Apolipoprotein-B, low-density lipoprotein cholesterol, and the long-term risk of coronary heart disease in men.

We examined whether plasma apolipoprotein-B (apo-B) levels add further information on the risk of coronary heart disease (CHD) after taking into account low-density lipoprotein (LDL) cholesterol concentrations and other traditional risk factors. Among 2,072 CHD-free men from the Québec Cardiovascular Study at entry and followed for 13 years, 230 had a first CHD event (CHD death or nonfatal myocardial infarction). Increased apo-B (tertile 1 vs 3) levels were associated with a significant increased risk of CHD after adjustment for nonlipid and lipid risk factors other than LDL cholesterol levels (relative risk 1.89, 95% confidence interval 1.31 to 2.73). High plasma LDL cholesterol concentrations (tertile 1 vs 3) were also associated with an increased risk of CHD independently of nonlipid and lipid risk factors (relative risk 2.02, 95% confidence interval 1.44 to 2.84). However, apo-B levels modulated to a significant extent the risk of CHD associated with increased concentrations of LDL cholesterol (>/=4.3 mmol/L). For instance, among men with high LDL cholesterol levels, those with an apo-B level <128 mg/dl were not at increased risk for CHD (relative risk 1.53, 95% confidence interval 0.89 to 2.62). In contrast, high levels of apo-B and LDL cholesterol were associated with a significant twofold increased risk of CHD (p <0.001). Receiver-operating curve analysis also indicated that plasma apo-B levels improved the ability to discriminate incident CHD cases among patients with high LDL cholesterol levels compared with a model based on LDL cholesterol levels (p = 0.04). In conclusion, plasma apo-B levels modulated the risk of CHD associated with LDL cholesterol over a 13-year follow-up.

Features of the metabolic syndrome and the risk of cardiovascular disease.

The metabolic syndrome is being increasingly recognized as an important risk factor for cardiovascular disease (CVD). While several clinical definitions have been proposed to identify patients with this syndrome, additional metabolic markers may be considered to improve one's ability to assess and predict the risk of CVD in this population. The objective of this short review is to provide an overview of the risk of CVD associated with specific features of the metabolic syndrome. The extent to which these markers may be used one day in clinical practice in primary prevention is also briefly discussed.

Inflammatory markers and long-term risk of ischemic heart disease in men A 13-year follow-up of the Quebec Cardiovascular Study.

We tested the hypothesis that elevated plasma interleukin-6 (IL-6), C-reactive protein (CRP) and fibrinogen concentrations are independent risk factors and interact in increasing the long-term risk of ischemic heart disease (IHD) in men. A total of 1982 IHD-free men from the Quebec Cardiovascular Study were followed over a period of 13 years during which 210 first fatal IHD events and non-fatal myocardial infarctions were recorded. Increased CRP levels (4th versus 1st quartile) were not associated with an increased risk of IHD after adjustment for non-lipid risk factors (age, body mass index, systolic blood pressure, diabetes, smoking and medication use at baseline), lipid risk factors (LDL and HDL cholesterol and triglyceride levels) and for IL-6 and fibrinogen (RR=0.70, 95% CI=0.43-1.13). High plasma IL-6 levels (4th versus 1st quartile) were associated with a 70% greater risk of IHD independent of confounding risk factors and of the other 2 inflammatory markers (RR=1.71, 95% CI=1.07-2.75). The relationship between high fibrinogen levels (4th versus 1st quartile) and IHD risk was borderline significant in multivariate analyses (RR=1.53, 95% CI=0.97-2.43). An inflammation score based on plasma IL-6 and fibrinogen levels improved the IHD risk predictive value of a multivariate model of traditional risk factors (p=0.03). Including plasma CRP levels into the inflammatory score provided no additional predictive value. In conclusion, elevated plasma IL-6 concentrations are more strongly related to IHD risk than CRP and fibrinogen. An inflammation score based on high plasma IL-6 and fibrinogen levels used in combination with traditional risk factors may improve our ability to adequately identify high risk individuals.

Insulin resistance syndrome, body mass index and the risk of ischemic heart disease.

