10-year risk for atherosclerotic cardiovascular disease and coronary heart disease among Korean adults: Findings from the Korean National Health and Nutrition Examination Survey 2009–2010

Background

This study examined the distribution of the 10-year risk for development of atherosclerotic cardiovascular disease (ASCVD) and coronary heart disease (CHD), and the proportion of participants eligible for lipid management, in the Korean population.

Methods

The risk was estimated using the Pooled Cohort Equations for non-Hispanic Whites and the Adult Treatment Panel (ATP) III equations. Eligibility for lipid-lowering treatment was assessed using the American College of Cardiology/American Heart Association Blood Cholesterol Guideline and the ATP III recommendation. Complex sampling design and area under the receiver operator characteristic curve (AUC) were used.

Results

Among 7594 ASCVD-free Korean adults, aged 40–79 years, 31.3% (men, 44.1%; women, 19%) had a 10-year risk for an ASCVD event of ≥ 7.5%, and 27.1% (men, 39.4%; women, 15.2%) had a 10-year risk for a CHD event of ≥ 10%. These proportions differed according to age groups, ranging from 6.1 to 91.9% and 8.7 to 58.7% for patients in their 40s–70s, using the ASCVD and CHD risk estimations, respectively. Overall, 78.7% of individuals remain in the same risk stratum. Those eligible for lipid management included 32.8% of the participants using the ACC/AHA Guideline and 11.9% of those using the ATP III recommendation. In discriminating ASCVD, AUCs for the ASCVD risk assessment method and the CHD risk assessment method were 0.70 and 0.64, respectively (P < 0.001).

Conclusions

The distribution of 10-year ASCVD and CHD risk was different according to the risk assessment methods.     

低密度与高密度脂蛋白胆固醇比值对冠心病的诊断价值

目的 探讨低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)浓度的比值与冠心病(CHD)的相关性。方法 对68例胸痛患者行冠状动脉造影,并同时测定其血脂成分。结果CHD组总胆固醇(TC)、血清甘油三酯(TG)、LDL-C、TC/HDL-C、TG/HDL-C、LDL-C/HDL-C高于对照组,HDL-C(低于对照组。LDL-C/HDL-C与CHD的相关性最强(OR=3.79,OR95％Cl=1.88-6.14)。结论 CHD患者存在多种血脂异常,LDL-C/HDL-C是一项有较好使用价值的CHD预测指标。     

The Role of Non-HDL Cholesterol in Risk Stratification for Coronary Artery Disease

Despite aggressive lipid-lowering therapy, patients continue to be at significant risk of coronary heart disease (CHD). Assessment of non–high-density lipoprotein cholesterol (non–HDL-C) provides a measure of cholesterol contained in all atherogenic particles. In the third Adult Treatment Panel (ATP III) guidelines of the US National Cholesterol Education Program, non–HDL-C was introduced as a secondary target of therapy in persons with triglycerides ≥200 mg/dL. A recent meta-analysis of the relationship between non–HDL-C reduction and CHD risk showed non–HDL-C as an important target of therapy for CHD prevention. Most lipid-modifying drugs used as monotherapy have a 1:1 relationship between percent non–HDL-C lowering and percent CHD reduction. In the EPIC-Norfolk prospective population study, 21,448 participants without diabetes or CHD between 45 and 79 years of age were followed for 11.0 years. Participants with high non–HDL-C levels were at increased CHD risk independently of their LDL-C levels. Also, compared to apolipoprotein B, non–HDL-C appears to be a better choice given the fact that no additional tests or costs are needed and established cut points are already available. Future guidelines should emphasize the importance of non–HDL-C for guiding cardiovascular prevention strategies with an increased need to have non–HDL-C reported on routine lipid panels.     

Therapy to reduce risk of coronary heart disease

Recent primary and secondary intervention studies have shown that reduction of low-density lipoprotein cholesterol (LDL-C) with statins significantly reduced coronary heart disease (CHD) morbidity and mortality. However, many patients with dyslipidemia who have or are at risk for CHD do not reach target LDL-C goals. The recently updated National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III guidelines identify a group of patients at very high risk for CHD for more aggressive LDL-C reduction and reaffirm the importance of high-density lipoprotein cholesterol (HDL-C) by raising the categorical threshold to 40 mg/dl. Lipid-lowering therapy needs to be more aggressive in both primary and secondary prevention settings, and therapy should be considered to increase HDL-C as well as lower LDL-C in order to improve patient outcomes. Both combination therapy and the next generation of statins may provide improved efficacy across the dyslipidemia spectrum.     

