Cardiac aging is characterized by slow and progressive changes in cardiac structure and function. With advancing age, although systolic ventricular function is relatively preserved, the same is not true for diastolic function.¹ With aging, there are also changes in cardiac valves, mainly in the left valves,¹ mainly calcification of the leaflets of the aortic and mitral valves.² Although age-related changes of the right valves are less frequent and milder, there is evidence of small fibroelastic nodules in the tricuspid valve, while the pulmonary valve remains almost unchanged.^3,4

Epicardial fat (EF) is a component of the visceral fat located between the surface of the myocardium and the visceral layer of the pericardium.^5-13 It can be deposited throughout the entire myocardium, but it is predominant in the atrioventricular and interventricular sulci, extending to the apex and around the coronary arteries.^6,8-9,14-16 The EF shares its embryological origin with the intra-abdominal visceral fat,^10,14 and the microcirculation with the myocardium and coronary arteries. It can be a potential cause of local inflammation and has direct effects on coronary atherosclerosis through the release of anti- and pro-inflammatory substances, with correlations with the severity of metabolic syndrome and heart diseases, especially coronary artery disease.^5-10,15-23 Although EF has been considered by some authors as an important predictive marker of cardiovascular and metabolic risk,^8,16 its association with other risk factors in elderly populations, makes its interpretation as an independent risk marker difficult.⁸

The association of EF thickness with age and gender has been controversial in the published studies. While some authors have reported that EF thickness tends to increase with age,^{9,19,22,24-28} others have not found statistically significant correlations between these two variables.^{7,11-12, 29,30} Regarding gender, some authors ^11,12,19,31 have reported higher EF thickness in males, while others^7,25-32found it to be higher in females. Regarding anthropometric parameters, EF thickness seems to correlate with weight,^25-31,33 height,³¹ abdominal circumference,^{10-13,19,22,25,28,29,33-34} and fat mass,^11,12 and and regarding the correlation correlation between EF thickness and body mass index (BMI) the results have been contradictory.^{2,9-12,22,25-26,28,29,31,33-34} The association of EF thickness with obesity has been widely described, ^{11,16-17,31,35-37} and significant changes in EF thickness in severely obese individuals undergoing weight loss programs or interventions have been reported.^30,37,38 Although the relationship between EF thickness and some clinical conditions such as diabetes and dyslipidemia is not in the literature, its correlation with hypertension seems to be more evident.^{11, 24, 30,33-34}

In addition, several studies have found correlations between EF thickness and some echocardiographic parameters, such as left ventricular mass index (LVMI),^24,29 left ventricular hypertrophy (LVH),^14,18,26 and left ventricular diastolic dysfunction.^7,26,36

Thus, the interest in the study of the EF thickness through echocardiography has been growing, since it reflects the intra-abdominal visceral fat regardless of obesity degree and age (differently from anthropometry), and has been proposed as a marker of visceral adiposity.^{10,11,13-15,39} Apparently, some clinical and demographic characteristics of the populations⁸ have an influence on determining the EF thickness limits; even so, while Natale et al.,²⁴ have suggested an upper limit of 7 mm in a healthy population, Bertaso et al.,⁸have suggested that a thicknesses greater than 5 mm may already be considered abnormal in a low- risk population.

The aim of this study was to present echocardiographic features of the heart, with emphasis on EF characterization, and its correlations with clinical, anthropometric and other echocardiographic variables in an old adult population.

Mean age of the sample was 81.9 ± 7.8 years, mean weight 65.8 ± 11.6 kg, and mean BMI was 28.2 ± 4.1 kg/m². The results obtained from the questionnaire showed that 17.6% of the individuals had a family history of cardiovascular disease, 23.5% were diabetic and 55.9% had dyslipidemia. Echocardiography revealed both structural and functional cardiac changes, which is in accordance with the fact that the sample was composed of a very elderly population – 88% of individuals had aortic fibrosis (...), 73% had mitral fibrosis, and 29% had tricuspid valve regurgitation (four with pulmonary artery systolic pressure greater than 35 mmHg). No significant changes were detected in the pulmonary valve. Other less frequent changes were changes in the left ventricular (LV) segmental contractility, basal septal hypertrophy (BSH), calcification of the mitral valve annulus and ascending aorta dilatation. General characteristics of the study sample are presented in Table 1.

