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Importance: It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE)., Objective: To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism., Design, Setting, and Participants: This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731 728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421 537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018., Exposures: A panel of several established cardiovascular risk factors., Main Outcomes and Measures: Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CHD], 25 131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI)., Results: Of the 731 728 participants from the ERFC, 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421 537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers., Conclusions and Relevance: Older age, smoking, and adiposity were consistently associated with higher VTE risk.

Introduction: Obesity is associated with decreased heart rate variability (HRV). Rosiglitazone, a PPARγ agonist, is generally associated with increases in body mass., Purpose: To assess whether the gain in body mass and adiposity expected from rosiglitazone treatment has an influence on HRV in patients with type 2 diabetes and coronary artery disease., Methods: One hundred and twenty-five patients with type 2 diabetes and coronary artery disease aged between 40 and 75 years were studied. Anthropometric measurements: (1) body mass index (BMI), (2) waist circumference (WC), (3) abdominal computed tomography (CT) scan, and HRV (using a 24 h Holter) were measured at baseline and after 12 months of treatment. Patients were randomized to rosiglitazone or placebo regimen., Results: In the rosiglitazone vs. placebo group, there were significant increases in body mass [3.5 (2.6;4.4); mean (95 % CI) vs. 0.2 (-0.4;0.8)] kg), BMI [1.3 (1.0;1.6) vs. 0.1 (-0.1;0.3) kg/m 2 ], WC [2.1 (0.9;3.3) vs. 0.4 (-0.4;1.2) cm, all p ≤ 0.001] and subcutaneous adipose tissue [253 (187;319) vs. 6 (-24;36) cm 3 , p ≤ 0.001] without statistically significant changes in visceral adipose tissue [-22 (-91;47) vs. 57 (43;71) cm 3 , p = 0.546], respectively. There was no change in HRV in either group after 12 months. There were no correlations between changes in HRV variables and fat distribution., Conclusion: Our results suggest that changes in adiposity indices observed after 12 months of rosiglitazone therapy have no deleterious influence on HRV in patients with type 2 diabetes and coronary artery disease.

Objective: The aim of this study was to examine the effect of brisk walking on cardiometabolic risk profile and on the gene expression (ie, messenger RNA [mRNA] levels) of inflammatory and thrombotic markers in abdominal and femoral subcutaneous adipose tissues (SATs) among sedentary overweight to obese women with different menopause statuses., Methods: Sixteen late premenopausal (mean [SD] age, 49 [3] y; mean [SD] body mass index, 31.9 [3.0] kg/m) and 14 early postmenopausal (53 [2] y; 30.8 [1.9] kg/m) women were involved in a 16-week walking program (three sessions of 45 min/wk at 60% of heart rate reserve). Glucose-insulin homeostasis, lipid-lipoprotein profile, and inflammatory (tumor necrosis factor-α, interleukin-6 [IL-6], and adiponectin) and thrombotic (plasminogen activator inhibitor-1) SAT mRNA and plasma levels were measured before and after the intervention., Results: Glucose area under the curve was reduced in all participants (P = 0.03) after the walking program. Increases in plasma tumor necrosis factor-α were observed in both groups (P = 0.001), whereas increases in plasminogen activator inhibitor-1 levels were found in postmenopausal women only (P = 0.014). However, plasma IL-6 and adiponectin levels remained unchanged after the intervention (0.07 < P < 0.98). Although femoral SAT adiponectin mRNA levels decreased in postmenopausal women only (P = 0.008), abdominal SAT IL-6 mRNA levels were reduced in both groups (P = 0.01)., Conclusions: Taken together, our results show that, despite a reduced abdominal SAT IL-6 expression, brisk walking does not seem to exert a favorable impact on the cardiometabolic risk profile of overweight to obese women, irrespective of their menopause status.

Studies published in 2012 in the field of HDL research have provided further evidence suggesting that a low HDL-cholesterol level, in the absence of related lipid or nonlipid risk factors, is not associated with increased risk of coronary heart disease.

The objective of the present study was to evaluate the association between adiponectin levels and incidence of coronary heart disease (CHD). We performed a prospective case-control analysis nested in the EPIC-Norfolk cohort. Participants were apparently healthy men and women 45 to 79 years of age who developed fatal or nonfatal CHD during an average follow-up period of 7.7 ± 1.1 years. In total 1,035 participants with incident CHD were matched for age, gender, and enrollment time to 1,920 controls who remained free of CHD over the study follow-up. Baseline nonfasting plasma adiponectin concentrations were determined by enzyme-linked immunosorbent assay. Adiponectin levels were lower in participants with CHD than in matched controls (men 8.74 vs 9.13 μg/ml, p = 0.01; women 12.6 vs 13.4 μg/ml, p = 0.03). A 1-μg/ml increment in adiponectin was associated with decreased CHD risk (odds ratio 0.78, 95% confidence interval 0.63 to 0.96, p = 0.02, in men; odds ratio 0.73, 95% confidence interval 0.55 to 0.96, p = 0.03, in women). However, this association was no longer significant after adjustment for established cardiovascular risk factors. Stratification of participants according to metabolic syndrome status showed that men and women with metabolic syndrome had a higher CHD risk, irrespective of their adiponectin levels. In conclusion, although a low adiponectin concentration is associated with an increased CHD risk, findings of the present study do not suggest that its measurement is useful to refine CHD risk assessment once traditional risk factors and clinical features of the metabolic syndrome have been considered., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Aims: The aim of this study was to determine the contribution of physical activity and abdominal obesity to the variation in inflammatory biomarkers and incident coronary heart disease (CHD) in a European population., Methods and Results: In a prospective case-control study nested in the European Prospective Investigation into Cancer and Nutrition-Norfolk cohort, we examined the associations between circulating levels or activity of C-reactive protein, myeloperoxidase (MPO), secretory phospholipase A2 (sPLA2), lipoprotein-associated phospholipase A2 (Lp-PLA2), fibrinogen, adiponectin, waist circumference, physical activity, and CHD risk over a 10-year period among healthy men and women (45-79 years of age). A total of 1002 cases who developed fatal or non-fatal CHD were matched to 1859 controls on the basis of age, sex, and enrolment period. Circulating levels of C-reactive protein, sPLA2 (women only), fibrinogen, and adiponectin were linearly associated with increasing waist circumference and decreasing physical activity levels. After adjusting for waist circumference, physical activity, smoking, diabetes, systolic blood pressure, low-density lipoprotein and high-density lipoprotein cholesterol levels, and further adjusted for hormone replacement therapy in women, C-reactive protein, MPO (men only), sPLA2, fibrinogen, but not Lp-PLA2 and adiponectin were associated with an increased CHD risk., Conclusion: Inactive participants with an elevated waist circumference were characterized by deteriorated levels of inflammatory markers. However, several inflammatory markers were associated with an increased CHD risk, independent of underlying CHD risk factors such as waist circumference and physical activity levels.

