acutely increases energy expenditure and may reduce appetite.<xref ref-type="bibr" rid="B27">27</xref> This effect could explain the trend of smokers having lower body weight than nonsmokers, and weight gain generally occurring after smoking cessation.<xref ref-type="bibr" rid="B28">28</xref> In this report, subjects with T2D that used ST had lower BMIs than those not using ST, similar to the findings observed in smokers. Also, this report found a lower heart rate in ST users, which also may be due to exposure to a negative chronotropic activity of some component of chim&#243;.</p>
      <p>The present study has some limitations. First, chim&#243; in Venezuela is mostly produced using traditional methods, which generate many different formulations for sale, with no fixed doses, and therefore, dosing cannot be characterized as with cigarettes. Moreover, the majority of the components and their respective doses derived from the tobacco leaf in chim&#243; preparations are unknown. Second, blood concentrations of nicotine or cotinine were not measured. Third, oral examination was not used to evaluate the use of ST. Finally, T2D was only diagnosed by self-report.</p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclusion</title>
      <p>This study demonstrates for the first time a negative association of chim&#243; use and hypertension. Many forms of ST have been associated (with contradictory evidence in some cases) with cardiovascular disease, cancer, and metabolic alterations. The biological basis of the findings in this report remains elusive. Even though ST use was not associated with a higher frequency of hypertension in this study, it is stressed that ST use is not a healthy practice in patients with T2D, and more importantly, ST use should not be interpreted as a means to reduce the risk of hypertension. The effects of chim&#243; are complex, overall unhealthy, and, in practice, a public health problem requiring further scientific study.</p>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="financial-disclosure">
        <p>
          <bold>Sources of Funding</bold>
        </p>
        <p>There were no external funding sources for this study.</p>
      </fn>
      <fn fn-type="other">
        <p>
          <bold>Study Association</bold>
        </p>
        <p>This study is not associated with any thesis or dissertation work.</p>
      </fn>
    </fn-group>
    <ref-list>
      <title>References</title>
      <ref id="B1">
        <label>1</label>
        <mixed-citation>1 World Health Organization. (WHO). Global status report on noncommunicable diseases 2014: a 30% relative reduction in prevalence of current tobacco use. Geneva; 2014. p. 53-66.</mixed-citation>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <collab>World Health Organization. (WHO)</collab>
          </person-group>
          <source>Global status report on noncommunicable diseases 2014: a 30% relative reduction in prevalence of current tobacco use</source>
          <publisher-loc>Geneva</publisher-loc>
          <year>2014</year>
          <fpage>53</fpage>
          <lpage>66</lpage>
        </element-citation>
      </ref>
      <ref id="B2">
        <label>2</label>
        <mixed-citation>2 Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2224-60. doi: 10.1016/S0140-6736(12)61766-8</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Lim</surname>
              <given-names>SS</given-names>
            </name>
            <name>
              <surname>Vos</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Flaxman</surname>
              <given-names>AD</given-names>
            </name>
            <name>
              <surname>Danaei</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Shibuya</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Adair-Rohani</surname>
              <given-names>H</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010</article-title>
          <source>Lancet</source>
          <year>2012</year>
          <volume>380</volume>
          <issue>9859</issue>
          <fpage>2224</fpage>
          <lpage>2260</lpage>
          <pub-id pub-id-type="doi">10.1016/S0140-6736(12)61766-8</pub-id>
        </element-citation>
      </ref>
      <ref id="B3">
        <label>3</label>
        <mixed-citation>3 World Health Organization. (WHO). Noncommunicable diseases and mental health. NCD global monitoring framework: indicator definitions and specifications. Geneva; 2014. [Accessed on 2015 Jul 10]. Available from: <ext-link ext-link-type="uri" xlink:href="http://www.who.int/nmh/global_monitoring_framework/en/">http://www.who.int/nmh/global_monitoring_framework/en/</ext-link>
				</mixed-citation>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <collab>World Health Organization. (WHO)</collab>
          </person-group>
          <chapter-title>Noncommunicable diseases and mental health</chapter-title>
          <source>NCD global monitoring framework: indicator definitions and specifications</source>
          <publisher-loc>Geneva</publisher-loc>
          <year>2014</year>
          <date-in-citation content-type="access-date">2015 Jul 10</date-in-citation>
          <comment>Available from: <ext-link ext-link-type="uri" xlink:href="http://www.who.int/nmh/global_monitoring_framework/en/">http://www.who.int/nmh/global_monitoring_framework/en/</ext-link>
					</comment>
        </element-citation>
      </ref>
      <ref id="B4">
        <label>4</label>
        <mixed-citation>4 Teo KK, Ounpuu S, Hawken S, Pandey MR, Valentin V, Hunt D, et al; INTERHEART Study Investigators. Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case-control study. Lancet. 2006;368(9536):647-58. doi: 10.1016/S0140-6736(06)69249-0.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Teo</surname>
              <given-names>KK</given-names>
            </name>
            <name>
              <surname>Ounpuu</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Hawken</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Pandey</surname>
              <given-names>MR</given-names>
            </name>
            <name>
              <surname>Valentin</surname>
              <given-names>V</given-names>
            </name>
            <name>
              <surname>Hunt</surname>
              <given-names>D</given-names>
            </name>
            <etal/>
            <collab>INTERHEART Study Investigators</collab>
          </person-group>
          <article-title>Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case-control study</article-title>
          <source>Lancet</source>
          <year>2006</year>
          <volume>368</volume>
          <issue>9536</issue>
          <fpage>647</fpage>
          <lpage>658</lpage>
          <pub-id pub-id-type="doi">10.1016/S0140-6736(06)69249-0</pub-id>
        </element-citation>
      </ref>
      <ref id="B5">
        <label>5</label>
        <mixed-citation>5 Hergens MP, Lambe M, Pershagen G, Ye W. Risk of hypertension amongst Swedish male snuff users: a prospective study. J Intern Med. 2008;264(2):187-94. doi: 10.1111/j.1365-2796.2008.01939.x.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Hergens</surname>
              <given-names>MP</given-names>
            </name>
            <name>
              <surname>Lambe</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Pershagen</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Ye</surname>
              <given-names>W</given-names>
            </name>
          </person-group>
          <article-title>Risk of hypertension amongst Swedish male snuff users: a prospective study</article-title>
          <source>J Intern Med</source>
          <year>2008</year>
          <volume>264</volume>
          <issue>2</issue>
          <fpage>187</fpage>
          <lpage>194</lpage>
          <pub-id pub-id-type="doi">10.1111/j.1365-2796.2008.01939.x</pub-id>
        </element-citation>
      </ref>
      <ref id="B6">
        <label>6</label>
        <mixed-citation>6 Norberg M, Stenlund H, Lindahl B, Boman K, Weinehall L. Contribution of Swedish moist snuff to the metabolic syndrome: a wolf in sheep's clothing? Scand J Public Health. 2006;34(6):576-83. doi: 10.1080/14034940600665143.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Norberg</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Stenlund</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Lindahl</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Boman</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Weinehall</surname>
              <given-names>L</given-names>
            </name>
          </person-group>
          <article-title>Contribution of Swedish moist snuff to the metabolic syndrome: a wolf in sheep's clothing?</article-title>
