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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">Rnp5yzzDt8BKgVWm7kYqD5M</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2016004100093</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20160120</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Special Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>I RBH - First Brazilian Hypertension Registry</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Jardim</surname>
            <given-names>Paulo C&#233;sar Brand&#227;o Veiga</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Souza</surname>
            <given-names>Weimar Kunz Sebba Barroso de</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lopes</surname>
            <given-names>Renato Delascio</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Brand&#227;o</surname>
            <given-names>Andr&#233;a Ara&#250;jo</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Malachias</surname>
            <given-names>Marcus V. Bol&#237;var</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">4</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Gomes</surname>
            <given-names>Marco Mota</given-names>
          </name>
          <xref ref-type="aff" rid="aff5">5</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Moreno</surname>
            <given-names>Heitor</given-names>
            <suffix>J&#250;nior</suffix>
          </name>
          <xref ref-type="aff" rid="aff6">6</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Barbosa</surname>
            <given-names>Eduardo Costa Duarte</given-names>
          </name>
          <xref ref-type="aff" rid="aff7">7</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>P&#243;voa</surname>
            <given-names>Rui Manoel dos Santos</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgname">Universidade Federal de Goi&#225;s</institution>
        <addr-line>
          <named-content content-type="city">Goi&#226;nia</named-content>
          <named-content content-type="state">GO</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Universidade Federal de Goi&#225;s, Goi&#226;nia, GO - Brazil</institution>
        <institution content-type="normalized">Universidade Federal de Goi&#225;s</institution>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution content-type="orgname">Universidade Federal de S&#227;o Paulo</institution>
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">SP</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Universidade Federal de S&#227;o Paulo, S&#227;o Paulo, SP - Brazil</institution>
        <institution content-type="normalized">Universidade Federal de S&#227;o Paulo</institution>
      </aff>
      <aff id="aff3">
        <label>3</label>
        <institution content-type="orgname">Universidade Estadual do Rio de Janeiro</institution>
        <addr-line>
          <named-content content-type="city">Rio de Janeiro</named-content>
          <named-content content-type="state">RJ</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Universidade Estadual do Rio de Janeiro, Rio de Janeiro, RJ - Brazil</institution>
        <institution content-type="normalized">Universidade do Estado do Rio de Janeiro</institution>
      </aff>
      <aff id="aff4">
        <label>4</label>
        <institution content-type="orgname">Faculdade de Ci&#234;ncias M&#233;dicas de Minas Gerais</institution>
        <addr-line>
          <named-content content-type="city">Belo Horizonte</named-content>
          <named-content content-type="state">MG</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Faculdade de Ci&#234;ncias M&#233;dicas de Minas Gerais, Belo Horizonte, MG - Brazil</institution>
        <institution content-type="normalized">Faculdade de Ci&#234;ncias M&#233;dicas de Minas Gerais</institution>
      </aff>
      <aff id="aff5">
        <label>5</label>
        <institution content-type="orgname">Universidade Estadual de Alagoas</institution>
        <addr-line>
          <named-content content-type="city">Alto Cruzeiro Arapiraca</named-content>
          <named-content content-type="state">AL</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Universidade Estadual de Alagoas, Alto Cruzeiro Arapiraca, AL - Brazil</institution>
        <institution content-type="normalized">Universidade Estadual de Alagoas</institution>
      </aff>
      <aff id="aff6">
        <label>6</label>
        <institution content-type="orgname">Universidade Estadual de Campinas</institution>
        <addr-line>
          <named-content content-type="city">Campinas</named-content>
          <named-content content-type="state">SP</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Universidade Estadual de Campinas, Campinas, SP - Brazil</institution>
        <institution content-type="normalized">Universidade Estadual de Campinas</institution>
      </aff>
      <aff id="aff7">
        <label>7</label>
        <institution content-type="orgname">Instituto de Cardiologia de Porto Alegre</institution>
        <addr-line>
          <named-content content-type="city">Porto Alegre</named-content>
          <named-content content-type="state">RS</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Instituto de Cardiologia de Porto Alegre, Porto Alegre, RS - Brazil</institution>
      </aff>
      <author-notes>
        <corresp id="c1"><bold>Mailing address: Paulo C&#233;sar Brand&#227;o Veiga Jardim,</bold> Faculdade de Medicina da Universidade Federal de Goias. 115 F, n. 135, Setor Sul. CEP 74085300, Goi&#226;nia, GO - Brazil. E-mail: <email>pcbveiga@cardiol.br</email>, <email>fvjardim@terra.com.br</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Conception and design of the research, Acquisition of data, Analysis and interpretation of the data, Writing of the manuscript and Critical revision of the manuscript for intellectual content: Jardim PCBV, Souza WKSB, Lopes RD, Brand&#227;o AA, Malachias MB, Gomes MM, Moreno J&#250;nior H, Barbosa E, P&#243;voa RMS; Statistical analysis: Jardim PCBV, Souza WKSB, Lopes RD, Brand&#227;o AA, Malachias MB, Gomes MM,; Obtaining financing: Jardim PCBV, Souza WKSB, Lopes RD, Brand&#227;o AA, Malachias MB, Gomes MM, P&#243;voa RMS.</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">
        <month>08</month>
        <year>2016</year>
      </pub-date>
      <volume>107</volume>
      <issue>2</issue>
      <fpage>93</fpage>
      <lpage>98</lpage>
      <history>
        <date date-type="received">
          <day>20</day>
          <month>05</month>
          <year>2016</year>
        </date>
        <date date-type="rev-recd">
          <day>20</day>
          <month>05</month>
          <year>2016</year>
        </date>
        <date date-type="accepted">
          <day>20</day>
          <month>05</month>
          <year>2016</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> A registry assessing the care of hypertensive patients in daily clinical practice in public and private centers in various Brazilian regions has not been conducted to date. Such analysis is important to elucidate the effectiveness of this care.</p>
        </sec>
        <sec>
          <title>Objective:</title>
          <p> To document the current clinical practice for the treatment of hypertension with identification of the profile of requested tests, type of administered treatment, level of blood pressure (BP) control, and adherence to treatment.</p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p> National, observational, prospective, and multicenter study that will include patients older than 18 years with hypertension for at least 4 weeks, following up in public and private centers and after signing a consent form. The study will exclude patients undergoing dialysis, hospitalized in the previous 30 days, with class III or IV heart failure, pregnant or nursing, with severe liver disease, stroke or acute myocardial infarction in the past 30 days, or with diseases with a survival prognosis &lt; 1 year. Evaluations will be performed at baseline and after 1 year of follow-up. The parameters that will be evaluated include anthropometric data, lifestyle habits, BP levels, lipid profile, metabolic syndrome, and adherence to treatment. The primary outcomes will be hospitalization due to hypertensive crisis, cardiocirculatory events, and cardiovascular death, while secondary outcomes will be hospitalization for heart failure and requirement of dialysis. A subgroup analysis of 15% of the sample will include noninvasive central pressure evaluation at baseline and study end. The estimated sample size is 3,000 individuals for a prevalence of 5%, sample error of 2%, and 95% confidence interval.</p>
        </sec>
        <sec>
          <title>Results:</title>
          <p> The results will be presented after the final evaluation, which will occur at the end of a 1-year follow-up.</p>
        </sec>
        <sec>
          <title>Conclusion:</title>
          <p> The analysis of this registry will improve the knowledge and optimize the treatment of hypertension in Brazil, as a way of modifying the prognosis of cardiovascular disease in the country.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords:</title>
        <kwd>Evidence-Based Practice</kwd>
        <kwd>Hypertension</kwd>
        <kwd>Risk Factors</kwd>
        <kwd>Multicenter Studies as Topic</kwd>
        <kwd>Epidemiology</kwd>