Background: Although the total to high-density lipoprotein cholesterol ratio (TC/HDL-C) has been used for decades to identify individuals at risk for coronary heart disease (CHD), apolipoprotein-based (apolipoprotein B/apolipoprotein A-I [apoB/apoA-I]) and nuclear magnetic resonance spectroscopy (NMR)-based lipoprotein concentrations (low-density lipoprotein(NMR) /high-density lipoprotein(NMR) [LDL(NMR) /HDL(NMR)]) may also be useful for CHD risk stratification., Materials and Methods: In a case-control study conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk study population, 870 individuals who developed CHD during a 6-year follow-up were matched to 1659 controls on the basis of gender, age and enrollment time. LDL(NMR) and HDL(NMR) were measured by proton NMR spectroscopy., Results: After adjusting for traditional CHD risk factors, men in the top quintile of the various lipoprotein ratios proved to be at increased CHD risk (OR = 2·59 [95% IC, 1·76-3·83] for TC/HDL-C ratio, 2·59 [1·75-3·83] for apoB/apoA-I ratio and 2·78 [1·86-4·17] for LDL(NMR) /HDL(NMR) ratio) compared with men in the bottom quintile. Similar associations were observed in women (OR = 2·86 [1·71-4·80] for TC/HDL-C ratio, 2·94 [1·74-4·97] for apoB/apoA-I ratio and 2·03 [1·21-3·43] for LDL(NMR)/HDL(NMR) ratio). Compared with participants with only one component of the metabolic syndrome, those who had five had an increased TC/HDL-C ratio (73·0% and 80·4% in men and women respectively), apoB/apoA-I ratio (58·0% and 62·9% in men and women respectively) and for LDL(NMR)/HDL(NMR) ratio (52·6% and 54·1% in men and women respectively)., Conclusion: In this European study population, the TC/HDL-C, apoB/apoA-I and LDL(NMR) /HDL(NMR) ratios were similarly associated with components of the metabolic syndrome and CHD risk., (© 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Screening for increased waist circumference and hypertriglyceridemia (the hypertriglyceridemic-waist phenotype) has been proposed as an inexpensive approach to identify patients with excess intra-abdominal adiposity and associated metabolic abnormalities. We examined the relationship between the hypertriglyceridemic-waist phenotype to the risk of coronary artery disease in apparently healthy individuals., Methods: A total of 21,787 participants aged 45-79 years were followed for a mean of 9.8 (standard deviation 1.7) years. Coronary artery disease developed in 2109 of them during follow-up. The hypertriglyceridemic-waist phenotype was defined as a waist circumference of 90 cm or more and a triglyceride level of 2.0 mmol/L or more in men, and a waist circumference of 85 cm or more and a triglyceride level of 1.5 mmol/L or more in women., Results: Compared with participants who had a waist circumference and triglyceride level below the threshold, those with the hypertriglyceridemic-waist phenotype had higher blood pressure indices, higher levels of apolipoprotein B and C-reactive protein, lower levels of high-density lipoprotein cholesterol and apolipoprotein A-I, and smaller low-density lipoprotein particles. Among men, those with the hypertriglyceridemic-waist phenotype had an unadjusted hazard ratio for future coronary artery disease of 2.40 (95% confidence interval [CI] 2.02-2.87) compared with men who did not have the phenotype. Women with the phenotype had an unadjusted hazard ratio of 3.84 (95% CI 3.20-4.62) compared with women who did not have the phenotype., Interpretation: Among participants from a European cohort representative of a contemporary Western population, the hypertriglyceridemic-waist phenotype was associated with a deteriorated cardiometabolic risk profile and an increased risk for coronary artery disease.

Background: The association of metabolic syndrome and risk of CHD is now well established. The association between 'metabolic dyslipidemia' as defined by high triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) levels and the risk of coronary heart disease (CHD) risk is not known. The aim of this study was to investigate the association between metabolic dyslipidemia, and risk of coronary heart disease (CHD) in apparently healthy men and women., Methods: Metabolic dyslipidemia was defined by combination of increased triglyceride (TG) levels (≥150 mg/dl) and low high-density lipoprotein cholesterol (HDL-C) levels (≤50 mg/dl for women and ≤40 mg/dl for men). In the EPIC-Norfolk prospective population study, 21,340 participants without diabetes (9326 men and 12,014 women) were followed for a mean of 11.4 years during which 2075 CHD events occurred. Three multivariate models were used adjusting for other metabolic risk factors including low-density lipoprotein cholesterol (LDL-C)., Results: Compared to men with normal HDL and normal TG, men with metabolic dyslipidemia had an increased risk for CHD (HR 1.61, 95% CI 1.40-1.86). The increased risk remained significant after adjustment for LDL-C and other metabolic risk factors. Among women, metabolic dyslipidemia was associated with increased CHD risk (HR 1.78, 95% CI 1.47-2.15). This association was lost when the model was additionally adjusted for other metabolic syndrome risk factors. In men and women Kaplan-Meier survival curves according to HDL and TG levels revealed that participants with metabolic dyslipidemia had poorer survival compared to people without metabolic dyslipidemia (logrank p<0.001 for each)., Conclusions: Metabolic dyslipidemia is associated with an increased risk of CHD. This relationship was independent from LDL-C and other risk factors of the metabolic syndrome in men, but not in women. A better management of this phenotype via lifestyle modification or pharmacotherapy may be warranted., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Background: Gradient gel electrophoresis (GGE) and nuclear magnetic resonance (NMR) spectroscopy are both widely accepted methods for measuring LDL and HDL particle size. However, whether or not GGE- or NMR-measured LDL or HDL particle size predicts coronary heart disease (CHD) risk to a similar extent is currently unknown., Methods: We used GGE and NMR to measure LDL and HDL particle size in a nested case-control study of 1025 incident cases of CHD and 1915 controls from the EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk study. The study sample included apparently healthy men and women age 45-79 years followed for an average of 6 years., Results: Pearson correlation coefficients showed that the overall agreement between NMR and GGE was better for the measurement of HDL size (r = 0.78) than for LDL size (r = 0.47). The odds ratio for future CHD among participants in the bottom tertile of LDL size (smallest LDL particles) was 1.35 (95% CI, 1.12-1.63) for GGE and 1.74 (1.41-2.15) for NMR. For HDL size, these respective odds ratios were 1.41 (1.16-1.72) and 1.85 (1.47-2.32). After adjustment for potential confounders, the relationship between small LDL or HDL particles and CHD was no longer significant, irrespective of the method., Conclusions: In this prospective population study, we found that the relationships between NMR-measured LDL and HDL sizes and CHD risk were slightly higher than those obtained with GGE.

Objective: Test the hypothesis that considering leisure-time and work-related physical activity habits in addition to the Framingham risk score (FRS) would result into better classification of coronary heart disease (CHD) risk than FRS alone., Methods: Prospective, population-based study of 9564 men and 12165 women aged 45-79 years followed for an average of 11.4 years. A modified FRS which takes into account physical activity (evaluated using a validated lifestyle questionnaire taking into account leisure-time and work-related physical activity) was computed., Results: During follow-up, 2191 CHD events occurred. Among 3369 men who were classified as intermediate risk (event rate of 12.4%) according to the FRS, 413 were reclassified into the low-risk category and 279 were reclassified into the high-risk category after modification of the FRS. After reclassification of these men, CHD event rate was of 5.3% and 18.6%, respectively for men classified at low and high CHD risk. Among 4766 women initially classified as intermediate risk (event rate of 8.4%), 1282 were reclassified into the low-risk category whereas 1071 women were reclassified into the high-risk category. After reclassification of these women, CHD event rate was of 6.8% and 12.2%, respectively for women classified at low and high CHD risk., Conclusions: Results of the present study suggest that asking simple questions about leisure-time and work-related physical activity which can be rapidly obtained by any physician at no cost could be helpful in the estimation of patients' CHD risk.

