Endurance exercise training raises high-density lipoprotein cholesterol and lowers small low-density lipoprotein and very low-density lipoprotein independent of body fat phenotypes in older men and women

Endurance exercise training improves plasma lipoprotein and lipid profiles and reduces cardiovascular disease risk. However, the effect of endurance exercise training, independent of diet and body fat phenotypes, on plasma lipoprotein subfraction particle concentration, size, and composition as measured by nuclear magnetic resonance (NMR) spectroscopy is not known. We hypothesized that 24 weeks of endurance exercise training would independently improve plasma lipoprotein and lipid profiles as assessed by both conventional and novel NMR measurement techniques. One hundred sedentary, healthy 50- to 75-year-olds following a standardized diet were studied before and after 24 weeks of aerobic exercise training. Lipoprotein and lipid analyses, using both conventional and NMR measures, were performed at baseline and after 24 weeks of exercise training. Relative and absolute maximum oxygen consumption increased 15% with exercise training. Most lipoprotein and lipid measures improved with 24 weeks of endurance exercise training, and these changes were consistently independent of baseline body fat and body fat changes with training. For example, with exercise training, total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C) decreased significantly (2.1+/-1.8 mg/dL, P=.001; -17+/-3.5 mg/dL, P<.0001; and -0.7+/-1.7 mg/dL, P<.0001, respectively), and high-density lipoprotein cholesterol subfractions (HDL3-C and HDL2-C) increased significantly (1.9+/-0.5 mg/dL, P=.01, and 1.2+/-0.3 mg/dL, P=.02, respectively). Particle concentrations decreased significantly for large and small very low-density lipoprotein particles (-0.7+/-0.4 nmol/L, P<.0001, and -1.1+/-1.7 nmol/L, P<.0001, respectively), total, medium, and very small LDL particles (-100+/-26 nmol/L, P=.01; -26+/-7.0 nmol/L, P=.004; and -103+/-27 nmol/L, P=.02, respectively), and small HDL particles (-0.03+/-0.4 micromol/L, P=.007). Mean very low-density lipoprotein particle size also decreased significantly (-1.7+/-0.9 nm, P<.0001) and mean HDL particle size increased significantly with exercise training (0.1+/-0.0 nm, P=.04). These results show that 24 weeks of endurance exercise training induced favorable changes in plasma lipoprotein and lipid profiles independent of diet and baseline or change in body fat.     

Prevalence of low high-density lipoprotein cholesterol in patients with documented coronary heart disease or risk equivalent and controlled low-density lipoprotein cholesterol

Current guidelines identify low-density lipoprotein (LDL) cholesterol as the primary target for cardiovascular prevention but also recognize low high-density lipoprotein (HDL) cholesterol as an important secondary target. This study was conducted to determine the prevalence of low HDL cholesterol in a contemporary ambulatory high-risk population across various LDL cholesterol levels, including patients taking statins. Screening of 44,052 electronic medical records from a primary care practice identified 1,512 high-risk patients with documented coronary heart disease (CHD) or CHD risk equivalents. Low HDL cholesterol (< or =40 mg/dl in men, < or =50 mg/dl in women) was present in 66% of the 1,512 patients. Low HDL cholesterol was prevalent across all LDL cholesterol levels but most prevalent in patients with LDL cholesterol < or =70 mg/dl (79% vs 66% in those with LDL cholesterol 71 to 100 mg/dl and 64% in patients with LDL cholesterol >100 mg/dl, p <0.01). Low HDL cholesterol was equally and highly prevalent in patients taking statins (67%) and those not taking statins (64%) (p = NS). HDL cholesterol and LDL cholesterol levels correlated poorly (R(2) = 0.01), and this was unaffected by gender or statin treatment. In conclusion, in high-risk patients with CHD or CHD risk equivalents, low HDL cholesterol levels remain prevalent despite statin treatment and the achievement of aggressive LDL cholesterol goals.     