Table 1

Variables	Women			Men			Total
	Minimum	Maximum	Mean ± SD	Minimum	Maximum	Mean ± SD	Minimum	Maximum	Mean ± SD
Age (years)	65	92	82.9 ± 7.4	66	90	79.2 ± 8.7	65	92	81.9 ± 7.8
Weight (kg)	37.1	86.2	63.5 ± 10.7	53.8	95.5	72.1 ± 12.2	37.1	95.5	65.8 ± 11.6
Height (cm)	137	160	149.0 ± 6.6	149	172	164.1 ± 7.3	137	172	153.0 ± 9.5
BSA (m2)	1.2	1.8	1.6 ± 0.2	1.5	2	1.8 ± 0.2	1.2	2	1.6 ± 0.2
BMI (Kg/m2)	19.8	37.3	28.8 ± 4.4	24.2	34.7	26.9 ± 3.4	19.8	37.3	28.2 ± 4.1
AC (cm)	84	122	102.3 ± 8.8	79	115	100.4 ± 10.1	79	122	101.7 ± 9.0
LM (%)	13.3	24.7	18.8 ± 2.9	24	33.1	28.1 ± 3.2	13.3	33.1	21.5 ± 5.2
FM (%)	10.1	44.4	27.5 ± 8.4	6.8	37	21.8 ± 8.7	6.8	44.4	25.9 ± 8.7
CC (cm)	28	45.5	34.0 ± 3.8	31	36.5	33.9 ± 1.8	28	45.5	34.0 ± 3.3
HR (bpm)	53	102	70.2 ± 11.1	44	90	64.7 ± 12.6	44	102	68.7 ± 11.6
SBP (mmHg) (mm(mmHg)	92	238	147.5 ± 31.2	125	200	152.4 ± 25.7	92	238	148.8 ± 29.5
DBP (mmHg)	56	135	79.9 ± 15.3	46	90	75.4 ± 14.8	46	135	78.7 ± 15.1

SD: Standard deviation, BSA: Body surface area, BMI: Body mass index, AC: Arm circumference,, LM: Lean mass, FM: Fat mass, CC: calf circumference, HR: Heart rate, SBP: Systolic blood pressure, DBP: Diastolic blood pressure.

Mean heart rate was 68.7 ± 11.6 bpm and the mean values of SBP and DBP were 148.8 ± 29.5 mmHg and 78.7 ± 15.1 mmHg, respectively. Table 2 shows the structural variables calculated by echocardiography.

Table 2

	Women			Men			Total
Variables	Minimum	Maximum	Mean ± SD	Minimum	Maximum	Mean ± SD	Minimum	Maximum	Mean ± SD
LVESD (mm)	26	46	33.9 ± 3.8	35	48	38.6 ± 4.1	26	48	35.2 ± 4.4
LVEDD (mm)	41	63	52.3 ± 5.1	55	64	59.2 ± 3.5	41	64	54.2 ± 5.6
PWd (mm)	6.7	8.2	7.4 ± 0.4	7.2	8.7	7.7 ± 0.5	6.7	8.7	7.5 ± 0.4
IVSd (mm)	6.7	9	7.5 ± 0.6	7.2	8.7	7.7 ± 0.6	6.7	9	7.5 ± 0.6
AOR_D (mm)	22	35	29.5 ± 2.8	29	40	34.9 ± 3.7	22	40	30.9 ± 3.8
LA_D (mm)	27	53	36.8 ± 5.9	32	53	38.9 ± 6.2	27	53	37.4 ± 5.9
LVSF (%)	28	41	34.9 ± 3.3	24	38	34.8 ± 4.5	24	41	34.9 ± 3.6
LVM/BSA (g/m2)	60	128	86.0 ± 15.8	82	120	99.7 ± 12.9	60	128	89.6 ± 16.1
EF (mm)	4	8	5.2 ± 0.9	4	9	6.0 ± 1.4	4	9	5.4 ± 1.1

SD: Standard deviation, LVESD: Left ventricular end-systolic diameter, LVEDD: Left ventricular end-diastolic diameter, PWd: Left ventricular posterior wall end-diastolic thickness, IVSd: Interventricular septum end-diastolic thickness, AOR_D: Aortic root diameter, LA_D: Left atrial diameter, LVSF: Left ventricular shortening fraction, LVM/BSA: Left ventricular mass corrected for body surface area, EF: Epicardial fat.

Tables 3 and 4 refer to the correlation between EF and age, anthropometric parameters, and clinical variables.