Can change in high-density lipoprotein cholesterol levels reduce cardiovascular risk?

Background

The cardiovascular risk reduction observed in many trials of lipid-lowering agents is greater than expected on the basis of observed low-density lipoprotein cholesterol (LDL-C) level reductions. Our objective was to explore the degree to which high-density lipoprotein cholesterol (HDL-C) level changes explain cardiovascular risk reduction.

Methods

A systematic review identified trials of lipid-lowering agents reporting changes in HDL-C and LDL-C levels and the incidence of coronary heart disease (CHD). The observed relative risk reduction (RRR) in CHD morbidity and mortality rates was calculated. The expected RRR, given the treatment effect on total cholesterol level, was calculated for each trial with logistic regression coefficients from observational studies. The difference between observed and expected RRR was plotted against the change in HDL-C level, and a least-squares regression line was calculated.

Results

Fifty-one trials were identified. Nineteen statin trials addressed the association of HDL-C with CHD. Limited numbers of trials of other therapies precluded additional analyses. Among statin trials, therapy reduced total cholesterol levels as much as 32% and LDL-C levels as much as 45%. HDL-C level increases were <10%. Treatment effect on HDL-C levels was not a significant linear predictor of the difference in observed and expected CHD mortality rates, although we observed a trend in this direction (P = .08). Similarly, HDL-C effect was not a significant linear predictor of the difference between observed and expected RRRs for CHD morbidity (P = .20).

Conclusions

Although a linear trend toward greater risk reduction was observed with greater effects on HDL-C, differences were not statistically significant. The narrow range of HDL-C level increases in the statin trials likely reduced our ability to detect a beneficial HDL-C effect, if present.     

Large scale cohort study of the relationship between serum cholesterol concentration and coronary events with low-dose simvastatin therapy in Japanese patients with hypercholesterolemia.

Hyperlipidemia is a well-established risk factor for primary coronary heart disease (CHD). Although simvastatin is known to lower serum lipid concentrations, the protective effect of such lipid-lowering therapy against primary CHD has not been established in Japanese patients with hypercholesterolemia. The Japan Lipid Intervention Trial was a 6-year, nationwide cohort study of 47,294 patients treated with open-labeled simvastatin (5-10 mg/day) and monitored by physicians under standard clinical conditions. The aim of the study was to determine the relationship between the occurrence of CHD and the serum lipid concentrations during low-dose simvastatin treatment. Simvastatin reduced serum concentrations of total cholesterol (TC), low-density lipoprotein- cholesterol (LDL-C) and triglyceride (TG), by 18.4%, 26.8% and 16.1% on average, respectively, during the treatment period. The risk of coronary events was higher when the average TC concentration was > or =240 mg/dl and the average LDL-C concentration was > or =160 mg/dl. The incidence of coronary events increased in the patients with TG concentration > or =300 mg/dl compared with patients with TG concentration <150 mg/dl. The high-density lipoprotein cholesterol (HDL-C) inversely correlated with the risk of coronary events. The J-curve association was observed between average TC or LDL-C concentrations and total mortality. Malignancy was the most prevalent cause of death. The health of patients should be monitored closely when there is a remarkable decrease in TC and LDL-C concentrations with low-dose statin. A reasonable strategy to prevent coronary events in Japanese hypercholesterolemic patients without prior CHD under low-dose statin treatment might be regulating the serum lipid concentrations to at least <240 mg/dl for TC, <160 mg/dl for LDL-C, <300 mg/dl for TG, and >40 mg/dl for HDL-C.     

Large scale cohort study of the relationship between serum cholesterol concentration and coronary events with low-dose simvastatin therapy in Japanese patients with hypercholesterolemia and coronary heart disease: secondary prevention cohort study of the Japan Lipid Intervention Trial (J-LIT).