        <kwd>Prevalence</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>Hypertension is a polygenic disease of multifactorial etiology, characterized by sustained increased blood pressure (BP) levels.<xref ref-type="bibr" rid="B1">1</xref> It is currently the main risk factor for cardiovascular diseases (CVDs), which are the most frequent causes of death in Brazil and worldwide.<xref ref-type="bibr" rid="B1">1</xref><sup>-</sup><xref ref-type="bibr" rid="B3">3</xref> Hypertension is also associated with target-organ (kidney, heart, brain) damage and other comorbidities such as dyslipidemia and type 2 diabetes,<xref ref-type="bibr" rid="B1">1</xref> which in turn also increase the risk of cardiovascular events.</p>
      <p>A classic meta-analysis that evaluated more than 1 million individuals in 61 observational studies concluded that the mortality associated with CVDs increases progressively in a linear, continuous, and independent fashion with increases in BP levels above 115 / 75 mmHg.<xref ref-type="bibr" rid="B4">4</xref>
			</p>
      <p>The INTERHEART study analyzed the risk factors for acute myocardial infarction (AMI) in 52 countries (six of which in Latin America), including 15,000 cases of patients with first AMI and a similar number of control individuals.<xref ref-type="bibr" rid="B5">5</xref><sup>,</sup><xref ref-type="bibr" rid="B6">6</xref> The increased risk of AMI in Latin America was associated with hypertension (odds ratio [OR] 2.48; 95% confidence interval [95%CI], 2.03-3.04), diabetes (OR 2.45; 95%CI, 1.86-3.24), smoking (OR 2.35; 95% CI, 1.92-2.87), dyslipidemia - apoB/apoA1 (OR 2.79; 95% CI, 1.85-4.23), and abdominal obesity (OR 2.41; 95% CI, 1.79-3.25). Considering that these are all modifiable risk factors, the INTERHEART study alerted to the need for implementation of preventive strategies throughout Latin America.</p>
      <p>The prevalence of hypertension in Brazil is similar to that in other countries. Surveys conducted in the Brazilian population point out to a prevalence of hypertension of approximately 30%.<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B8">8</xref> Considering BP values &#8805; 140 / 90 mmHg, 22 studies found prevalences between 22.3% and 43.9% (mean 32.5%), with a higher prevalence in men compared with women, and in elderly individuals.<xref ref-type="bibr" rid="B9">9</xref>
			</p>
      <p>A study in which 613 patients in the city of S&#227;o Paulo were interviewed by phone found a 32% prevalence of hypertension among the respondents. Of these, 89% reported current treatment for hypertension but only 35% mentioned proper control of BP levels.<xref ref-type="bibr" rid="B10">10</xref> Another study conducted in S&#227;o Jos&#233; do Rio Preto in 1,717 individuals found a prevalence of hypertension of 25.2% and reported as associated factors the presence of advanced age, low educational level, and obesity.<xref ref-type="bibr" rid="B11">11</xref> Among the treated hypertensive individuals, 52.4% showed adequate BP control, but only 34.3% of the overall treated and untreated hypertensive individuals had controlled BP levels.</p>
      <p>Since hypertension is multifactorial, frequent in the adult population, and commonly associated with other cardiovascular risk factors and/or target-organ damage, it is an important public health problem. When the diagnosis of hypertension is established early, and the goals of BP control are met, the treatment of the disease may be effective; however, when left untreated, hypertension can cause severe complications and follow a slow and silent course.<xref ref-type="bibr" rid="B1">1</xref>
			</p>
      <p>Data from the National Health and Nutrition Examination Survey (NHANES) collected between 2009 and 2012 have shown that 84.7% of the surveyed adults with hypertension were aware of the diagnosis of the disease and that the percentage of patients undergoing antihypertensive treatment was 76.5%, with a 54.1% rate of BP control. These numbers demonstrate a significant improvement in the diagnosis and control of hypertension in the American population.<xref ref-type="bibr" rid="B12">12</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref>
			</p>
      <p>Lifestyle modifications lead to decreases in BP and cardiovascular mortality.<xref ref-type="bibr" rid="B14">14</xref><sup>-</sup><xref ref-type="bibr" rid="B16">16</xref> Even though consistently recommended for prevention and treatment of hypertension, lifestyle modifications are difficult to implement from the patient's perspective and, often, also from the physician's perspective, who is frequently unable to rely on the support of a multiprofessional team.</p>
      <p>With the objective of achieving proper BP control and consequently decreasing the deaths associated with CVD, it is essential to know the prevalence of hypertension in Brazil, clarify how the care and treatment of hypertensive patients are being conducted in daily clinical practice, and understand the role of multidisciplinary teams in this scenario.</p>
    </sec>
    <sec>
      <title>Objectives</title>
      <sec>
        <title>Main objective</title>
        <p>
          <list list-type="bullet">
            <list-item>
              <p>To document the current clinical practice for the treatment of hypertension in Brazil.</p>
            </list-item>
          </list>
        </p>
      </sec>
      <sec>
        <title>Secondary objectives</title>
        <p>
          <list list-type="bullet">
            <list-item>
              <p>Stratify additional cardiovascular risks, considering associated comorbidities, target-organ damage, and presence of manifested cardiovascular disease;</p>
            </list-item>
            <list-item>
              <p>Analyze the profile of tests routinely requested for patients with hypertension;</p>
            </list-item>
            <list-item>
              <p>Verify the proportion of patients receiving antihypertensive treatment who are within the goals recommended by the Brazilian Society of Cardiology;</p>
            </list-item>
            <list-item>
              <p>Estimate the adherence to proposed pharmacological and non-pharmacological therapies using the Morisky scale;</p>
            </list-item>
            <list-item>
              <p>Evaluate the presence of a multiprofessional team in the regular care of the patients and, when present, the effectiveness of its performance in controlling the BP levels;</p>
            </list-item>
            <list-item>
              <p>Assess eventual differences in the approach to hypertensive patients in private and public centers.</p>
            </list-item>
          </list>
        </p>
      </sec>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <sec>
        <title>Study design and population</title>
        <p>This first Brazilian registry of hypertension will be a prospective, observational, multicenter, national study in which the subjects will be screened and evaluated in internal medicine and specialized outpatient clinics during a follow-up of 12 months.</p>
        <p>The study will include individuals undergoing primary or secondary prevention, diagnosed with hypertension and meeting the inclusion criteria. After the subjects sign a free and informed consent form (FICF), their medical records will be analyzed, and they will be interviewed for completion of the electronic clinical charts (electronic case report form, eCRF) for inclusion in the study.</p>
        <p>A follow-up visit will be scheduled between 6 months and 1 year from the inclusion in the study. In the event of more than one visit during this period, this additional visit may also be documented as an intermediate visit.</p>
      </sec>
      <sec>
        <title>Study population</title>
        <p>Patients older than 18 years, with a diagnosis of hypertension for at least 4 weeks.</p>
      </sec>
      <sec>
        <title>Inclusion criteria</title>
        <p>Signature of the FICF; age above 18 years; diagnosis of hypertension for at least 4 weeks, with a systolic BP (SBP) &#8805; 140 mmHg and/or diastolic BP (DBP) &#8805; 90 mmHg, measured with the participant seated and according to the VI Brazilian Hypertension Guidelines (<italic>VI Diretrizes Brasileiras de Hipertens&#227;o</italic>) or use of antihypertensive medication; and regular registration in the participating center/institution.</p>
      </sec>
      <sec>
        <title>Exclusion criteria</title>
        <p>Renal failure requiring dialysis treatment; hospital admission at the moment of inclusion or in the previous 30 days; hemodynamic instability requiring vasoactive drugs in the previous 30 days; functional class III or IV heart failure; pregnancy and/or nursing; severe hepatic disease; psychiatric diseases preventing compliance with the protocol; history of stroke or AMI up to 30 days from the inclusion in the study; severe diseases according to the researcher's evaluation; neoplasms with a survival prognosis below 1 year.</p>
      </sec>
      <sec>
        <title>Criteria for interruption of the study</title>
        <p>Individuals who wish to interrupt the participation in the study or who during follow-up present one or more exclusion criteria.</p>
      </sec>
      <sec>
        <title>Clinical evaluation</title>
        <p>
          <list list-type="bullet">
            <title>The following clinical data will be assessed:</title>
            <list-item>
              <p>Family history of premature coronary artery disease (FH CAD, including a first-degree relative with a history of CAD before the age of 55 years if men or 65 years if women);</p>
            </list-item>
            <list-item>