          <source>Scand J Public Health</source>
          <year>2006</year>
          <volume>34</volume>
          <issue>6</issue>
          <fpage>576</fpage>
          <lpage>583</lpage>
          <pub-id pub-id-type="doi">10.1080/14034940600665143</pub-id>
        </element-citation>
      </ref>
      <ref id="B7">
        <label>7</label>
        <mixed-citation>7 Persson PG, Carlsson S, Svanstrom L, Ostenson CG, Efendic S, Grill V. Cigarette smoking, oral moist snuff use and glucose intolerance. J Intern Med. 2000;248(2):103-10.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Persson</surname>
              <given-names>PG</given-names>
            </name>
            <name>
              <surname>Carlsson</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Svanstrom</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Ostenson</surname>
              <given-names>CG</given-names>
            </name>
            <name>
              <surname>Efendic</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Grill</surname>
              <given-names>V</given-names>
            </name>
          </person-group>
          <article-title>Cigarette smoking, oral moist snuff use and glucose intolerance</article-title>
          <source>J Intern Med</source>
          <year>2000</year>
          <volume>248</volume>
          <issue>2</issue>
          <fpage>103</fpage>
          <lpage>110</lpage>
        </element-citation>
      </ref>
      <ref id="B8">
        <label>8</label>
        <mixed-citation>8 Lee P, Hamling J. Systematic review of the relation between smokeless tobacco and cancer in Europe and North America. BMC Med. 2009;7(1):36. doi: 10.1186/1741-7015-7-36.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Lee</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Hamling</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
          <article-title>Systematic review of the relation between smokeless tobacco and cancer in Europe and North America</article-title>
          <source>BMC Med</source>
          <year>2009</year>
          <volume>7</volume>
          <issue>1</issue>
          <fpage>36</fpage>
          <lpage>36</lpage>
          <pub-id pub-id-type="doi">10.1186/1741-7015-7-36</pub-id>
        </element-citation>
      </ref>
      <ref id="B9">
        <label>9</label>
        <mixed-citation>9 Piano MR, Benowitz NL, FitzGerald GA, Corbridge S, Heath J, Hahn E, et al; American Heart Association Council on Cardiovascular Nursing. Impact of smokeless tobacco products on cardiovascular disease: implications for policy, prevention, and treatment: a policy statement from the American Heart Association. Circulation. 2010;122(15):1520-44. doi: 10.1161/CIR.0b013e3181f432c3.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Piano</surname>
              <given-names>MR</given-names>
            </name>
            <name>
              <surname>Benowitz</surname>
              <given-names>NL</given-names>
            </name>
            <name>
              <surname>FitzGerald</surname>
              <given-names>GA</given-names>
            </name>
            <name>
              <surname>Corbridge</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Heath</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Hahn</surname>
              <given-names>E</given-names>
            </name>
            <etal/>
            <collab>American Heart Association Council on Cardiovascular Nursing</collab>
          </person-group>
          <article-title>Impact of smokeless tobacco products on cardiovascular disease: implications for policy, prevention, and treatment: a policy statement from the American Heart Association</article-title>
          <source>Circulation</source>
          <year>2010</year>
          <volume>122</volume>
          <issue>15</issue>
          <fpage>1520</fpage>
          <lpage>1544</lpage>
          <pub-id pub-id-type="doi">10.1161/CIR.0b013e3181f432c3</pub-id>
        </element-citation>
      </ref>
      <ref id="B10">
        <label>10</label>
        <mixed-citation>10 Gonz&#225;lez-Rivas J, Garc&#237;a Santiago R, Araujo Linares N, Echenique Zureche P. Prevalencia de consumo de tabaco no inhalado (chim&#243;) en el municipio Miranda del Estado M&#233;rida, Venezuela. Rev Ven Endocrinol Metab. 2011;9(3):99-105.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Gonz&#225;lez-Rivas</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Garc&#237;a Santiago</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Araujo Linares</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Echenique Zureche</surname>
              <given-names>P</given-names>
            </name>
          </person-group>
          <article-title>Prevalencia de consumo de tabaco no inhalado (chim&#243;) en el municipio Miranda del Estado M&#233;rida, Venezuela</article-title>
          <source>Rev Ven Endocrinol Metab</source>
          <year>2011</year>
          <volume>9</volume>
          <issue>3</issue>
          <fpage>99</fpage>
          <lpage>105</lpage>
        </element-citation>
      </ref>
      <ref id="B11">
        <label>11</label>
        <mixed-citation>11 Smokeless Tobacco Fact Sheets. In: 3rd International Conference on Smokeless Tobacco. Stockholm (Sweden). September 22 - 25, 2002. Stockholm: Centre of Public Health Centre for Tobacco Prevention; 2002.</mixed-citation>
        <element-citation publication-type="confproc">
          <person-group person-group-type="author">
            <collab>Smokeless Tobacco Fact Sheets</collab>
          </person-group>
          <conf-name>3rd International Conference on Smokeless Tobacco</conf-name>
          <source>Stockholm (Sweden)</source>
          <season>22-25</season>
          <month>09</month>
          <year>2002</year>
          <publisher-loc>Stockholm</publisher-loc>
          <publisher-name>Centre of Public Health Centre for Tobacco Prevention</publisher-name>
          <year>2002</year>
        </element-citation>
      </ref>
      <ref id="B12">
        <label>12</label>
        <mixed-citation>12 Furberg H, Lichtenstein P, Pedersen NL, Bulik C, Sullivan PF. Cigarettes and oral snuff use in Sweden: prevalence and transitions. Addiction. 2006;101(10):1509-15. doi: 10.1111/j.1360-0443.2006.01550.x.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Furberg</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Lichtenstein</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Pedersen</surname>
              <given-names>NL</given-names>
            </name>
            <name>
              <surname>Bulik</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Sullivan</surname>
              <given-names>PF</given-names>
            </name>
          </person-group>
          <article-title>Cigarettes and oral snuff use in Sweden: prevalence and transitions</article-title>
          <source>Addiction</source>
          <year>2006</year>
          <volume>101</volume>
          <issue>10</issue>
          <fpage>1509</fpage>
          <lpage>1515</lpage>
          <pub-id pub-id-type="doi">10.1111/j.1360-0443.2006.01550.x</pub-id>
        </element-citation>
      </ref>
      <ref id="B13">
        <label>13</label>
        <mixed-citation>13 Johansson SE, Sundquist K, Qvist J, Sundquist J. Smokeless tobacco and coronary heart disease: a 12-year follow-up study. Eur J Cardiovasc Prev Rehabil. 2005;12(4):387-92. Erratum in: Eur J Cardiovasc Prev Rehabil. 2007 Oct;14(5):722.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Johansson</surname>
              <given-names>SE</given-names>
            </name>
            <name>
              <surname>Sundquist</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Qvist</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Sundquist</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
          <article-title>Smokeless tobacco and coronary heart disease: a 12-year follow-up study</article-title>
          <source>Eur J Cardiovasc Prev Rehabil</source>
          <year>2005</year>
          <volume>12</volume>
          <issue>4</issue>
          <fpage>387</fpage>
          <lpage>392</lpage>
          <comment>Erratum in: Eur J Cardiovasc Prev Rehabil. 2007 Oct;14(5):722</comment>
        </element-citation>
      </ref>
      <ref id="B14">
        <label>14</label>
        <mixed-citation>14 Yoshikawa H, Hellstrom-Lindahl E, Grill V. Evidence for functional nicotinic receptors on pancreatic beta cells. Metabolism. 2005;54(2):247-54. doi: 10.1016/j.metabol.2004.08.020.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Yoshikawa</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Hellstrom-Lindahl</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Grill</surname>
              <given-names>V</given-names>