Hyperlipidemia is primarily implicated in the progression of coronary heart disease (CHD) and its treatment is essential for patients with a history of CHD. Statins such as simvastatin, the lipid-lowering agents, are well-known for their ability to normalize patient's serum lipid levels. The Japan Lipid Intervention Trial study of simvastatin is the first nationwide investigation of the relationship between serum lipid levels and the development of CHD in Japanese patients with hypercholesterolemia. Of 5,127 patients, exclusively with a history of documented CHD at enrollment, 4,673 were treated with open-labeled simvastatin at an initial dose of 5-10 mg/day and were monitored for 6 years. The risk of coronary events tended to be higher in patients with a serum total cholesterol (TC) > or =240 mg/dl compared with total cholesterol <240 mg/dl. The concentration of low-density lipoprotein cholesterol (LDL-C) positively correlated and that of high-density lipoprotein cholesterol (HDL-C) inversely correlated with the risk of CHD. Each 10 mg/dl decrease in LDL-C and each 10 mg/dl increase in HDL-C concentration reduced the risk of CHD by 8.0% (95% confidence interval 3.8-12.0) and 28.3% (95% CI 13.9-40.3), respectively. A reasonable therapeutic strategy to reduce CHD progression in patients with prior CHD under low-dose statin treatment might be regulating the serum LDL-C concentration to at least <120 mg/dl and HDL-C >40 mg/dl, respectively.     

Major CHD risk factors predominate among African-American women who are eligible for lipid-lowering drug therapy under the new ATP III guidelines.

BACKGROUND: Coronary heart disease remains the leading cause of morbidity and death among African-Americans. We studied the cardiovascular risk factor distributions among African-American men and women deemed eligible for lipid-lowering treatment under the new Adult Treatment Panel Guidelines (ATPIII). DESIGN AND METHODS: A sub-sample of African-American NHANES III subjects aged 20-79 years, with known cardiovascular risk factors and LDL-C levels was identified (n=4,213). We assessed their eligibility for drug therapy using the new ATP III criteria and compared CHD risk factor distributions across gender. Both conservative and drug-optional LDL-C target levels were applied. RESULTS: An estimated 5.7 million African-Americans aged 20-79 are eligible for drug therapy under ATP III, and the overall eligibility prevalence is 24.3%; 47.8% are males and 52.2% are females (P<0.001). Of these, 1.87 million are eligible based on drug-optional LDL-C targets and 54.5% of these are female. Of treatment-eligible individuals, 61% of males versus 72% of females exhibited LDL-C > or =160 mg/dl (P=0.0001). The prevalence and levels of important CHD risk factors such as diabetes, hypertension, mean total and LDL-C cholesterol levels, and body mass index were all greater for eligible females compared to males despite lower absolute Framingham risk estimates for females. CONCLUSIONS: Among African-Americans, more women than men are eligible for treatment under the new ATP III guidelines. Eligibility in women is based primarily on diabetes and lipid levels rather than absolute Framingham risk, which seems to be underestimated in African-American women. As compensation for this underestimate, drug-optional (lower) targets should be applied to this population.     

Exploring the causal pathway from omega-6 levels to coronary heart disease: A network Mendelian randomization study

Background and aimsEvidence on the effect of omega-6 fats on coronary heart disease (CHD) risk remains inconclusive. We applied a network MR framework to determine the causal effects between omega-6 levels and CHD and the potential cholesterol metabolic risk factors (Total cholesterol, TC; Low-density lipoprotein cholesterol, LDL-C; High-density lipoprotein cholesterol, HDL-C; Triglycerides, TG) which might act as mediators in the link between omega-6 levels and CHD by integrating summary-level genome wide association study (GWAS) data.Methods and resultsNetwork MR analysis-an approach using genetic variants as the instrumental variables for both the exposure and mediator to infer causality was performed to examine the causal effects between omega-6 levels and CHD and cholesterol metabolic risk factors. Summary statistics from the Kettunen et al. ’s consortium were used (n = 13506) for omega-6, CARDIoGRAMplusC4D consortium data were used (n = 184305) for CHD, and GLGC consortia data were used (n = 108363) for TC, LDL-C, HDL-C, and TG. The IVW method estimate indicated that the odds ratio (OR) (95% confidence interval [CI]) for CHD was 1.210 (1.118–1.310) per standard deviation increase in omega-6. Results were consistent in MR Egger method (OR, 1.418; 95% CI, 1.087–1.851; P = 0.050) and weighted median methods (OR, 1.239; 95% CI, 1.125–1.364; P = 0.000). Omega-6 was positively causal associated with TC, LDL-C, and TG but was not associated with HDL-C. Moreover, TC, LDL-C, and TG were positively associated with CHD.ConclusionsUsing a network MR framework, we provided evidence supporting a positive causal relationship between omega-6 and CHD, which might be partially mediated by TC, LDL-C, and TG.     

