High triglycerides and low HDL cholesterol and blood pressure and risk of ischemic heart disease

Treatment of high blood pressure (BP) has not produced the expected reduction in risk of ischemic heart disease (IHD). Subjects with high BP often have the metabolic syndrome X, an aggregation of abnormalities in glucose and lipid metabolism. We tested the hypothesis that the BP level would be less predictive of risk of IHD in those with high triglycerides (TG) and low HDL cholesterol (HDL-C), the characteristic dyslipidemia in the metabolic syndrome than in those without. Baseline measurements of fasting lipids, systolic BP (SBP), diastolic BP (DBP), and other risk factors were obtained in 2906 men, age 53 to 74 years, free of overt cardiovascular disease. High TG/low HDL-C was defined as TG >1.59 mmol/L and HDL-C <1.18 mmol/L. Within an 8-year period, 229 men developed IHD. In men with high TG/low HDL-C, the incidence of IHD according to SBP (<120, 120 to 140, >140 mm Hg) was 12.5%, 12.9%, and 10.0% (P=NS), respectively, and according to DBP, the incidence of IHD was (<75, 75 to 90, >90 mm Hg) 13.7%, 10.6%, and 13.7% (P=NS), respectively. The corresponding figures for other men were 5.2%, 8. 0%, and 9.7% for SBP (P<0.001), and 6.1%, 7.5%, and 9.9% for DBP (P<0.03). In conclusion, the BP level did not predict the risk of IHD in those with high TG/low HDL-C. This finding may explain the reason lowering BP has not produced the expected reduction in IHD.     

High triglycerides/low high-density lipoprotein cholesterol,ischemic electrocardiogram changes,and risk of ischemic heart disease

Background High triglycerides (TG)/low high-density lipoprotein cholesterol (HDL-C)(TG ≥1.60 and HDL-C ≤1.18 mmol/L) and ischemic ST-T changes in the resting electrocardiogram (ECG) are both strong risk factors of ischemic heart disease (IHD) in men without clinical cardiovascular diseases. This study tested the hypothesis that men free of clinical IHD with high TG/low HDL-C and resting ischemic ECG changes would have a particularly poor prognosis with respect to IHD.Methods We conducted a cohort study of 2906 men, aged 53 to 74 years, without overt IHD at baseline.Results During 8 years, IHD developed in 229 men; 61 cases were fatal. Of the risk factors recorded, ischemic ECG changes and high TG/low HDL-C were the strongest risk factors of IHD. Compared with men without high TG/low HDL-C and without ischemic ECG changes, age-adjusted relative risk of total IHD (95% CI) was 3.5 (1.7-7.2) in men with both high TG/low HDL-C and ischemic ECG changes; the corresponding value for fatal IHD was 11.2 (4.9-25.8). Adjusted for conventional risk factors, the interaction term high TG/low HDL-C × ischemic ECG changes was a significant predictor of IHD death, with a relative risk of 2.6 (1.0-6.9).Conclusions In men free of clinical IHD, ischemic ECG changes were significantly more predictive of fatal IHD in men with high TG/low HDL-C, indicating an adverse synergistic effect of these 2 risk factors. (Am Heart J 2003;145:103-8.)     

High attributable risk of elevated C-reactive protein level to conventional coronary heart disease risk factors: the Third National Health and Nutrition Examination Survey