Objectives: This study was designed to test the hypothesis that at any low-density lipoprotein cholesterol (LDL-C) level, other lipid parameters such as non-high-density lipoprotein cholesterol (HDL-C) levels, triglyceride (TG) levels, and the total cholesterol (TC)/HDL-C are still associated with an increased coronary heart disease (CHD) risk., Background: Although LDL-C is considered to be the primary target of lipid-lowering therapy, other parameters of the lipoprotein-lipid profile may more closely associated with CHD risk., Methods: In the EPIC (European Prospective Investigation Into Cancer and Nutrition)-Norfolk prospective population study, 21,448 participants without diabetes or CHD between age 45 and 79 years were followed for 11.0 years. A total of 2,086 participants developed CHD during follow-up., Results: Among individuals with low LDL-C levels (<100 mg/dl), after adjustment for age, sex, smoking, systolic blood pressure, waist circumference, physical activity, and hormone replacement therapy (in women), those with non-HDL-C >130 mg/dl had a hazard ratio (HR) for future CHD of 1.84 (95% confidence interval [CI]: 1.12 to 3.04) when compared with those with non-HDL-C levels <130 mg/dl. In a similar model, individuals with TG levels >150 mg/dl had an HR of 1.63 (95% CI: 1.02 to 2.59) when compared with those with TG levels <150 mg/dl, and individuals with a TC/HDL-C ratio >5 had an HR of 2.19 (95% CI: 1.22 to 3.93) when compared with those with a TC/HDL-C ratio <5., Conclusions: In this prospective study, independently of their plasma LDL-C levels, participants with high non-HDL-C levels, high TG levels, or with an elevated TC/HDL-C ratio were at increased CHD risk. CHD risk assessment algorithms as well as lipid targets of lipid-lowering trials may also need to consider other easily available parameters such as non-HDL-C., (Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the association between HDL particle size measured by gradient gel electrophoresis and risk of incident coronary heart disease (CHD) in apparently healthy men and women., Methods: We performed a prospective case-control study nested in the EPIC-Norfolk cohort. Cases were apparently healthy men and women aged 45-79 years who developed fatal or nonfatal CHD (n=1035). They were matched to 1920 controls who remained free of CHD over the follow-up period of 6 years., Results: Participants with the smallest HDL particles had the most unfavourable cardiometabolic risk profile whereas those with the largest HDL particles had the most favourable risk profile. Plasma HDL cholesterol levels were found to be the best correlate of HDL particle size (r=0.58 and r=0.62, respectively, for men and women, p<0.001). Men in the highest quartile of HDL particle size had an unadjusted odds ratio (OR) for future CHD of 0.75 (95% CI, 0.57-0.97) compared to those in the bottom quartile. For women, the equivalent OR was 0.50 (0.35-0.71). After additional adjustment for diabetes, body mass index, systolic blood pressure, LDL and HDL cholesterol levels, the ORs were 1.43 (1.01-2.03) in men and 0.84 (0.52-1.35) in women., Conclusions: A decreased HDL particle size is associated with an adverse cardiometabolic risk profile. Small HDL particle size was also associated with an increased CHD risk, but this association was largely explained by traditional risk factors.

Aims: To evaluate the association of low-density lipoprotein cholesterol (LDL-C) levels in small and large LDL particles with risk of incident coronary heart disease (CHD)., Methods and Results: We performed a prospective case-control study nested in the EPIC-Norfolk cohort. Cases were apparently healthy men and women aged 45-79 years who developed fatal or non-fatal CHD (n = 1035), and who were matched by age, gender, and enrollment time to 1920 controls who remained free of CHD. Electrophoretic characteristics of LDL particles were measured using 2-16% polyacrylamide gradient gel electrophoresis. Concentrations of LDL-C(<255 A) were higher in cases than controls in men (1.34 +/- 0.88 vs. 1.15 +/- 0.80 mmol/L, P < 0.001) as well as in women (1.12 +/- 0.84 vs. 0.94 +/- 0.74 mmol/L, P < 0.001). The unadjusted odds ratio (OR) for future CHD in men of the top tertile of LDL-C(<255 A) was 1.68 (95% CI, 1.33-2.13; P < 0.001) whereas in women the unadjusted OR was 1.53 (95% CI, 1.13-2.07; P < 0.001). However, after further adjustments for confounding variables, the association between LDL-C(<255 A) and CHD was no longer significant in men and in women., Conclusion: Cholesterol concentrations in different LDL subclasses show different relationships with CHD risk in this European cohort.

Objectives: The aim of this study was to determine the impact of the metabolic syndrome (MS) on operative mortality after a coronary artery bypass grafting surgery (CABG)., Background: Diabetes and obesity are highly prevalent among patients undergoing CABG. However, it remains unclear whether these factors have a significant impact on operative mortality after this procedure. We hypothesized that the metabolic abnormalities associated with MS could negatively influence the operative outcome of CABG surgery., Methods: We retrospectively analyzed the data of 5,304 consecutive patients who underwent an isolated CABG procedure between 2000 and 2004. Of these 5,304 patients, 2,411 (46%) patients met the National Cholesterol Education Program-Adult Treatment Panel III criteria for MS. The primary end point was operative mortality., Results: The operative mortality after CABG surgery was 2.4% in patients with MS and 0.9% in patients without MS (p < 0.0001). The MS was a strong independent predictor of operative mortality (relative risk 3.04 [95% confidence interval (CI) 1.73 to 5.32], p = 0.0001). After adjusting for other risk factors, the risk of mortality was increased 2.69-fold (95% CI 1.43 to 5.06; p = 0.002) in patients with MS and diabetes and 2.36-fold (95% CI 1.26 to 4.41; p = 0.007) in patients with MS and no diabetes, whereas it was not significantly increased in the patients with diabetes and no MS., Conclusions: This is the first study to report that MS is a highly prevalent and powerful risk factor for operative mortality in patients undergoing a CABG surgery. Thus, interventions that could contribute to reduce the prevalence of MS in patients with coronary artery disease or that could acutely modify the metabolic perturbations of MS at the time of CABG might substantially improve survival in these patients.