              <p>Smoking, considering as smokers those individuals who routinely smoke one or more cigarettes or who routinely smoked up to 1 year before inclusion, and as previous smokers those individuals who stopped smoking more than 1 year before inclusion;</p>
            </list-item>
            <list-item>
              <p>Alcoholism, considering as current alcoholism the consumption of at least 30 g of ethanol for men (equal to approximately two cans of beer with 365 mL, two glasses of wine of 150 mL, or two doses of whiskey with 50 mL) and 15 g of ethanol for women (the equivalent of half of the doses described for men) at least three times a week, and as previous alcoholism the interruption of the habit for at least 1 year;</p>
            </list-item>
            <list-item>
              <p>Physical activity, considering as regularly performed those physical activities performed for at least 30 minutes three times a week;</p>
            </list-item>
            <list-item>
              <p>Menopause, characterized by the absence of menstrual periods for at least 1 year;</p>
            </list-item>
            <list-item>
              <p>Weight and height, measured with an anthropometric scale;</p>
            </list-item>
            <list-item>
              <p>Body mass index (BMI), calculated with the formula weight divided by the square of the height. Will be considered as eutrophic those individuals with a BMI &lt; 25 kg/m<xref ref-type="bibr" rid="B2">2</xref> and &gt; 18 kg/m<xref ref-type="bibr" rid="B2">2</xref>, as overweight those with a BMI &#8805; 25 kg/m<xref ref-type="bibr" rid="B2">2</xref> and &lt; 30 kg/m<xref ref-type="bibr" rid="B2">2</xref>, and as obese those with a BMI &#8805; 30 kg/m<xref ref-type="bibr" rid="B2">2</xref>;</p>
            </list-item>
            <list-item>
              <p>Waist circumference (WC), measured with an inelastic measuring tape at the middle distance between the anterior superior iliac crest and the lower edge of the last costal arch with the patient standing and at the end of expiration;</p>
            </list-item>
            <list-item>
              <p>BP, measured with any type of regulated sphygmomanometer used routinely at the center, with two measures taken with the subject seated with an interval of at least 1 minute between each. Hypertension will be considered as the routine use of antihypertensive drugs or measurement of office BP equal to or above 140 x 90 mmHg. Individuals will be considered as having resistant hypertension when presenting uncontrolled BP levels despite the use of three classes of synergistic antihypertensive drugs in optimized doses, ideally including a diuretic; or if using four antihypertensive classes or more to achieve BP control;<xref ref-type="bibr" rid="B17">17</xref>
							</p>
            </list-item>
            <list-item>
              <p>Dyslipidemia, considered present in subjects using any hypolipidemic drug or with an LDL-c measurement above 160 mg/dL, and/or triglyceride level above 150 mg/dL, and/or HDL-c level below 40 mg/dL in men and 50 mg/dL in women, and/or total cholesterol above 200 mg/dL;</p>
            </list-item>
            <list-item>
              <p>Metabolic syndrome (MS), which will be diagnosed according to the International Diabetes Federation (IDF) criteria, detailed in <xref ref-type="table" rid="t1">Table 1</xref>, except for WC measurements, which will be considered &#8805; 102 cm in men and &#8805; 88 cm in women.</p>
            </list-item>
          </list>
        </p>
        <p>
          <table-wrap id="t1">
            <label>Table 1</label>
            <caption>
              <title>IDF Diagnostic criteria for metabolic syndrome<xref ref-type="bibr" rid="B18">18</xref>
							</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="36%"/>
                <col width="32%"/>
                <col width="32%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">
                    <bold>Criteria</bold>
                  </th>
                  <th align="center" colspan="2">
                    <bold>Definition</bold>
                  </th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>Waist circumference</td>
                  <td align="center">Men</td>
                  <td align="center">Women</td>
                </tr>
                <tr>
                  <td>White Europeans and Blacks</td>
                  <td align="center">&#8805; 94 cm</td>
                  <td align="center">&#8805; 80 cm</td>
                </tr>
                <tr>
                  <td>South Asians, Native Americans, and Chinese</td>
                  <td align="center">&#8805; 90 cm</td>
                  <td align="center">&#8805; 80 cm</td>
                </tr>
                <tr>
                  <td>Japanese</td>
                  <td align="center">&#8805; 85 cm</td>
                  <td align="center">&#8805; 90 cm</td>
                </tr>
                <tr>
                  <td>Triglycerides</td>
                  <td align="center" colspan="2">&#8805; 150 mg/dL or treatment for hypertriglyceridemia</td>
                </tr>
                <tr>
                  <td>HDL cholesterol</td>
                  <td align="center">Men &lt; 40 mg/dL</td>
                  <td align="center">Women &lt; 50 mg/dL</td>
                </tr>
                <tr>
                  <td rowspan="2"> Blood pressure</td>
                  <td align="center">Systolic &#8805; 130 mmHg</td>
                  <td align="center">Diastolic &#8805; 85 mmHg</td>
                </tr>
                <tr>
                  <td align="center" colspan="2">or anti-hypertensive treatment</td>
                </tr>
                <tr>
                  <td>Fasting blood glucose</td>
                  <td align="center" colspan="2">&#8805; 100 mg/dL or DM treatment</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN1">
                <p>The diagnosis of metabolic syndrome includes the occurrence of abdominal obesity as an essential condition, and two or more of the remaining criteria. DM: diabetes.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </p>
      </sec>
      <sec>
        <title>Clinical outcomes</title>
        <sec>
          <title>Primary outcomes</title>
          <p>The primary outcomes will include hospital admission for at least 24 hours due to hypertensive crisis; cardiovascular event (acute coronary syndrome [ACS] and/or stroke / transient ischemic attack [TIA]) documented in medical records or summary of hospital discharge; cardiovascular death (due to ACS, stroke / TIA, heart failure) confirmed by descriptions in the medical records and/or death certificate.</p>
        </sec>
        <sec>
          <title>Secondary outcomes</title>
          <p>The secondary outcomes will include hospitalization due to decompensated heart failure documented in medical records or summary of hospital discharge, and requirement of dialysis therapy.</p>
        </sec>
      </sec>
      <sec>
        <title>Recruitment</title>
        <p>The patients will be recruited from outpatient clinics, and their participation in the study will begin after they sign the FICF previously approved by the Research Ethics Committee (<italic>Comit&#234; de &#201;tica em Pesquisa</italic>, CEP).</p>
        <p>In the inclusion visit, the following information will be collected: demographic data, personal history, family history, hypertension history, BP assessment, medications in use within the previous 30 days, laboratory data and electrocardiogram (ECG) in the last 6 months (if available), analysis of other relevant tests in the investigator's opinion and performed in the previous year, lifestyle questionnaire, ambulatory BP in the previous 6 months (if available), and treatment adherence assessed with the Morisky scale.</p>
        <p>In the follow-up visit, the evaluating data will include BP measurements, medications in use, estimate of adherence to pharmacological and non-pharmacological treatment using the Morisky scale, hospitalization due to CVD (hypertensive crisis, AMI, angina, stroke, TIA, heart failure), beginning of dialysis, and death.</p>
      </sec>
      <sec>
        <title>Subgroup analysis</title>
        <p>A protocol subgroup including 15% of the sample will undergo a noninvasive assessment of the central BP with a validated Mobil-O-Graph equipment (DINA MAP CARDIOS - I.E.M. GmbH, Stolberg, Germany) in the inclusion and follow-up visits.</p>
        <p>The central hemodynamic parameters will be obtained using a noninvasive method that verifies simultaneously the pulse wave of the arterial blood flow, allowing analysis of the BP, central systolic pressure (cSP), pulse wave velocity (PWV), and augmentation index (AIx) by the method ARCsolver, Austrian Institute of Technology. This method determines the cSP based on brachial pulse waves recorded with a cuff connected to the Mobil-O-Graph, the oscillometric device that records the BP. The records will be obtained by inflating the cuff for 10 seconds at the DBP level, using conventional cuffs for adults (available in the sizes 24-34 cm and 32-42 cm) and a high-fidelity MPX50550 pressor sensor (Freescale Inc., Tempe, AZ, USA). The method considers the influence of arterial impedance using a transfer function, as well as the hemodynamics of the aorta using a mathematic method. The Mobil-O-Graph is a device that allows simultaneous measurement of central and peripheral pressure. Depending on the protocol adopted, these measurements may be carried out at pre-established intervals. The same preparation methodology described for the measurement of casual BP will be adopted, with the use of a suitable cuff, according to the circumference of the chosen arm.</p>
