Background —The present study tested the hypothesis that simple variables, such as waist circumference and fasting plasma triglyceride (TG) concentrations, could be used as screening tools for the identification of men characterized by a metabolic triad of nontraditional risk factors (elevated insulin and apolipoprotein [apo] B and small, dense LDL particles). Methods and Results —Results of the metabolic study (study 1) conducted on 185 healthy men indicate that a large proportion (>80%) of men with waist circumference values ≥90 cm and with elevated TG levels (≥2.0 mmol/L) were characterized by the atherogenic metabolic triad. Validation of the model in an angiographic study (study 2) on a sample of 287 men with and without coronary artery disease (CAD) revealed that only men with both elevated waist and TG levels were at increased risk of CAD (odds ratio of 3.6, P <0.03) compared with men with low waist and TG levels. Conclusions —It is suggested that the simultaneous measurement and interpretation of waist circumference and fasting TG could be used as inexpensive screening tools to identify men characterized by the atherogenic metabolic triad (hyperinsulinemia, elevated apo B, small, dense LDL) and at high risk for CAD.

DESPITE considerable advances during the past 40 years, there is increasing awareness among scientists, epidemiologists, and clinicians that current approaches to evaluation of coronary heart disease (CHD) risk in asymptomatic individuals remain suboptimal.¹ There is also controversy around recommending widespread use of additional metabolic markers, such as apolipoprotein (APO) levels, indices of fibrinolytic activity and of susceptibility to thrombosis (eg, plasminogen activator inhibitor–1 and lipoprotein[a] levels), markers of inflammation (eg, C-reactive protein levels), and markers of insulin resistance (waist circumference and fasting insulin levels).^2-9 Although all of these markers have been shown to predict CHD events, whether these variables contribute to CHD risk independently of the variation in traditional risk factors and lipid variables remains a matter of debate.

—Abdominal obesity is associated with numerous metabolic alterations, such as hypertriglyceridemia and low levels of high density lipoprotein (HDL) cholesterol. However, compared with abdominally obese white individuals, abdominally obese black individuals have been characterized by higher plasma HDL cholesterol levels, suggesting that the impact of abdominal fat accumulation on the lipoprotein-lipid profile may differ among ethnic groups. Therefore, we have compared the associations between body fatness, visceral adipose tissue (AT) accumulation, and metabolic risk variables in a sample of 247 white men and 240 white women versus a sample of 93 black men and 143 black women. Although no difference in mean total body fatness was found between the 2 race groups, white men had higher levels of visceral AT than did black men ( P <0.001). Despite the fact that black women had a greater body fat content than did white women, black women had levels of visceral AT that were similar to those of white women, suggesting a lower susceptibility to visceral obesity in black women. This lower accumulation of visceral AT in blacks was accompanied by significantly reduced apolipoprotein B concentrations and ratios of total cholesterol to HDL cholesterol as well as higher plasma HDL cholesterol levels ( P <0.05) compared with those values in whites. Irrespective of sex, higher postheparin plasma hepatic lipase (HL) and lower lipoprotein lipase (LPL) activities were found in whites, resulting in an HL/LPL ratio that was twice as high in whites as in blacks ( P <0.005). Although differences in lipoprotein-lipid levels were noted between whites and blacks, results from multiple regression analyses revealed that after control for morphometric and metabolic variables of the study (body fat mass, visceral AT, LPL, HL, and age), ethnicity had, per se, only a minor contribution to the variance in plasma lipoprotein levels. Thus, our results suggest that the higher plasma HDL cholesterol levels and the generally more cardioprotective plasma lipoprotein profile found in abdominally obese black versus white individuals are explained, at least to a certain extent, by a lower visceral AT deposition and a higher plasma LPL activity in black individuals.