Table 3 shows positive moderate/strong correlations between EF thickness and calc circumference (r = 0.5; p = 0.01) , and moderate correlation between EF thickness and weight (r = 0.4; p = 0.02), BSA (r = 0.4; p = 0.02) and lean mass (r = 0.4; p = 0.03) (Figure 2). No other statistically significant correlations were found.

Table 3

Variables	Age (anos)	Weight (Kg)	Height (cm)	BSA (m2)	BMI (Kg/m2)	AC (cm)	LM (%)	FM (%)	CC (cm)
Pearson’s correlation (r)	- 0.1	0.4	0.3	0.4	0.3	0.2	0.4	0.2	0.5
Significance (p)	0.7	0.02	0.1	0.02	0.2	0.2	0.03	0.2	0.01

BSA: Body surface area, BMI: Body mass index, AC: Abdominal circumference, LM: Lean mass, FM: Fat mass, CC: calf circumference

Figure 2

As can be seen from Table 4, no statistically significant correlations were found between EF and previous history of cardiovascular disease or any of the clinical variables studied.

Table 4

Variables	Cardiovascular history	Hypertension	Dyslipidemia	Diabetes	SBP (mmHg)	DBP (mmHg)
Point-biserial correlation coefficient (rpbiss)	- 0.2	- 0.1	- 0.1	- 0.3	0.2	0.1
Significance (p)	0.2	0.8	0.5	0.2	0.4	0.5

SBP: Systolic blood pressure, DBP: Diastolic blood pressure.

Table 5 correlates EF with LVM (corrected for BSA), left atrial and right atrial areas, LV shortening fraction and the LV end-diastolic diameter.

Table 5

Variables	LVM/BSA (g/m2)	LA_A (cm2)	RA_A (cm2)	LVSF (%)	LVEDD (mm)
Pearson’s correlation (r)	0.2	- 0.2	- 0.04	0.2	0.3
Significance (p)	0.2	0.3	0.8	0.3	0.04

LVM/BSA: Left ventricular mass corrected for body surface area, LA_A : Left atrial area, RA_A: Right atrial area, LVSF: Left ventricular shortening fraction, LVEDD: Left ventricular end-diastolic diameter

Table 5 shows a positive, but a low to moderate correlation (r = 0.3; p = 0.04) between EF thickness and LV end-diastolic diameter (Figure 3). For the remaining echocardiographic variables evaluated, no statistically significant correlations were found.

Figure 3

Figure 4 shows the measurement of the EF in two extreme cases, representative of the sample (highest EF value - panel A; lowest EF value - panel B). The participant with the highest EF value was male, 89 years, body weight of 95.5 kg, BSA of 2.03 m², BMI of 34.7 kg/m², waist/hip ratio of 1.08, CC of 36.5 cm, lean mass of 33% and fat mass of 37%, presenting with hypertension, dyslipidemia and diabetes. On the other hand, the participant with the lowest EF value was an 85-year-old man, body weight of 63.5 kg, BSA of 1.68 m², BMI of 24.2 kg/m², waist/hip ratio of 0.89, CC of 34.5 cm, lean mass of 26% and fat mass of 16%, dyslipidemic. This comparative analysis suggests the tendency of a positive correlation of EF with body weight and a more unfavorable clinical profile.

Figure 4

During the aging process, there is a decrease in lean mass, increase in fat mass and a redistribution of adipose tissue to the trunk and viscera.⁴³ EF is a component of visceral fat, distributed around the heart, located between the myocardial surface and the visceral layer of the pericardium.^5-13 Iacobellis et al.,¹³ found a wide variation in EF thickness (1-23 mm), which probably reflects not only a high variation in the distribution of visceral fat,¹⁴ but also in the clinical and demographic characteristics of the studied populations.⁸

In our study, mean EF thickness was 5.4 ± 1.1 mm, with higher values in males (6.0 ± 1.4 mm vs 5.2 ± 0.9 mm). While Iacobellis et al.,^11,12 Calabuig et al.,¹⁹ and Alexopoulos et al.,³¹ (these using computerized tomography) found similar results, different findings have been reported by other groups.^7,25-32 The correlation between EF and age has not been consensual also; some studies have shown a correlation between these variables,^{9,19,22,24,25,27,28,31} in contrast to others.^{7,11-12,29-30}

The association between EF and obesity has been widely described, since there is a predisposition for increased EF in obese individuals compared to non-obese individuals.^{13,18,19,27,30,36,37} However, in our study, no statistically significant correlations were found between EF and BMI, possibly because our sample was not overweight (63.5 ± 10.7 kg for women and 72.1 ± 12.2 kg for men). These are in agreement with Bertaso et al. ⁸ and Magliano et al.,⁹ but in contrast to others^{10-12,22,25,26,29} Also, other studies reported statistically significant correlations for the male gender only²⁸ (r = 0.329 and p = 0.041 in men vs r = 0.105 and p = 0.362 in women). Such discrepancy in results may be due to the characteristics and age of the studied populations.