This study tested the hypothesis that the "hypertriglyceridemic waist" phenotype (waist girth >90 cm [35.4 inches] in men and >85 cm [33.5 inches] in women, along with a plasma triglyceride concentration of >or=2.0 mmol/L [177 mg/dl]) as a covariate of metabolic syndrome features (hyperinsulinemia, hyperapolipoprotein B, and small low-density lipoprotein particles), is predictive of premature coronary artery disease (CAD) among patients with glucose intolerance or type 2 diabetes. Glucose intolerance and type 2 diabetes were assessed after an oral glucose tolerance test among 1,190 men and women using the American Diabetes Association criteria. Glycemic control was evaluated using hemoglobin A1c levels. CAD was considered present on the basis of a clinical history of retrosternal pains on exertion, electrophysiologically and clinically documented myocardial infarction, or angiographic evidence of coronary lesions. More than 53% of men (n = 103) with a waist circumference >or=90 cm (35.4 inches) and nearly 80% of women (n = 122) with a waist circumference >or=85 cm (33.5 in.) with triglyceride levels >or=2 mmol/L (177 mg/dl) were diagnosed with glucose intolerance or type 2 diabetes. Survival models revealed that those with glucose intolerance or type 2 diabetes with the "hypertriglyceridemic waist" phenotype experienced their first CAD symptoms 5 years earlier than those without this phenotype. This elevated and earlier risk of CAD was statistically significant (hazard ratio 2.0, 95% confidence interval 1.2 to 3.7, p = 0.02). In conclusion, the "hypertriglyceridemic waist" phenotype, an inexpensive and simple tool identifying subjects with metabolic syndrome features, is a significant marker of CAD manifestations occurring at an earlier age in those with glucose intolerance or type 2 diabetes.

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.

Atherosclerosis is a chronic inflammatory disease characterized by infiltration of blood vessels by lipids and leukocytes. There is a growing body of evidence that among risk factors that promote atherosclerosis, the metabolic syndrome is a powerful and prevalent predictor of cardiovascular events. The systemic inflammatory process associated with the metabolic syndrome has numerous deleterious effects that promote plaque activation, which is responsible for clinical events. Interactions between the innate immune system with lipid-derived products seem to play a major role in the pathophysiology of atherosclerosis in relation with the metabolic syndrome. The multiple links among adipose tissue, the vascular wall, and the immune system are the topics of this review, which examines the roles of oxidized low-density lipoprotein, inflammatory cytokines, and adipokines in triggering and perpetuating a danger signal response that promotes the development of atherosclerosis. Furthermore, therapeutic options that specifically target the metabolic syndrome components are reviewed in light of recent developments.

Low-density lipoprotein (LDL) size, a coronary heart disease risk factor, is influenced by both genetic and environmental factors. Results from the Quebec Family Study (QFS) revealed that the LDL peak particle diameter (LDL-PPD) aggregates in families with a heritability coefficient above 50% and is affected by a major quantitative trait locus on chromosome 17q (LOD=6.8). Complex segregation analyses have consistently demonstrated a major gene effect influencing LDL size. In the present study, we report a similar analysis in the QFS cohort, which suggests that a major gene explains 23% of the variance in age-body mass index and triglyceride-adjusted LDL-PPD. The most intuitive positional candidate gene on chromosome 17q is the apolipoprotein H gene. Direct sequencing of the promoter, coding regions, and exon-intron splicing boundaries of this gene revealed the presence of three missense mutations and two polymorphisms in the untranslated regions. Using family-based association tests, none of these variants was individually associated with LDL-PPD. However, analysis of the haplotypes constructed from the three missense mutations, suggested that one particular haplotype (frequency=20.9%) was associated with a significant increase in LDL-PPD trait values (p=0.046). Taken together, these results suggest the presence of a major gene effect influencing LDL-PPD and a positive association with a positional candidate gene located on chromosome 17q. Replication of the association between apolipoprotein H gene haplotype and LDL-PPD is required before reaching firm conclusion.

Although elevated low-density lipoprotein (LDL)-cholesterol is a well established coronary heart disease (CHD) risk factor, the ability to adequately discriminate high-risk individuals by this risk factor alone is limited and other metabolic risk variables are known to modulate CHD risk. For instance, it has been reported that the cluster of metabolic disturbances observed among individuals with abdominal obesity, the so-called metabolic syndrome, is associated with a substantially increased risk of CHD. Among the features of the dyslipidaemic profile observed in these individuals, the high triglyceride-low high-density lipoprotein (HDL)-cholesterol dyslipidaemia is predictive of an elevated risk of CHD. Fibric acid derivatives (fibrates) have been used in clinical practice for more than 2 decades as a class of agents known to decrease triglyceride levels while substantially increasing HDL-cholesterol levels, with a limited but significant additional lowering effect on LDL-cholesterol levels. Although the clinical benefits of HMG-CoA reductase inhibitors (statins) have been well documented by primary and secondary prevention trials that justify their widespread use, it was not until the publication of the VA-HIT (Veterans Affairs High-Density Lipoprotein Intervention Trial) that the relevance of identifying HDL-cholesterol as a therapeutic target to reduce the risk of recurrent CHD events was finally confirmed. The clinical benefits of fibrate therapy are especially important in the subpopulation of patients with low HDL-cholesterol levels with the metabolic syndrome, particularly in patients with type 2 diabetes mellitus or in abdominally obese, hyperinsulinaemic patients. Evidence also suggests that there is a 'fibrate effect' that mediates the reduction in CHD risk beyond the favourable impact of these agents on HDL-cholesterol levels. This last notion is consistent with the pleiotropic effects of fibrates which are known to be related to their mechanisms of action. Through peroxisome proliferator-activated alpha-receptors, fibrates have a significant impact on the synthesis of several apolipoproteins (apo) and enzymes of lipoprotein metabolism as well as on the expression of several genes involved in fibrinolysis and inflammation. Fibrate therapy has been reported to decrease apo CIII levels (a powerful inhibitor of lipoprotein lipase) and increase apo AI levels, as well as to increase lipoprotein lipase activity. Such changes contribute to improve the catabolism of triglyceride-rich lipoproteins, leading to a substantial increase in HDL-cholesterol levels accompanied by a shift in the size and density of LDL particles (from small, dense LDL particles to larger, more buoyant cholesteryl ester-rich LDL). It is proposed that some of these pleiotropic effects could explain some of the clinical benefits of fibrate therapy beyond its HDL-raising properties, particularly among patients with abdominal obesity, hyperinsulinaemia or type 2 diabetes with both low HDL- and low/normal LDL-cholesterol levels.

The purpose of this study was to assess the association between the international overweight cutoffs for children and youth and coronary heart disease risk factors. The sample included 410 boys and 337 girls 9-18 years of age from the Québec Family Study. Participants were classified as normal weight or overweight using the international BMI cutoffs, and into normal and elevated risk groups based on the 90th percentile of sex-specific age-adjusted risk factors [blood pressure, fasting total cholesterol (CHOL), LDL-C, HDL-C, CHOL/HDL-C, triglycerides, glucose, and physical work capacity]. Overweight participants had between 1.6 and 9.1 times the risk of elevated risk factors compared to normal-weight participants. Further, boys and girls with four or more risk factors were 19 and 43 times more likely to be overweight, respectively, compared to participants with no risk factors. The results add evidence that the international cutoffs are related to health risks in youth, supporting the adoption of the guidelines.

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.