            </name>
          </person-group>
          <article-title>Evidence for functional nicotinic receptors on pancreatic beta cells</article-title>
          <source>Metabolism</source>
          <year>2005</year>
          <volume>54</volume>
          <issue>2</issue>
          <fpage>247</fpage>
          <lpage>254</lpage>
          <pub-id pub-id-type="doi">10.1016/j.metabol.2004.08.020</pub-id>
        </element-citation>
      </ref>
      <ref id="B15">
        <label>15</label>
        <mixed-citation>15 Ejiri K, Taniguchi H, Baba S. Participation of nicotinic receptor in hormone release from isolated rat islets of Langerhans. Diabetes Res Clin Pract. 1989;6(1):53-9.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Ejiri</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Taniguchi</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Baba</surname>
              <given-names>S</given-names>
            </name>
          </person-group>
          <article-title>Participation of nicotinic receptor in hormone release from isolated rat islets of Langerhans</article-title>
          <source>Diabetes Res Clin Pract</source>
          <year>1989</year>
          <volume>6</volume>
          <issue>1</issue>
          <fpage>53</fpage>
          <lpage>59</lpage>
        </element-citation>
      </ref>
      <ref id="B16">
        <label>16</label>
        <mixed-citation>16 Axelsson T, Jansson PA, Smith U, Eliasson B. Nicotine infusion acutely impairs insulin sensitivity in type 2 diabetic patients but not in healthy subjects. J Intern Med. 2001;249(6):539-44.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Axelsson</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Jansson</surname>
              <given-names>PA</given-names>
            </name>
            <name>
              <surname>Smith</surname>
              <given-names>U</given-names>
            </name>
            <name>
              <surname>Eliasson</surname>
              <given-names>B</given-names>
            </name>
          </person-group>
          <article-title>Nicotine infusion acutely impairs insulin sensitivity in type 2 diabetic patients but not in healthy subjects</article-title>
          <source>J Intern Med</source>
          <year>2001</year>
          <volume>249</volume>
          <issue>6</issue>
          <fpage>539</fpage>
          <lpage>544</lpage>
        </element-citation>
      </ref>
      <ref id="B17">
        <label>17</label>
        <mixed-citation>17 Nieto-Mart&#237;nez R, Gonz&#225;lez-Rivas J, Garc&#237;a RJ, Ugel E, Osuna D, Salazar L. Prevalencia de hipertensi&#243;n arterial y dislipidemias en adultos del p&#225;ramo del Estado M&#233;rida y su relaci&#243;n con obesidad. Results from VEMSOLS study. Avances Cardiol. 2011;31(3):193-200.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Nieto-Mart&#237;nez</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Gonz&#225;lez-Rivas</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Garc&#237;a</surname>
              <given-names>RJ</given-names>
            </name>
            <name>
              <surname>Ugel</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Osuna</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Salazar</surname>
              <given-names>L</given-names>
            </name>
          </person-group>
          <article-title>Prevalencia de hipertensi&#243;n arterial y dislipidemias en adultos del p&#225;ramo del Estado M&#233;rida y su relaci&#243;n con obesidad. Results from VEMSOLS study</article-title>
          <source>Avances Cardiol</source>
          <year>2011</year>
          <volume>31</volume>
          <issue>3</issue>
          <fpage>193</fpage>
          <lpage>200</lpage>
        </element-citation>
      </ref>
      <ref id="B18">
        <label>18</label>
        <mixed-citation>18 Hernandez-Hernandez R, Silva H, Velasco M, Pellegrini F, Macchia A, Escobedo J, et al. Hypertension in seven Latin American cities: the Cardiovascular Risk Factor Multiple Evaluation in Latin America (CARMELA) study. J Hypertens. 2010;28(1):24-34. doi: 10.1097/HJH.0b013e328332c353.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Hernandez-Hernandez</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Silva</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Velasco</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Pellegrini</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Macchia</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Escobedo</surname>
              <given-names>J</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Hypertension in seven Latin American cities: the Cardiovascular Risk Factor Multiple Evaluation in Latin America (CARMELA) study</article-title>
          <source>J Hypertens</source>
          <year>2010</year>
          <volume>28</volume>
          <issue>1</issue>
          <fpage>24</fpage>
          <lpage>34</lpage>
          <pub-id pub-id-type="doi">10.1097/HJH.0b013e328332c353</pub-id>
        </element-citation>
      </ref>
      <ref id="B19">
        <label>19</label>
        <mixed-citation>19 El Assaad MA, Topouchian JA, Darne BM, Asmar RG. Validation of the Omron HEM-907 device for blood pressure measurement. Blood Press Monit. 2002;7(4):237-41.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>El Assaad</surname>
              <given-names>MA</given-names>
            </name>
            <name>
              <surname>Topouchian</surname>
              <given-names>JA</given-names>
            </name>
            <name>
              <surname>Darne</surname>
              <given-names>BM</given-names>
            </name>
            <name>
              <surname>Asmar</surname>
              <given-names>RG</given-names>
            </name>
          </person-group>
          <article-title>Validation of the Omron HEM-907 device for blood pressure measurement</article-title>
          <source>Blood Press Monit</source>
          <year>2002</year>
          <volume>7</volume>
          <issue>4</issue>
          <fpage>237</fpage>
          <lpage>241</lpage>
        </element-citation>
      </ref>
      <ref id="B20">
        <label>20</label>
        <mixed-citation>20 Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013;31(7):1281-357. doi: 10.1097/01.hjh.0000431740.32696.cc</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Mancia</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Fagard</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Narkiewicz</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Redon</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Zanchetti</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Bohm</surname>
              <given-names>M</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC)</article-title>
          <source>J Hypertens</source>
          <year>2013</year>
          <volume>31</volume>
          <issue>7</issue>
          <fpage>1281</fpage>
          <lpage>1357</lpage>
          <pub-id pub-id-type="doi">10.1097/01.hjh.0000431740.32696.cc</pub-id>
        </element-citation>
      </ref>
      <ref id="B21">
        <label>21</label>
        <mixed-citation>21 Rani M, Bonu S, Jha P, Nguyen SN, Jamjoum L. Tobacco use in India: prevalence and predictors of smoking and chewing in a national cross sectional household survey. Tob Control. 2003;12(4):e4.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Rani</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Bonu</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Jha</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Nguyen</surname>
              <given-names>SN</given-names>
            </name>
            <name>
              <surname>Jamjoum</surname>
              <given-names>L</given-names>
            </name>
          </person-group>
          <article-title>Tobacco use in India: prevalence and predictors of smoking and chewing in a national cross sectional household survey</article-title>
          <source>Tob Control</source>
          <year>2003</year>
          <volume>12</volume>
          <issue>4</issue>
          <elocation-id>e4</elocation-id>
        </element-citation>
      </ref>
      <ref id="B22">
        <label>22</label>
        <mixed-citation>22 Pandey A, Patni N, Sarangi S, Singh M, Sharma K, Vellimana AK, et al. Association of exclusive smokeless tobacco consumption with hypertension in an adult male rural population of India. Tob Induc Dis. 2009;5:15. doi: 10.1186/1617-9625-5-15.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Pandey</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Patni</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Sarangi</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Singh</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Sharma</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Vellimana</surname>