BACKGROUND: C-reactive protein (CRP), a marker of systemic inflammation, is predictive of coronary heart disease (CHD) events. However, the extent to which high CRP levels (>3 mg/L) may be attributable to high cholesterol levels and other CHD risk factors has not been well defined. METHODS: The prevalence of high CRP levels in the third National Health and Nutrition Examination Survey (n = 15 341) was studied using CHD risk-factor cut points designated as abnormal (total cholesterol values, >or=240 mg/dL [>or=6.22 mmol/L]; fasting blood glucose levels, >or=126 mg/dL [>or=6.99 mmol/L]; blood pressure, >or=140/90 mm Hg; body mass index [BMI], >or=30 kg/m(2); high-density lipoprotein cholesterol values, <40 mg/dL [<1.04 mmol/L] for men and <50 mg/dL [<1.30 mmol/L] for women; triglyceride levels, >or=200 mg/dL [>or=2.26 mmol/L]; current smoking status) or borderline (total cholesterol values, 200-239 mg/dL [5.18-6.19 mmol/L]; fasting blood glucose levels, 100-125 mg/dL [5.55-6.94 mmol/L]; blood pressure, 120-139/80-89 mm Hg; BMI, 25.0-29.9 kg/m(2), and triglyceride values 150-199 mg/dL [1.70-2.25 mmol/L], former smoking status), or normal. RESULTS: Weighted multiple logistic regression analysis demonstrated that high CRP level was significantly more common with obesity (odds ratio [OR], 3.78; 95% confidence interval [CI], 3.28-4.35]), overweight (OR, 1.88; 95% CI, 1.62-2.18), and diabetes (OR, 1.91; 95% CI, 1.54-2.38) and that high CRP level was rare in the absence of any borderline or abnormal CHD risk factor in men (4.4%) and women (10.3%). Overall, the risk of elevated CRP level attributable to the presence of any abnormal or borderline CHD risk factor was 78% in men and 67% women. CONCLUSIONS: These data suggest that elevated CRP levels in the general population are in large measure attributable to traditional CHD risk factors. Moreover, CRP level elevation is rare in the absence of borderline or abnormal risk factors. As such, CRP measurements may have limited clinical utility as a screening tool beyond other known CHD risk factors.     

Prevalence and phenotypic distribution of dyslipidemia in type 1 diabetes mellitus: effect of glycemic control

BACKGROUND: Data on the prevalence of dyslipidemia in type 1 diabetes mellitus are scarce and are based on total triglyceride and total cholesterol concentrations alone. OBJECTIVE: To assess the effect of glycemic optimization on the prevalence of dyslipidemia and low-density lipoprotein cholesterol (LDL-C) concentrations requiring intervention in patients with type 1 diabetes. PATIENTS: A total of 334 adults with type 1 diabetes and 803 nondiabetic control subjects. METHODS: Levels of glycosylated hemoglobin, total cholesterol, total triglyceride, high-density lipoprotein cholesterol (HDL-C), and LDL-C were assessed at baseline and after 3 to 6 months of intensive therapy with multiple insulin doses. RESULTS: Levels of LDL-C greater than 4.13 mmol/L (>160 mg/dL) and total triglyceride greater than 2.25 mmol/L (>200 mg/dL) and low HDL-C levels (<0.9 mmol/L [<35 mg/dL] in men or <1.1 mmol/L [<45 mg/dL] in women) were found in 16%, 5%, and 20% of patients and 13%, 6%, and 9% of controls, respectively (P<.001 for HDL-C). Diabetic women showed more hypercholesterolemia than nondiabetic women (15.6% vs 8.5%; P =.04). After glycemic optimization (mean +/- SD glycosylated hemoglobin decrease, 2.2 +/- 1.96 percentage points), the prevalence of LDL-C levels greater than 4.13 mmol/L (>160 mg/dL) became lower in diabetic men than in nondiabetic men (9.7% vs 17.5%; P =.04), but women showed frequencies of dyslipidemia similar to their nondiabetic counterparts. The proportion of patients with LDL-C concentrations requiring lifestyle (>2.6 mmol/L [>100 mg/dL]) or drug (>3.4 mmol/L [>130 mg/dL]) intervention decreased from 78% and 42% to 66% and 26%, respectively. CONCLUSIONS: Low HDL-C is the most frequent dyslipidemic disorder in patients with poorly controlled insulin-treated type 1 diabetes, and a high proportion show LDL-C levels requiring intervention. Less favorable lipid profiles could explain the absence of sex protection in diabetic women. The improvement caused by glycemic optimization puts forward intensive therapy as the initial treatment of choice for dyslipidemia in poorly controlled type 1 diabetes.     

Obesity, insulin resistance and isolated low high-density-lipoprotein cholesterol in Chinese subjects.