Association of high-density lipoprotein cholesterol with coronary heart disease risk across categories of low-density lipoprotein cholesterol: the atherosclerosis risk in communities study

IntroductionNational cholesterol treatment guidelines include a low level of high-density lipoprotein (HDL) cholesterol (< 40 mg/dL) as a major risk factor for coronary heart disease (CHD) that should be considered when making decisions on treatment of low- density lipoprotein (LDL) cholesterol.MethodsWe investigated the association of HDL and LDL-cholesterol with incident CHD events (fatal or nonfatal CHD) over 14 years of follow-up among 13,615 adults aged 45 to 64 years in the Atherosclerosis Risk in Communities study.ResultsA total of 966 (7.1%) participants had a CHD event during follow-up. After adjustment for age, race, sex, diabetes, smoking, alcohol consumption, systolic blood pressure, waist circumference, chronic kidney disease and physical activity, a graded association was present between progressively lower levels of HDL-cholesterol and higher CHD risk, overall (P < 0.001) and within each level of LDL-cholesterol (< 100, 100–129, 130–159, 160–189 and ≥ 190 mg/ dL) investigated (all P < 0.05). In addition, after multivariable adjustment including LDL-cholesterol, each standard deviation higher HDL- cholesterol (18 mg/dL) was associated with a hazard ratio of incident CHD of 0.70 (95% Cl: 0.63–0.77).ConclusionsThese data suggest a graded association exists between lower levels of HDL-cholesterol and CHD across the full range of LDL-cholesterol levels. As interventions targeting HDL levels are developed, the combinatorial effects of lower HDL levels with various levels of LDL-cholesterol should be examined.     

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

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

Prospective association between low and high total and low-density lipoprotein cholesterol and coronary heart disease in elderly men

OBJECTIVES: To examine the relationship between total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) and the incidence of coronary heart disease (CHD) in elderly men. DESIGN: Prospective. SETTING: Population based. PARTICIPANTS: A sample of 2,424, Japanese-American men aged 71 to 93 was used. MEASUREMENTS: Six years of data on incident fatal plus nonfatal CHD were examined. RESULTS: Analysis revealed a significant U-shaped relationship between age-adjusted CHD rates and both TC and LDL-C. The ranges of TC and LDL-C with the lowest risk of CHD were 200 to 219 mg/dL and 120 to 139 mg/dL, respectively. As cholesterol concentrations declined and increased beyond these ranges, the risk of CHD increased. These U-shaped relationships remained significant after adjusting for age and other risk factors. CONCLUSION: The U-shaped associations between TC and LDL-C and CHD imply a complex relationship between lipids and CHD in late life. The results indicate that elevated lipid levels should continue to be treated in healthy elderly individuals, as they are in those who are younger, although pharmacologically lowering lipids to excessively low levels in the elderly may warrant further study, as does the contribution of subclinical frailty to the relationship of lipids to CHD risk.     

Usefulness of the total cholesterol to high-density lipoprotein cholesterol ratio in predicting angiographic coronary artery disease in women

To investigate the relation between lipids and angiographic coronary artery disease (CAD) in women, fasting lipid profiles were obtained on 108 women undergoing coronary angiography (group I). CAD, defined as ≥25% luminal diameter narrowing in a major coronary artery, was present in 57 (53%). Neither serum total cholesterol nor triglyceride levels correlated with the presence of CAD. Mean total/high-density lipoprotein (HDL) cholesterol ratio was higher among women with than without CAD (5.5 ± 0.3 vs 4.2 ± 0.2, p < 0.0001). Multiple regression analyses identified a higher total/HDL cholesterol ratio as the variable most predictive of the presence (p < 0.001), extent (number of narrowed arteries) (p < 0.0001), and severity (% maximum stenosis) (p < 0.001) of CAD. Age and lack of estrogen use were also independently associated with the presence of CAD, age and lowdensity lipoprotein cholesterol level were additional indicators of extent, and age was the only other discriminator of severity of CAD.

In 56 women with total cholesterol <200 mg/dl (group II), mean total/HDL cholesterol ratio was higher in women with (n = 24) than without CAD (4.3 ± 0.2 vs 3.5 ± 0.2, P = 0.01). Higher total/HDL cholesterol ratio was the variable most predictive of the presence of CAD (p = 0.01), and the tone variable associated with severity (p < 0.001) after adjustment for other risk factors. Age was independently associated with presence and extent, and hypertension was also independently related to extent. Thus, among these women, total/HDL cholesterol ratio is the best predictor of the presence, severity and extent of CAD in general, and is the best predictor of presence, and severity in patients with total cholesterol <200 mg/dl.     