              <given-names>AK</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Association of exclusive smokeless tobacco consumption with hypertension in an adult male rural population of India</article-title>
          <source>Tob Induc Dis</source>
          <year>2009</year>
          <volume>5</volume>
          <fpage>15</fpage>
          <lpage>15</lpage>
          <pub-id pub-id-type="doi">10.1186/1617-9625-5-15</pub-id>
        </element-citation>
      </ref>
      <ref id="B23">
        <label>23</label>
        <mixed-citation>23 Benowitz NL. Sodium intake from smokeless tobacco. N Engl J Med. 1988;319(13):873-4. doi: 10.1056/NEJM198809293191318.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Benowitz</surname>
              <given-names>NL</given-names>
            </name>
          </person-group>
          <article-title>Sodium intake from smokeless tobacco</article-title>
          <source>N Engl J Med</source>
          <year>1988</year>
          <volume>319</volume>
          <issue>13</issue>
          <fpage>873</fpage>
          <lpage>874</lpage>
          <pub-id pub-id-type="doi">10.1056/NEJM198809293191318</pub-id>
        </element-citation>
      </ref>
      <ref id="B24">
        <label>24</label>
        <mixed-citation>24 Siegel D, Benowitz N, Ernster VL, Grady DG, Hauck WW. Smokeless tobacco, cardiovascular risk factors, and nicotine and cotinine levels in professional baseball players. Am J Public Health. 1992;82 (3):417-21.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Siegel</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Benowitz</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Ernster</surname>
              <given-names>VL</given-names>
            </name>
            <name>
              <surname>Grady</surname>
              <given-names>DG</given-names>
            </name>
            <name>
              <surname>Hauck</surname>
              <given-names>WW</given-names>
            </name>
          </person-group>
          <article-title>Smokeless tobacco, cardiovascular risk factors, and nicotine and cotinine levels in professional baseball players</article-title>
          <source>Am J Public Health</source>
          <year>1992</year>
          <volume>82</volume>
          <issue>3</issue>
          <fpage>417</fpage>
          <lpage>421</lpage>
        </element-citation>
      </ref>
      <ref id="B25">
        <label>25</label>
        <mixed-citation>25 Mann SJ, James GD, Wang RS, Pickering TG. Elevation of ambulatory systolic blood pressure in hypertensive smokers. A case-control study. JAMA. 1991;265(17):2226-8.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Mann</surname>
              <given-names>SJ</given-names>
            </name>
            <name>
              <surname>James</surname>
              <given-names>GD</given-names>
            </name>
            <name>
              <surname>Wang</surname>
              <given-names>RS</given-names>
            </name>
            <name>
              <surname>Pickering</surname>
              <given-names>TG</given-names>
            </name>
          </person-group>
          <article-title>Elevation of ambulatory systolic blood pressure in hypertensive smokers</article-title>
          <article-title>A case-control study</article-title>
          <source>JAMA</source>
          <year>1991</year>
          <volume>265</volume>
          <issue>17</issue>
          <fpage>2226</fpage>
          <lpage>2228</lpage>
        </element-citation>
      </ref>
      <ref id="B26">
        <label>26</label>
        <mixed-citation>26 Wing LM, Brown MA, Beilin LJ, Ryan P, Reid CM; ANBP2 Management Committee and Investigators. Second Autralian National Blood Pressure Study. Reverse white-coat hypertension' in older hypertensives. J Hypertens. 2002;20(4):639-44.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Wing</surname>
              <given-names>LM</given-names>
            </name>
            <name>
              <surname>Brown</surname>
              <given-names>MA</given-names>
            </name>
            <name>
              <surname>Beilin</surname>
              <given-names>LJ</given-names>
            </name>
            <name>
              <surname>Ryan</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Reid</surname>
              <given-names>CM</given-names>
            </name>
            <collab>ANBP2 Management Committee and Investigators</collab>
            <collab>Second Autralian National Blood Pressure Study</collab>
          </person-group>
          <article-title>Reverse white-coat hypertension' in older hypertensives</article-title>
          <source>J Hypertens</source>
          <year>2002</year>
          <volume>20</volume>
          <issue>4</issue>
          <fpage>639</fpage>
          <lpage>644</lpage>
        </element-citation>
      </ref>
      <ref id="B27">
        <label>27</label>
        <mixed-citation>27 Hofstetter A, Schutz Y, Jequier E, Wahren J. Increased 24-hour energy expenditure in cigarette smokers. N Engl J Med. 1986;314(2):79-82. doi: 10.1056/NEJM198601093140204.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Hofstetter</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Schutz</surname>
              <given-names>Y</given-names>
            </name>
            <name>
              <surname>Jequier</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Wahren</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
          <article-title>Increased 24-hour energy expenditure in cigarette smokers</article-title>
          <source>N Engl J Med</source>
          <year>1986</year>
          <volume>314</volume>
          <issue>2</issue>
          <fpage>79</fpage>
          <lpage>82</lpage>
          <pub-id pub-id-type="doi">10.1056/NEJM198601093140204</pub-id>
        </element-citation>
      </ref>
      <ref id="B28">
        <label>28</label>
        <mixed-citation>28 Chiolero A, Faeh D, Paccaud F, Cornuz J. Consequences of smoking for body weight, body fat distribution, and insulin resistance. Am J Clin Nutr. 2008;87(4):801-9.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Chiolero</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Faeh</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Paccaud</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Cornuz</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
          <article-title>Consequences of smoking for body weight, body fat distribution, and insulin resistance</article-title>
          <source>Am J Clin Nutr</source>
          <year>2008</year>
          <volume>87</volume>
          <issue>4</issue>
          <fpage>801</fpage>
          <lpage>809</lpage>
        </element-citation>
      </ref>
    </ref-list>
  </back>
  <sub-article article-type="translation" id="s1" xml:lang="pt">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>O Chim&#243;, uma Prepara&#231;&#227;o de Tabaco sem Fuma&#231;a, est&#225; Associado a uma Frequ&#234;ncia mais Baixa de Hipertens&#227;o em Indiv&#237;duos com Diabetes Tipo 2</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Gonz&#225;lez-Rivas</surname>
            <given-names>Juan P.</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">1</xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Santiago</surname>
            <given-names>Raul Jos&#233; Garc&#237;a</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mechanick</surname>
            <given-names>Jeffrey I.</given-names>
          </name>
          <xref ref-type="aff" rid="aff7">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Nieto-Mart&#237;nez</surname>
            <given-names>Ramfis</given-names>
          </name>
          <xref ref-type="aff" rid="aff8">3</xref>
          <xref ref-type="aff" rid="aff9">4</xref>
          <xref ref-type="aff" rid="aff10">5</xref>
        </contrib>
      </contrib-group>
      <aff id="aff6">
        <label>1</label>
        <institution content-type="original">The Andes Clinic of Cardio-Metabolic Studies, M&#233;rida - Venezuela</institution>
      </aff>
      <aff id="aff7">
        <label>2</label>
        <institution content-type="original">Division of Endocrinology, Diabetes and Bone Disease, Icahn School of Medicine at Mount Sinai, New York - EUA</institution>
      </aff>
      <aff id="aff8">
        <label>3</label>
        <institution content-type="original">Department of Physiology, School of Medicine, Universidad Centro-Occidental "Lisandro Alvarado" (UCLA) and Cardio-Metabolic Unit 7</institution>
      </aff>
      <aff id="aff9">
        <label>4</label>