AIM: Recent studies have shown that the risk of developing coronary heart disease in subjects with 'isolated low high-density-lipoprotein cholesterol (HDL-C)' (defined as HDL-C < 0.9 mmol/l and total cholesterol (TC) < 5.2 mmol/l) was similar to those with hypercholesterolaemia. We examined the prevalence of isolated low HDL-C in Hong Kong Chinese and its relationship with insulin resistance and triglyceride (TG) level. METHODS: Hong Kong Chinese subjects (n = 1493) recruited in a population-based prevalence survey for cardiovascular risk factors were examined. Insulin resistance was calculated using a computer-solved homeostasis model assessment method. RESULTS: Of the 1493 subjects, 72 (4.8%) had isolated low HDL-C, in whom half (n = 36) had TG > or = 1.7 mmol/l and half (n = 36) had TG < 1.7 mmol/l. Compared with the 'controls' (subjects with TC < 5.2 mmol/l and HDL-C > or = 0.9 mmol/l; TC > or = 5.2 mmol/l and HDL-C < 0.9 mmol/l; or TC > or = 5.2 mmol/l and HDL-C > or = 0.9 mmol/l, n = 1421), subjects with isolated low HDL-C and high TG were more obese, had higher plasma glucose, fasting and 2 h plasma insulin concentrations and insulin resistance. Subjects with isolated low HDL-C and TG < 1.7 mmol/l had similar insulin concentrations and insulin resistance, but were more obese than the 'controls'. Subjects with isolated low HDL-C and high TG also had higher fasting PG, insulin and insulin resistance than those with isolated low HDL-C and low TG. CONCLUSIONS: In this population-based study, 4.8% of Hong Kong Chinese had isolated low HDL-C, which was closely associated with obesity. The coexistence of high TG suggests an insulin-resistant state.     

Effects of pravastatin on coronary events in 2073 patients with low levels of both low-density lipoprotein cholesterol and high-density lipoprotein cholesterol: results from the LIPID study.

AIMS: Fibrates or nicotinic acid are usually recommended for secondary prevention of coronary heart disease in patients with low plasma levels of both low-density lipoprotein cholesterol (LDL-C) < or =140 mg/dL (< or =3.6 mmol/L) and high-density lipoprotein cholesterol (HDL-C) < or =40 mg/dL (< or =1.03 mmol/L). The LIPID trial, a randomised, placebo-controlled trial in 9014 patients at 87 centres in Australia and New Zealand, provided an opportunity to investigate the effects of an HMG-CoA reductase inhibitor in patients with low LDL-C and low HDL-C. METHODS AND RESULTS: Participants in this post hoc substudy were 2073 patients aged 31-75 years with baseline LDL-C < or =140 mg/dL (< or =3.6 mmol/L), HDL-C < or =40 mg/dL (< or =1.03 mmol/L), and triglyceride < or =300 mg/dL (< or =3.4 mmol/L). The relative risk reduction with pravastatin treatment was 27% for major coronary events (95% CI 8-42%), 27% for coronary heart disease mortality (95% CI 0-47%), 21% for all-cause mortality (95% CI 0-38%), and 51% for stroke (95% CI 24-69%). The number needed to treat to prevent a major coronary event over 6 years was 22. CONCLUSIONS: Treatment with pravastatin in patients with both low LDL-C and low HDL-C significantly reduced major coronary events, stroke, and all-cause mortality. The level of HDL-C is crucial to the risk of recurrent CHD events and, consequently, the benefit of lowering LDL-C.     

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 a 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.     

Intra-abdominal thickness by ultrasonography to predict risk factors for cardiovascular disease and its correlation with anthropometric measurements

The aim of this study was to determine if intra-abdominal thickness measured by ultrasonography (IATU) in men and women had a correlation with cardiovascular risk factors, to compare it with anthropometric measures (waist circumference [WC] and abdominal sagittal diameter [SDi]), and to find a cut-off value for IATU to predict risk factors for cardiovascular disease (CVD). In a cross-validation study, intra-abdominal fat tissue measured by CT at L4-L5 was significantly correlated with ultrasonography (US) intra-abdominal thickness. A total of 191 and 231 healthy men and women, respectively, aged 20 to 60 years, were evaluated by anthropometric indexes (body mass index [BMI], WC, and SDi), and systolic blood pressure (SBP) and diastolic blood pressure (DBP), fasting total plasma cholesterol (Chol), high-density lipoprotein (HDL) cholesterol, triglyceride (TG), and glucose (Glu) levels. IATU was evaluated by the distance between the internal face of abdominal muscles and posterior wall of the aorta. All measurements were taken by the same physician. The subjects were divided into 3 cardiovascular risk groups, according to the presence of 2 or more risk factors-(1) moderate-risk (MR) group with 2 or more of the following: total Chol > 200 mg/dL, HDL cholesterol < 45 mg/dL, TG > 200 mg/dL, Glu > 126 mg/dL, SBP > 140 mm Hg, DBP > 90 mm Hg, comprising 68 men and 72 women; (2) high-risk (HR) group with 2 or more of the following: total Chol > 240 mg/dL, HDL cholesterol < 35 mg/dL, TG > 200 mg/dL + HDL cholesterol < 35 mg/dL, Glu > 126 mg/dL, SBP > 140 mm Hg, DBP > 90 mm Hg, comprising 34 men and 55 women; and (3) no-risk (NR) group with only 1 or none of the risk factors indicated in the MR and HR groups. IATU presented association with risk factors and presented a higher level of accuracy and specificity than SDi and WC (odds ratio [OR] = 2.27 [95% confidence interval (CI), 1.05 to 4.80] for men and OR = 3.69 [95% CI, 1.98 to 66.90] for women). The cut-off length to predict moderate risk was 7 cm for both sexes (OR = 2.86 [95% CI, 1.44-5.68] for men and OR = 3.01 [95% CI, 11.61 to 5.62] for women), whereas the value of 9 cm predicted high risk for CVD (OR = 5.55 [95% CI, 2.32 to 13.28]) in men and of 8 cm in women (OR = 3.27 [95% CI, 1.63 to 6.56]). In conclusion, IATU is a useful tool to evaluate visceral fat and seems to be predictive of risk factors associated with CVD.     