Background: A triad of metabolic markers (high insulin and apolipoprotein B levels, and small, dense, low density lipoprotein particles) is associated with a substantially increased risk of coronary artery disease (CAD) in men. Also, the simultaneous presence of an elevated waist circumference (90 cm or greater) and moderate hypertriglyceridemia (triglyceride concentration 2.0 mmol/L or higher) in men has been shown to be associated with this atherogenic metabolic triad, with a probability of more than 80%., Objectives: To quantify the prevalence of the 'hypertriglyceridemic waist' phenotype in a sample of adult men and to compare the metabolic risk profile of nondiabetic men with hypertriglyceridemic waist with the CAD risk profile of patients with type 2 diabetes., Methods: The sample of people who participated in the Quebec Health Survey was used to obtain representative data on the prevalence and distribution of cardiovascular disease risk factors in the Quebec population. Fasting plasma lipoprotein-lipid, insulin and glucose concentrations were measured, and anthropometric measurements were taken in a sample of 907 men., Results: Among men who participated in the Quebec Health Survey, 19% had an elevated waist circumference (90 cm or greater) plus elevated triglyceride levels (2.0 mmol/L or higher). Men with this hypertriglyceridemic waist phenotype were characterized by the highest values for fasting plasma insulin, and the highest total cholesterol to high density lipoprotein cholesterol ratios. They also displayed a metabolic risk profile that was deteriorated to the same extent as that of men with diabetes who had participated in the survey., Conclusions: The results of the the present study of men who participated in the Quebec Health Survey provide further evidence that the simultaneous measurement and interpretation of waist circumference and fasting triglyceride concentrations may improve the physician's ability to identify abdominally obese men with atherogenic and diabetogenic profiles. Furthermore, this high risk clinical phenotype is highly prevalent (about 20%) among adult men.

Fibrinogen has been prospectively found to correlate with coronary heart disease (CHD) but a similar association has not been well established for lipoprotein (a) (Lp(a)). Plasma lipids, Lp(a), and fibrinogen levels were measured in 2,125 men (aged 47 to 76 years) who were free of clinical CHD. During a 5-year follow-up period, 116 first CHD events were documented. Men with CHD were older, smoked more, had a higher prevalence of diabetes, and higher levels of systolic blood pressure, cholesterol, low-density lipoprotein cholesterol, Lp(a), and fibrinogen, and lower plasma high-density lipoprotein cholesterol levels. Only fibrinogen levels in the upper tertile of the distribution compared with the lower tertiles were associated with a significant risk of CHD (adjusted risk ratio 2.5; 95% confidence interval [CI] 1.4 to 4.2; p = 0.0010). Such an association was not observed with Lp(a). To assess a possible relation between fibrinogen and Lp(a) to the risk of CHD events, men were assigned to 1 of 4 groups according to fibrinogen median levels and a Lp(a) cut-off level of 300 mg/L: group 1: fibrinogen < 4.05 g/L and Lp(a) < 300 mg/L; group 2: fibrinogen < 4.05 g/L and Lp(a) > or =300 mg/L; group 3: fibrinogen > or =4.05 g/L and Lp(a) < 300 mg/L; and group 4: fibrinogen > or =4.05 g/L and Lp(a) > or =300 mg/L. Using group 1 as a reference, a significant risk ratio was only documented in group 4 (2.5; 95% CI 1.2 to 5.1; p = 0.0132). In this population, high fibrinogen levels associated with high Lp(a) levels significantly increased the risk of CHD.

A low plasma HDL-cholesterol concentration is an important risk factor for coronary heart disease (CHD) and is often accompanied by increased triglyceride concentrations. Women have generally higher HDL-cholesterol and lower triglyceride concentrations and concomitantly are at lower risk of CHD than men. As HDL particle size is a new and potentially important marker of CHD risk, we have examined the potential gender difference in HDL particle size, assessed by nondenaturing 4-30% polyacrylamide gradient gel electrophoresis, in a sample of men (n=231) and women (n=183). Overall, men were characterized by a less favorable lipoprotein--lipid profile, which was accompanied by smaller HDL particle size compared to women. However, when men and women were matched for HDL particle size and compared for their metabolic profile, it was found that both genders were characterized by similar plasma lipoprotein--lipid profile despite the fact that women were characterized by higher levels of total body fat but lower waist girth than men. In summary, HDL particle size is a strong marker of the gender-related difference in the determination of the metabolic risk profile.

Targeting metabolic determinants of exercise performance with pharmacological agents that would mimic/potentiate the effects of exercise represents an attractive clinical alternative to counterbalance the poor exercise capacity in patients with type 2 diabetes mellitus (T2DM). We examined the effect of 1-yr treatment with the insulin sensitizer peroxisome proliferator-activated receptor (PPAR)γ agonist rosiglitazone on aerobic exercise capacity and body fat composition/distribution in men with T2DM and stable coronary artery disease (CAD). One-hundred four men (age: 64 ± 7 yr; body mass index: 30.0 ± 4.4 kg/m2) with T2DM and CAD were randomized to receive rosiglitazone or placebo for 1 yr. Aerobic exercise capacity (exercise duration) was assessed with a maximal treadmill test, and body composition/distribution were assessed by dual-energy X-ray absorptiometry/computed tomography scans. At 1 yr, patients with T2DM under PPARγ agonist treatment showed a reduction in aerobic exercise capacity compared with the control group (exercise duration change, -31 ± 8 versus 7 ± 11 s, P = 0.009). Significant increases in body fat mass (3.1 ± 0.4 kg, 12%), abdominal and mid-thigh subcutaneous adipose tissue (AT) levels, and mid-thigh skeletal muscle fat were found (all P < 0.01), whereas no effect on visceral AT levels was observed (P > 0.05) under treatment. Subcutaneous fat mass gained under PPARγ agonist was the strongest predictor of the worsening in aerobic exercise capacity (P > 0.0001); no association was found with skeletal muscle fat infiltration nor visceral AT. Treatment with the insulin sensitizer PPARγ agonist rosiglitazone in patients with T2DM and CAD is associated with a worsening in aerobic exercise capacity, which seems to be mainly attributable to weight gain and subcutaneous fat mass expansion. [ABSTRACT FROM AUTHOR]

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Background Patients with coronary artery disease (CAD) are characterized by an impaired cardiometabolic risk profile including high levels of atherogenic apolipoprotein (apo) B-containing lipoprotein levels. Genetic studies have highlighted a critical role for proprotein convertase subtilisin/kexin type 9 (PCSK9) in lipoprotein metabolism and CAD risk. Objective To determine whether improving dietary quality and increasing physical activity levels improve parameters of the cardiometabolic risk profile such as plasma apoB and PCSK9 levels in patients with CAD. Methods We recruited 86 men aged between 39 and 80 years (82 of them on statins) undergoing coronary artery bypass graft (CABG) surgery. These patients participated in a 1-year lifestyle modification program aiming at achieving a minimum of 150 minutes/week of physical activity and improving diet quality by following dietary guidelines. We used magnetic resonance imaging to measure visceral adipose tissue and a modified Bruce protocol to measure fitness levels before and after the intervention. Results Plasma apoB and low-density lipoprotein cholesterol levels were not modified by the intervention (−3.0%, P = .08 and 1.3%, P = .56, respectively), whereas non-HDL cholesterol decreased by 4.5% ( P = .04) and triglycerides by 13% ( P = .002). In contrast, PCSK9 levels increased by 5.2% after the intervention ( P = .05). HDL cholesterol and apolipoprotein A-I levels also increased (+12%, P < .0001 and + 6%, P < .0001, respectively). PCSK9 levels increased with improvements in fitness ( r = 0.23, P = .04) and visceral fat mobilization ( r = −0.23, P = .04). Conclusion In post-CABG patients, a lifestyle modification program lead to significant improvements in some parameters of the lipoprotein profile but unexpectedly increased plasma PCSK9 levels. [ABSTRACT FROM AUTHOR]

The article focuses on the risks of cardiovascular diseases due to accumulation of body fat. It mentions the decreased mortality rate through coronary heart diseases due to proper focus on the risk factors including smoking, hypertension and high cholesterol level. It discusses the harmful effects of obesity causing several health problems.