        <institution content-type="original">Geriatric Research, Education and Clinical Center (GRECC), Miami VA Healthcare System, Miami, FL, USA</institution>
      </aff>
      <aff id="aff10">
        <label>5</label>
        <institution content-type="original">South Florida Veterans Affairs Foundation for Research &amp; Education, Miami - USA</institution>
      </aff>
      <author-notes>
        <corresp id="c2"><bold>Correspond&#234;ncia: Juan P. Gonz&#225;lez</bold> &#8211; Rivas The Andes Clinic of Cardio-Metabolic Studies. Av. Miranda, 3112, Sector Centre, Timotes, M&#233;rida &#8211; Venezuela. E-mail: <email>juanpgonzalezr@hotmail.com</email>; <email>juanpgonzalezr79@gmail.com</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Contribui&#231;&#227;o dos autores</bold>
          </p>
          <p>Concep&#231;&#227;o e desenho da pesquisa: Gonz&#225;lez-Rivas JP, Santiago RJG. Obten&#231;&#227;o de dados: Gonz&#225;lez-Rivas JP. An&#225;lise e interpreta&#231;&#227;o dos dados: Gonz&#225;lez-Rivas JP, Santiago RJG, Mechanick JI, Nieto-Mart&#237;nez R. An&#225;lise estat&#237;stica: Gonz&#225;lez-Rivas JP. Reda&#231;&#227;o do manuscrito: Gonz&#225;lez-Rivas JP. Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Santiago RJG, Mechanick JI, Nieto-Mart&#237;nez R. Supervis&#227;o / como investigador principal: Mechanick JI, Nieto-Mart&#237;nez R.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potencial Conflito de Interesse</bold>
          </p>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
        </fn>
      </author-notes>
      <abstract>
        <title>Resumo</title>
        <sec>
          <title>Fundamentos:</title>
          <p>O uso do tabaco e a hipertens&#227;o arterial sist&#234;mica (HAS) s&#227;o as principais causas preven&#237;veis de morte a n&#237;vel global. O tabaco &#233; apresentado nas formas com ou sem fuma&#231;a (TSF). O uso do TSF tem sido relacionado &#224; doen&#231;a cardiovascular, diabetes tipo 2 (DM2) e c&#226;ncer. Na Venezuela, o chim&#243; &#233; a prepara&#231;&#227;o de TSF mais comum e a sua rela&#231;&#227;o com a HAS &#233; desconhecida.</p>
        </sec>
        <sec>
          <title>Objetivo:</title>
          <p>Avaliar a rela&#231;&#227;o entre o uso de chim&#243; e HAS em uma popula&#231;&#227;o com alta preval&#234;ncia de uso de TSF na Venezuela.</p>
        </sec>
        <sec>
          <title>M&#233;todos:</title>
          <p>Entre 2013-2014, um total de 1.938 indiv&#237;duos com 20 anos ou mais foram avaliados consecutivamente em um centro m&#233;dico. Foram obtidas medidas antropom&#233;tricas e de press&#227;o arterial (PA), al&#233;m de respostas a um question&#225;rio padr&#227;o.</p>
        </sec>
        <sec>
          <title>Resultados:</title>
          <p>Os participantes tinham uma m&#233;dia de idade de 49,2 anos, 59,5% eram do sexo feminino, 38,9% apresentavam HAS, 23,2% relataram uso de TSF e 11,6% relataram ter DM2. Um ter&#231;o dos indiv&#237;duos com DM2 eram usu&#225;rios de TSF, e este grupo mostrou valores mais baixos de frequ&#234;ncia card&#237;aca, PA sist&#243;lica, &#237;ndice de massa corporal (IMC) e frequ&#234;ncia de HAS quando comparado a sujeitos com DM2 n&#227;o usu&#225;rios de TSF (p &lt; 0,05). Em indiv&#237;duos com DM2 com 50 anos ou mais, o uso de TSF foi associado a uma frequ&#234;ncia 69% mais baixa de HAS quando comparados a indiv&#237;duos que n&#227;o usavam TSF. Em regress&#227;o log&#237;stica ajustada pela frequ&#234;ncia card&#237;aca, idade, ocorr&#234;ncia de DM2, sobrepeso/obesidade e hist&#243;ria familiar de HAS, o uso de TSF esteve associado a uma frequ&#234;ncia 30% mais baixa de HAS (raz&#227;o de chances 0,70; intervalo de confian&#231;a de 95% 0,55 - 0,90).</p>
        </sec>
        <sec>
          <title>Conclus&#227;o:</title>
          <p>O chim&#243;, um TSF frequentemente utilizado na regi&#227;o dos Andes na Venezuela, est&#225; associado a valores mais baixos de PA, frequ&#234;ncia card&#237;aca, IMC e frequ&#234;ncia mais baixa de HAS em indiv&#237;duos com DM2 com mais de 50 anos. Esta associa&#231;&#227;o contraintuitiva negativa entre o chim&#243; e alguns fatores de risco cardiometab&#243;licos real&#231;a o car&#225;ter complexo destas rela&#231;&#245;es e a necessidade de estudos adicionais.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave</title>
        <kwd>Uso de Tabaco</kwd>
        <kwd>Produtos do Tabaco</kwd>
        <kwd>Hipertens&#227;o</kwd>
        <kwd>Doen&#231;a da Art&#233;ria Coronariana</kwd>
        <kwd>Venezuela</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introdu&#231;&#227;o</title>
        <p>O uso de tabaco e a hipertens&#227;o arterial sist&#234;mica (HAS) s&#227;o as principais causas de doen&#231;as em todo o mundo. Juntos, eles causaram globalmente 15,4 milh&#245;es de mortes preven&#237;veis em 2012<xref ref-type="bibr" rid="B1">1</xref> e 13,3% de anos de vida ajustados por incapacidade (<italic>disability-adjusted life years</italic>, DALY) em 2010.<xref ref-type="bibr" rid="B2">2</xref> O uso do tabaco &#233; definido como o uso corrente de qualquer produto de tabaco para fumo ou n&#227;o.<xref ref-type="bibr" rid="B3">3</xref> H&#225; muitas formas de tabaco sem fuma&#231;a (TSF) no mundo e tem sido relatado que o uso do tabaco aumenta o risco de doen&#231;a card&#237;aca coronariana,<xref ref-type="bibr" rid="B4">4</xref> acidente vascular cerebral,<xref ref-type="bibr" rid="B5">5</xref> s&#237;ndrome metab&#243;lica,<xref ref-type="bibr" rid="B6">6</xref> diabetes tipo 2 (DT2)<xref ref-type="bibr" rid="B7">7</xref> e c&#226;ncer de orofaringe.<xref ref-type="bibr" rid="B8">8</xref>
				</p>
        <p>A preval&#234;ncia de uso de TSF varia de 2% a 40%, dependendo da regi&#227;o mundial.<xref ref-type="bibr" rid="B9">9</xref> Uma alta preval&#234;ncia de uso de TSF (38%) tem sida descrita na regi&#227;o dos Andes na Venezuela. A preval&#234;ncia foi descrita como sendo maior em homens do que mulheres (58% <italic>versus</italic> 18%, respectivamente, p &lt; 0,0001) e aumentou com a idade.<xref ref-type="bibr" rid="B10">10</xref> O chim&#243; &#233; a prepara&#231;&#227;o de TSF mais comum nesta regi&#227;o e &#233; composto por folha de tabaco, bicarbonato de s&#243;dio, a&#231;&#250;car mascavo, cinzas da &#225;rvore mamoncillo (<italic>Melicocca bijuga</italic>) e aromatizante de baunilha e anis. Os ingredientes variam de acordo com a regi&#227;o venezuelana. Uma pequena quantidade de chim&#243; &#233; colocada entre os l&#225;bios ou bochecha e a gengiva e mantido por algum tempo, normalmente 30 minutos. A mistura de chim&#243; e saliva &#233; ent&#227;o cuspida.<xref ref-type="bibr" rid="B11">11</xref>
				</p>
        <p>A rela&#231;&#227;o entre uso de TSF e HAS n&#227;o &#233; inteiramente compreendida. Na Su&#233;cia, o uso de TSF n&#227;o &#233; banido como ocorre em outros pa&#237;ses europeus e tem uma maior taxa entre os homens (27,2%).<xref ref-type="bibr" rid="B12">12</xref> Em um estudo prospectivo observacional, Hergens et al.<xref ref-type="bibr" rid="B5">5</xref> relataram um risco 36% maior de HAS entre usu&#225;rios suecos de rap&#233; (feito a partir de folhas de tabaco mo&#237;das ou pulverizadas) comparados com n&#227;o usu&#225;rios. Em outro estudo de coorte utilizando dados do <italic>Swedish Annual Level-of-Living Survey</italic>, Johansson et al.<xref ref-type="bibr" rid="B13">13</xref> n&#227;o observaram diferen&#231;a nas taxas de incid&#234;ncia de HAS ajustada por idade entre indiv&#237;duos em uso di&#225;rio de rap&#233; e n&#227;o usu&#225;rios de tabaco. Al&#233;m disso, indiv&#237;duos com DM2 s&#227;o sens&#237;veis &#224; nicotina atrav&#233;s de receptores nicot&#237;nicos de acetilcolina (nAChRs) neuronais,<xref ref-type="bibr" rid="B14">14</xref><sup>,</sup><xref ref-type="bibr" rid="B15">15</xref> o que pode prejudicar a a&#231;&#227;o da insulina na presen&#231;a, mas n&#227;o na aus&#234;ncia de DM2.<xref ref-type="bibr" rid="B16">16</xref>
				</p>
        <p>A preval&#234;ncia de HAS na regi&#227;o dos Andes na Venezuela &#233; elevada (25,0%)<xref ref-type="bibr" rid="B17">17</xref> e semelhante &#224; encontrada na cidade de Barquisimeto (24,7%),<xref ref-type="bibr" rid="B18">18</xref> localizada na regi&#227;o oeste do pa&#237;s e identificada como tendo a segunda maior preval&#234;ncia de HAS de acordo com o estudo <italic>Cardiovascular Risk Factor Multiple Evaluation in Latin America</italic> (CARMELA), quase o dobro da preval&#234;ncia geral da Am&#233;rica Latina (16,3%).<xref ref-type="bibr" rid="B18">18</xref> Dadas as dimens&#245;es globais da HAS e do uso de tabaco, juntamente com a elevada preval&#234;ncia de HAS e uso chim&#243; na regi&#227;o dos Andes na Venezuela, o objetivo fundamental deste estudo foi compreender as rela&#231;&#245;es e intera&#231;&#245;es entre HAS, uso do tabaco, DM2 e outros fatores de risco.</p>