Extended-release niacin vs gemfibrozil for the treatment of low levels of high-density lipoprotein cholesterol. Niaspan-Gemfibrozil Study Group

OBJECTIVE: To provide a direct comparison of agents that raise plasma levels of high-density lipoprotein cholesterol (HDL-C) to help devise strategies for coronary risk reduction. METHODS: In a multicenter, randomized, double-blind trial, we compared the effects of extended-release niacin (Niaspan), at doses increased sequentially from 1000 to 2000 mg at bedtime, with those of gemfibrozil, 600 mg given twice daily, in raising low levels of HDL-C. Enrollment criteria included an HDL-C level of 1.03 mmol/L or less (< or =40 mg/dL), a low-density lipoprotein cholesterol level of 4.14 mmol/L or less (< or =160 mg/dL) or less than 3.36 mmol/L (<130 mg/dL) with atherosclerotic disease, and a triglyceride level of 4.52 mmol/L or less (< or =400 mg/dL). RESULTS: Among 173 patients, 72 (82%) of the 88 assigned to Niaspan treatment and 68 (80%) of the 85 assigned to gemfibrozil treatment completed the study. Niaspan, at 1500 and 2000 mg, vs gemfibrozil raised the HDL-C level more (21% and 26%, respectively, vs 13%), raised the apolipoprotein A-I level more (9% and 11% vs 4%), reduced the total cholesterol-HDL-C ratio more (-17% and -22% vs -12%), reduced the lipoprotein(a) level (-7% and -20% vs no change), and had no adverse effect on the low-density lipoprotein cholesterol level (2% and 0% change vs a 9% increase). Significance levels for comparisons between medications ranged from P<.001 to P<.02. Gemfibrozil reduced the triglyceride level more than Niaspan (P<.001 to P = .06, -40% for gemfibrozil vs -16% to -29% for Niaspan, 1000 to 2000 mg). Effects on plasma fibrinogen levels were significantly favorable for Niaspan compared with gemfibrozil (P<.02), as gemfibrozil increased the fibrinogen level (from 5% to 9%) and Niaspan tended to decrease the fibrinogen level (from -1% to -6%). CONCLUSIONS: In patients with a low baseline HDL-C level, Niaspan at its higher doses provided up to 2-fold greater HDL-C increases, decreases in lipoprotein(a), improvements in lipoprotein cholesterol ratios, and lower fibrinogen levels compared with gemfibrozil. Gemfibrozil gave a greater triglyceride reduction but also increased the low-density lipoprotein cholesterol level, which did not occur with Niaspan.     

Prevalence and control of dyslipidemia among persons with diabetes in the United States

OBJECTIVE: We assessed the prevalence, treatment, and control of dyslipidemia among United States (U.S.) adults with diabetes. METHODS: Among 498 adults (projected to 13.4 million) aged >or=18 years with diabetes representative of the U.S. population and surveyed within the cross-sectional National Health and Nutrition Examination Survey 1999-2000, control of lipids was classified according to American Diabetes Association criteria. The extent of low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), and triglyceride (TG) control was examined by gender and ethnicity, in comparison to those without diabetes, and according to lipid-lowering treatment. Analyses were weighted to the U.S. population. RESULTS: Less than one-third of men and only one-fifth of women with diabetes are in control for LDL-C, defined as <2.6 mmol/l (<100mg/dl); over 70% are not at goal. Over half of men and over two-thirds of women have low levels of HDL-C (or=1.7 mmol/l [150 mg/dl]). Low HDL-C was more common in Caucasians (70.1%) than in Hispanics (58.8%) or African-Americans (41.5%) (p<0.001). 28.2% of subjects with diabetes were on lipid-lowering treatment. Control of LDL-C did not differ by treatment status and only 3% of subjects were controlled to target levels for all lipids. CONCLUSION: Many persons with diabetes remain uncontrolled for dyslipidemia. Intensified efforts at screening and treatment according to current guidelines are warranted.     