        <p>Central parameters are usually performed in a single evaluation. With this equipment, the assessments can be performed by several protocols with multiple measurements.</p>
        <p>For those research centers with patients participating in this subgroup, the following variables will be collected and entered in the registry's eCRF: cSP, central diastolic pressure (cDP), PWV, AIx (corrected for 75% of the heart rate), and peripheral arterial resistance.</p>
        <p>This analysis aims to offer an understanding of the reality of the Brazilian population regarding the information mentioned above, and to correlate different classes of antihypertensive drugs in terms of action on peripheral BP levels and on variables regulating the central BP control.</p>
      </sec>
      <sec>
        <title>Statistical analysis and sample size</title>
        <p>A sample of 3,000 individuals will be sufficient to estimate prevalences of 5% (or greater) with an absolute sample error (precision) of 2% (or greater) and a 95%CI considering a 20% loss to follow-up.<xref ref-type="bibr" rid="B19">19</xref> Survival curves will be calculated with the product-limit Kaplan-Meier method<xref ref-type="bibr" rid="B20">20</xref> and compared with the log-rank test proposed by Mantel,<xref ref-type="bibr" rid="B21">21</xref> followed by Sidak's multiple comparisons test, when appropriate. Survival probabilities will be estimated with 95%CI using log-log transformation.<xref ref-type="bibr" rid="B22">22</xref> Cox univariate and multivariate analyses (controlling for factors of interest such as comorbidities, sociodemographic variables, demographic regions, age, etc.) will be conducted to identify factors associated with the survival outcomes evaluated. The proportional hazards assumptions and functional form (for continuous covariables) in Cox regression models will be assessed according to the Kolmogorov-type supremum test based on a sample of 1,000 simulations of residuals.<xref ref-type="bibr" rid="B23">23</xref> If the linear form is rejected for a continuous covariate, the covariate will be categorized according to the cutoff points of clinical importance or according to distribution percentiles. Adjusted and unadjusted hazard ratios with corresponding 95%CIs will be estimated by Cox univariate and multivariate regression analyses, respectively. In addition, statistical analyses will be conducted in previously defined subgroups in different Brazilian regions (North, Northeast, Midwest, South, and Southeast) and according to the type of service performed (academic or non-academic, public or private).</p>
        <p>If a violation of the assumption is observed, weighted Cox regression will be used.<xref ref-type="bibr" rid="B24">24</xref> Before determining the multivariate model, a diagnosis of multicollinearity will be conducted according to the variance inflation factor (VIF). The cases confirmed as loss to follow-up will be censored at the date of the last follow-up / contact. Associations between categorical variables will be evaluated in 2x2 and greater than 2x2 contingency tables with Fisher's exact test and its extension, the Fisher-Freeman-Halton test, respectively. Unpaired Student's <italic>t</italic> test and analysis of variance (ANOVA) will be used to compare averages among groups of two or more than two, respectively. In cases of considerable data asymmetry, nonparametric alternatives will be applied: Wilcoxon's rank sum and Kruskal-Wallis tests, respectively.<xref ref-type="bibr" rid="B25">25</xref> The normality of the data will be evaluated with a visual inspection of the histograms and/or application of the D'Agostino and Pearson's comprehensive normality test, when appropriate.<xref ref-type="bibr" rid="B26">26</xref> Continuous variables will be described as mean &#177; standard deviation or median (interquartile range), when appropriate. Categorical variables will be described as numbers (percentages). In addition, statistical analyses will be conducted in previously defined subgroups. All probabilities of significance (p values) presented will be bilateral and values below 0.05 will be considered statistically significant. The data will be statistically analyzed with SAS 9.3 (Statistical Analysis System, Cary, NC, USA).</p>
      </sec>
      <sec>
        <title>Legal and ethical aspects</title>
        <p>This registry is conducted in accordance with national and international resolutions such as the Declaration of Helsinki, Resolution CNS196/96 and all the complementary CNS/MS, ICH Good Clinical Practices guide(1996), and the Document of the Americas (2005).</p>
        <p>Each clinical research center will submit this protocol, the FICFs, and all other applicable documents to the institutional CEP for analysis and approval prior to any procedure included in the registry.</p>
      </sec>
      <sec>
        <title>Organization of the study</title>
        <sec>
          <title>Coordinating Center</title>
          <p>The Brazilian Clinical Research Institute (<italic>Instituto Brasileiro de Pesquisa Cl&#237;nica</italic>, BCRI) in S&#227;o Paulo, Brazil, was responsible for the development of the protocol and operational coordination of the study, development and implementation of the electronic platform for data collection (electronic case report form), distribution of required materials to the research centers, preparation of regulatory dossier, newsletter, quality assurance of the collected data and organization of meetings for researchers, preparation of a monitoring plan, determination of training for the research centers, periodic monitoring visits, and remote study closure. The Institute for Teaching and Research of <italic>Hospital do Cora&#231;&#227;o</italic> (<italic>Instituto de Ensino e Pesquisa do Hospital do Cora&#231;&#227;o</italic>) will be responsible for maintaining the database and analyzing the data.</p>
        </sec>
      </sec>
      <sec>
        <title>Steering Committee</title>
        <p>The Steering Committee will be responsible for the design, implementation, analysis of the study data and allocation of appropriate responsibilities to other committees of the study.</p>
        <sec>
          <title>Research Centers/National Researchers</title>
          <p>Andr&#233;a Ara&#250;jo Brand&#227;o, Adriana de S. Thiago Papinutto, &#193;lvaro Rabelo Jr., Antonio Felipe Sanjuliani, Ant&#244;nio Carlos Sobral Sousa, Celso Amodeo, Cristiano Pederneiras Jaeger, Dalton Bertolim Pr&#233;coma, Est&#234;v&#227;o Lanna Figueiredo, Epotamenides Maria Good God, Evandro Jos&#233; Cesarino, F&#225;bio Argenta, Fernando Augusto Alves da Costa, Gilberto Campos Guimar&#227;es Filho, Gustavo Freitas Feitosa, Helder Jos&#233; Ant&#244;nio Miranda Abrantes, Iran Castro, Jos&#233; Lima Reis, Joaquim David Carneiro Neto, Jo&#227;o Carlos Ferreira Braga, Jo&#227;o Miguel Malta Dantas, Jo&#227;o Soares Fel&#237;cio, Jo&#227;o Roberto Gemelli, Jose Albuquerque de Figueiredo Neto, Jos&#233; Carlos Ayub, Jos&#233; Fernando Vilela Martin, Leila Beltrami Moreira, L&#237;via Figueira Avezum Oliveira, Luiz Bortolotto, Luciana Reis Katz Weiand, Luciano Marcelo Backes, Luiz Carlos Bodanese, Luiz C&#233;sar Naz&#225;rio Scala, M&#225;rcio Kalil, Marco Mota Gomes, Margaret Assad Cavalcante, Maria das Dores de Oliveira Jeh&#225;, Mario Fritsch Neves, Pedro Barros, Renato Delascio Lopes, Roberto Dischinger Mirand, Rodrigo Pinto Pedrosa, Rodrigo Ricardo Silva da Costa, Rog&#233;rio Toshiro Passos Okawa, Rui Manoel dos Santos P&#243;voa, Sergio Kaiser, Thiago de Souza Veiga Jardim, Wladmir Saporito, Weimar Sebba Barroso, Wilson Nadruz Junior.</p>
        </sec>
      </sec>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclusion</title>
      <p>A better understanding of the way that hypertensive patients are treated in Brazil will allow the implementation of policies aimed at improving the treatment of hypertension, contributing to changes in the epidemiological profile and decrease in cardiovascular morbidity and mortality in the country.</p>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="supported-by">
        <p>
          <bold>Sources of Funding</bold>
        </p>
        <p>This study was funded by Sociedade Brasileira de Cardiologia.</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>
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  <sub-article article-type="translation" id="s1" xml:lang="pt">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigo Especial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>I RBH &#8211; Primeiro Registro Brasileiro de Hipertens&#227;o Arterial</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Jardim</surname>
            <given-names>Paulo C&#233;sar Brand&#227;o Veiga</given-names>
          </name>
          <xref ref-type="aff" rid="aff8">1</xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
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            <given-names>Weimar Kunz Sebba Barroso de</given-names>
          </name>
          <xref ref-type="aff" rid="aff8">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lopes</surname>
            <given-names>Renato Delascio</given-names>
          </name>
          <xref ref-type="aff" rid="aff9">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Brand&#227;o</surname>
            <given-names>Andr&#233;a Ara&#250;jo</given-names>
          </name>