      </sec>
      <sec sec-type="methods">
        <title>M&#233;todos</title>
        <sec>
          <title>Caracter&#237;sticas da popula&#231;&#227;o</title>
          <p>Entre 2013 e 2014, um total de 1.938 indiv&#237;duos com idade de 20 anos ou mais foram atendidos consecutivamente em um centro m&#233;dico localizado em Timotes na regi&#227;o dos Andes na Venezuela. Timotes &#233; composta por uma popula&#231;&#227;o essencialmente agr&#237;cola na regi&#227;o andina da Venezuela, tem 18.179 habitantes, est&#225; localizada a uma altitude de 2.025 metros e apresenta uma temperatura m&#233;dia anual de 16 &#176;C. Os participantes do estudo responderam a um question&#225;rio. Informa&#231;&#245;es sobre a idade, sexo, hist&#243;ria pessoal de DM2, hist&#243;ria familiar e pessoal de HAS e uso de tabaco foram obtidas. O uso de chim&#243; foi questionado e as poss&#237;veis respostas est&#227;o apresentadas na <xref ref-type="table" rid="t5">Tabela 1</xref>. As medidas antropom&#233;tricas foram tamb&#233;m obtidas. O peso foi medido com os sujeitos vestindo o m&#237;nimo poss&#237;vel de roupas e sem sapatos, com uso de uma balan&#231;a calibrada (OMRON&#174; HBF-510LA; Omron Healthcare, Inc., 2011, Illinois, EUA). A altura foi medida com uma fita m&#233;trica fixada na parede. O &#237;ndice de massa corporal (IMC, kg/m<xref ref-type="bibr" rid="B2">2</xref>) foi calculado. A press&#227;o arterial (PA) foi medida duas vezes com um dispositivo automatizado (OMRON&#174; HEM-907XL; Omron Healthcare, Inc., 2007, Illinois, EUA)<xref ref-type="bibr" rid="B19">19</xref> colocado no bra&#231;o direito ao n&#237;vel do cora&#231;&#227;o, com o indiv&#237;duo em posi&#231;&#227;o sentada e ap&#243;s 5 minutos de repouso. Todos os sujeitos assinaram um termo de consentimento livre e esclarecido para a participa&#231;&#227;o.</p>
          <table-wrap id="t5">
            <label>Tabela 1</label>
            <caption>
              <title>Question&#225;rio Sobre o Uso de Tabaco sem Fuma&#231;a</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="50%"/>
                <col width="50%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left" style="background-color:#B2B2B2">Perguntas</th>
                  <th align="center" style="background-color:#B2B2B2">Respostas</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">Voc&#234; j&#225; usou tabaco sem fuma&#231;a, tais como chim&#243;, tabaco de mascar, ou <italic>snus</italic>?</td>
                  <td align="center">Sim, eu uso atualmente</td>
                </tr>
                <tr>
                  <td align="left">
									</td>
                  <td align="center">Sim, mas n&#227;o usei nos &#250;ltimos 12 meses</td>
                </tr>
                <tr>
                  <td align="left">
									</td>
                  <td align="center">N&#227;o, eu nunca usei</td>
                </tr>
                <tr>
                  <td align="left">N&#250;mero de anos de uso</td>
                  <td align="center">_________ anos</td>
                </tr>
                <tr>
                  <td align="left">Frequ&#234;ncia de uso</td>
                  <td align="center">Diariamente</td>
                </tr>
                <tr>
                  <td align="left">
									</td>
                  <td align="center">Semanalmente</td>
                </tr>
                <tr>
                  <td align="left">
									</td>
                  <td align="center">Menos do que semanalmente</td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
        </sec>
      </sec>
      <sec>
        <title>Defini&#231;&#245;es de vari&#225;veis</title>
        <p>A HAS foi definida como uma PA sist&#243;lica &#8805; 140 mmHg, PA diast&#243;lica &#8805; 90 mmHg, ou uso atual de medicamentos anti-hipertensivos.<xref ref-type="bibr" rid="B20">20</xref> O uso de TSF foi definido como um consumo di&#225;rio ou semanal de chim&#243; durante os &#250;ltimos 12 meses. O DM2 foi definido com base em autorrelato.</p>
        <sec>
          <title>An&#225;lise estat&#237;stica</title>
          <p>Todos os c&#225;lculos foram realizados com o programa SPSS 20 (IBM Corp., 2011, Armonk, NY, EUA). Os dados de vari&#225;veis cont&#237;nuas s&#227;o apresentados como m&#233;dia &#177; desvio padr&#227;o. Ap&#243;s a avalia&#231;&#227;o da normalidade, diferen&#231;as entre os valores m&#233;dios foram avaliadas pelo teste <italic>t</italic> de Student n&#227;o pareado. As frequ&#234;ncias s&#227;o apresentadas como taxas de preval&#234;ncia e intervalos de confian&#231;a de 95% (IC95%). O teste do qui-quadrado foi aplicado para comparar as diferentes frequ&#234;ncias. Foi realizada regress&#227;o log&#237;stica para estimar os fatores de risco associados &#224; HAS. A signific&#226;ncia estat&#237;stica foi considerada ao n&#237;vel alfa de p &lt; 0,05.</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Resultados</title>
        <sec>
          <title>Caracter&#237;sticas dos sujeitos</title>
          <p>O estudo incluiu 1.938 adultos com idade m&#233;dia de 49,2 anos, 59,5% do sexo feminino, 38,9% com HAS, 23,2% usu&#225;rios de TSF e 11,6% com DM2. Um ter&#231;o dos indiv&#237;duos com DM2 eram usu&#225;rios TSF (<xref ref-type="table" rid="t6">Tabela 2</xref>). Os sujeitos com DM2 que eram usu&#225;rios de TSF apresentaram valores mais baixos de frequ&#234;ncia card&#237;aca, PA sist&#243;lica e IMC, bem como uma menor frequ&#234;ncia de HAS quando comparados a n&#227;o usu&#225;rios de TSF. Em indiv&#237;duos sem DM2, o uso de TSF foi mais frequente em homens e em indiv&#237;duos mais velhos. Al&#233;m disso, entre participantes sem DM2, a frequ&#234;ncia card&#237;aca foi mais baixa entre usu&#225;rios do que n&#227;o usu&#225;rios de TSF.</p>
          <table-wrap id="t6">
            <label>Tabela 2</label>
            <caption>
              <title>Caracter&#237;sticas dos sujeitos</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="20%"/>
                <col width="20%"/>
                <col width="20%"/>
                <col width="20%"/>
                <col width="20%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left" rowspan="3" style="background-color:#B2B2B2">
									</th>
                  <th align="center" colspan="2" style="border-bottom-width:thin;border-bottom-style:solid;background-color:#B2B2B2">Diabetes tipo 2</th>
                  <th align="center" colspan="2" style="border-bottom-width:thin;border-bottom-style:solid;background-color:#B2B2B2">Sem diabetes tipo 2</th>
                </tr>
                <tr>
                  <th align="center" colspan="2" style="border-bottom-width:thin;border-bottom-style:solid;background-color:#B2B2B2">
                    <bold>Tabaco sem fuma&#231;a</bold>
                  </th>
                  <th align="center" colspan="2" style="border-bottom-width:thin;border-bottom-style:solid;background-color:#B2B2B2">
                    <bold>Tabaco sem fuma&#231;a</bold>
                  </th>
                </tr>
                <tr>
                  <th align="center" style="background-color:#B2B2B2">
                    <bold>Usu&#225;rios</bold>
                  </th>
                  <th align="center" style="background-color:#B2B2B2">
                    <bold>N&#227;o usu&#225;rios</bold>
                  </th>
                  <th align="center" style="background-color:#B2B2B2">
                    <bold>Usu&#225;rios</bold>
                  </th>
                  <th align="center" style="background-color:#B2B2B2">
                    <bold>N&#227;o usu&#225;rios</bold>
                  </th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">Total: n</td>
                  <td align="center">68</td>
                  <td align="center">157</td>
                  <td align="center">381</td>
                  <td align="center">1332</td>
                </tr>
                <tr>
                  <td align="left">Sexo masculino (%)</td>
                  <td align="center">51,5</td>
                  <td align="center">40,1</td>
                  <td align="center">55,6<xref ref-type="table-fn" rid="TFN10">**</xref>
									</td>
                  <td align="center">35,7</td>
                </tr>
                <tr>
                  <td align="left">Idade (anos)</td>
                  <td align="center">61,9 &#177; 9,6</td>
                  <td align="center">62,6 &#177; 13,8</td>
                  <td align="center">50,0 &#177; 17,7<xref ref-type="table-fn" rid="TFN10">**</xref>
									</td>
                  <td align="center">46,7 &#177; 16,9</td>
                </tr>