中国成人血脂异常诊断和危险分层方案的研究

目的为配合制订《中国成人血脂异常防治指南》,提出适合我国人群疾病和危险因素特点的血脂异常诊断界值和以血脂异常为基础的危险分层方案建议,以期更好地指导我国的血脂异常防治工作。方法汇总“中美心肺疾病流行病学合作研究”和“中国多省市心血管病队列研究”资料（基线入组共计40719人,年龄35—64岁,男女约各半,随访总计345140．5人年）,用统一的分析方案分析血脂异常与缺血性心血管病发病（ICVD,包括冠心病事件和缺血性脑卒中事件）的关系。相对危险的估计采用多元Cox比例风险模型,并控制其他危险因素。采用该模型计算不同危险因素组合时一个50岁的人今后10年发生缺血性心血管病的绝对危险,用于确定危险分层方案。结果两队列均呈现如下规律：（1）TC和LDL-C水平与ICVD发病危险的关系是连续性的,并无明显的拐点;（2）LDL—C〈3．37mmol／L（130mg／dl）与TC〈5．18mmol／L（200mg／dl）的发病率（绝对危险）基本接近,而LDL—C〈4．14mmol／L（160mg／dl）与TC〈6．22mmol／L（240mg／dl）的发病率基本接近;（3）TC〈5．18mmol／L（200mg／dl）时的绝对危险略高于理想血压[〈120／80mmHg（1mmHg=0．133kPa）]时的绝对危险,TC≥6．22mmol／L（240mg／dl）时的绝对危险略低于高血压1级的绝对危险;（4）随着HDL—C水平的降低,ICVD发病危险增加;（5）TG与ICVD发病危险间未见显著关联;（6）在任一TC水平,仅合并高血压时ICVD发病的绝对危险已高于合并3个其他危险因素时ICVD发病的绝对危险。结论我国人群血脂异常诊断标准可准确定为：TC〈5．18mmol／L（200mg／dl）或LDL—C〈3．37mmol／L（130mg／dl）为合适范围,TC5．18—6．19mmol／L（200～239mg／dl）或LDL．C3．37～4．12mmol／L（130～159mg／dl）为边缘升高,TC≥6．22mmol／L（240mg／dl）或LDL-C≥4．14mmol／L（160ms／dl）为升高。HDL—C〈1．04mmol／L（40mg／dl）为减低,1．04～1．53mmol／L（40～59mg／dl）为正常,≥1．55mmol／L（60mg／dl）为理想水平。此标准与国际相关标准一致。在危险分层方案中高血压的作用相当于其他任意3个危险因素的作用之和。     

Total cholesterol/HDL cholesterol ratio vs LDL cholesterol/HDL cholesterol ratio as indices of ischemic heart disease risk in men: the Quebec Cardiovascular Study.

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 LDL-C/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.     

Determinants of serum HDL-C level in a Tehran urban population: the Tehran Lipid and Glucose Study