Risk factors for cardiovascular disease in women with subclinical hypothyroidism.

Overt hypothyroidism may result in accelerated atherosclerosis and coronary heart disease (CHD) presumably because of the associated hypertension, hypercholesterolemia, and hyperhomocysteinemia. As many as 10%-15% of older women have subclinical hypothyroidism (SH) and thyroid autoimmunity. Whether SH is associated with risk for CHD is controversial. We examined 57 women with SH and 34 healthy controls. SH was defined as an elevated thyrotropin (TSH) (>4.5 mU/L) and normal free thyroxine (FT(4)) level (8.7-22.6 nmol/L). None of the patients had been previously treated with thyroxine. In all participants we determined blood pressure, body mass index (BMI), and fasting TSH, FT(4), antibodies to thyroid peroxidase and thyroglobulin, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, folic acid, vitamin B(12), creatinine, and total plasma homocysteine levels. The SH and control groups did not differ in their total homocysteine values. Mean diastolic blood pressure was increased in SH patients versus controls (82 vs. 75 mm Hg; p < 0.01). Mean values of TC, HDL-C, LDL-C, triglycerides, TC/HDL-C, and LDL-C/HDL-C were not different in patients with SH compared with controls. Individual analysis revealed that the percentage of patients with SH having hypertension (20%), hypertriglyceridemia (26.9%), elevated TC/HDL-C (11.5%), and LDL-C/HDL-C (4%) ratios were higher than the percentages in controls. Hyperhomocysteinemia (> or = 10.98 micromol/L) was observed in 29.4% of SH and was not significantly different from the percentage in controls (21.4%). No significant correlation between TSH and biochemical parameters was detected. We conclude that subclinical hypothyroidism in middle-aged women is associated with hypertension, hypertriglyceridemia, and elevated TC/HDL-C ratio. This may increase the risk of accelerated atherosclerosis and premature coronary artery disease in some patients.     

Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines

The Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program issued an evidence-based set of guidelines on cholesterol management in 2001. Since the publication of ATP III, 5 major clinical trials of statin therapy with clinical end points have been published. These trials addressed issues that were not examined in previous clinical trials of cholesterol-lowering therapy. The present document reviews the results of these recent trials and assesses their implications for cholesterol management. Therapeutic lifestyle changes (TLC) remain an essential modality in clinical management. The trials confirm the benefit of cholesterol-lowering therapy in high-risk patients and support the ATP III treatment goal of low-density lipoprotein cholesterol (LDL-C) <100 mg/dL. They support the inclusion of patients with diabetes in the high-risk category and confirm the benefits of LDL-lowering therapy in these patients. They further confirm that older persons benefit from therapeutic lowering of LDL-C. The major recommendations for modifications to footnote the ATP III treatment algorithm are the following. In high-risk persons, the recommended LDL-C goal is <100 mg/dL, but when risk is very high, an LDL-C goal of <70 mg/dL is a therapeutic option, ie, a reasonable clinical strategy, on the basis of available clinical trial evidence. This therapeutic option extends also to patients at very high risk who have a baseline LDL-C <100 mg/dL. Moreover, when a high-risk patient has high triglycerides or low high-density lipoprotein cholesterol (HDL-C), consideration can be given to combining a fibrate or nicotinic acid with an LDL-lowering drug. For moderately high-risk persons (2+ risk factors and 10-year risk 10% to 20%), the recommended LDL-C goal is <130 mg/dL, but an LDL-C goal <100 mg/dL is a therapeutic option on the basis of recent trial evidence. The latter option extends also to moderately high-risk persons with a baseline LDL-C of 100 to 129 mg/dL. When LDL-lowering drug therapy is employed in high-risk or moderately high-risk persons, it is advised that intensity of therapy be sufficient to achieve at least a 30% to 40% reduction in LDL-C levels. Moreover, any person at high risk or moderately high risk who has lifestyle-related risk factors (eg, obesity, physical inactivity, elevated triglycerides, low HDL-C, or metabolic syndrome) is a candidate for TLC to modify these risk factors regardless of LDL-C level. Finally, for people in lower-risk categories, recent clinical trials do not modify the goals and cutpoints of therapy.     

Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines

The Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program issued an evidence-based set of guidelines on cholesterol management in 2001. Since the publication of ATP III, 5 major clinical trials of statin therapy with clinical end points have been published. These trials addressed issues that were not examined in previous clinical trials of cholesterol-lowering therapy. The present document reviews the results of these recent trials and assesses their implications for cholesterol management. Therapeutic lifestyle changes (TLC) remain an essential modality in clinical management. The trials confirm the benefit of cholesterol-lowering therapy in high-risk patients and support the ATP III treatment goal of low-density lipoprotein cholesterol (LDL-C) <100 mg/dL. They support the inclusion of patients with diabetes in the high-risk category and confirm the benefits of LDL-lowering therapy in these patients. They further confirm that older persons benefit from therapeutic lowering of LDL-C. The major recommendations for modifications to footnote the ATP III treatment algorithm are the following. In high-risk persons, the recommended LDL-C goal is <100 mg/dL, but when risk is very high, an LDL-C goal of <70 mg/dL is a therapeutic option, ie, a reasonable clinical strategy, on the basis of available clinical trial evidence. This therapeutic option extends also to patients at very high risk who have a baseline LDL-C < 100 mg/dL. Moreover, when a high-risk patient has high triglycerides or low high-density lipoprotein cholesterol (HDL-C), consideration can be given to combining a fibrate or nicotinic acid with an LDL-lowering drug. For moderately high-risk persons (2+ risk factors and 10-year risk 10% to 20%), the recommended LDL-C goal is <130 mg/dL, but an LDL-C goal <100 mg/dL is a therapeutic option on the basis of recent trial evidence. The latter option extends also to moderately high-risk persons with a baseline LDL-C of 100 to 129 mg/dL. When LDL-lowering drug therapy is employed in high-risk or moderately high-risk persons, it is advised that intensity of therapy be sufficient to achieve at least a 30% to 40% reduction in LDL-C levels. Moreover, any person at high risk or moderately high risk who has lifestyle-related risk factors (eg, obesity, physical inactivity, elevated triglycerides, low HDL-C, or metabolic syndrome) is a candidate for TLC to modify these risk factors regardless of LDL-C level. Finally, for people in lower-risk categories, recent clinical trials do not modify the goals and cutpoints of therapy.     

血脂康对冠心病纤维蛋白原、血粘度和胰岛素抵抗的影响

目的;观察国产血脂康在调脂治疗的同时对冠心病患者纤维蛋白原、血粘度和胰岛素抵抗的影响。方法:54例冠心病伴血清总胆固醇(TC)>5.2mmol/L或低密度脂蛋白胆固醇(LDL-C)>3.12mmol/L患者口服血脂康(0,6,2次/d),治疗8周,观察治疗前、后TC、LDL\IC、高密度脂蛋白胆固醇(HDL-C)、甘油三酯(TG)及纤维蛋白原、血粘度和胰岛素敏感性指数(ISI)变化,另选择20例正常健康者作为对照组。结果:血脂康治疗8周后,TC、LDL-C和TG水平分别下降24.6％、34.1％和17.5％,HDL-C水平升高13.4％(P均<0.05或<0.01);纤维蛋白原和不同切变率的血粘度均显著降低(P<0.05或<0.01)。血脂康治疗前胰岛素敏感指数显著低于正常对照组,而治疗后则明显升高(P<0.05)。结论;血脂康对于冠心病患者不仅能够有效调整血脂,而且还具有降低纤维蛋白原和血粘度及改善胰岛素抵抗的有益作用。     

Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines

The Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program issued an evidence-based set of guidelines on cholesterol management in 2001. Since the publication of ATP III, 5 major clinical trials of statin therapy with clinical end points have been published. These trials addressed issues that were not examined in previous clinical trials of cholesterol-lowering therapy. The present document reviews the results of these recent trials and assesses their implications for cholesterol management. Therapeutic lifestyle changes (TLC) remain an essential modality in clinical management. The trials confirm the benefit of cholesterol-lowering therapy in high-risk patients and support the ATP III treatment goal of low-density lipoprotein cholesterol (LDL-C) <100 mg/dL. They support the inclusion of patients with diabetes in the high-risk category and confirm the benefits of LDL-lowering therapy in these patients. They further confirm that older persons benefit from therapeutic lowering of LDL-C. The major recommendations for modifications to footnote the ATP III treatment algorithm are the following. In high-risk persons, the recommended LDL-C goal is <100 mg/dL, but when risk is very high, an LDL-C goal of <70 mg/dL is a therapeutic option, ie, a reasonable clinical strategy, on the basis of available clinical trial evidence. This therapeutic option extends also to patients at very high risk who have a baseline LDL-C <100 mg/dL. Moreover, when a high-risk patient has high triglycerides or low high-density lipoprotein cholesterol (HDL-C), consideration can be given to combining a fibrate or nicotinic acid with an LDL-lowering drug. For moderately high-risk persons (2+ risk factors and 10-year risk 10% to 20%), the recommended LDL-C goal is <130 mg/dL, but an LDL-C goal <100 mg/dL is a therapeutic option on the basis of recent trial evidence. The latter option extends also to moderately high-risk persons with a baseline LDL-C of 100 to 129 mg/dL. When LDL-lowering drug therapy is employed in high-risk or moderately high-risk persons, it is advised that intensity of therapy be sufficient to achieve at least a 30% to 40% reduction in LDL-C levels. Moreover, any person at high risk or moderately high risk who has lifestyle-related risk factors (eg, obesity, physical inactivity, elevated triglycerides, low HDL-C, or metabolic syndrome) is a candidate for TLC to modify these risk factors regardless of LDL-C level. Finally, for people in lower-risk categories, recent clinical trials do not modify the goals and cutpoints of therapy.     

久居亚高原地区的冠心病患者血脂异常分析

目的探讨久居亚高原地区的冠心病患者总胆固醇(TC)/高密度脂蛋白胆固醇(HDL-C)和(TC-HDL-C)/HDL-C值异常及其它传统危险因素对冠心病发病的影响.方法分析105例冠状动脉造影(CAG)确诊的冠心病患者(冠心病组)及65例CAG阴性者(非冠心病组)的TC/HDL-C和(TC-HDL-C)/HIDL-C值及血压、血糖、吸烟等与冠心病之间的关系.结果TC、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)浓度升高率在2组中无显著性差异,但TC/HDL-C、(TC-HDL-C)/I-IDLC值异常率在冠心病组显著高于非冠心病组,有非常显著性差异(P<0.001),其比值升高与冠心病的危险性是非冠心病组的7倍.结论TC/HDL-C、(TC-HDL-C)/HDL-C值升高可能对亚高原地区冠心病发病更为敏感;冠心病的一级预防重点在于提高体内HDL-C水平,降低TC水平外,更重要的是调整二者之间的比值.     

Beyond the Statins: New Therapeutic Perspectives in Cardiovascular Disease Prevention

Reduction of low-density lipoprotein cholesterol (LDL-C) with statin therapy is currently identified in treatment guidelines as the primary focus for patients with or at risk of coronary heart disease (CHD). Yet despite effective statin therapy there is still an unacceptably high residual coronary risk. A substantial proportion of patients with CHD have mixed dyslipidemia, including low levels of high-density lipoprotein cholesterol (HDL-C), an independent and predictive risk factor for CHD. Although effective in reducing LDL-C, statin therapy has only modest effects in raising HDL-C. Fibrate therapy is an alternative lipid-modifying strategy, and is effective in reducing CHD mortality and morbidity, with the magnitude of clinical benefit similar to statin therapy. Multi-drug therapy with complementary mechanisms of action has been proposed as a means of improving lipid-modifying efficacy. Nicotinic acid is the most potent agent for increasing HDL-C and also substantially reduces LDL-C and triglycerides. Addition of nicotinic acid to statin therapy would be a logical management approach, given the potential for complementary therapeutic benefit. The clinical benefits of this combination are supported by the results of the HDL Atherosclerosis Treatment Study, which showed reduction of 60–90% in the incidence of major coronary events when both agents were administered. In addition, combination treatment led to angiographic regression of stenosis, compared with placebo, rather than slowed progression as previously reported with statin monotherapy. Given that the prevalence of low HDL-C, particularly amongst individuals with CHD, is higher than previously anticipated, combining nicotinic acid and a statin represents an innovative approach to further reducing CHD risk.This review paper was funded by an unrestricted educational grant form Merck KgaA, Darmtadt, Germany.     