                <tr>
                  <td align="left">Frequ&#234;ncia Card&#237;aca</td>
                  <td align="center">77,8 &#177; 11,7<xref ref-type="table-fn" rid="TFN9">*</xref>
									</td>
                  <td align="center">82,2 &#177; 13,2</td>
                  <td align="center">74,3 &#177; 13,9<xref ref-type="table-fn" rid="TFN9">*</xref>
									</td>
                  <td align="center">78,6 &#177; 14,3</td>
                </tr>
                <tr>
                  <td align="left">PAS (mmHg)</td>
                  <td align="center">129,1 &#177; 22,8<xref ref-type="table-fn" rid="TFN9">*</xref>
									</td>
                  <td align="center">136,6 &#177; 25,1</td>
                  <td align="center">126,9 &#177; 20,6</td>
                  <td align="center">126,3 &#177; 20,6</td>
                </tr>
                <tr>
                  <td align="left">PAD (mmHg)</td>
                  <td align="center">76,2 &#177; 12,2</td>
                  <td align="center">78,7 &#177; 12,8</td>
                  <td align="center">78,2 &#177; 12,4</td>
                  <td align="center">79,0 &#177; 12,3</td>
                </tr>
                <tr>
                  <td align="left">IMC (kg/m<sup>2</sup>)</td>
                  <td align="center">25,8 &#177; 4,2<xref ref-type="table-fn" rid="TFN10">**</xref>
									</td>
                  <td align="center">28,5 &#177; 4,8</td>
                  <td align="center">27,5 &#177; 4,7</td>
                  <td align="center">27,9 &#177; 5,1</td>
                </tr>
                <tr>
                  <td align="left">Hipertens&#227;o na Fam&#237;lia (%)</td>
                  <td align="center">52,9 (41,04 - 64,76)</td>
                  <td align="center">51,0 (43,18 - 58,82)</td>
                  <td align="center">50,4 (45,38 - 55,42)</td>
                  <td align="center">54,7 (52,03 - 57,37)</td>
                </tr>
                <tr>
                  <td align="left">Sobrepeso/Obesidade (%)</td>
                  <td align="center">61,8 (50,25 - 73,35)</td>
                  <td align="center">74,5 (67,68 - 81,32)</td>
                  <td align="center">69,8 (65,19 - 74,41)</td>
                  <td align="center">70,2 (67,74 - 72,66)</td>
                </tr>
                <tr>
                  <td align="left">Hipertens&#227;o (%)</td>
                  <td align="center">50,0 (38,12 - 61,88)<xref ref-type="table-fn" rid="TFN9">*</xref>
									</td>
                  <td align="center">69,4 (62,19 - 76,61)</td>
                  <td align="center">33,3 (28,57 - 38,03)</td>
                  <td align="center">36,3 (33,72 - 38,88)</td>
                </tr>
                <tr>
                  <td align="left">Cigarro Atual (%)</td>
                  <td align="center">4,4 (0,47 - 9,27)</td>
                  <td align="center">4,5 (1,26 - 7,74)</td>
                  <td align="center">5,5 (3,21 - 7,79)</td>
                  <td align="center">7,9 (6,45 - 9,35)</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN7">
                <p>As vari&#225;veis cont&#237;nuas s&#227;o expressas como m&#233;dia &#177; desvio padr&#227;o (DP).</p>
              </fn>
              <fn id="TFN8">
                <p>As frequ&#234;ncias s&#227;o expressas como porcentagens (intervalo de confian&#231;a de 95%).</p>
              </fn>
              <fn id="TFN9">
                <label>*</label>
                <p>p &lt; 0,05;</p>
              </fn>
              <fn id="TFN10">
                <label>**</label>
                <p>p &lt; 0,0001 indicam diferen&#231;as entre usu&#225;rios e n&#227;o usu&#225;rios de TSF analisadas com o teste t de Student para m&#233;dias e teste do qui-quadrado para frequ&#234;ncias. PAS: Press&#227;o arterial sist&#243;lica; PAD: Press&#227;o arterial diast&#243;lica; IMC: &#237;ndice de massa corporal. Sobrepeso/Obesidade: IMC &#8805; 25 kg/m<sup>2</sup>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>Tabaco sem fuma&#231;a e hipertens&#227;o arterial</title>
          <p>O uso de TSF mostrou uma rela&#231;&#227;o significativa com a HAS em indiv&#237;duos com DM2 com idade acima de 50 anos (<xref ref-type="table" rid="t7">Tabela 3</xref>). Neste grupo, usu&#225;rios de TSF apresentaram uma frequ&#234;ncia 69% mais baixa de HAS quando comparados a n&#227;o usu&#225;rios de TSF. A associa&#231;&#227;o entre uso de TSF e menor frequ&#234;ncia de HAS permaneceu significativa ap&#243;s as vari&#225;veis terem sido ajustadas de acordo com o IMC (<xref ref-type="fig" rid="f2">Figura 1</xref>). A regress&#227;o log&#237;stica ajustada pela frequ&#234;ncia card&#237;aca, idade, DM2, sobrepeso/obesidade e hist&#243;ria familiar de HAS mostrou que o uso de TSF esteve associado com uma frequ&#234;ncia 30% menor de HAS (raz&#227;o de chances = 0,70, IC 95% 0,55 - 0,90) (<xref ref-type="table" rid="t8">Tabela 4</xref>).</p>
          <table-wrap id="t7">
            <label>Tabela 3</label>
            <caption>
              <title>Rela&#231;&#227;o entre o uso de TSF e hipertens&#227;o arterial em indiv&#237;duos com diabetes tipo 2 com idade acima de 50 anos<xref ref-type="table-fn" rid="TFN11">*</xref>
							</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="20%"/>
                <col width="20%"/>
                <col width="20%"/>
                <col width="20%"/>
                <col width="20%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left" style="background-color:#B2B2B2">
									</th>
                  <th align="center" style="background-color:#B2B2B2">
									</th>
                  <th align="center" style="background-color:#B2B2B2">Hipertens&#227;o</th>
                  <th align="center" style="background-color:#B2B2B2">Normotens&#227;o</th>
                  <th align="center" style="background-color:#B2B2B2">OR (IC95%)</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">DM2</td>
                  <td align="center">Tabaco sem Fuma&#231;a</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="left" rowspan="2">Presente</td>
                  <td align="center">Usu&#225;rios de TSF</td>
                  <td align="center">23,2 (15,80 - 30,60)</td>
                  <td align="center">49,2 (36,85 - 61,55)</td>
                  <td align="center" rowspan="2">0,31 (0,16 - 0,59)</td>
                </tr>
                <tr>
                  <td align="left">N&#227;o usu&#225;rios de TSF</td>
                  <td align="center">76,8 (69,40 - 84,20)</td>
                  <td align="center">50,8 (38,45 - 63,15)</td>
                </tr>
                <tr>
                  <td align="left" rowspan="2">Ausente</td>
                  <td align="center">Usu&#225;rios de TSF</td>
                  <td align="center">21,4 (17,34 - 25,46)</td>
                  <td align="center">27,3 (22,46 - 32,14)</td>
                  <td align="center" rowspan="2">0,72 (0,51 - 1,02)</td>
                </tr>
                <tr>
                  <td align="left">N&#227;o usu&#225;rios de TSF</td>
                  <td align="center">78,6 (74,54 - 82,66)</td>
                  <td align="center">72,7 (67,86 - 77,54)</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN11">
                <label>*</label>
                <p>Sujeitos mais jovens do que 50 anos mostraram uma rela&#231;&#227;o n&#227;o significativa. Os dados s&#227;o expressos como percentagem (intervalo de confian&#231;a de 95% [IC 95%]). OR: Raz&#227;o de chances (odds ratio); TSF: Tabaco sem fuma&#231;a; DM2: Diabetes tipo 2.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <p>
            <fig id="f2">
              <label>Figura 1</label>
              <caption>
                <title>Frequ&#234;ncia da hipertens&#227;o arterial de acordo com o estado nutricional e o uso de tabaco sem fuma&#231;a. Obesidade: &#205;ndice de massa corporal (IMC) &#8805; 30 kg/m<sup>2</sup>; Sobrepeso: IMC de 25 a 29,9 kg/m<sup>2</sup>; Peso Normal: IMC &lt; 25 kg/m<sup>2</sup>. p: diferen&#231;as entre usu&#225;rios e n&#227;o usu&#225;rios de tabaco por meio do teste do qui-quadrado.</title>
              </caption>
              <graphic xlink:href="2359-5647-ijcs-30-05-0373-70066-gf01-pt.jpg"/></fig>
          </p>
          <table-wrap id="t8">
            <label>Tabela 4</label>
            <caption>
              <title>Fatores de risco associados &#224; hipertens&#227;o*</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="33%"/>
                <col width="33%"/>
                <col width="33%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left" style="background-color:#B2B2B2">
									</th>
                  <th align="center" style="background-color:#B2B2B2">OR</th>