Background: High-density lipoprotein (HDL) cholesterol levels are inversely related to risk for coronary artery disease (CAD). Because HDL particles are heterogeneous in size and composition, they may be differentially associated with other cardiovascular risk factors and with cardiovascular risk. Objective: To study the independent relationships of HDL size and particle concentration to risk for future CAD. Design: Nested case-control study within the EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk cohort; baseline survey between 1993 and 1997, follow-up until November 2003. Setting: Norfolk, United Kingdom. Participants: Case patients were 822 apparently healthy men and women who developed CAD during follow-up. Control participants were 1401 participants who remained without CAD and were matched to case patients by sex, age, and enrollment time. Measurements: First CAD event leading to either hospitalization or death. Results: Nuclear magnetic resonance spectroscopy-measured HDL particle concentration (mean, 33.9 μmol/L [SD, 5] vs. 32.9 μmol/L [SD, 6]; P = 0.001) and HDL size (mean, 8.9 nm [SD, 0.5] vs. 8.8 nm [SD, 0.5]; P < 0.001), as well as gradient gel electrophoresis- measured HDL size (mean, 8.9 nm [SD, 0.4] vs. 8.8 nm [SD, 0.4]; P < 0.005) were lower in case patients than in control participants. High-density lipoprotein size and HDL particle concentration were only weakly correlated (r = 0.08, for those measured with nuclear magnetic resonance spectroscopy; r = 0.10, for those measured with gradient gel electrophoresis). High-density lipoprotein size was strongly associated with risk factors characteristic of the metabolic syndrome, including waist-to-hip ratio, triglyceride level, and apolipoprotein B level, whereas HDL particle concentration was not. Both HDL size and HDL particle concentration were independently associated with CAD risk. The association between HDL size and CAD risk was abolished on adjustment for apolipoprotein B and triglyceride levels (adjusted odds ratio, 1.00 [95% CI, 0.71 to 1.39] for top vs. bottom quartile), whereas HDL particle concentration remained independently associated with CAD risk (adjusted odds ratio, 0.50 [CI, 0.37 to 0.66]). Limitation: Measurements were performed in nonfasting blood samples, and residual confounding cannot be excluded. Conclusion: Both HDL size and HDL particle concentration were independently associated with other cardiovascular risk factors and with the risk for CAD. The relationship between HDL size and CAD risk was explained by markers associated with the metabolic syndrome, indicating that part of the relationship between HDL cholesterol and CAD risk is merely a reflection of this metabolic risk. Funding: The Medical Research Council and Cancer Research UK, the European Union, Stroke Association, British Heart Foundation, United Kingdom Department of Health, Food Standards Agency, the Wellcome Trust, and the Future Forum. [ABSTRACT FROM AUTHOR]

This article reports on a study that examined coronary disease in patients with abdominal obesity and the effect of the selective cannabinoid type 1 receptor antagonist rimonabant on slowing the progression of heart disease. Through a randomized controlled trial patients received either rimonabant or a placebo and underwent coronary intravascular ultrasonography at the beginning and end of the trial. The article discusses the results of the trial and the conclusion that rimonabant had a favorable effect on patients at the secondary endpoint of the study. The article also notes that more imaging and outcomes trials are necessary.

The article presents a study on visceral adipose tissue (AT) accumulation in relation to cardiorespiratory fitness (CRF) and metabolic syndrome features. The study examines if obese individuals are at lower risk of coronary heart disease and type 2 diabetes mellitus if they have sufficient level of (CRF). A cross-sectional study of 169 asymptotic men without diabetes mellitus proved the significance of visceral AT accumulation in association between coronary heart disease and diabetes mellitus.

The aim of the present study was to evaluate the relation among alcohol consumption, the metabolic syndrome, and the risk of ischemic heart disease (IHD). The study was conducted in a cohort of 1966 men from the Quebec Cardiovascular Study. All men were initially free of IHD and, during the follow-up period of 13 y, 219 first cases of IHD were diagnosed. Alcohol consumption was determined by calculating the g/d intake based on standard portions of beer, wine, and spirits. Metabolic syndrome was diagnosed according to a modification of the National Cholesterol Education Program Adult Treatment Panel III definition. Men who consumed ≥15.2 g of alcohol/d (4th quartile of the distribution) were younger (P < 0.001 ), had elevated plasma HDL-C concentrations (P < 0.001), and lower plasma concentrations of insulin (P = 0.01), CRP (P = 0.01), and fibrinogen (P < 0.001) than men in the 1st quartile (<1.3 g of alcohol/d). After adjustment for a series of coronary risk factors, alcohol consumption ≥15.2 g/d was associated with a 39% reduction in the 13-y risk of IHD [relative risk (RR) of IHD = 0.61, P = 0.02). Finally, an alcohol consumption <15.2 g/d was associated with an increase of the risk of IHD in men with the metabolic syndrome (RR = 2.24, P < 0.001) but not in men without the metabolic syndrome (RR = 1.31, P = 0.22). These results confirm that moderate daily alcohol consumption has cardioprotective properties and suggest that the effects may be more important in subjects with a deteriorated risk profile, such as those with the metabolic syndrome. [ABSTRACT FROM AUTHOR]

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 Québec 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 ≥ 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/m&sup2) (RH 1.26, 95% confidence interval [CI] 0.8--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 1.0--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. INSET: Features of insulin resistance syndrome. [ABSTRACT FROM AUTHOR]

Background: Total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)/HDL-C ratios are used to predict ischemic heart disease risk. There is, however, no consensus on which of these 2 indices is superior. The objective of the present study was to present evidence that the LDL-C/HDL-C ratio may underestimate ischemic heart disease risk in overweight hyperinsulinemic patients with high triglyceride (TG)—low HDL-C dyslipidemia. Methods: A total of 2103 middle-aged men in whom measurements of the metabolic profile were performed in the fasting state were recruited from 7 suburbs of the Quebec metropolitan area. Results: The relationship of LDL-C/HDL-C to TC/HDL-C ratios was examined among men in the Quebec Cardiovascular Study classified into tertiles of fasting TG levels. For any given LDL-C/HDL-C ratio, the TC/HDL-C ratio was higher among men in the top TG tertile (>168 mg/dL [>1.9 mmol/L]) than in men in the first and second TG tertiles. Adjustment of the TC/HDL-C ratio for LDL-C/HDL-C by covariance analysis generated significant differences in average TC/HDL-C ratios among TG tertiles (P<.001). Greater differences in features of the insulin resistance syndrome (insulinemia, apolipoprotein B, and LDL size) were noted across tertiles of the TC/HDL-C ratio than tertiles of the LDLC/HDL-C ratio. Conclusion: Variation in the TC/HDL-C ratio may be associated with more substantial alterations in metabolic indices predictive of ischemic heart disease risk and related to the insulin resistance syndrome than variation in the LDL-C/HDL-C ratio. [ABSTRACT FROM AUTHOR]