Low HDL-C: a secondary target of dyslipidemia therapy

Current guidelines for the prevention of coronary heart disease (CHD) focus on lowering low-density lipoprotein cholesterol (LDL-C) as the primary target of lipid-modifying therapy. However, there is increasing interest in high-density lipoprotein cholesterol (HDL-C) as a secondary target of therapy. A wealth of epidemiologic data demonstrate that low levels of HDL-C are associated with an increased risk of CHD events, and data from large-scale clinical trials with statins and fibrates indicate that observed clinical benefits are related, at least in part, to improvements in HDL-C levels. Raising HDL-C levels with therapeutic lifestyle changes and pharmacologic intervention might afford opportunities to further reduce the risk of CHD beyond LDL-C lowering. Statins are first-line pharmacotherapy for dyslipidemia and can also improve HDL-C levels, although the extent to which they modify HDL-C varies. Combining a fibrate or niacin with statin therapy raises HDL-C more than a statin alone but might be associated with reduced tolerability and increased adverse reactions. Several new therapeutic approaches to raising HDL-C are in development, including an HDL mimetic and inhibitors of cholesteryl ester transfer protein. Although lowering LDL-C remains the primary target of lipid-modifying therapy, dyslipidemia therapies that are efficacious for both LDL-C reduction and raising HDL-C might offer further improvements in CHD risk reduction.     

The control of dyslipidemia in outpatient clinics in Greece (OLYMPIC) Study

The objective of this study was to determine the proportion of Greek patients referred to outpatient clinics for dyslipidemia who achieved the low-density lipoprotein cholesterol (LDL-C) goal defined by the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) guidelines, using lifestyle changes, lipid-lowering drug treatment (LLDT), or both. Adult patients with dyslipidemia, who had been receiving a hypolipidemic diet and/or LLDT for at least 3 months were assessed in a multicenter study performed at 66 sites across Greece. Patients were followed up for an additional 3-month treatment period. Lipid levels were recorded at baseline and at the end of the study. The primary endpoint was the proportion of patients achieving their individual LDL-C target at the end of the study, according to their coronary heart disease (CHD) risk status or its equivalents, as defined by the NCEP-ATP III guidelines. Multivariate logistic models were used to identify determinants of undertreatment. The study included 2,660 adults (20-75 years) from 7 regions of Greece. Of the evaluable sample (n = 2,211; men 51%; mean age 62 +/-9 years) 81% were receiving LLDT (96% with statins and 3% with fibrates), 44% had a history of CHD, 61% arterial hypertension, 36% diabetes, and 26% a family history of premature CHD. Overall, 6% were at low CHD risk, 30% at medium CHD risk, and 63% at high CHD risk. At the end of the study, 26% of all patients and 30% of those receiving LLDT achieved the NCEP-specified LDL-C target levels. The percentage of patients at LDL-C goal according to CHD risk status was: low risk 67% (95% CI = 59-75), medium risk 29% (95% CI = 26-33), and high risk 20% (95% CI = 18-22). Statins proved to be more effective than fibrates (p <0.0001). Atorvastatin-treated subjects (n = 1,222, mean dose 19 mg/day) attained the LDL-C target (31% of the cases) at a higher rate than those receiving other LLDT (n = 574, 26% at target, p <0.01) or not receiving drug treatment (n = 415, 8%, p <0.001). This outcome was more evident in the high-CHD risk group (n = 1,402, 26% with atorvastatin vs 16% with other LLDT and 3% not receiving LLDT attained the LDL-C goal, ANOVA, p <0.001). The majority of dyslipidemic patients receiving LLDT, mainly those with high-CHD risk, are not achieving the NCEP LDL-C target. This is mainly explained by inadequate dose titration to ensure target goals are met. Promoting healthy lifestyle and appropriate LLDT (potent statins with sufficient dose titration) must be implemented to ensure that patients attain LDL-C treatment goals and thus benefit from the reduction in individual CHD risk.     