          <xref ref-type="aff" rid="aff10">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Malachias</surname>
            <given-names>Marcus V. Bol&#237;var</given-names>
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          <xref ref-type="aff" rid="aff11">4</xref>
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        <contrib contrib-type="author">
          <name>
            <surname>Gomes</surname>
            <given-names>Marco Mota</given-names>
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        <contrib contrib-type="author">
          <name>
            <surname>Moreno</surname>
            <given-names>Heitor</given-names>
            <suffix>J&#250;nior</suffix>
          </name>
          <xref ref-type="aff" rid="aff13">6</xref>
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          <name>
            <surname>Barbosa</surname>
            <given-names>Eduardo Costa Duarte</given-names>
          </name>
          <xref ref-type="aff" rid="aff14">7</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>P&#243;voa</surname>
            <given-names>Rui Manoel dos Santos</given-names>
          </name>
          <xref ref-type="aff" rid="aff9">2</xref>
        </contrib>
      </contrib-group>
      <aff id="aff8">
        <label>1</label>
        <institution content-type="original">Universidade Federal de Goi&#225;s, Goi&#226;nia, GO - Brasil</institution>
      </aff>
      <aff id="aff9">
        <label>2</label>
        <institution content-type="original">Universidade Federal de S&#227;o Paulo, S&#227;o Paulo, SP - Brasil</institution>
      </aff>
      <aff id="aff10">
        <label>3</label>
        <institution content-type="original">Universidade Estadual do Rio de Janeiro, Rio de Janeiro, RJ - Brasil</institution>
      </aff>
      <aff id="aff11">
        <label>4</label>
        <institution content-type="original">Faculdade de Ci&#234;ncias M&#233;dicas de Minas Gerais, Belo Horizonte, MG - Brasil</institution>
      </aff>
      <aff id="aff12">
        <label>5</label>
        <institution content-type="original">Universidade Estadual de Alagoas, Alto Cruzeiro Arapiraca, AL - Brasil</institution>
      </aff>
      <aff id="aff13">
        <label>6</label>
        <institution content-type="original">Universidade Estadual de Campinas, Campinas, SP - Brasil</institution>
      </aff>
      <aff id="aff14">
        <label>7</label>
        <institution content-type="original">Instituto de Cardiologia de Porto Alegre, Porto Alegre, RS - Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c2"><bold>Correspond&#234;ncia: Paulo C&#233;sar Brand&#227;o Veiga Jardim,</bold> Faculdade de Medicina da Universidade Federal de Goias. 115 F, n&#176;. 135, Setor Sul. CEP 74085-300, Goi&#226;nia, GO - Brasil. E-mail: <email>pcbveiga@cardiol.br</email>, <email>fvjardim@terra.com.br</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, Obten&#231;&#227;o de dados, An&#225;lise e interpreta&#231;&#227;o dos dados, Reda&#231;&#227;o do manuscrito e Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Jardim PCBV, Souza WKSB, Lopes RD, Brand&#227;o AA, Malachias MB, Gomes MM, Moreno J&#250;nior H, Barbosa E, P&#243;voa RMS; An&#225;lise estat&#237;stica: Jardim PCBV, Souza WKSB, Lopes RD, Brand&#227;o AA, Malachias MB, Gomes MM,; Obten&#231;&#227;o de financiamento: Jardim PCBV, Souza WKSB, Lopes RD, Brand&#227;o AA, Malachias MB, Gomes MM, P&#243;voa RMS.</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>Fundamento:</title>
          <p> Ainda n&#227;o foi realizado um registro brasileiro para avaliar, na pr&#225;tica cl&#237;nica di&#225;ria, o atendimento a pacientes hipertensos tanto em servi&#231;os p&#250;blicos quanto privados distribu&#237;dos pelas diversas regi&#245;es do pa&#237;s. Este conhecimento &#233; importante como forma de verificar a efetividade deste atendimento.</p>
        </sec>
        <sec>
          <title>Objetivo:</title>
          <p> Documentar a pr&#225;tica cl&#237;nica vigente para o tratamento da hipertens&#227;o arterial, atrav&#233;s do conhecimento do perfil dos exames realizados, do tipo de tratamento recebido, do n&#237;vel de controle da press&#227;o arterial (PA) e da ades&#227;o ao tratamento.</p>
        </sec>
        <sec>
          <title>M&#233;todos:</title>
          <p> Estudo nacional, observacional, prospectivo e multic&#234;ntrico que incluir&#225; pacientes &gt; 18 anos, hipertensos h&#225; &#8805; 4 semanas, em acompanhamento em servi&#231;os p&#250;blicos e privados e com assinatura do consentimento. Ser&#227;o exclu&#237;dos pacientes em di&#225;lise, internados nos &#250;ltimos 30 dias, com insufici&#234;ncia card&#237;aca classe III ou IV, gravidez ou amamenta&#231;&#227;o, hepatopatia grave, acidente vascular cerebral ou infarto agudo nos 30 dias anteriores e doen&#231;as com progn&#243;stico de sobrevida &lt; 1 ano. As avalia&#231;&#245;es ser&#227;o realizadas ao in&#237;cio e final do estudo, ap&#243;s acompanhamento por 1 ano. Par&#226;metros a serem avaliados incluir&#227;o dados antropom&#233;tricos, h&#225;bitos de vida, PA, perfil lip&#237;dico, s&#237;ndrome metab&#243;lica e ades&#227;o ao tratamento. Os desfechos prim&#225;rios ser&#227;o interna&#231;&#227;o por crise hipertensiva, evento cardiocirculat&#243;rio e &#243;bito cardiovascular, e os desfechos secund&#225;rios ser&#227;o interna&#231;&#227;o por insufici&#234;ncia card&#237;aca e necessidade de di&#225;lise. Uma an&#225;lise de subgrupo avaliar&#225; a press&#227;o central de forma n&#227;o invasiva em 15% da amostra no in&#237;cio e final do estudo. A amostra estimada &#233; de 3.000 indiv&#237;duos para preval&#234;ncia de 5%, erro amostral de 2% e intervalo de confian&#231;a de 95%.</p>
        </sec>
        <sec>
          <title>Resultados:</title>
          <p> Os resultados ser&#227;o apresentados ap&#243;s a avalia&#231;&#227;o final que ocorrer&#225; quando encerrado 1 ano de seguimento.</p>
        </sec>
        <sec>
          <title>Conclus&#227;o:</title>
          <p> A an&#225;lise deste registro trar&#225; melhor conhecimento sobre o tratamento da hipertens&#227;o no Brasil e possibilitar&#225; a otimiza&#231;&#227;o do mesmo, como forma de interferir no progn&#243;stico da doen&#231;a cardiovascular em nosso meio.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave:</title>
        <kwd>Pr&#225;tica Cl&#237;nica Baseada em Evid&#234;ncias</kwd>
        <kwd>Hipertens&#227;o</kwd>
        <kwd>Fatores de Risco</kwd>
        <kwd>Estudos Multic&#234;ntricos como Assunto</kwd>
        <kwd>Epidemiologia</kwd>
        <kwd>Preval&#234;ncia</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introdu&#231;&#227;o</title>
        <p>A hipertens&#227;o arterial (HA) &#233; uma doen&#231;a polig&#234;nica de etiologia multifatorial que se caracteriza por n&#237;veis sustentadamente elevados da press&#227;o arterial (PA).<xref ref-type="bibr" rid="B1">1</xref> Atualmente, a HA representa o principal fator de risco para doen&#231;as cardiovasculares (DCV), que s&#227;o a causa mais frequente de &#243;bito em nosso pa&#237;s e no mundo.<xref ref-type="bibr" rid="B1">1</xref><sup>-</sup><xref ref-type="bibr" rid="B3">3</xref> Adicionalmente, a HA associa-se a les&#245;es em &#243;rg&#227;os-alvo (rim, cora&#231;&#227;o, c&#233;rebro) e a outras comorbidades como a dislipidemia e o diabetes tipo 2,<xref ref-type="bibr" rid="B1">1</xref> que tamb&#233;m aumentam o risco de eventos cardiovasculares.</p>
        <p>Uma metan&#225;lise cl&#225;ssica que avaliou mais de 1 milh&#227;o de indiv&#237;duos inclu&#237;dos em 61 estudos observacionais concluiu que a mortalidade por DCV aumenta progressivamente com a eleva&#231;&#227;o da PA a partir de 115 / 75 mmHg de forma linear, cont&#237;nua e independente.<xref ref-type="bibr" rid="B4">4</xref>
				</p>
        <p>O estudo INTERHEART analisou os fatores de risco para infarto agudo do mioc&#225;rdio (IAM) em 52 pa&#237;ses (seis deles latino-americanos), em 15.000 casos de pacientes com primeiro IAM e em n&#250;mero semelhante de indiv&#237;duos controle.<xref ref-type="bibr" rid="B5">5</xref><sup>,</sup><xref ref-type="bibr" rid="B6">6</xref> O maior risco de IAM na Am&#233;rica Latina associou-se &#224; HA (<italic>odds ratio</italic> [OR] 2,48; intervalo de confian&#231;a de 95% [IC95%], 2,03-3,04), diabetes (OR 2,45; IC95%, 1,86-3,24), tabagismo (OR 2,35; IC95%, 1,92-2,87), dislipidemia - apoB/apoA1 (OR 2,79; IC95%, 1,85-4,23) e obesidade abdominal (OR 2,41; IC95%, 1,79-3,25). Considerando-se que todos esses fatores de risco s&#227;o modific&#225;veis, o estudo INTERHEART alerta para a necessidade da implementa&#231;&#227;o de estrat&#233;gias preventivas em toda a Am&#233;rica Latina.</p>
        <p>A preval&#234;ncia de HA no Brasil assemelha-se &#224; de outros pa&#237;ses. Inqu&#233;ritos populacionais brasileiros apontam para uma preval&#234;ncia de HA de aproximadamente 30%.<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B8">8</xref> Considerando-se valores de PA &#8805; 140 / 90 mmHg, 22 estudos encontraram preval&#234;ncias entre 22,3% e 43,9% (m&#233;dia de 32,5%), com taxa maior entre os homens comparados &#224;s mulheres e entre os indiv&#237;duos mais idosos.<xref ref-type="bibr" rid="B9">9</xref>
				</p>