BACKGROUND AND AIM: Decreased serum high-density lipoprotein cholesterol (HDL-C) is one of the most common lipid disorders in patients with coronary artery disease (CAD). Existing evidence suggests that every 1 mg/dL decrease in serum HDL-C increases the risk of CAD by 2-3%. This study was performed in the year 2000 to study HDL-C determinants in a Tehran population. METHODS AND RESULTS: We studied 9514 subjects (3942 men and 5572 women) aged 20-69 years, who participated in the Tehran Lipid and Glucose Study (TLGS), completed a personal history questionnaire (especially concerning physical activity and cigarette smoking), and underwent a clinical examination including anthropometric and blood pressure measurements. Serum total cholesterol, triglyceride and HDL-C levels were measured, and OGTT was used to define diabetic patients according to WHO criteria. The women had a significantly higher mean HDL-C level than the mean (45 +/- 11 vs 38 +/- 9 mg/dL; p < 0.001); low HDL-C levels (< 35 mg/dL) were observed in 31% of the men and 13% of the women (p < 0.001). Obese subjects (BMI > or = 30 kg/m2) had a significantly lower HDL-C level than the normal subjects (42 +/- 11 vs 44 +/- 11 mg/dL: p < 0.001), and those with truncal obesity (WHR > or = 0.95 in men and > or = 0.8 in women) lower HDL-C levels than the normal subjects (37 +/- 9 vs 39 +/- 10 mg/dL in men and 44 +/- 11 vs 42 +/- 11 mg/dL in women; p < 0.001 for both). Smokers had a significantly lower HDL-C level than non-smokers (38 +/- 10 vs 43 +/- 11 mg/dL; p < 0.001) and a low HDL-C level was twice as common (36.4 vs 18.2%). Passive smokers also had lower HDL-C levels (42 +/- 11 vs 43 +/- 11 mg/dL; p < 0.001). Mean serum HDL-C was significantly lower in hypertriglyceridemic than those with normal triglycerides levels (men: 4 +/- 8 vs 40 +/- 9 mg/dL, p < 0.001; women: 40 +/- 10 vs 47 +/- 11 mg/dL, p < 0.01). Mean HDL-C levels were similar in subjects with different degrees of physical activity, as well as between diabetics and non-diabetics and hypertensive and normotensive subjects. Multiple stepwise regression analysis showed that the determinants of serum HDL-C levels were, in order of entering the model: hypertriglyceridemia (OR 3.4, p < 0.001), male sex (OR 3.1, p < 0.001), cigarette smoking (OR 1.7, p < 0.001), obesity (OR 1.4, p < 0.01), age (OR 0.9, p < 0.05), high WHR (OR 1.2, p < 0.05), and passive smoking (OR 1.1, p < 0.05). Physical activity, hypertension, and diabetes mellitus did not enter the predictive model. CONCLUSION: Apart from age and sex which are constitutional, and unmodifiable variables, the determinants of HDL-C level (hypertriglyceridemia, obesity, truncal obesity, cigarette smoking, and passive smoking) can be used in community CAD prevention programmes.     

Study Design, Rationale, and Baseline Characteristics: Evaluation of Fenofibric Acid on Carotid Intima-Media Thickness in Patients with Type IIb Dyslipidemia with Residual Risk in Addition to Atorvastatin Therapy (FIRST) Trial

Purpose

Elevated triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) levels contribute to cardiovascular disease risk and can be effectively treated with fenofibric acid. A trial is under way to evaluate the effect of once-daily fenofibric acid or placebo on carotid intima-media thickness (CIMT) progression in patients with controlled low-density lipoprotein cholesterol (LDL-C) levels achieved through atorvastatin treatment, but with high TG and low HDL-C levels.

Methods

In this multicenter, double-blind study, 682 patients were randomized to once-daily delayed-release capsules of choline fenofibrate 135?mg (fenofibric acid [Trilipix?; Abbott, North Chicago, IL]) or placebo plus atorvastatin treatment after a 2- to 10-week diet and atorvastatin run-in period. Key inclusion criteria included age ≥45?years; posterior-wall common CIMT ≥0.7?mm on at least one side at baseline; fasting results of TG ≥150?mg/dL, and HDL-C ≤45?mg/dL for men or HDL-C ≤55?mg/dL for women at screening while receiving atorvastatin; controlled LDL-C; and known coronary heart disease (CHD) or a CHD risk equivalent. The primary efficacy variable is the rate of change from baseline through week 104 in the mean posterior-wall intima-media thickness of the common carotid arteries (composite value of left and right sides).

Conclusions

This trial is the first to examine the effect of fenofibric acid on CIMT and the first CIMT trial to select patients with controlled LDL-C and elevated TG and low HDL-C as inclusion criteria. Also, this trial will prospectively evaluate the effect of treatment on LDL particles and address shortcomings of previous CIMT trials.     