小剂量辛伐他汀在老年人中的调脂疗效

目的观察小剂量辛伐他汀在军队离退休老干部中的调脂疗效及减少心血管事件危险性的作用。方法选择北京军区驻京部分离退休老干部综合干预中TC控制未达标者,且从2002年6月～2006年12月服用辛伐他汀10～20 mg/d的冠心病及其高危患者245例作为辛伐他汀组。同期未进行综合干预、未服用他汀类药物的冠心病及高危患者221例作为对照组,并进行对比分析。结果与基线比较,研究结束时辛伐他汀组TC、LDL C、TG分别下降了21.24%、34.09%和18.44%(P<0.01),HDLC下降了3.10%(P>0.05);对照组TC、LDL-C分别下降了3.11%、4.34%(P<0.05),TG下降了10.50%(P>0.05),HDL-C下降了10.24%(P<0.01)。与对照组比较,辛伐他汀组TC、LDLC分别下降了18.13%、29.75%(P<0.01),TG下降了7.94%(P<0.05),HDL-C上升了7.14%(P<0.01);心血管事件危险性降低了43.21%(P<0.05),脑卒中危险性降低了35.58%(P>0.05)。结论小剂量辛伐他汀在老年血脂异常人群中的调脂效果显著,心血管事件危险性明显降低。     

Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin

Background

Despite the efficacy of statins in lowering low-density lipoprotein cholesterol (LDL-C) levels, many patients who are at high risk for heart disease with hypercholesterolemia require additional LDL-C level reduction. The cholesterol absorption inhibitor, ezetimibe, has been shown to provide significant incremental reductions in LDL-C levels when co-administered with statins. This study was performed to compare the efficacy and safety of ezetimibe (10 mg) plus response-based atorvastatin titration versus response-based atorvastatin titration alone in the attainment of LDL-C goals in subjects who are at high risk for coronary heart disease (CHD) and are not at their LDL-C goal on the starting dose of atorvastatin.

Methods

This was a 14-week, multicenter, randomized, double-blind, active-controlled study conducted in 113 clinical research centers in 21 countries. Participants were adults with heterozygous familial hypercholesterolemia (HeFH), CHD, or multiple (≥2) cardiovascular risk factors, and a LDL-C level ≥130 mg/dL after a 6- to10-week dietary stabilization and atorvastatin (10 mg/day) open-label run-in period. Eligible subjects continued to receive atorvastatin (10 mg) and were randomized to receive blinded treatment with ezetimibe (10 mg/day; n = 305) or an additional 10 mg/day of atorvastatin (n = 316). The atorvastatin dose in both groups was doubled after 4 weeks, 9 weeks, or both when the LDL-C level was not at its goal (≤100 mg/dL), so that patients receiving combined therapy could reach 40 mg/day and patients receiving atorvastatin alone could reach 80 mg/day. The primary end point was the proportion of subjects achieving their LDL-C level goal at week 14. A secondary end point was the change in LDL-C level and other lipid parameters at 4 weeks after ezetimibe co-administration with 10 mg/day of atorvastatin versus 20 mg/day of atorvastatin monotherapy.

Results

The proportion of subjects reaching their target LDL-C level goal of ≤100 mg/dL was significantly higher in the co-administration group than in the atorvastatin monotherapy group (22% vs 7%; P <.01). At 4 weeks, levels of LDL-C, triglycerides, and non-high-density lipoprotein cholesterol were reduced significantly more by combination therapy than by doubling the dose of atorvastatin (LDL-C −22.8% versus −8.6%; P <.01). The combination regimen had a safety and tolerability profile similar to that of atorvastatin alone.

Conclusions

The addition of ezetimibe to the starting dose of 10 mg/day of atorvastatin followed by response-based atorvastatin dose titration to a maximum of 40 mg/day provides a more effective means for reducing LDL-C levels in patients at high risk for CHD than continued doubling of atorvastatin as high as 80 mg/day alone.