Low-density lipoprotein particle size, triglycerides, and high-density lipoprotein cholesterol as risk factors for coronary heart disease in older Japanese-American men

Decreased low-density lipoprotein (LDL) particle size is associated with coronary heart disease (CHD) risk among middle-aged Caucasian populations, and has been consistently correlated with increased plasma levels of triglyceride and decreased levels of high-density lipoprotein (HDL) cholesterol. This study examines whether these risk factors predict CHD among older Japanese-American men. With use of the Honolulu Heart Program Lipoprotein Exam 3 (1980 to 1982) as baseline, and 12-year follow-up for CHD events, a nested, case-control study was designed. One hundred forty-five incident CHD cases were identified and matched to 2 controls each. LDL particle diameter (size) was determined by gradient gel electrophoresis. A 10-angstrom (A) decrease in LDL size at baseline was associated with increased risk of incident CHD (relative risk 1.28, 95% confidence interval 1.01 to 1.63). After adjustment for baseline risk factors, the LDL size association was no longer statistically significant (relative risk 1.13, 95% confidence interval 0.86 to 1.49). When principal components analysis was used to define a composite variable for LDL size, triglycerides, and HDL cholesterol, this component predicted CHD independent of smoking, alcohol consumption, physical activity, body mass index, hypertension, diabetes, and beta-blocker use (p <0.01). Therefore, this prospective analysis of data from older, Japanese-American men demonstrated that decreased LDL size is a univariate predictor of incident CHD, and that a composite risk factor of LDL size, triglyceride, and HDL cholesterol was a risk factor for CHD independent of other risk factors.     

Treatment of high-risk patients with ezetimibe plus simvastatin co-administration versus simvastatin alone to attain National Cholesterol Education Program Adult Treatment Panel III low-density lipoprotein cholesterol goals

This study assessed whether the co-administration of ezetimibe and simvastatin would be more effective than simvastatin monotherapy in allowing high-risk patients to achieve a low-density lipoprotein (LDL) cholesterol goal of <100 mg/dl. Men and women with LDL cholesterol ≥130 mg/dl and meeting National Cholesterol Education Program Adult Treatment Panel III criteria for coronary heart disease (CHD) or CHD risk equivalent were randomized to 1 of 4 daily treatments for 23 weeks: simvastatin 20 mg (n = 253), ezetimibe 10 mg plus simvastatin 10 mg (n = 251), ezetimibe 10 mg plus simvastatin 20 mg (n = 109), and ezetimibe 10 mg plus simvastatin 40 mg (n = 97). In all groups, patients not at goal had their simvastatin doses doubled at weeks 6, 12, and/or 18, up to a maximum of 80 mg. The primary efficacy objective was LDL cholesterol goal attainment (<100 mg/dl) after 5 weeks of treatment. Ezetimibe plus any dose of simvastatin produced greater reductions in LDL cholesterol and allowed more patients to achieve goal after 5 weeks (p <0.001) and at the end of the study (p <0.001) than simvastatin 20 mg alone. At 5 weeks, 75%, 83%, and 87% of patients receiving ezetimibe plus simvastatin 10, 20, and 40 mg had LDL cholesterol <100 mg/dl compared with 46% of patients receiving simvastatin 20 mg. In patients who started on ezetimibe plus simvastatin 10, 20 and 40 mg, 33%, 22%, and 12%, respectively, required simvastatin titration during the study compared with 68% of patients who started on simvastatin 20 mg. The corresponding median simvastatin doses used were 10, 20, 40, and 40 mg, respectively. Ezetimibe plus simvastatin was well tolerated, with an overall safety profile similar to that of simvastatin monotherapy. Thus, through the dual inhibition of cholesterol absorption and synthesis, ezetimibe plus simvastatin allowed more patients to reach LDL cholesterol <100 mg/dl at a lower simvastatin dose and with fewer dose titrations than simvastatin monotherapy.     

Therapeutic lifestyle changes and drug treatment for high blood cholesterol in China and application of the Adult Treatment Panel III guidelines

The prevalence of elevated blood cholesterol in China has increased during the past several decades. We estimated the percentage of the Chinese population for whom therapeutic lifestyle changes and drug therapy to lower blood cholesterol should be considered by applying the United States' National Cholesterol Education Panel's Adult Treatment Panel III guidelines to a nationally representative sample of the Chinese population from the International Collaborative Study of Cardiovascular Disease in Asia. Serum samples were collected for 14,919 Chinese adults, 35 to 74 years old, in 2000 and 2001, after an overnight fast of > or =8 hours and their low-density lipoprotein (LDL) cholesterol level was calculated using the Freidewald equation. Using the Adult Treatment Panel III guidelines, 85.9 million Chinese adults (18.2%) should initiate therapeutic lifestyle changes to lower their LDL cholesterol and 35.0 million (7.4%) should be considered for lifestyle changes and lipid-lowering drug therapy. Of those for whom drug therapy should be considered, 4.7 million (13.4%) reported having been told they had "high cholesterol" by a healthcare provider and 1.6 million (33.7% of those aware of their high cholesterol) were receiving lipid-lowering medication-leaving 33.4 million Chinese adults with untreated elevated LDL cholesterol (95.5% of those with elevated LDL cholesterol). A 10% population-wide reduction in LDL cholesterol would reduce the number of Chinese adults who should be considered for drug therapy by 45% to 19.3 million (4.1% of adults). In conclusion, most adults in China with an elevated LDL cholesterol remain untreated.     