        <p>Na cidade de S&#227;o Paulo, um estudo avaliando 613 pacientes atrav&#233;s de entrevista por telefone encontrou uma preval&#234;ncia de HA de 32% entre os participantes. Destes, 89% referiram estar em tratamento para a HA, por&#233;m, apenas 35% relataram estar com controle adequado da PA.<xref ref-type="bibr" rid="B10">10</xref> Outro estudo, realizado em S&#227;o Jos&#233; do Rio Preto, analisou 1.717 indiv&#237;duos e encontrou uma preval&#234;ncia de HA de 25,2% e como fatores associados, a idade mais avan&#231;ada, baixo n&#237;vel educacional e obesidade.<xref ref-type="bibr" rid="B11">11</xref> Entre os hipertensos tratados, 52,4% apresentaram controle adequado da PA, por&#233;m apenas 34,3% dos hipertensos em geral (tratados ou n&#227;o) tinham a PA controlada.</p>
        <p>Vemos, portanto, que por ser uma doen&#231;a multifatorial, muito frequente na popula&#231;&#227;o adulta e comumente associada a outros fatores de risco cardiovasculares e/ou les&#245;es em &#243;rg&#227;os-alvo, a HA representa um importante problema de sa&#250;de p&#250;blica. O tratamento pode ser eficaz quando o diagn&#243;stico da HA &#233; realizado precocemente e as metas de controle da PA s&#227;o atingidas; entretanto quando n&#227;o &#233; tratada, a HA pode causar complica&#231;&#245;es graves e ter evolu&#231;&#227;o lenta e silenciosa.<xref ref-type="bibr" rid="B1">1</xref>
				</p>
        <p>Dados do <italic>National Health and Nutrition Examination Survey</italic> (NHANES) de 2009 a 2012 mostraram que 84,7% dos adultos com HA sabiam do seu diagn&#243;stico e que o percentual de pacientes em tratamento anti-hipertensivo foi de 76,5%, com uma taxa de controle da PA de 54,1%. Esses n&#250;meros denotam uma melhora significativa no diagn&#243;stico e controle da HA na popula&#231;&#227;o americana.<xref ref-type="bibr" rid="B12">12</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref>
				</p>
        <p>As mudan&#231;as no estilo de vida reduzem a PA, bem como a mortalidade cardiovascular.<xref ref-type="bibr" rid="B14">14</xref><sup>-</sup><xref ref-type="bibr" rid="B16">16</xref> Apesar de sempre recomendadas na preven&#231;&#227;o e no tratamento da HA, s&#227;o de dif&#237;cil implementa&#231;&#227;o por parte do paciente e muitas vezes pelo m&#233;dico, que nem sempre disp&#245;e de uma equipe multiprofissional.</p>
        <p>Com o objetivo de se atingir o controle adequado da PA e, consequentemente, uma diminui&#231;&#227;o de &#243;bitos por DCV, &#233; fundamental se ter al&#233;m do conhecimento sobre a preval&#234;ncia da HA no Brasil, esclarecimentos sobre como a forma de atendimento e o tratamento do paciente hipertenso v&#234;m sendo conduzidos na pr&#225;tica cl&#237;nica di&#225;ria, e qual o papel das equipes multiprofissionais neste cen&#225;rio.</p>
      </sec>
      <sec>
        <title>Objetivos</title>
        <sec>
          <title>Objetivo principal</title>
          <p>
            <list list-type="bullet">
              <list-item>
                <p>Documentar a pr&#225;tica cl&#237;nica vigente para o tratamento da HA no Brasil.</p>
              </list-item>
            </list>
          </p>
        </sec>
        <sec>
          <title>Objetivos secund&#225;rios</title>
          <p>
            <list list-type="bullet">
              <list-item>
                <p>Estratificar o risco cardiovascular adicional, considerando comorbidades associadas, les&#245;es em &#243;rg&#227;o-alvo, e presen&#231;a de doen&#231;a cardiovascular manifesta;</p>
              </list-item>
              <list-item>
                <p>Analisar o perfil de exames realizados de rotina nos pacientes com HA;</p>
              </list-item>
              <list-item>
                <p>Verificar a propor&#231;&#227;o de pacientes recebendo tratamento anti-hipertensivo que est&#227;o dentro das metas preconizadas pela Sociedade Brasileira de Cardiologia;</p>
              </list-item>
              <list-item>
                <p>Estimar a ades&#227;o aos tratamentos propostos (n&#227;o medicamentoso e medicamentoso), atrav&#233;s da Escala de Morisky;</p>
              </list-item>
              <list-item>
                <p>Avaliar a presen&#231;a de uma equipe multiprofissional no atendimento regular dos pacientes e, quando existente, a efic&#225;cia da sua atua&#231;&#227;o no controle da PA;</p>
              </list-item>
              <list-item>
                <p>Avaliar as poss&#237;veis diferen&#231;as entre os servi&#231;os p&#250;blicos e privados na abordagem de pacientes hipertensos.</p>
              </list-item>
            </list>
          </p>
        </sec>
      </sec>
      <sec sec-type="methods">
        <title>M&#233;todos</title>
        <sec>
          <title>Desenho do estudo e popula&#231;&#227;o</title>
          <p>Este primeiro registro brasileiro de HA sist&#234;mica ser&#225; um estudo prospectivo, observacional, multic&#234;ntrico e nacional, no qual os sujeitos ser&#227;o triados e avaliados em ambulat&#243;rios de cl&#237;nica m&#233;dica e de especialidades em um per&#237;odo de seguimento de 12 meses.</p>
          <p>Ser&#227;o selecionados indiv&#237;duos em preven&#231;&#227;o prim&#225;ria ou secund&#225;ria com o diagn&#243;stico de HA e que preencherem aos crit&#233;rios de inclus&#227;o. Ap&#243;s assinatura do termo de consentimento livre e esclarecido (TCLE), ser&#225; realizada an&#225;lise de prontu&#225;rio e os sujeitos ser&#227;o entrevistados para preenchimento da ficha cl&#237;nica eletr&#244;nica (<italic>electronic case report form</italic>, eCRF) de inclus&#227;o.</p>
          <p>Ser&#225; programada uma visita de seguimento entre 6 meses e 1 ano da inclus&#227;o. Em caso de mais de um retorno neste per&#237;odo, essa visita adicional tamb&#233;m poder&#225; ser documentada como visita intermedi&#225;ria.</p>
        </sec>
        <sec>
          <title>Popula&#231;&#227;o do estudo</title>
          <p>Pacientes maiores de 18 anos com diagn&#243;stico de HA h&#225; pelo menos 4 semanas.</p>
        </sec>
        <sec>
          <title>Crit&#233;rios de inclus&#227;o</title>
          <p>Assinatura do TCLE; idade acima de 18 anos; diagn&#243;stico de HA h&#225; pelo menos 4 semanas, com PA sist&#243;lica (PAS) &#8805; 140 mmHg e/ou PA diast&#243;lica (PAD) &#8805; 90 mmHg na posi&#231;&#227;o sentada e de acordo com as VI Diretrizes Brasileiras de Hipertens&#227;o, ou sob uso de medica&#231;&#227;o anti-hipertensiva; matr&#237;cula regular no centro/institui&#231;&#227;o participante.</p>
        </sec>
        <sec>
          <title>Crit&#233;rios de exclus&#227;o</title>
          <p>Insufici&#234;ncia renal em programa de di&#225;lise; interna&#231;&#227;o hospitalar no momento ou 30 dias antes da inclus&#227;o; instabilidade hemodin&#226;mica com necessidade de uso de f&#225;rmacos vasoativos at&#233; 30 dias antes da inclus&#227;o;insufici&#234;ncia card&#237;aca em classe funcional III ou IV; gravidez e/ou amamenta&#231;&#227;o;hepatopatia grave;doen&#231;as psiqui&#225;tricas que impe&#231;am o cumprimento do protocolo;antecedente de acidente vascular cerebral (AVC) ou IAM at&#233; 30 dias antes da inclus&#227;o;doen&#231;as graves na avalia&#231;&#227;o do investigador; neoplasias com progn&#243;stico de sobrevida inferior a 1 ano.</p>
        </sec>
        <sec>
          <title>Crit&#233;rios de interrup&#231;&#227;o do estudo</title>
          <p>Indiv&#237;duos que desejarem cancelar a participa&#231;&#227;o no estudo, ou que durante o seguimento apresentarem um ou mais crit&#233;rios de exclus&#227;o.</p>
        </sec>
        <sec>
          <title>Avalia&#231;&#227;o cl&#237;nica</title>
          <p>
            <list list-type="bullet">
              <title>Os seguintes dados cl&#237;nicos ser&#227;o avaliados:</title>
              <list-item>
                <p>Hist&#243;ria familiar de doen&#231;a arterial coronariana (AF DAC) prematura (parente de primeiro grau com antecedente de DAC abaixo de 55 anos para o sexo masculino e de 65 anos para o sexo feminino);</p>
              </list-item>
              <list-item>
                <p>Tabagismo, considerando como tabagista atual o indiv&#237;duo que fumar um ou mais cigarros rotineiramente ou que fumou de forma rotineira at&#233; 1 ano antes da inclus&#227;o e como ex-tabagista o indiv&#237;duo que abandonou o v&#237;cio mais de 1 ano antes da inclus&#227;o;</p>
              </list-item>
              <list-item>
                <p>Etilismo, considerando como etilismo atual a ingest&#227;o de ao menos 30 g de etanol para homens (equivalente a aproximadamente duas latas de cerveja de 365 mL, duas ta&#231;as de vinho de 150 mL, ou duas doses de u&#237;sque de 50 mL) e 15 g de etanol para mulheres (equivalente &#224; metade das doses descritas para homens) ao menos tr&#234;s vezes na semana, e como ex-etilismo o abandono do v&#237;cio h&#225; pelo menos 1 ano da inclus&#227;o;</p>
              </list-item>
              <list-item>
                <p>Atividade f&#237;sica, considerando como regular qualquer atividade f&#237;sica realizada por no m&#237;nimo 30 minutos tr&#234;s vezes na semana;</p>
              </list-item>
              <list-item>
                <p>Menopausa, caracterizada pela aus&#234;ncia de ciclos menstruais pelo menos 1 ano antes da inclus&#227;o;</p>
              </list-item>
              <list-item>
                <p>Peso e altura aferidos em balan&#231;a antropom&#233;trica;</p>
              </list-item>
              <list-item>
                <p>&#205;ndice de massa corp&#243;rea (IMC), calculado pela f&#243;rmula do peso dividido pelo quadrado da altura. Ser&#227;o considerados como eutr&#243;ficos os sujeitos com IMC &lt; 25 kg/m<sup>2</sup> e &gt; 18 kg/m<sup>2</sup>, com sobrepeso aqueles com IMC &#8805; 25 kg/m<sup>2</sup> e &lt; 30 kg/m<sup>2</sup> e como obesos aqueles com IMC &#8805; 30 kg/m<sup>2</sup>;</p>