BACKGROUND: Many people who are not obese according to standard height and weight criteria may still display features of insulin resistance syndrome and thus be at high risk of ischemic heart disease. We sought to investigate the effect of cumulative features of insulin resistance syndrome on the risk of ischemic heart disease associated with variations in body mass index (BMI) among men who participated in the Quebec Cardiovascular Study. METHODS: A cohort of 1824 nondiabetic men free of ischemic heart disease was evaluated at the 1985 baseline evaluation and followed for a period of 13 years, during which 284 first ischemic heart disease events were recorded. Relative hazards (RHs) of ischemic heart disease in 3 BMI groups (normal weight, overweight and obese) were estimated using Cox proportional hazards regression. RESULTS: Although obese men (BMI > or = 30 kg/m2) were the most likely to accumulate features of insulin resistance syndrome, the univariate risk of ischemic heart disease in this group was not significantly increased compared with normal-weight men (BMI < 25 kg/m2) (RH 1.26, 95% confidence interval [CI] 0.88-1.80). However, obese men who accumulated more than 4 features of insulin resistance syndrome were at increased risk of ischemic heart disease (RH 1.81, 95% CI 1.02-3.19) compared with normal-weight men who had fewer than 3 features of the syndrome. Conversely, having more than 4 features of insulin resistance syndrome was associated with a 3-fold increase in the risk of ischemic heart disease among normal-weight men (RH 3.01, 95% CI 1.70-5.32). INTERPRETATION: Although obesity is an important risk factor for ischemic heart disease, variations in BMI alone poorly reflect the risk of ischemic heart disease associated with features of insulin resistance syndrome.

Low-density lipoprotein subfractions and the long-term risk of ischemic heart disease in men: 13-year follow-up data from the Québec Cardiovascular Study.

OBJECTIVE: The objective of the present study was to investigate the association between large and small low-density lipoprotein (LDL) and long-term ischemic heart disease (IHD) risk in men of the Quebec Cardiovascular Study. METHODS AND RESULTS: Cholesterol levels in the large and small LDL subfractions (termed LDL-C> or =260A and LDL-C<255A, respectively) were estimated from polyacrylamide gradient gel electrophoresis of whole plasma in the cohort of 2072 men of the population-based Quebec Cardiovascular Study. All men were free of IHD at the baseline examination and followed-up for a period of 13 years, during which 262 first IHD events (coronary death, nonfatal myocardial infarction, and unstable angina pectoris) were recorded. Our study confirmed the strong and independent association between LDL-C<255A levels as a proxy of the small dense LDL phenotype and the risk of IHD in men, particularly over the first 7 years of follow-up. However, elevated LDL-C> or =260A levels (third versus first tertile) were not associated with an increased risk of IHD over the 13-year follow-up (RR=0.76; P=0.07). CONCLUSIONS: These results indicated that estimated cholesterol levels in the large LDL subfraction were not associated with an increased risk of IHD in men and that the cardiovascular risk attributable to variations in the LDL size phenotype was largely related to markers of a preferential accumulation of small dense LDL particles.

The triglyceride/high-density lipoprotein cholesterol ratio, the small dense low-density lipoprotein phenotype, and ischemic heart disease risk.

This study investigated the relevance of using the plasma triglyceride to high-density lipoprotein cholesterol ratio (Log TG/HDL-C) for the prediction of the small dense lowdensity lipoprotein (LDL) phenotype and the risk of ischemic heart disease (IHD). Analyses were based on data from the Quebec Cardiovascular Study in a cohort of 2072 men free of IHD at baseline, among whom 262 had a first IHD event (coronary death, non fatal myocardial infarction and unstable angina) during a 13-year follow-up period. LDL particle size phenotype was characterized using 2-16% polyacrylamide gradient gel electrophoresis (PAGGE) of whole plasma. There were significant associations between the Log TG/HDL-C ratio and features of LDL size phenotype such as the proportion of LDL with a diameter <255A (r = 0.43, p < 0.001) and LDL peak particle size (r = -20.55, p < 0.001). However, the Log TG/HDL-C ratio brought no additional value (p â yen 0.1) in predicting the small dense LDL phenotype (area under the receiver operating curve (AUROC = 71.9%) compared to TG alone (AUROC = 71.2%) or to a combination of Log TG and HDL-C (AUROC = 72.4%) after multivariate adjustment for non lipid risk factors. Finally, elevations in the Log TG/HDL-C ratio did not improve the discrimination of incident IHD cases from non IHD cases compared to the use of plasma TG levels alone (p = 0.5) or a combination of the individual TG and HDL-C values (p = 0.5). The Log TG/HDL-C ratio does not improve our ability to identify individuals with the small dense LDL phenotype compared to plasma TG levels alone. The Log TG/HDLC is also not superior to plasma TG levels alone in predicting IHD risk in men of the QuA(c)bec Cardiovascular Study.