Magnesium deficiency in patients with ischemic heart disease with and without acute myocardial infarction uncovered by an intravenous loading test

An intravenous magnesium-loading test with 30 mmol/L of magnesium was used to evaluate the magnesium status in 38 patients with ischemic heart disease (IHD) admitted to the coronary care unit with suspected acute myocardial infarction (AMI), in ten healthy volunteers (control group), and in nine patients with chronic IHD in a stable phase of their disease (chronic IHD group). Sixteen of the patients admitted with acute disease proved to have AMI (AMI group) and 22 did not (non-AMI group). Patients with IHD both with and without AMI retained significantly more magnesium (9.3 and 10.7 mmol/L [22.6 and 26 mg/dL], respectively) than did the control group (1.4 mmol/L [3.4 mg/dL]). This 34% magnesium retention points to a state of magnesium deficiency in patients with IHD. However, since the patients with and without AMI did not differ, the observations do not indicate that AMI is associated with a more severe magnesium deficiency than that found in other IHD patients without AMI. When the patients with IHD were subgrouped according to long-term diuretic treatment, the patients (n = 19) receiving long-term diuretic treatment had a 39% retention of magnesium (11.6 mmol/L [28.2 mg/dL]) compared with a 29% retention (8.7 mmol/L [21.1 mg/dL]) observed in 19 patients who were not receiving long-term diuretic treatment. This observation was not influenced by the presence or absence of AMI. An even higher level of magnesium retention (17.1 mmol/L [41.6 mg/dL] equals 57% retention) was found when investigating patients with chronic ischemic heart disease in a stable phase of their disease. This indicates that patients with IHD may be severely magnesium deficient; that long-term diuretic treatment contributes to this deficiency, but that diuretic treatment per se is not the only cause of this condition.     

Effects of sibutramine on body weight and serum lipids: a double-blind, randomized, placebo-controlled study in 322 overweight and obese patients with dyslipidemia

BACKGROUND: Cardiovascular risk factors associated with obesity, including dyslipidemia, can be improved by weight loss. The main dyslipidemia associated with obesity is elevated serum triglyceride and decreased serum high-density lipoprotein cholesterol (HDL-C) levels. METHODS: A total of 322 obese patients (body mass index > or = 27) with serum triglyceride levels > or = 250 mg/dL and < or = 1000 mg/dL and serum HDL-C levels < or = 45 mg/dL (women) and < or = 40 mg/dL (men) were placed on a step I American Heart Association diet and subsequently randomized to sibutramine 20 mg (n = 162) or placebo (n = 160) once daily for 24 weeks. RESULTS: Patients taking sibutramine had significantly greater mean weight loss than those receiving placebo (-4.9 kg vs -0.6 kg, P < or = .05). Forty-two percent of the sibutramine group lost > or = 5% of baseline weight and 12% lost > or = 10% compared with 8% and 3%, respectively, of the placebo group (P < or = .05). Mean decreases in serum triglyceride levels among 5% and 10% weight-loss responders in the sibutramine group were 33.4 mg/dL and 72.3 mg/dL, respectively, compared with an increase of 31.7 mg/dL among all patients receiving placebo (P < or = .05). Mean increases in serum HDL-C levels for 5% and 10% weight-loss responders in the sibutramine group were 4.9 mg/dL and 6.7 mg/dL, respectively, compared with an increase of 1.7 mg/dL among all patients in the placebo group (P < or = .05). Adverse events and discontinuation rates were similar in the sibutramine and placebo groups, although sibutramine-treated patients had mean increases in systolic and diastolic blood pressure of 2 to 3 mm Hg relative to placebo. CONCLUSIONS: In overweight and obese patients with high serum triglyceride levels and low serum HDL-C levels, treatment with sibutramine was associated with significant improvements in body weight and in serum triglyceride and HDL-C levels.     

Diabetes,plasma insulin,and cardiovascular disease: subgroup analysis from the Department of Veterans Affairs high-density lipoprotein intervention trial (VA-HIT)

BACKGROUND: Diabetes mellitus, impaired fasting glucose level, or insulin resistance are associated with increased risk of cardiovascular disease. OBJECTIVES: To determine the efficacy of gemfibrozil in subjects with varying levels of glucose tolerance or hyperinsulinemia and to examine the association between diabetes status and glucose and insulin levels and risk of cardiovascular outcomes. METHODS: Subgroup analyses from the Department of Veterans Affairs High-Density Lipoprotein Intervention Trial, a randomized controlled trial that enrolled 2531 men with coronary heart disease (CHD), a high-density lipoprotein cholesterol level of 40 mg/dL or less (/=271 pmol/L) was associated with a 31% increased risk of events (P =.03). Gemfibrozil was effective in persons with diabetes (risk reduction for composite end point, 32%; P =.004). The reduction in CHD death was 41% (HR, 0.59; 95% CI, 0.39-0.91; P =.02). Among individuals without diabetes, gemfibrozil was most efficacious for those in the highest fasting plasma insulin level quartile (risk reduction, 35%; P =.04). CONCLUSION: In men with CHD and a low high-density lipoprotein cholesterol level, gemfibrozil use was associated with a reduction in major cardiovascular events in persons with diabetes and in nondiabetic subjects with a high fasting plasma insulin level.     