Background: LDL-cholesterol is usually calculated using the Friedewald formula. This calculation method does not take into account the presence of Lp(a), which is associated with LDL-cholesterol. Dahlen has suggested that the Friedewald formula should be modified to account for Lp(a) associated cholesterol. This study was undertaken to determine if correction of the Friedewald formula would result in a better evaluation of ischemic heart disease (IHD) risk. Methods: 2222 men free from IHD were prospectively followed for 5 years for the appearance of myocardial infarction, coronary insufficiency or coronary death. At the baseline evaluation all had a complete fasting lipid profile which included Lp(a) determinations. LDL-cholesterol levels were calculated from total cholesterol, total triglycerides and HDL-cholesterol using the Friedewald formula and also using the Dahlen modification of the Friedewald formula. Results: During the follow-up there were 89 first IHD events. Both types of LDL-cholesterol calculations showed that the last tertile of the LDL-cholesterol distribution in comparison to the first tertile, doubles the relative risk (RR: 2.15; 95% confidence limits: 1.23–3.75) using the Friedewald formula (RR: 2.18; 95% confidence limits: 1.25–3.81) using the Dahlen modification. Lp(a) levels were not an independent predictor of IHD risk. Conclusion: Modification of the Friedewald formula to account for Lp(a) levels does not improve our evaluation of IHD risk. [Copyright &y& Elsevier]

Multiple logistic regression models were used in a cross-sectional study to determine the relation of fasting glycemia to angiographically assessed coronary artery disease (CAD) in 569 men (aged 18 to 69 years) who were stratified according to fasting blood glucose concentrations (<6.1 mmol/L, and 6.1 to 6.9 mmol/L or 110 to 124 mg/dl), waist circumference (<90 vs ≥90 cm), and fasting triglyceridemia (<2.0 vs ≥2.0 mmol/L or <177 vs ≥177 mg/dl). For this purpose, nondiabetic impaired fasting glucose was defined as from 6.1 to 6.9 mmol/L (110 to 124 mg/dl) compared with 250 normoglycemic controls (fasting glycemia <6.1 mmol/L or <124 mg/dl) without history of CAD. In the absence of “hypertriglyceridemic waist,” impaired fasting glucose was not predictive of CAD. However, the risk of CAD was markedly higher among subjects characterized by both the hypertriglyceridemic waist phenotype and the presence of impaired fasting glucose (odds ratio 8.5, 95% confidence intervals 3.5 to 20.4; p <0.05) compared with the normoglycemic group with low waist circumferences and triglyceride levels. Thus, the results of the present study emphasizes the importance of other underlying metabolic abnormalities, such as abdominal obesity and related atherogenic dyslipidemia, in the modulation of the CAD risk associated with hyperglycemia. [Copyright &y& Elsevier]

Objectives: The aims of this study were to examine prospectively the relationship between metabolic syndrome (MetS) and aortic stenosis (AS) progression and to evaluate the effect of age and statin therapy on AS progression in patients with or without MetS. Background: Despite the clear benefits of statin therapy in primary and secondary coronary heart disease prevention, several recent randomized trials have failed to demonstrate any significant effect of this class of drugs on the progression of AS. Previous retrospective studies have reported an association between MetS and faster AS progression. Methods: This predefined substudy included 243 of the 269 patients enrolled in the ASTRONOMER (AS Progression Observation: Measuring Effects of Rosuvastatin) trial. Follow-up was 3.4 ± 1.3 years. AS progression rate was measured by calculating the annualized increase in peak aortic jet velocity measured by Doppler echocardiography. Results: Patients with MetS (27%) had faster stenosis progression (+0.25 ± 0.21 m/s/year vs. +0.19 ± 0.19 m/s/year, p = 0.03). Predictors of faster AS progression in multivariate analysis were older age (p = 0.01), higher degree of valve calcification (p = 0.01), higher peak aortic jet velocity at baseline (p = 0.007), and MetS (p = 0.005). Impact of MetS on AS progression was most significant in younger (< 57 years) patients (MetS: +0.24 ± 0.19 m/s/year vs. no MetS: +0.13 ± 0.18 m/s/year, p = 0.008) and among patients receiving statin therapy (+0.27 ± 0.23 m/s/year vs. +0.19 ± 0.18 m/s/year, p = 0.045). In multivariate analysis, the MetS-age interaction was significant (p = 0.01), but the MetS-statin use interaction was not. Conclusions: MetS was found to be a powerful and independent predictor of faster AS progression, with more pronounced impact in younger patients. These findings emphasize the importance of routinely identifying and treating MetS in AS patients. The apparent faster stenosis progression in the subset of normocholesterolemic patients with MetS receiving the statin will need to be confirmed by future studies. [Copyright &y& Elsevier]

The present study tested whether in patients with type 2 diabetes mellitus (DM) the combination of increased waist circumference and increased plasma triglyceride (TG) levels can predict the presence of coronary artery disease (CAD) as assessed by multidetector computed tomographic coronary angiography (CTA). In 202 patients with type 2 DM who were clinically referred for CTA, waist circumference and TG levels were measured. Patients were divided into 4 groups according to waist circumference measurements and TG levels. Increased waist circumference and TG levels (n = 61, 31%) indicated the presence of the hypertriglyceridemic waist phenotype. Patients with low waist circumference and TG (n = 49, 24%) were considered the reference group. Physical examination and blood measurements were performed. CTA was used to determine presence and severity of CAD. In addition, plaque type was evaluated. Plasma cholesterol levels were significantly increased in the group with increased TG levels and waist circumference, whereas high-density lipoprotein cholesterol was significantly lower than in the reference group. There was a significant increase in the presence of any CAD (odds ratio 3.3, confidence interval 1.31 to 8.13, p <0.05) and obstructive CAD (≥50%, odds ratio 2.9, confidence interval 1.16 to 7.28, p <0.05) in the group with increased TG level and waist circumference. In addition, a significantly larger number of noncalcified and mixed plaques was observed. In conclusion, in patients with type 2 DM, presence of the hypertriglyceridemic waist phenotype translated into a deteriorated blood lipid profile and more extensive CAD on CTA. Accordingly, the hypertriglyceridemic waist phenotype may serve as a practical clinical biomarker to improve risk stratification in patients with type 2 DM. [ABSTRACT FROM AUTHOR]