High carbohydrate and high monounsaturated fatty acid diets similarly affect LDL electrophoretic characteristics in men who are losing weight.

We compared the effects of ad libitum consumption of a defined high complex carbohydrate (CHO) diet (% of energy: CHO, 58.3; fat, 25.8) vs. a defined high monounsaturated fatty acid (MUFA) diet (% of energy: CHO, 44.7; fat, 40.1; MUFA, 22.5) on LDL electrophoretic characteristics. Healthy men [n = 65; age, 37.5 +/- 11.2 (mean +/- SD) y; BMI, 29.2 +/- 4.9 kg/m2] were randomly assigned to one of the two diets that they consumed for 6-7 wk. The high CHO diet significantly reduced body weight (-2%). The diet-induced reduction in plasma LDL cholesterol (C) levels in the high-CHO diet group was due mainly to concurrent reductions in the cholesterol content of small (<25.5 nm, P < 0.01) and medium-sized LDL (25.5-26.0 nm, P = 0.01). The high MUFA diet also reduced body weight, and LDL-C and LDL-apolipoprotein (apo)B levels, which were comparable to those in the high CHO group. The cholesterol levels of small LDL particles tended to be reduced (P = 0.24) in the high MUFA group (-12%), similar to changes in the high CHO group. These results suggest that, when associated with weight loss, ad libitum consumption of high CHO and high MUFA diets may be considered to be equally beneficial for the management of LDL-related atherogenic dyslipidemia. However, the high MUFA diet more favorably affected triglyceride levels, suggesting that it may be preferable to a high CHO diet in cardiovascular disease prevention.

Concordance/discordance between plasma apolipoprotein B levels and the cholesterol indexes of atherosclerotic risk.

The objective of the present study was to examine concordance/discordance among 4 atherogenic indexes of cardiovascular risk: plasma total cholesterol, low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (non-HDL) cholesterol, and apolipoprotein B-100 (apoB). Analyses were conducted in a cohort of 2,103 men without coronary artery disease (CAD) at the onset of the Quebec Cardiovascular Study. Although there were strong and highly significant correlations among the 4 risk indexes (0.78 < r < 0.97), only 50% of all subjects had concordant apoB and LDL cholesterol levels (i.e., values that fell into the same quintile of the population distribution). Moreover, concordance/discordance was not the same throughout the range of both variables; it was greater at the extremes of their respective distributions (65%), but significantly less in the midpoints (<40%). ApoB appeared to be more concordant with non-HDL cholesterol than with LDL cholesterol, although >1/3 of all subjects had discordant levels. Kappa analysis confirmed that there was only fair agreement between apoB and total or LDL cholesterol (0.38 and 0.36, respectively) and only moderate agreement between non-HDL cholesterol and apoB (0.47). Finally, a significant proportion of subjects (528 of 2,103) who had disproportionately higher apoB levels than would have been predicted based on their LDL cholesterol concentrations was more obese and manifested several features of the metabolic syndrome. They also had a significantly increased cardiovascular risk. In summary, plasma apoB and the various cholesterol indexes are complementary rather than competitive indexes of atherosclerotic risk and provide further evidence as to why measurement of apoB should be part of a standard lipoprotein assessment of CAD risk.

Effect of plasma C-reactive protein levels in modulating the risk of coronary heart disease associated with small, dense, low-density lipoproteins in men (The Quebec Cardiovascular Study).

This purpose of this study was to investigate how plasma C-reactive protein (CRP), a nonspecific acute-phase reactant, modulates the risk of coronary heart disease (CHD) associated with the small, dense, low-density lipoprotein (LDL) phenotype. LDL particle size and plasma CRP were measured in the Quebec Cardiovascular Study cohort of 2,025 men free of CHD at baseline, among whom 103 had a first CHD event during a 5-year follow-up period. Plasma CRP levels were measured using the Behring Latex-Enhanced (highly sensitive) CRP assay. LDL particle size phenotype was characterized using 2% to 16% polyacrylamide gradient gel electrophoresis. There were weak but significant associations between plasma CRP levels and features of LDL size, such as the proportion of LDL with a diameter <255 A (r = 0.09, p <0.001) and LDL peak particle size (r = -0.09, p <0.001). Variations in plasma CRP levels modulated the risk of CHD associated with small LDL peak particle size (relative risk 4.3 vs 2.5 in men with high vs low plasma CRP levels, respectively) and with an elevated proportion of LDL <255 A (relative risk 6.6 vs 3.0). Thus, increased plasma CRP levels further elevate the risk of CHD associated with having small, dense LDL particles.