Alcohol consumption, TaqIB polymorphism of cholesteryl ester transfer protein, high-density lipoprotein cholesterol, and risk of coronary heart disease in men and women.

AIMS: To investigate whether a common polymorphism in the cholesteryl ester transfer protein (CETP) gene modifies the relationship of alcohol intake with high-density lipoprotein cholesterol (HDL-C) and risk of coronary heart disease (CHD). METHODS AND RESULTS: Parallel nested case-control studies among women [Nurses' Health Study (NHS)] and men [Health Professionals Follow-up Study (HPFS)] where 246 women and 259 men who developed incident CHD were matched to controls (1:2) on age and smoking. The TaqIB variant and alcohol consumption were associated with higher HDL-C, with the most pronounced effects of alcohol among B2 carriers. In the NHS we did not find an inverse association between alcohol and CHD in B2 non-carriers (P trend: 0.5), but did among B2 carriers (P trend <0.01). Among non-carriers the odds ratio (OR) for CHD among women with an intake of 5-14 g/day was 1.4 (95% CI: 0.6-3.7) compared with non-drinkers, whereas among B2 carriers the OR was 0.4 (0.2-0.8). Results in men were less suggestive of an interaction; corresponding OR's were 1.9 (0.8-4.5) and 0.9 (0.5-1.6), for B2 non-carriers and carriers, respectively. CONCLUSIONS: The association of alcohol with HDL-C levels was modified by CETP TaqIB2 carrier status, and there was also a suggestion of a gene-environment interaction on the risk of CHD.     

Predictive value for coronary heart disease of baseline high-density and low-density lipoprotein cholesterol among Fredrickson type IIa subjects in the Helsinki Heart Study

In the Helsinki Heart Study 2,590 subjects (63.5% of total) had a type IIa hyperlipoproteinemia at screening. Baseline low-density lipoprotein (LDL) cholesterol (mean 193 mg/dl; 5 mmol/liter) and high-density lipoprotein (HDL) cholesterol (mean 50.2 mg/dl; 1.3 mmol/liter) showed no statistical correlation (r = 0.046). Both the placebo (1,293 patients) and gemfibrozil groups (1,297 patients) were divided into tertiles by baseline HDL and LDL cholesterol to determine the relative predictive risk of developing coronary artery disease. In a population with elevated LDL cholesterol, it is significant that the lipoprotein fraction with the greatest predictive value was HDL cholesterol. The severity of LDL cholesterol elevation did not provide any differential predictive value for coronary artery disease.     

新疆维、哈族冠心病患者降低低密度脂蛋白-胆固醇疗效的比较

目的：对比明确诊断为冠心病的维、哈族患者治疗前后的低密度脂蛋白胆固醇（LDL-C）水平,进一步指导临床治疗。方法：对首次入院行冠脉造影检查并明确诊断为冠心病的维族（191例）、哈族（184例）患者测定其LDL-C浓度,并给予冠心病二级预防治疗8-12个月,住院后再次测定LDL-C浓度,并行统计学比较分析。结果：治疗后维、哈两族冠心病患者 LDL-C水平均有显著降低,且维族冠心病患者较哈族LDL-C [（2.21±0.17）mmol/L比（2.74±0.13）mmol/L]水平降低得更显著（t＝3.141,P＜0.01）。结论：维族冠心病患者低密度脂蛋白水平降脂的疗效显著好于哈族。     