—High density lipoprotein (HDL) cholesterol concentrations have been shown to increase with regular endurance exercise and, therefore, can contribute to a lower risk of coronary heart disease in physically active individuals compared with sedentary subjects. Although low HDL cholesterol levels are frequently observed in combination with hypertriglyceridemia, some individuals may be characterized by isolated hypoalphalipoproteinemia, ie, low HDL cholesterol levels in the absence of elevated triglyceride (TG) concentrations. The present study compared the responses of numerous lipoprotein-lipid variables to a 20-week endurance exercise training program in men categorized on the basis of baseline TG and HDL cholesterol concentrations: (1) low TG and high HDL cholesterol (normolipidemia), (2) low TG and low HDL cholesterol (isolated low HDL cholesterol), (3) high TG and high HDL cholesterol (isolated high TGs), and (4) high TGs and low HDL cholesterol (high TG/low HDL cholesterol). A series of physical and metabolic variables was measured before and after the training program in a sample of 200 men enrolled in the Health, Risk Factors, Exercise Training and Genetics (HERITAGE) Family Study. At baseline, men with high TG/low HDL cholesterol had more visceral adipose tissue than did men with isolated low HDL cholesterol and men with normolipidemia. The 0.4% (not significant) exercise-induced increase in HDL cholesterol levels in men with isolated low HDL cholesterol suggests that they did not benefit from the “HDL-raising” effect of exercise. In contrast, men with high TG/low HDL cholesterol showed a significant increase in HDL cholesterol levels (4.9%, P <0.005). Whereas both subgroups of men with elevated TG levels showed reductions in plasma TGs (≈−15.0%, P <0.005), only those with high TG/low HDL cholesterol showed significantly reduced apolipoprotein B levels at the end of the study (−6.0%, P <0.005). Multiple regression analyses revealed that the exercise-induced change in abdominal subcutaneous adipose tissue (10.6%, P <0.01) was the only significant correlate of the increase in plasma HDL cholesterol with training in men with high TG/low HDL cholesterol. Results of the present study suggest that regular endurance exercise training may be particularly helpful in men with low HDL cholesterol, elevated TGs, and abdominal obesity.

Although metabolic disturbances are often observed in obese patients, increased accumulation of visceral adipose tissue (AT) has been shown to be more closely associated with high fasting triglyceride (TG) and insulin levels as well as with low HDL cholesterol concentrations than with excess body fatness per se. Interestingly, the fasting concentration of plasma TGs has been shown to be an important determinant of the magnitude and duration of the postprandial TG response. Yet little is known about the respective contributions of obesity versus excess visceral AT to the variation in postprandial TG clearance. In the present study, we examined potential differences in postprandial triglyceride-rich lipoprotein (TRL) responses in subjects characterized by high versus low levels of visceral AT. In a sample of 43 men (mean age: 41.3 +/- 9.6 years), we found that both excess body fat and visceral obesity were associated with increased postprandial TG responses in total TRL (r = 0.33-0.45). We also found a strong relationship between fasting plasma TG levels and postprandial total TRL-TG concentrations (r = 0.79, P < 0.0001). When matched for total body fat mass, individuals with high levels of visceral AT (> or =130 cm2; n = 10) as assessed by computed tomography were characterized by increased medium- and small-TRL-TG responses (P < 0.05) compared with subjects with low visceral AT accumulation (<130 cm2; n = 10). Moreover, this elevated response of small-TRL triglycerides noted in men with high levels of visceral AT was not accompanied by a concomitant increased retinyl palmitate response in this TRL fraction, suggesting that visceral obesity in men is accompanied by higher postprandial VLDL production than is found in obese men with lower levels of visceral AT. Increased postprandial insulin and free fatty acid (FFA) responses were also noted in men with high levels of visceral AT. Finally, postheparin plasma lipoprotein lipase activity was negatively correlated with the total-TRL-TG response in a subsample of 32 individuals (r = -0.37, P < 0.05). The results of the present study suggest that visceral obesity is associated with an impaired postprandial TG clearance. Furthermore, the exaggerated postprandial FFA response observed in subjects with high visceral AT suggests that visceral obesity may contribute to fasting and postprandial hypertriglyceridemia by altering FFA metabolism in the postprandial state.

Context: It has been suggested that oxidative stress and endothelial dysfunction could play a role in the higher cardiovascular disease risk noted in the abdominally obese population. Objective: The objective of this study was to describe the associations between abdominal fat accumulation, oxidative stress, and endothelial dysfunction in men. Design: A complete physical and metabolic profile was assessed in a group of 56 men covering a wide range of adiposity and plasma oxidized low-density lipoprotein (OxLDL), and soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, E-selectin, and C-reactive protein concentrations were determined. Results: We found that abdominal visceral adipose tissue was positively associated with plasma OxLDL (r = 0.52; P < 0.0001) and C-reactive protein (r = 0.60; P < 0.0001) concentrations. We also found significant associations between plasma E-selectin levels and hyperinsulinemia (r = 0.39; P < 0.005) as well as with the homeostasis model assessment index of insulin resistance (r = 0.42; P < 0.005). Conclusions: Our study showed that plasma OxLDL levels and low-grade systemic inflammation are increased in men with a high visceral adipose tissue accumulation. Furthermore, our results support the notion that insulin resistance is associated with endothelial activation. Overall, our observations give us further insights on the increased cardiovascular disease risk frequently noted among viscerally obese, insulin-resistant individuals.