In our study, we did not find a correlation between EF and dyslipidemia or diabetes. Similar results were published by Kim et al.,²⁶ for dyslipidemia (p = 0.738), and Mazzoccoli et al.,²⁷ (p = 0.098) and Alexopoulos et al.,³¹ (p = 0.226 using CT) for diabetes, but contradictory results were observed by Mazzoccoli et al.,²⁷ (p = 0.01) and Alexopoulos et al.,³¹ (p < 0.05) for dyslipidemia and Iacobellis et al.,⁴⁴ for type 1 diabetes. Moreover, Iacobellis et al.,⁴⁴ reported that type 1 diabetes is associated with excess EF regardless of BMI, since EF thickness was significantly higher in diabetic individuals compared to non-diabetics (7.2 ± 2.1 mm vs 4.9 ± 2.5 mm; p < 0.01). Similar results were observed by Kim et al.,²⁶ (p = 0.022) and Li et al.,⁴⁵

With aging, calcium deposition and loss of elastic fibers in the middle layer of the arteries are observed, leading to a decrease in their distensibility.⁴⁶ In the aortic artery, this fact stimulates the development of hypertension, diastolic dysfunction and heart failure.^47-49 Although in our study 35.3% of the individuals had isolated systolic hypertension, no statistically significant correlations were found between EF and hypertension. However, in the study by Mazzoccoli et al.,²⁷ Kim et al.,²⁶ and Alexopoulos et al.,³¹ EF thickness was significantly higher in hypertensive individuals. Also, Natale et al.,²⁴in a study performed on 459 hypertensive individuals, found an increase in SBP (p = 0.01) and a reduction in DBP (p = 0.01) when the EF thickness was greater than 7 mm. Thus, they reported the existence of statistically significant positive correlations (r = 0.35; p < 0.0001) between EF thickness and SBP, and negative correlations between EF thickness and DBP (r = - 0.13; p < 0.01). However, Iacobellis et al.,²⁹ found statistically significant correlations only for DBP (r = 0.589; p = 0.02), and Wang et al., ³⁴ (using CT) did not obtain statistically significant results neither with SBP nor with DBP.

Regarding the anthropometric parameters, in our study, we found statistically significant correlations between EF and weight, BSA, lean mass and CC. Shetty et al.²⁵ (r = 0.346; p < 0.001) and Willens et al.,³⁰ (r = 0.51; p = 0.011) obtained similar results, but only for weight. Using CT, Nakazato et al.,³³ Wang et al.,³⁴ and Alexopoulos et al.,³¹ obtained statistically significant correlations between EF and weight, BMI, height, and abdominal circumference. Other studies refer the existence of statistically significant correlations between EF thickness and abdominal circumference ^{10-13,19,22,25,28,29} and between EF thickness and fat mass.^11,12

Among the echocardiographic variables evaluated in our study, statistically significant results were found between EF thickness and LV end-diastolic diameter only. Iacobellis et al.,²⁹ also obtained statistically significant results for the correlation between EF thickness and LVMI (r = 0.755; p = 0.01), although Natale et al.,²⁴ referred that this correlation is only significant for values of EF thickness higher than 7 mm. Thus, apparently, the increase of the EF thickness seems to be associated with LVH,^14,18 and Kim et al.,²⁶ even reported that, among hypertensive individuals, EF was higher in those with LVH (7.5 ± 2.3 mm vs 6.6 ± 1.9 mm; p = 0.034).

The results obtained demonstrate that EF is a common finding in the old adult, especially in males, and correlates with anthropometric parameters and LV end-diastolic diameter. Additional studies may give important contributions to a better understanding of the relationship between aging and EF. A cohort study, with a follow-up of an extended cohort during the aging process, will be important to evaluate the course of EF deposition throughout life, and determine the risks associated with it. Besides, a future challenge will be to understand if multidisciplinary and tailored interventions directed at optimizing functionality and promoting quality of life, including actions such as individualized physical exercise, and nutritional and therapeutic counseling, can be effective strategies to reduce EF and the associated risks.