Abstract: Small, dense LDL particles have been associated with an increased risk of coronary artery disease. In order to assess the potential contribution of the genotype of the LDL receptor to LDL particle size heterogeneity in familial hypercholesterolemia (FH), we examined the electrophoretic characteristics of LDL particles in a large cohort of FH heterozygotes and controls. A total of 259 FH heterozygotes and 208 controls participated in the study. FH subjects were carriers of one of the nine French Canadian mutations in the LDL receptor gene. LDL particles were characterized by polyacrylamide gradient gel electrophoresis following a 6-week lipid-lowering drug-free baseline period. LDL–peak particle diameter (LDL–PPD), representing the most abundant LDL particle subpopulation, was significantly smaller in FH heterozygotes carrying a negative-receptor mutation than in subjects carrying a defective-receptor mutation (negative-receptor=257.3±4.1Å versus defective-receptor=259.0±4.3Å, p =0.0006). No significant difference in plasma CETP concentrations was found between these two genotypic groups. Moreover, compared with controls having low triglyceride levels, negative-receptor subjects with high triglyceride levels had a relative risk of 19.6 (p <0.0001) of having small, dense LDL particles while this risk was not significantly increased among defective-receptor subjects. Multivariate analysis showed that the LDL receptor status accounted for 5.7% of the variance in the LDL–PPD after adjustment for covariates. These results suggest that the genotype of the mutant LDL receptor allele was independently associated with variations in LDL–PPD and could partly explain why negative-receptor FH heterozygotes may be at greater risk of cardiovascular disease than defective-receptor FH subjects. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Background: This study evaluated the prevalence of the atherogenic metabolic triad and the hypothesis that waist circumference and fasting triglyceride concentrations could be used as screening tools for identification of the atherogenic metabolic triad in a population of heart transplant men. It also evaluated the relationship between the atherogenic metabolic triad and coronary artery disease (CAD). Methods: In the study group of 83 consecutive male heart transplant patients having their routine annual coronarography, 23 patients (28%) were characterized by the atherogenic metabolic triad defined by the presence of elevated fasting insulin and apolipoprotein B concentrations and by small low-density lipoprotein (LDL) particles. Results: Seventy-seven per cent of patients with waist circumference values ≥ 90 cm and with elevated triglyceride levels (≥2.0 mmol/liter) were characterized by this atherogenic metabolic triad. Patients with the atherogenic metabolic triad were at markedly increased risk of CAD (odds ratio of 25.3, 95% CI: 1.11–577.3, p &#60; 0.04) compared to heart transplant patients without the atherogenic metabolic triad. Conclusions: About 30% of heart transplant patients showed the features of the atherogenic metabolic triad. Measurement and interpretation of waist circumference and fasting triglycerides could be used among heart transplant patients to early identify men characterized by the presence of elevated fasting insulin and apolipoprotein B concentrations and small LDL particles. The presence of the atherogenic metabolic triad identified patients at high risk of CAD even in the heart transplant population. [Copyright &y& Elsevier]

A low plasma HDL-cholesterol concentration is an important risk factor for coronary heart disease (CHD) and is often accompanied by increased triglyceride concentrations. Women have generally higher HDL-cholesterol and lower triglyceride concentrations and concomitantly are at lower risk of CHD than men. As HDL particle size is a new and potentially important marker of CHD risk, we have examined the potential gender difference in HDL particle size, assessed by nondenaturing 4–30% polyacrylamide gradient gel electrophoresis, in a sample of men (n=231) and women (n=183). Overall, men were characterized by a less favorable lipoprotein–lipid profile, which was accompanied by smaller HDL particle size compared to women. However, when men and women were matched for HDL particle size and compared for their metabolic profile, it was found that both genders were characterized by similar plasma lipoprotein–lipid profile despite the fact that women were characterized by higher levels of total body fat but lower waist girth than men. In summary, HDL particle size is a strong marker of the gender-related difference in the determination of the metabolic risk profile. [Copyright &y& Elsevier]

Insulin resistance, through numerous related disturbances in glucose and lipoprotein-lipid metabolism, is associated with an increased risk of ischemic heart disease (IHD). The purpose of the present study was to examine the relationship between increased plasma free fatty acid (FFA) concentrations, as a feature of the insulin resistance syndrome, and the risk of IHD in men. Analyses were carried out in a nested, case-control sample of men selected from a population of 2103 individuals without IHD at baseline among whom 114 developed IHD during a 5-year follow-up period. Incident IHD cases were matched with controls for age, body mass index, smoking habits and alcohol intake. Analyses were performed while excluding (88 cases and 98 controls) and including (103 cases and 99 controls) patients with type 2 diabetes. Among non-diabetic individuals, elevated plasma FFA concentrations (3rd tertile of the distribution) yielded a twofold increase in the risk of IHD (odds ratio [OR] 2.1, P=0.05) compared with lower plasma FFA levels (lowest tertile) after adjusting for non-lipid risk factors. Further adjustment for insulin, triglycerides, apolipoprotein B, HDL cholesterol and small dense LDL attenuated significantly the relationship between plasma FFA concentrations and the risk of IHD. High plasma FFA levels showed no synergism with selected features of the insulin resistance syndrome in determining the risk of IHD. Inclusion of diabetic subjects in the study did not improve FFA independent prognostic value to the risk of IHD. These results suggest that elevated plasma FFA concentrations are associated with an increased risk of IHD. However, a single fasting measurement of plasma FFA levels does not appear to improve our ability to predict IHD onset in men when information on other risk factors is considered. [Copyright &y& Elsevier]

Men with low-density lipoprotein receptor gene mutations causing familial hypercholesterolemia (FH) are at high risk of premature coronary artery disease (CAD). The dyslipidemic state found among patients who are heterozygous for mutations in the lipoprotein lipase (LPL) gene may also increase the risk of CAD. In the present study, the association of the heterozygous forms of low-density lipoprotein receptor gene mutations causing FH as well as of LPL gene mutations causing (P207L and G188E) or not causing (D9N and N291S) complete loss of LPL activity with angiographically assessed CAD was estimated in a cohort of 412 French Canadian men aged <60 years who consecutively underwent coronary angiography for the investigation of retrosternal pain. The frequency of FH as well as of LPL gene mutations tended to increase with the number of narrowed coronary arteries. However, CAD occurred earlier in FH patients than in partly LPL-deficient patients. Indeed, the proportion of men affected by FH was of 16.4% in those <45 years of age, and solely 4.3% among those between 56 and 60 years of age (p <0.0001). In contrast, the LPL gene defect was found in only 4.0% of men aged <45 years, whereas this prevalence reached 8.3% among those aged 56 to 60 years. In multivariate analyses, the association of LPL with CAD was not independent of age, high-density lipoprotein cholesterol concentrations, and other covariates included at baseline, and was not affected by the type of mutation in the LPL gene. In contrast, FH was associated with CAD with minimal contribution of other cardiovascular risk factors. However, the relation between FH and CAD was at least partly dependent on plasma apolipoprotein B concentrations. In the different regression models, fasting insulin and plasma high-density lipoprotein cholesterol concentrations were important covariates of CAD, whether or not patients were affected by FH or LPL deficiency. In conclusion, the association of LPL gene mutations with CAD was delayed compared with FH, appeared to be markedly exacerbated by the presence of additional risk factors, and was not affected by the type of mutation in the LPL gene. [ABSTRACT FROM AUTHOR]

Increased numbers of small, dense low-density lipoprotein particles may be present in patients with low high-density lipoprotein cholesterol and normal plasma triglycerides and cholesterol. Measurment of apolipoprotein B is the key to diagnosis and such patients should be considered for statin therapy. [ABSTRACT FROM AUTHOR]