Rationale and Objectives
Epicardial adipose tissue (EAT), pericardial adipose tissue (PAT), and subcutaneous adipose tissue (SAT) are mediators of metabolic risk and may be involved in the pathogenesis of coronary artery disease. The aim of this study was to investigate the association of visceral and subcutaneous fat depots with the presence and severity of coronary artery calcium (CAC) in asymptomatic individuals.
Materials and Methods
One hundred eleven consecutive subjects underwent CAC assessment, and their Framingham risk scores were measured. EAT, total thoracic adipose tissue, and SAT volumes were measured from slice level 15 mm above to 30 mm below the ostium of the left main coronary artery. PAT was calculated as thoracic adipose tissue − EAT. SAT was defined as the volume of fat depot anterior to the sternum and posterior to the vertebra. CAC was defined as 0, 1 to 100, 101 to 400, or ≥400. Relative risk regression analysis was used to assess the association between fat depots and CAC.
Results
There were modest correlations between EAT ( r = 0.58), PAT ( r = 0.47), SAT ( r = 0.34), and CAC ( P < .01). EAT, PAT, and SAT increased proportionally with the severity of CAC in both genders ( P < .05). After adjustment for cardiovascular risk factors and body mass index, the relative risks for each standard deviation increase in EAT, PAT, and SAT were 3.3 (95% confidence interval, 1.9–5.6), 2.7 (95% confidence interval, 1.6–3.9), and 2.6 (95% confidence interval, 1.5–4.4) for CAC ≥ 100 compared to CAC 0, respectively ( P < .05). The area under the receiver-operating characteristic curve to predict CAC ≥ 100 was higher in each fat depot compared to Framingham risk score, and addition of fat depots to Framingham risk score provided maximum prognostication value to detect CAC ≥ 100.
Conclusions
Increased EAT, PAT, and SAT are associated with the severity of CAC independent of risk factors.
Cardiovascular death has been reduced significantly because of improvements in detection and management of coronary artery disease (CAD) over the past few decades . However the recent increase in the rate of overweight and obesity, up to two thirds of the US population, may diminish the favorable effect of recent improvements in the diagnosis and treatment of CAD .
Adipocytes secrete numerous factors that could potentially modulate the development of vascular disease, including proinflammatory cytokines and adipokines, angiogenic molecules, and stem cell homing factors . Recent evidence indicates that adipose tissue is a functional component, exerting paracrine influences on blood vessel contractility .
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Materials and methods
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CAC Scanning
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PAT, Thoracic Adipose Tissue (TAT), and SAT Measurement
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Statistical Analysis
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Results
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Table 1
Cardiovascular Risk Factors, Adipose Tissue Volume, and Severity of CAC
CAC 0 CAC 1–100 CAC 101–400 CAC ≥ 400 Variable ( n = 33) ( n = 24) ( n = 20) ( n = 34)P Age (years) 56 ± 11 61 ± 10 64 ± 11 68 ± 11 .0001 Men 14 11 16 23 .01 Current smokers 0 13% 0 3% .10 Hypertension ∗ 30% 50% 40% 41% .50 Hypercholesterolemia † 42% 54% 70% 53% .30 Diabetes mellitus ‡ 6% 13% 5% 24% .10 Family history of CHD § 58% 46% 65% 62% .60 SBP (mm Hg) 125 ± 17 125 ± 18 133 ± 19 123 ± 16 .40 DBP (mm Hg) 77 ± 10 74 ± 8 77 ± 7 73 ± 8 .20 BMI (kg/m 2 ) 26.7 ± 3.4 26.9 ± 2.8 27.8 ± 3.8 28.2 ± 3.9 .20 Total cholesterol (mg/dL) 189 ± 31 190 ± 33 164 ± 34 173 ± 46 .50 HDL-C (mg/dL) 53 ± 18 56 ± 15 46 ± 9 46 ± 11 .30 LDL-C (mg/dL) 112 ± 40 103 ± 34 96 ± 28 94 ± 42 .60 Triglycerides (mg/dL) 119 ± 41 120 ± 44 114 ± 40 124 ± 47 .80 BMI (kg/m 2 ) 29.7 ± 4.1 30.3 ± 4.6 30.3 ± 4.6 30.4 ± 3.9 .30 FRS (%) 6.8 ± 3.9 9.5 ± 4.1 11.6 ± 4.3 14.7 ± 4.4 .001 EAT (cm 3 ) 68.3 ± 35.6 79.3 ± 38.5 102.1 ± 47.9 108.6 ± 38.8 .0001 PAT (cm 3 ) 57.3 ± 49.5 66.7 ± 46.1 83.7 ± 49.9 107.9 ± 49.3 .0001 SAT (cm 3 ) 53.9 ± 28.9 64.2 ± 32.1 83.4 ± 32.2 86.5 ± 40.1 .0001 Total TAT (cm 3 ) 125.6 ± 68.6 146.1 ± 59.1 185.7 ± 66.4 216.5 ± 65.5 .0001
Data are expressed as mean ± SD or as percentages.