              </list-item>
              <list-item>
                <p>Circunfer&#234;ncia da cintura (CC), determinada com fita m&#233;trica inel&#225;stica no ponto m&#233;dio da dist&#226;ncia entre a crista il&#237;aca &#226;ntero-superior e o rebordo inferior do &#250;ltimo arco costal com o paciente em p&#233; e ao final da expira&#231;&#227;o;</p>
              </list-item>
              <list-item>
                <p>PA, determinada com qualquer tipo de esfigmoman&#244;metro normatizado e utilizado na rotina do centro participante atrav&#233;s de duas medidas na posi&#231;&#227;o sentada com intervalo de pelo menos 1 minuto entre elas. Ser&#227;o considerados como portadores de HA os indiv&#237;duos em uso rotineiro de anti-hipertensivos ou com medida da PA de consult&#243;rio igual ou acima de 140 x 90 mmHg. Ser&#227;o considerados como portadores de HA resistente (HAR) os casos com PA n&#227;o controlada apesar do uso de tr&#234;s classes de anti-hipertensivos sin&#233;rgicos, em doses otimizadas e idealmente incluindo um diur&#233;tico, ou aqueles em uso de quatro classes ou mais para obter controle da PA;<xref ref-type="bibr" rid="B17">17</xref>
								</p>
              </list-item>
              <list-item>
                <p>Dislipidemia, considerada presente quando o sujeito fizer uso rotineiro de qualquer hipolipemiante ou apresentar dosagem de LDL-c acima de 160 mg/dL e/ou triglic&#233;rides acima de 150 mg/dL e/ou HDL-c abaixo de 40 mg/dL para homens ou 50 mg/dL para mulheres e/ou colesterol total acima de 200 mg/dL;</p>
              </list-item>
              <list-item>
                <p>S&#237;ndrome metab&#243;lica (SM), cujo diagn&#243;stico ser&#225; estabelecido pelos crit&#233;rios da International Diabetes Federation (IDF), detalhados na <xref ref-type="table" rid="t2">Tabela 1</xref>, com exce&#231;&#227;o dos valores da CC que ser&#227;o considerados &#8805; 102 cm em homens e &#8805; 88 cm em mulheres.</p>
              </list-item>
            </list>
          </p>
          <p>
            <table-wrap id="t2">
              <label>Tabela 1</label>
              <caption>
                <title>Crit&#233;rios diagn&#243;sticos de s&#237;ndrome metab&#243;lica segundo a IDF<xref ref-type="bibr" rid="B18">18</xref>
								</title>
              </caption>
              <table frame="hsides" rules="groups">
                <colgroup>
                  <col width="36%"/>
                  <col width="32%"/>
                  <col width="32%"/>
                </colgroup>
                <thead>
                  <tr>
                    <th align="left">
                      <bold>Crit&#233;rios</bold>
                    </th>
                    <th align="center" colspan="2">
                      <bold>Defini&#231;&#227;o</bold>
                    </th>
                  </tr>
                </thead>
                <tbody>
                  <tr>
                    <td>Circunfer&#234;ncia abdominal</td>
                    <td align="center">Homens</td>
                    <td align="center">Mulheres</td>
                  </tr>
                  <tr>
                    <td>Brancos de origem europ&#233;ia e negros</td>
                    <td align="center">&#8805; 94 cm</td>
                    <td align="center">&#8805; 80 cm</td>
                  </tr>
                  <tr>
                    <td>Sul-asi&#225;ticos, amer&#237;ndios e chineses</td>
                    <td align="center">&#8805; 90 cm</td>
                    <td align="center">&#8805; 80 cm</td>
                  </tr>
                  <tr>
                    <td>japoneses</td>
                    <td align="center">&#8805; 85 cm</td>
                    <td align="center">&#8805; 90 cm</td>
                  </tr>
                  <tr>
                    <td>Triglic&#233;rides</td>
                    <td align="center" colspan="2">&#8805; 150 mg/dL ou tratamento para hipertrigliceridemia</td>
                  </tr>
                  <tr>
                    <td>HDL-colesterol</td>
                    <td align="center">Homens &lt; 40 mg/dL</td>
                    <td align="center">Mulheres &lt; 50 mg/dL</td>
                  </tr>
                  <tr>
                    <td rowspan="2">Press&#227;o arterial</td>
                    <td align="center">Sist&#243;lica &#8805; 130 mmHg</td>
                    <td align="center">Diast&#243;lica &#8805; 85 mmHg</td>
                  </tr>
                  <tr>
                    <td colspan="2">ou tratamento anti-hipertensivo</td>
                  </tr>
                  <tr>
                    <td>Glicemia de jejum</td>
                    <td align="center" colspan="2">&#8805; 100 mg/dL ou tratamento para DM</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN2">
                  <p>O diagn&#243;stico de s&#237;ndrome metab&#243;lica inclui a presen&#231;a de obesidade abdominal, como condi&#231;&#227;o essencial, e dois ou mais dos outros crit&#233;rios. DM: diabetes melito.</p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
          </p>
        </sec>
        <sec>
          <title>Desfechos cl&#237;nicos</title>
          <sec>
            <title>Desfechos prim&#225;rios</title>
            <p>Os desfechos prim&#225;rios incluir&#227;o interna&#231;&#227;o por pelo menos 24 horas devida a crise hipertensiva; evento cardiovascular (s&#237;ndrome coronariana aguda [SCA] e/ou AVC / ataque isqu&#234;mico transit&#243;rio [AIT]) documentado em prontu&#225;rio ou resumo de alta hospitalar; &#243;bito de etiologia cardiovascular (por SCA, AVC / AIT, insufici&#234;ncia card&#237;aca) confirmado por descri&#231;&#227;o em prontu&#225;rio e/ou atestado de &#243;bito.</p>
          </sec>
          <sec>
            <title>Desfechos secund&#225;rios</title>
            <p>Os desfechos secund&#225;rios incluir&#227;o interna&#231;&#227;o por insufici&#234;ncia card&#237;aca descompensada documentada em prontu&#225;rio ou em resumo de alta hospitalar e necessidade de terapia por di&#225;lise.</p>
          </sec>
        </sec>
        <sec>
          <title>Recrutamento</title>
          <p>Os pacientes ser&#227;o recrutados ambulatorialmente e suas participa&#231;&#245;es no estudo ter&#227;o in&#237;cio ap&#243;s assinatura do TCLE previamente aprovado pelo Comit&#234; de &#201;tica em Pesquisa (CEP).</p>
          <p>Na visita de inclus&#227;o as seguintes informa&#231;&#245;es ser&#227;o coletadas: dados demogr&#225;ficos, antecedentes pessoais, antecedentes familiares, hist&#243;ria da HA, avalia&#231;&#227;o da PA, medica&#231;&#245;es em uso nos &#250;ltimos 30 dias, dados laboratoriais e eletrocardiograma (ECG) nos &#250;ltimos 6 meses (se dispon&#237;veis),an&#225;lise de outros exames relevantes na opini&#227;o do investigador e realizados no &#250;ltimo ano, question&#225;rio de estilo de vida, monitoriza&#231;&#227;o ambulatorial da PA nos &#250;ltimos 6 meses (se dispon&#237;vel) e ades&#227;o ao tratamento, avaliada atrav&#233;s da Escala de Morisky.</p>
          <p>Os dados avaliados nas visitas de seguimento ser&#227;o as medidas da PA, medica&#231;&#227;o em uso, estimativa de ades&#227;o ao tratamento medicamentoso e n&#227;o medicamentoso atrav&#233;s da Escala de Morisky, interna&#231;&#227;o por DCV (crise hipertensiva, IAM, angina, AVC, AIT, insufici&#234;ncia card&#237;aca), in&#237;cio de di&#225;lise e &#243;bito.</p>
        </sec>
        <sec>
          <title>An&#225;lise de subgrupo</title>
          <p>Em um subgrupo do protocolo correspondente a 15% da amostra, ser&#227;o coletadas medidas centrais da PA de forma n&#227;o invasiva, com o aparelho validado Mobil-O-Graph (DINA MAP CARDIOS - I.E.M. GmbH, Stolberg, Alemanha), tanto na visita de inclus&#227;o quanto na de seguimento do estudo.</p>
          <p>Os par&#226;metros da hemodin&#226;mica central ser&#227;o obtidos atrav&#233;s de um m&#233;todo n&#227;o invasivo, que verifica simultaneamente a onda de pulso do fluxo sangu&#237;neo arterial, permitindo a an&#225;lise da PA, da press&#227;o sist&#243;lica central (PSc), da velocidade de onda de pulso (VOP) e do <italic>augmentation index</italic> (AIx) pelo m&#233;todo ARCsolver, Instituto Austr&#237;aco de Tecnologia. Esse m&#233;todo determina a PSc com base em ondas de pulso braquial gravadas atrav&#233;s de um manguito ligado ao aparelho oscilom&#233;trico Mobil-O-Graph que verifica a PA. Os registros s&#227;o obtidos mantendo-se o manguito inflado por 10 segundos ao n&#237;vel da PAD com utiliza&#231;&#227;o de bra&#231;adeiras convencionais para adultos (dispon&#237;veis nos tamanhos 24-34 cm e 32-42 cm) e um sensor MPX50550 (Freescale Inc., Tempe, AZ, EUA) de press&#227;o com alta fidelidade. O m&#233;todo considera a influ&#234;ncia da imped&#226;ncia arterial utilizando uma fun&#231;&#227;o de transfer&#234;ncia, bem como a hemodin&#226;mica da aorta por meio de um m&#233;todo matem&#225;tico. O Mobil-O-Graph &#233; um dispositivo que permite medidas simult&#226;neas da press&#227;o central e perif&#233;rica. Na depend&#234;ncia do protocolo utilizado, essas medidas podem ser realizadas em intervalos de tempos pr&#233;-estabelecidos. Ser&#225; utilizada a mesma metodologia de preparo para medida casual da PA, com utiliza&#231;&#227;o de uma bra&#231;adeira adequada, de acordo com a circunfer&#234;ncia do bra&#231;o escolhido.</p>