绝经后女性单核细胞/高密度脂蛋白胆固醇与冠状动脉SYNTAX评分的关系

目的探讨绝经后女性单核细胞/高密度脂蛋白胆固醇比值(MHR)与冠状动脉SYNTAX评分的相关性。方法入组接受冠状动脉造影术确诊为冠状动脉粥样硬化性心脏病(冠心病)的绝经后女性180例,根据MHR(以第33和第66百分位点为截点)分为三组:低MHR组:MHR0.28(n=59);中MHR组:0.28≤MHR≤0.43(n=61);高MHR组:MHR0.43(n=60)。比较三组SYNTAX评分差异,采用Spearman相关性分析和多重线性回归分析MHR与SYNTAX评分的关系。结果高MHR组的SYNTAX评分(25±13)高于低MHR组(18±13)和中MHR组(19±12)(P=0.003)。高MHR组的白细胞计数、中性粒细胞计数、血清C反应蛋白水平均高于低MHR组和中MHR组(P0.001)。Spearman相关分析表明MHR与SYNTAX评分相关(r=0.263,P0.001)。多因素线性回归分析结果提示SYNTAX评分受MHR的影响,冠状动脉病变严重程度与MHR密切相关(F=4.777,P=0.031)。结论绝经后女性冠心病患者MHR与冠状动脉SYNTAX评分呈正相关,可预测冠状动脉病变的严重程度。     

Distribution of lipid phenotypes in community-living men with coronary heart disease. High prevalence of isolated low levels of high-density lipoprotein cholesterol.

BACKGROUND--Risk factor modification, including treatment of dyslipidemias, has been recommended for the prevention of future coronary events in patients with coronary heart disease (CHD). Since the prevalence of various dyslipidemias among outpatients with CHD has not been well documented, the purpose of this study was to determine the frequency of specific lipid phenotypes among ambulatory men with CHD. METHODS--Lipid profiles were obtained in 255 men (mean age, 65.5 +/- 9.1 years) with CHD in three Veterans Affairs medical centers. Desirable levels of lipids were defined according to National Cholesterol Education Program guidelines as follows: low-density lipoprotein cholesterol (LDL-C) levels less than 3.36 mmol/L (130 mg/dL); high-density lipoprotein cholesterol (HDL-C) levels equal to or greater than 0.90 mmol/L (35 mg/dL); and triglyceride levels less than 2.83 mmol/L. RESULTS--Seventy-six percent of the group had one or more abnormalities on lipid profile: 51% had high LDL-C levels with or without abnormalities of HDL-C and/or triglyceride levels; 22% had low HDL-C levels with desirable levels of LDL-C; and 3% had hypertriglyceridemia without any cholesterol abnormalities. Normal lipid profiles were significantly more prevalent in subjects over the age of 65 years than in younger patients (40% vs 14%). CONCLUSIONS--These data suggest that (1) a high proportion of men with CHD have dyslipidemia, including 50% with LDL-C level elevations. For these men, the potential benefits of therapeutic intervention have been documented in clinical trials, although the cost-efficiency of wide-scale treatment has not been determined; (2) isolated hypertriglyceridemia is rare in this population; and (3) low HDL-C levels in association with desirable LDL-C levels are present in more than one fifth of male patients with CHD. Clinical trials focusing on this large group are urgently needed to determine whether efforts to raise HDL-C levels result in reduced cardiac morbidity and/or mortality.     

单核细胞/高密度脂蛋白胆固醇比值与绝经后女性冠心病患者急性心力衰竭的关系

目的 探讨入院时基线水平单核细胞/高密度脂蛋白胆固醇比值(MHR)与绝经后女性冠心病患者住院期间发生急性心力衰竭(AHF)的关系。方法 入组2014年12月—2016年7月在汕头市中心医院接受冠状动脉造影术确诊为冠心病的绝经后女性180例,根据住院期间是否出现AHF分为两组:AHF组(n＝55)和对照组(n＝125)。采用Logistic回归分析MHR与AHF的关系。结果 AHF组MHR水平[0.48(0.1,0.61)]比对照组[0.35(0.3,0.44)]升高(P＝0.005)。Spearman相关分析显示MHR与左心室射血分数(LVEF)呈负相关(r＝－0.304,P＝0.001)。校正年龄后,MHR与LVEF仍呈负相关(r＝－0.215,P＝0.005)。MHR预测绝经后女性冠心病患者住院期间发生AHF的最佳截点是0.367 7(特异度70.6%,灵敏度59.8%,曲线下面积0.646,标准误0.048,P＝0.003,95%CI 0.551~0.740)。多因素Logistic回归分析显示绝经后女性冠心病患者住院期间发生AHF的独立危险因素包括MHR(OR 2.0,5%CI 1.141~5.743,P＝0.023)、糖尿病(OR 2.245,95%CI 1.012~4.977,P＝0.047)、脑钠肽(OR 5.518,95%CI 2.140~14.226,P＜0.001)和血清肌酐(OR 1.014,95%CI 1.001~1.026,P＝0.032)。结论 MHR是绝经后女性冠心病患者住院期间发生AHF的独立预测因子。