Establishing the benefit of statins in low-to-moderate--risk primary prevention: the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS)

AFCAPS/TexCAPS was the first prevention trial of a statin conducted in a low-to-moderate-risk cohort that included men (> or =45 years) and women (> or =55 years) with no evidence of atherosclerotic cardiovascular disease. At study entry, LDL-C had to be 130-190 mg/dL and HDL-C < or =45 mg/dL for men and < or =47 mg/dL for women. Participants were randomized to either lovastatin 20-40 mg/day (n=3304) or placebo (n=3301) for a mean follow-up period of 5.2 years. At 1 year, in the lovastatin group TC, LDL-C, and TG were reduced by 18.4%, 25.0%, and 15%, respectively. HDL-C increased by 6.0%. At 5 years, there was a 37% decrease in the relative risk for having a first acute coronary event in the lovastatin versus placebo group. Women showed similar relative risk reduction as men. Older individuals benefited as much as younger ones from lovastatin. Subjects with > or =2 risk factors benefited more from statin than those with <2 risk factors. At baseline, HDL-C but not TC or LDL-C was determined a significant predictor of risk. On treatment, ApoB and ApoA1 were the best predictors. Based on AFCAPS/TexCAPS, a simple heuristic could be that individuals with "age plus one other risk factor" may benefit from statin therapy in primary prevention.     

Differences in the pathology of the metabolic syndrome with or without visceral fat accumulation: a study in pre-diabetic Japanese middle-aged men

To elucidate the role of visceral fat accumulation in the metabolic syndrome, differences in the pathology of the metabolic syndrome with or without visceral fat accumulation were investigated. A total of 472 prediabetic Japanese men (mean age, 47.5 +/- 7.2 yr) with impaired fasting glycemia (IFG) levels of 110-125 mg/dL were eligible for participation in the study. The study subjects were divided into the following four groups, and intergroup comparisons were made: group I without visceral fat area [VFA] > or = 100 cm2 but presenting with fewer than two other risk factors (i.e., TG > or =150 mg/dL, HDL-C < 40 mg/dL, BP > or = 130/ > or = 85 mmHg, or FPG > or = 110 mg/dL) (n = 231); group II without VFA of > or = 100 cm2 but presenting with three or more other risk factors (n = 57); group III with VFA of > or = 100 cm2 accompanied by FPG 110 mg/dL alone (n = 27); and group IV with VFA > or =100 cm2 and two or more other risk factors (n = 157). The prevalence of patients who had three or more risk factors with or without VFA > or = 100 cm2 was 45.3% (214 out of 472 patients), while that of those with VFA > or = 100 cm2 who had two or more other risk factors was 33% (157 out of 472 patients). Group II had significantly higher VFA values than group I (p < 0.05), and group IV had significantly higher VFA values than group II (p < 0.001). While no significant differences in HOMA-R values were seen between groups I and II, these values were significantly higher in group IV compared to groups I and II (p < 0.001 and p < 0.05, respectively). Furthermore, group IV showed significantly higher 2-h insulin levels after glucose loading compared to group I (p < 0.001). While no significant differences were seen between groups II and IV, insulin levels tended to be higher in group IV. Adiponectin levels showed an incremental fall in VFA from group I through groups II and III to group IV. Groups III and IV showed significantly lower adiponectin levels compared to group I (p < 0.05, p < 0.001, respectively); and group IV showed significantly lower adiponectin levels than group II (p < 0.05). A logistic regression analysis using VFA, TG and HDL-C, and BP as explanatory variables showed that the relative risk for high HOMAR values were 2.65 (p < 0.001) for patients with VFA > or =100 cm2; 1.64 (p < 0.05) for those with TG > or = 150 mg/dL and HDL < 40 mg/dL; and 1.79 (p < 0.01) for those with BP > or = 130/ > or = 85 mmHg. These findings demonstrate that the degree of insulin resistance and the risk of arteriosclerosis vary depending on whether or not the metabolic syndrome accompanied by a clustering of risk factors has visceral fat accumulation as an underlying pathology, strongly suggesting a crucial role for visceral fat accumulation in the metabolic syndrome.