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Objective-To estimate the heritability of carotid intima-media thickness (IMT), a surrogate marker for atherosclerosis, independent of traditional coronary risk factors.Methods and Results-We performed a classical twin study of carotid IMT using 98 middleaged male twin pairs, 58 monozygotic (MZ) and 40 dizygotic (DZ) pairs, from the Vietnam Era Twin Registry. All twins were free of overt cardiovascular disease. Carotid IMT was measured by ultrasound. Bivariate and multivariate analyses were used to determine the association between traditional cardiovascular risk factors and carotid IMT. Intraclass correlation coefficients and genetic modeling techniques were used to determine the relative contributions of genes and environment to the variation in carotid IMT. In our sample, the mean of the maximum carotid IMT was 0.75 ± 0.11. Age, systolic blood pressure and HDL were significantly associated with carotid IMT. The intraclass correlation coefficient for carotid IMT was larger in MZ (0.66; 95% confidence interval [CI], 0.62-0.69) than in DZ twins (0.37; 95% CI, 0.29-0.44), and the unadjusted heritability was 0.69 (95% CI, 0.54-0.79). After adjusting for traditional coronary risk factors, the heritability of carotid IMT was slightly reduced but still of considerable magnitude (0.59; 95% CI, 0.39-0.73).Conclusion-Genetic factors have a substantial influence on the variation of carotid IMT. Most of this genetic effect occurs through pathways independent of traditional coronary risk factors.

OBJECTIVE: (1) To determine the prevalence of small dense low-density lipoprotein (SDLDL) particles in obese youths and (2) to compare youths with SDLDL and large buoyant LDL (LBLDL) subclass phenotypes in total body and abdominal fatness, cardiovascular (CV) fitness, and markers of the insulin resistance syndrome (IRS). DESIGN: For group comparisons, subjects were dichotomized into either SDLDL phenotype group or LBDL phenotype group based on LDL particle size. SUBJECTS: Obese 13 to 16-y-olds (n ¼ 80) who had a triceps skinfold greater than the 85th percentile for gender, ethnicity, and age. MEASUREMENTS: LDL particle size, plasma lipids and lipoprotein concentrations, plasma glucose and insulin concentrations, and blood pressures; percentage body fat, visceral adipose tissue (VAT); VO 2 at a heart rate of 170 bpm as an index of CV fitness. RESULTS: The prevalence of the SDLDL phenotype was 54% among the 80 obese youths. Although overall body fatness (ie BMI and percentage body fat) and CV fitness were similar between the two LDL phenotype groups, the SDLDL phenotype group had significantly higher weight, waist circumference and VAT than the LBLDL phenotype group. With respect to the IRS markers, youths with the SDLDL phenotype had significantly higher triacylglycerol (TAG), very low-density lipoprotein cholesterol (VLDLC), apolipoprotein B (apo B), and total cholesterol-to-high-density lipoprotein ratio (TC=HDLC) than youths with the LBLDL phenotype. LDL particle size as a continuous variable was significantly correlated with TAG, VLDLC, apo B, HDLC, and TC=HDLC. Plasma TAG and HDLC concentrations were independent predictors of LDL particle size. CONCLUSION: (1) The SDLDL phenotype was common in obese youths and (2) the relationships of LDL particle size with several of the IRS markers suggested that already in adolescence the expression of the SDLDL phenotype might be an important risk factor for future coronary heart disease mortality and morbidity.

Atherosclerosis is a chronic disease associated with accumulation of lipids in lesions along blood vessels, leading to the occlusion of blood flow. Much of the focus has been on the role of low-density lipoprotein (LDL), and of oxidatively modified LDL, in the initiation and progression of this disease. LDL is in fact a metabolic end-product of the triglyceride-rich lipoproteins (ie, very-low density lipoproteins). Over the years, univariate analyses have implicated triglycerides as a contributor in atherosclerosis. However, depending on the studies, the significance of this relationship is either reduced or nullified when other co-variates are taken into account. This review summarizes more recent data that support the role of triglyceride-rich lipoproteins in the atherosclerotic process, both in the fasted as well as in the postprandial state.

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