          <p>Habitualmente, par&#226;metros centrais s&#227;o obtidos em uma &#250;nica avalia&#231;&#227;o. Este equipamento permite que essa avalia&#231;&#227;o seja realizada por v&#225;rios protocolos de m&#250;ltiplas medidas.</p>
          <p>Para os centros de pesquisa com pacientes participantes desse subgrupo as seguintes vari&#225;veis ser&#227;o coletadas e inseridas na eCRF do registro: PSc, press&#227;o diast&#243;lica central (PDc), VOP, AIx (corrigido para 75% da frequ&#234;ncia card&#237;aca) e resist&#234;ncia arterial perif&#233;rica.</p>
          <p>Esta an&#225;lise visa conhecer a realidade da popula&#231;&#227;o brasileira em rela&#231;&#227;o aos dados acima descritos e correlacionar as diferentes classes de anti-hipertensivos, n&#227;o somente no que tange &#224;s suas a&#231;&#245;es nos n&#237;veis perif&#233;ricos da PA, como tamb&#233;m nas vari&#225;veis que regem o controle central da PA.</p>
        </sec>
        <sec>
          <title>An&#225;lise estat&#237;stica e tamanho da amostra</title>
          <p>Uma amostra de 3.000 indiv&#237;duos ser&#225; suficiente para estimar preval&#234;ncias de 5% (ou maior) com um erro amostral absoluto (precis&#227;o) de 2% (ou maior) e IC95% considerando perda de seguimento de no m&#225;ximo 20%.<xref ref-type="bibr" rid="B19">19</xref> Curvas de sobreviv&#234;ncia ser&#227;o calculadas com o m&#233;todo produto-limite de Kaplan-Meier<xref ref-type="bibr" rid="B20">20</xref> e comparadas com o teste <italic>log-rank</italic> proposto por Mantel,<xref ref-type="bibr" rid="B21">21</xref> seguido de teste de compara&#231;&#245;es m&#250;ltiplas de Sidak, quando adequado. Probabilidades de sobreviv&#234;ncia ser&#227;o estimadas com IC95% segundo m&#233;todo de transforma&#231;&#227;o complementar log-log.<xref ref-type="bibr" rid="B22">22</xref> An&#225;lises univariadas e multivariadas de Cox (com controle por fatores de interesse como comorbidades, vari&#225;veis sociodemogr&#225;ficas, regi&#245;es demogr&#225;ficas, idade, etc.) ser&#227;o efetuadas com objetivo de identificar fatores associados aos desfechos de sobreviv&#234;ncia avaliados. As suposi&#231;&#245;es de riscos proporcionais e a forma funcional (para covari&#225;veis cont&#237;nuas) em modelos de regress&#227;o de Cox ser&#227;o avaliadas segundo o <italic>Kolmogorov-type supremum test</italic> com base em uma amostra de 1.000 simula&#231;&#245;es de res&#237;duos.<xref ref-type="bibr" rid="B23">23</xref> Se a forma linear for rejeitada para uma covari&#225;vel cont&#237;nua, essa covari&#225;vel ser&#225; categorizada segundo ponto de corte de import&#226;ncia cl&#237;nica ou segundo percentis da distribui&#231;&#227;o. As taxas de risco (<italic>hazard ratios</italic>) n&#227;o ajustadas e ajustadas, com IC95%, ser&#227;o estimadas nas an&#225;lises de regress&#227;o univariada e multivariada de Cox, respectivamente. Adicionalmente, as an&#225;lises estat&#237;sticas ser&#227;o conduzidas em subgrupos previamente definidos entre as diferentes regi&#245;es do Brasil (Norte, Nordeste, Centro-Oeste, Sul e Sudeste) e de acordo com o tipo de servi&#231;o prestado (acad&#234;mico ou n&#227;o acad&#234;mico, p&#250;blico ou privado).</p>
          <p>Se observada viola&#231;&#227;o da suposi&#231;&#227;o, ser&#225; utilizada a regress&#227;o ponderada de Cox (<italic>weighted Cox regression</italic>).<xref ref-type="bibr" rid="B24">24</xref> Antes de determinar o modelo multivariado, um diagn&#243;stico de multicolinearidade ser&#225; conduzido de acordo com o fator de infla&#231;&#227;o da vari&#226;ncia (<italic>variance inflation factor</italic>, VIF). Os casos confirmados como perda de seguimento ser&#227;o censurados na data referente ao &#250;ltimo acompanhamento/contato. Associa&#231;&#245;es entre vari&#225;veis categ&#243;ricas ser&#227;o avaliadas em tabelas de conting&#234;ncia 2x2 e maiores que 2x2 segundo teste exato de Fisher e sua generaliza&#231;&#227;o, o teste de Fisher-Freeman-Halton, respectivamente. O teste <italic>t</italic> de Student n&#227;o pareado e an&#225;lise de vari&#226;ncia (ANOVA) ser&#227;o utilizados na compara&#231;&#227;o de m&#233;dias entre dois grupos ou mais de dois grupos, respectivamente. Em casos de consider&#225;vel assimetria nos dados, alternativas n&#227;o param&#233;tricas ser&#227;o aplicadas: teste da soma dos postos de Wilcoxon e teste de Kruskal-Wallis, respectivamente.<xref ref-type="bibr" rid="B25">25</xref> A normalidade dos dados ser&#225; avaliada com a inspe&#231;&#227;o visual de histogramas e/ou aplica&#231;&#227;o do teste abrangente de normalidade de D'Agostino e Pearson, quando adequado.<xref ref-type="bibr" rid="B26">26</xref> Vari&#225;veis cont&#237;nuas ser&#227;o descritas como m&#233;dia &#177; desvio padr&#227;o ou mediana (intervalo interquartil), quando adequado. Vari&#225;veis categ&#243;ricas ser&#227;o descritas como n&#250;meros (percentagens). Adicionalmente, an&#225;lises estat&#237;sticas ser&#227;o conduzidas em subgrupos previamente definidos. Todas as probabilidades de signific&#226;ncia (valores de p) apresentadas ser&#227;o do tipo bilateral e valores inferiores a 0,05 ser&#227;o considerados estatisticamente significantes. A an&#225;lise estat&#237;stica dos dados ser&#225; efetuada com o programa SAS 9.3 (<italic>Statistical Analysis System, Cary</italic>, NC, EUA).</p>
        </sec>
        <sec>
          <title>Aspectos &#233;ticos e legais</title>
          <p>Este registro ser&#225; conduzido em conformidade com resolu&#231;&#245;es nacionais e internacionais, como a Declara&#231;&#227;o de Helsinque, Resolu&#231;&#227;o CNS196/96 e todas suas complementares do CNS/MS, Guia de Boas Pr&#225;ticas Cl&#237;nicas da ICH (1996) e Documento das Am&#233;ricas (2005).</p>
          <p>Cada centro de pesquisa cl&#237;nica encaminhar&#225; este protocolo, os TCLEs e todos os outros documentos aplic&#225;veis ao CEP da sua institui&#231;&#227;o para an&#225;lise e aprova&#231;&#227;o antes de qualquer procedimento do registro.</p>
        </sec>
        <sec>
          <title>Organiza&#231;&#227;o do estudo</title>
          <sec>
            <title>Centro Coordenador</title>
            <p>O Instituto Brasileiro de Pesquisa Cl&#237;nica (BCRI) de S&#227;o Paulo, Brasil, foi respons&#225;vel pelo desenvolvimento do protocolo e pela coordena&#231;&#227;o operacional do estudo, cria&#231;&#227;o e implementa&#231;&#227;o da plataforma eletr&#244;nica de coleta de dados (ficha cl&#237;nica eletr&#244;nica), disponibiliza&#231;&#227;o de materiais necess&#225;rios aos centros de pesquisa, prepara&#231;&#227;o do dossi&#234; regulat&#243;rio, <italic>newsletter</italic>, garantia da qualidade dos dados coletados e organiza&#231;&#227;o de reuni&#245;es de investigadores, prepara&#231;&#227;o de um plano de monitora&#231;&#227;o, determina&#231;&#227;o do treinamento para os centros de pesquisa, visitas de monitora&#231;&#227;o peri&#243;dicas, remotas e de fechamento do estudo. O Instituto de Ensino e Pesquisa do Hospital do Cora&#231;&#227;o &#233; respons&#225;vel pela manuten&#231;&#227;o do banco de dados e pela an&#225;lise dos dados.</p>
          </sec>
        </sec>
        <sec>
          <title>Comit&#234; Diretivo</title>
          <p>O Comit&#234; Diretivo &#233; respons&#225;vel pelo desenho, execu&#231;&#227;o, an&#225;lise dos dados do estudo e atribui&#231;&#227;o de responsabilidades apropriadas a outros comit&#234;s do estudo.</p>
          <sec>
            <title>Centros de Pesquisa/Investigadores Nacionais:</title>
            <p>Andr&#233;a Ara&#250;jo Brand&#227;o, Adriana de S. Thiago Papinutto, &#193;lvaro Rabelo Jr., Antonio Felipe Sanjuliani, Ant&#244;nio Carlos Sobral Sousa, Celso Amodeo, Cristiano Pederneiras Jaeger, Dalton Bertolim Pr&#233;coma, Est&#234;v&#227;o Lanna Figueiredo, Epotamenides Maria Good God, Evandro Jos&#233; Cesarino, F&#225;bio Argenta, Fernando Augusto Alves da Costa, Gilberto Campos Guimar&#227;es Filho, Gustavo Freitas Feitosa , Helder Jos&#233; Ant&#244;nio Miranda Abrantes, Iran Castro, Jos&#233; Lima Reis, Joaquim David Carneiro Neto, Jo&#227;o Carlos Ferreira Braga, Jo&#227;o Miguel Malta Dantas, Jo&#227;o Soares Fel&#237;cio, Jo&#227;o Roberto Gemelli, Jose Albuquerque de Figueiredo Neto, Jos&#233; Carlos Ayub, Jos&#233; Fernando Vilela Martin, Leila Beltrami Moreira, L&#237;via Figueira Avezum Oliveira, Luiz Bortolotto, Luciana Reis Katz Weiand, Luciano Marcelo Backes, Luiz Carlos Bodanese, Luiz C&#233;sar Naz&#225;rio Scala, M&#225;rcio Kalil, Marco Mota Gomes, Margaret Assad Cavalcante, Maria das Dores de Oliveira Jeh&#225;, Mario Fritsch Neves, Pedro Barros, Renato Delascio Lopes, Roberto Dischinger Mirand , Rodrigo Pinto Pedrosa, Rodrigo Ricardo Silva da Costa, Rog&#233;rio Toshiro Passos Okawa, Rui Manoel dos Santos P&#243;voa, Sergio Kaiser, Thiago de Souza Veiga Jardim, Wladmir Saporito, Weimar Sebba Barroso, Wilson Nadruz Junior.</p>
          </sec>
        </sec>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclus&#227;o</title>
        <p>O melhor conhecimento sobre o modo como ocorre o tratamento dos hipertensos no pa&#237;s ir&#225; permitir a implementa&#231;&#227;o de pol&#237;ticas que visem o aperfei&#231;oamento deste procedimento e, com isto, contribuir para uma mudan&#231;a no perfil epidemiol&#243;gico e diminui&#231;&#227;o da morbidade e mortalidade cardiovascular no Brasil.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="supported-by">
          <p>
            <bold>Fontes de financiamento</bold>
          </p>
          <p>O presente estudo foi financiado pela Sociedade Brasileira de Cardiologia.</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>