BMI, body mass index; CAC, coronary artery calcium; CHD, coronary heart disease; DBP, diastolic blood pressure; EAT, epicardial adipose tissue; FRS, Framingham risk score; HDL-C, high-density lipoprotein cholesterol; LDL-C, high-density lipoprotein cholesterol; PAT, pericardial adipose tissue; SAT, subcutaneous adipose tissue; SBP, systolic blood pressure; TAT, thoracic adipose tissue.
CAC Coronary Artery Calcium Score; SBP Systolic Blood Pressure; DBP Diastolic Blood Pressure.
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Adipose Tissue and CAC
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Table 2
Linear Regression Analysis of the Association Between Cardiovascular Risk Factors and CAC
Model_R__R_ 2 β 95% CI_P_ Single variables I: EAT 0.58 0.34 0.21 0.11 to 0.62 .0001 II: PAT 0.47 0.22 0.15 0.05 to 0.22 .0001 III: SAT 0.34 0.12 0.11 0.02 to 0.21 .0001 IV: TAT 0.51 0.27 0.19 0.07 to 0.32 .0001 V: BMI 0.17 0.03 0.02 −0.01 to 0.03 .10 Combination variables VI SAT 0.08 0.03 to 0.11 .01 + PAT 0.10 0.03 to 0.14 .001 + 0.65 0.45 EAT 0.16 0.08 to 0.23 .0001 + FRS 0.09 0.02 to 0.12 .03 VII SAT 0.06 0.01 to 0.11 .01 + PAT 0.08 0.02 to 0.15 .01 + EAT 0.13 0.03 to 0.32 .001 + Age 0.02 0.01 to 0.08 .001 + Gender (male) 0.15 0.02 to 0.35 .02 + 0.74 0.55 Hypercholesterolemia 0.12 −0.02 to 0.19 .10 + Diabetes mellitus 0.17 −0.01 to 0.21 .10 + Hypertension 0.08 −0.03 to 0.15 .30 + Smoking status 0.05 −0.02 to 0.11 .10 + Family history of CHD 0.03 −0.05 to 0.15 .50 + BMI 0.02 −0.01 to 0.06 .10
Dependent variable: CAC.
BMI, body mass index; CAC, coronary artery calcium; CHD, coronary heart disease; CI, confidence interval; EAT, epicardial adipose tissue; FRS, Framingham risk score; PAT, pericardial adipose tissue; SAT, subcutaneous adipose tissue; TAT, thoracic adipose tissue.
Table 3
Multivariate Relative Risk Regression Analysis of the Association Between Adipose Tissues and CAC
Model CAC 0 CAC ≥ 100P Unadjusted SAT 1 (reference) 1.76 (1.22–2.54) .003 PAT 1 (reference) 1.88 (1.22–7.92) .004 TAT 1 (reference) 2.25 (1.43–4.91) .0001 EAT 1 (reference) 2.98 (1.92–4.62) .0001 Adjusted for age and gender SAT 1 (reference) 1.95 (1.58–4.79) .0001 PAT 1 (reference) 2.16 (1.41–3.32) .0001 TAT 1 (reference) 2.69 (1.55–4.66) .0001 EAT 1 (reference) 3.04 (1.78–5.18) .0001 Adjusted for age, gender, and BMI SAT 1 (reference) 2.46 (1.49–4.15) .001 PAT 1 (reference) 2.50 (1.51–3.64) .0001 TAT 1 (reference) 2.94 (1.57–5.51) .0001 EAT 1 (reference) 3.17 (1.72–5.47) .0001 Adjusted for age, gender, hypertension, hypercholesterolemia, diabetes mellitus, family of history of CHD, smoking status, and BMI SAT 1 (reference) 2.57 (1.48–4.45) .001 PAT 1 (reference) 2.72 (1.64–3.94) .0001 TAT 1 (reference) 3.06 (1.87–5.03) .0001 EAT 1 (reference) 3.32 (1.95–5.62) .0001
Relative risk (95% confidence interval) of SAT, TAT, and PAT per standard deviation increase.
BMI, body mass index; CAC, coronary artery calcium; CHD, coronary heart disease; EAT, epicardial adipose tissue; PAT, pericardial adipose tissue; SAT, subcutaneous adipose tissue; TAT, thoracic adipose tissue.
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Table 4
C Statistics to Assess the Diagnostic Accuracy of Regional Adipose Tissues and Clinical Variables for the Detection of Significant CAC
Variable AUC ± SE 95% CI_P_ Comparison P with FRS FRS 0.63 ± 0.04 0.58-0.73 .0001 — SAT 0.69 ± 0.03 0.58-0.81 .0001 .05 PAT 0.77 ± 0.03 0.65-0.83 .0001 .01 EAT 0.83 ± 0.02 0.67-0.87 .0001 .004 SAT + PAT + EAT 0.86 ± 0.02 0.78-0.92 .0001 .0001 SAT + PAT + EAT + FRS 0.88 ± 0.02 0.81-0.91 .0001 .0001
AUC, area under the receiver-operating characteristic curve; CAC, coronary artery calcium; CI, confidence interval; EAT, epicardial adipose tissue; FRS, Framingham risk score; PAT, pericardial adipose tissue; SAT, subcutaneous adipose tissue; SE, standard error.
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Discussion
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Pathophysiology
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Adipose Tissue and Coronary Atherosclerosis
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Implications
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Limitations
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Conclusions
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