                  <th align="center" style="background-color:#B2B2B2">IC 95%</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">Tabaco sem fuma&#231;a (chim&#243;)</td>
                  <td align="center">0,70</td>
                  <td align="center">0,55 - 0,90</td>
                </tr>
                <tr>
                  <td align="left">Frequ&#234;ncia card&#237;aca</td>
                  <td align="center">1,01</td>
                  <td align="center">1,01 - 1,01</td>
                </tr>
                <tr>
                  <td align="left">Idade</td>
                  <td align="center">1,06</td>
                  <td align="center">1,05 - 1,06</td>
                </tr>
                <tr>
                  <td align="left">Diabetes tipo 2</td>
                  <td align="center">1,62</td>
                  <td align="center">1,17 - 2,22</td>
                </tr>
                <tr>
                  <td align="left">Sobrepeso/Obesidade</td>
                  <td align="center">1,65</td>
                  <td align="center">1,30 - 2,09</td>
                </tr>
                <tr>
                  <td align="left">Hipertens&#227;o na Fam&#237;lia</td>
                  <td align="center">2,19</td>
                  <td align="center">1,75 - 2,70</td>
                </tr>
                <tr>
                  <td align="left">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="left">* Regress&#227;o log&#237;stica m&#250;ltipla.</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN12">
                <p>OR: Raz&#227;o de chances (odds ratio); IC 95%: Intervalo de confian&#231;a. Sobrepeso/Obesidade: IMC &#8805; 25 kg/m<sup>2</sup>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
      </sec>
      <sec sec-type="discussion">
        <title>Discuss&#227;o</title>
        <p>O uso de chim&#243;, uma forma de TSF frequentemente consumida na regi&#227;o dos Andes na Venezuela, est&#225; associado a valores mais baixos de PA, frequ&#234;ncia card&#237;aca, IMC e HAS em indiv&#237;duos com DM2 com idade acima de 50 anos. Este &#233; o primeiro estudo mostrando uma associa&#231;&#227;o entre chim&#243; e taxas mais baixas de HAS e a raz&#227;o para esta associa&#231;&#227;o contraintuitiva &#233; desconhecida. Este resultado alimenta a controv&#233;rsia em torno do uso de TSF e HAS e pode ser devido a um ou mais fatores.</p>
        <p>A &#205;ndia tem uma alta preval&#234;ncia de uso de TSF.<xref ref-type="bibr" rid="B21">21</xref> Em um estudo transversal naquele pa&#237;s, avaliando 443 homens com mais de 15 anos de idade em um cen&#225;rio rural, a preval&#234;ncia de uso exclusivo de TSF (sem tabaco fumado) foi de 21%.<xref ref-type="bibr" rid="B22">22</xref> O grupo que utilizou apenas TSF apresentou valores mais elevados de PA diast&#243;lica e uma preval&#234;ncia mais elevada de HAS diast&#243;lica em compara&#231;&#227;o a indiv&#237;duos que n&#227;o faziam uso de TSF, ou com usu&#225;rios de TSF e tabaco fumado.<xref ref-type="bibr" rid="B22">22</xref> A associa&#231;&#227;o entre a PA elevada e uso de TSF pode estar relacionada aos n&#237;veis de nicotina e concentra&#231;&#245;es de s&#243;dio na composi&#231;&#227;o do TSF. Este resultado pode ser explicado pelo fato de alguns produtos de TSF conterem grandes quantidades de s&#243;dio como parte do bicarbonato de s&#243;dio, tamp&#227;o alcalino necess&#225;rio para facilitar a absor&#231;&#227;o da nicotina. O excesso de s&#243;dio (excesso de 30 a 40 mEq de s&#243;dio por dia) poderia aumentar a PA.<xref ref-type="bibr" rid="B23">23</xref> No entanto, em 1.061 jogadores profissionais de beisebol, o uso de TSF n&#227;o esteve relacionado com PA mais elevada em compara&#231;&#227;o com indiv&#237;duos que n&#227;o faziam uso de TSF.<xref ref-type="bibr" rid="B24">24</xref> No estudo mencionado acima, a dosagem s&#233;rica de nicotina e cotinina (o principal metab&#243;lito da nicotina) foi avaliada. Os participantes que utilizaram rap&#233; apresentaram n&#237;veis s&#233;ricos de cotinina e nicotina mais elevados do que aqueles que utilizaram o tabaco de mascar. Os participantes com n&#237;veis mais elevados de nicotina apresentaram PA diast&#243;lica mais elevada.<xref ref-type="bibr" rid="B24">24</xref> Assim, o teor de s&#243;dio e o teor e absor&#231;&#227;o de nicotina podem variar em diferentes prepara&#231;&#245;es de TSF, potencialmente conferindo diferentes efeitos sobre a PA.</p>
        <p>Outra poss&#237;vel explica&#231;&#227;o para o nosso resultado seria a ocorr&#234;ncia de HAS mascarada em usu&#225;rios de tabaco. Este efeito foi relatado anteriormente em fumantes, mas n&#227;o em usu&#225;rios de TSF. Os fumantes tendem a ter uma PA ambulatorial diurna elevada (quando &#233; mais prov&#225;vel que estes indiv&#237;duos fumem) em compara&#231;&#227;o com suas PAs de consult&#243;rio (quando &#233; menos prov&#225;vel que fumem).<xref ref-type="bibr" rid="B25">25</xref> O <italic>Second Australian National Blood Pressure Study</italic> tamb&#233;m demonstrou que o tabagismo prediz a HAS mascarada.<xref ref-type="bibr" rid="B26">26</xref>
				</p>
        <p>O efeito do uso de TSF sobre o n&#237;vel da PA, observado no presente estudo, foi significativo apenas em sujeitos com DM2. A sensibilidade &#224; nicotina no DM2 foi avaliada comparando os efeitos da infus&#227;o aguda de nicotina em pacientes com e sem diabetes.<xref ref-type="bibr" rid="B16">16</xref> A infus&#227;o de nicotina n&#227;o afetou a quantidade de insulina necess&#225;ria para manter os n&#237;veis de glicose em volunt&#225;rios saud&#225;veis, por&#233;m n&#237;veis mais elevados de insulina foram necess&#225;rios em pacientes com diabetes, indicando que pacientes com DM2 s&#227;o mais suscet&#237;veis a um efeito negativo da nicotina sobre a sensibilidade &#224; insulina.<xref ref-type="bibr" rid="B16">16</xref>
				</p>
        <p>Em fumantes, a nicotina aumenta agudamente o gasto de energia e pode reduzir o apetite.<xref ref-type="bibr" rid="B27">27</xref> Esse efeito poderia explicar a tend&#234;ncia apresentada por fumantes de terem peso corporal mais baixo do que n&#227;o fumantes, al&#233;m do ganho de peso que geralmente ocorre ap&#243;s a cessa&#231;&#227;o do tabagismo.<xref ref-type="bibr" rid="B28">28</xref> Neste estudo, sujeitos com DM2 que usavam TSF tinham IMC mais baixo que os que n&#227;o a usavam TSF, resultados semelhantes aos observados nos tabagistas. Este estudo encontrou tamb&#233;m uma frequ&#234;ncia card&#237;aca mais baixa em usu&#225;rios de TSF, que pode tamb&#233;m ter sido ocasionada pela exposi&#231;&#227;o a uma atividade cronotr&#243;pica negativa de alguns componentes do chim&#243;.</p>
        <p>O presente estudo tem algumas limita&#231;&#245;es. Em primeiro lugar, o chim&#243; na Venezuela &#233; produzido principalmente atrav&#233;s de m&#233;todos tradicionais que geram muitas formula&#231;&#245;es diferentes para venda, sem doses fixas, e portanto, a dosagem n&#227;o pode ser caracterizada como ocorre com cigarros. Al&#233;m disso, a maioria dos componentes derivados da folha de tabaco e suas respectivas doses nas prepara&#231;&#245;es de chim&#243; &#233; desconhecida. Segundo, as concentra&#231;&#245;es sangu&#237;neas de nicotina ou cotinina n&#227;o foram avaliadas. Terceiro, n&#227;o foi realizado um exame oral para avaliar o uso de TSF. Por &#250;ltimo, o DM2 foi diagnosticado apenas por autorrelato.</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclus&#227;o</title>
        <p>Este estudo demonstra pela primeira vez uma associa&#231;&#227;o negativa entre o uso de chim&#243; e HAS. Muitas formas de TSF t&#234;m sido associadas (com evid&#234;ncias contradit&#243;rias em alguns casos) com doen&#231;a cardiovascular, c&#226;ncer e altera&#231;&#245;es metab&#243;licas. A base biol&#243;gica dos achados deste estudo permanece desconhecida. Embora o uso de TSF n&#227;o tenha sido associado a uma maior frequ&#234;ncia de HAS neste estudo, enfatiza-se que o uso de TSF n&#227;o &#233; uma pr&#225;tica saud&#225;vel em pacientes com DM2 e, mais importante ainda, o TSF n&#227;o deve ser interpretado como um meio para reduzir o risco de HAS. Os efeitos da chim&#243; s&#227;o complexos, em geral n&#227;o saud&#225;veis e, na pr&#225;tica, um problema de sa&#250;de p&#250;blica que requer mais estudo cient&#237;fico.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="financial-disclosure">
          <p>
            <bold>Fontes de Financiamento</bold>
          </p>
          <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
        </fn>
        <fn fn-type="other">
          <p>
            <bold>Vincula&#231;&#227;o Acad&#234;mica</bold>
          </p>
          <p>N&#227;o h&#225; vincula&#231;&#227;o deste estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
