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.     

Lifetime risk of coronary heart disease by cholesterol levels at selected ages

BACKGROUND: We sought to assess how cholesterol levels at different ages modify the remaining lifetime risk of coronary heart disease (CHD). METHODS: We included all Framingham Heart Study participants examined from 1971 through 1996 who did not have CHD and were not receiving lipid-lowering therapy. At index ages of 40, 50, 60, 70, and 80 years, participants were stratified by total cholesterol level and by cholesterol subfractions. Lifetime risk of CHD was calculated with death free of CHD as a competing event. RESULTS: Among 3269 men and 4019 women, 1120 developed CHD and 1365 died free of CHD during follow-up. At each index age, lifetime risk of CHD increased with higher cholesterol levels, and time to event decreased. At age 40 years, the lifetime risks of CHD through age 80 years for men with total cholesterol levels less than 200 mg/dL (<5.20 mmol/L), 200 to 239 mg/dL (5.20-6.19 mmol/L), and 240 mg/dL or greater (> or =6.20 mmol/L), respectively, were 31%, 43%, and 57%; for women, the lifetime risks were 15%, 26%, and 33%, respectively. Lifetime risks contrasted sharply with shorter-term risks: at age 40 years, the 10-year cumulative risks of CHD were 3%, 5%, and 12% for men, and 1%, 2%, and 5% for women, respectively. CONCLUSIONS: Lifetime risk of CHD increases sharply with higher total cholesterol levels for men and women at all ages. These data support an important role for cholesterol screening in younger patients, and they may help target high-risk patients for lifestyle modification or drug therapy.     

Usefulness of parental serum total cholesterol levels in identifying children with hypercholesterolemia.

It was hypothesized that healthy children with high cholesterol levels may have parents who exceed acceptable cholesterol levels established by the National Cholesterol Education Program. One hundred sixty families (320 parents, 263 children aged 3 to 10 years) were evaluated for total cholesterol and other risk factors. Before the study, almost half of the parents had not had serum total cholesterol measured. The odds ratio for a child having a total cholesterol greater than or equal to 5.17 mmol/liter (200 mg/dl) was 13.6:1 (confidence interval 5.7 to 32.5) for a child with at least 1 parent having cholesterol greater than or equal to 6.20 mmol/liter (240 mg/dl) versus a child whose parents had low total cholesterol. Testing only children who had at least 1 parent with a total cholesterol greater than or equal to 5.17 mmol/liter (200 mg/dl) had a sensitivity of 98% for detecting children's total cholesterol greater than or equal to 5.17 mmol/liter. It is concluded that parental total cholesterol is useful in identifying children with high total cholesterol levels. Pediatricians may identify a large number of parents with hypercholesterolemia not previously recognized.     

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.     

中国35～64岁人群胆固醇水平与10年心血管病发病危险的前瞻性研究

目的探讨我国35～64岁人群血清总胆固醇（TC）水平与心血管病（包括急性冠心病事件和急性脑卒中事件）发病危险的关系。方法采用前瞻性队列研究的方法,对1992年建立的11省市35—64岁队列人群共30384人的基线TC水平和1992-2002年发生的急性冠心病事件和急性脑卒中事件的关系进行分析。应用Cox比例风险模型对TC水平与心血管病发病危险进行多因素分析。结果（1）以TC〈3．64mmol／L（140mg／d1）组为对照,随着TC水平的增加,缺血性心血管病发病危险呈持续增加变化。（2）TC水平与不同类型的心血管病的关系有所差别：缺血性脑卒中事件发病危险从TC很低水平（〈3．64mmol／L）开始,随着TC水平的增加呈持续上升的变化;而出血性脑卒中事件与TC水平的关系缺乏一致性。多因素分析结果显示：与TC〈5．72mmol／L（220mg／d1）相比,TC≥5．72mmol／L时急性冠心病发病危险增加74％（RR=1．743,P〈0．01）,缺血性脑卒中发病危险增加12％（RR=1．119,P〉0．05）。（3）在缺血性心血管病事件中,5．9％可归因于高TC血症;其中11．7％的急性冠心病事件和2．9％的急性缺血性脑卒中事件可归因于高TC血症。（4）不同TC水平时,随着合并其他心血管病危险因素个数的增加,10年心血管病发病的绝对危险增加。结论从TC低水平〈3．64mmol／L（140mg／dl）开始,随着TC水平的增加缺血性心血管病的发病危险持续上升。应该加强多重危险因素的综合干预,以减少心血管病的综合危险。     

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.     

Effects of high-dose atorvastatin on cerebrovascular events in patients with stable coronary disease in the TNT (treating to new targets) study.

OBJECTIVE: We sought to assess the effects on cerebrovascular events of treating patients with stable coronary disease with low-density lipoprotein cholesterol (LDL-C) levels substantially below 100 mg/dl. BACKGROUND: Lowering LDL-C with statins has been shown to reduce the risk of stroke in patients with stable coronary disease. In observational studies, naturally low cholesterol levels have been associated with an increased risk of hemorrhagic stroke. The cerebrovascular benefits of treating patients with stable coronary disease to LDL-C levels substantially below 100 mg/dl have not been previously investigated. METHODS: We describe an analysis of cerebrovascular events in the Treating to New Targets study, a trial where 10,001 patients with documented coronary disease were randomized to treatment with atorvastatin at 10 mg/day or 80 mg/day and followed for a median of 4.9 years. RESULTS: Mean LDL-C levels were 101 mg/dl on 10 mg atorvastatin and 77 mg/dl on 80 mg. In addition to the reduction in major cardiovascular events (hazard ratio 0.78, 95% confidence interval [CI] 0.69 to 0.89; p = 0.0002), the primary end point of the trial, patients in the 80-mg arm experienced a reduction in cerebrovascular events (hazard ratio 0.77, 95% CI 0.64 to 0.93; p = 0.007) and stroke (hazard ratio 0.75, 95% CI 0.59 to 0.96; p = 0.02). Each 1-mg/dl reduction in LDL-C with treatment was associated with a 0.6% relative risk reduction in cerebrovascular events (p = 0.002) and a 0.5% relative risk reduction in stroke (p = 0.041). The incidence of hemorrhagic stroke was similar in the 80-mg and 10-mg groups, 16 and 18 respectively, and the hemorrhagic strokes were distributed evenly across quintiles of achieved LDL-C during treatment. CONCLUSIONS: Among patients with established coronary disease, treating to an LDL-cholesterol substantially below 100 mg/dl with 80 mg/day atorvastatin reduces both stroke and cerebrovascular events by an additional 20% to 25% compared with the 10 mg/day dose. An increase in hemorrhagic stroke was not seen at low LDL-C levels. (Treating to New Targets; http://www.clinicaltrials.gov; NCT00327691).     

Dyslipidemia in veterans. Multiple risk factors may break the bank

The National Cholesterol Education Program guidelines for treatment of high cholesterol levels especially target patients who have multiple risk factors for coronary heart disease. Veterans have an increased prevalence of smoking, are predominantly male, and may have higher rates of other risk factors than other groups; therefore, they may require more aggressive screening and treatment for dyslipidemias. To assess the prevalence of cardiac risk factors, current cholesterol screening practices, and the potential impact of the National Cholesterol Education Program guidelines on the Veterans Affairs health care system, we reviewed 185 randomly selected charts of outpatients who were actively receiving follow-up at the Denver (Colo) Veterans Affairs Medical Center. The patients had an average age of 58.3 years and 99.5% were male. Of these patients, 60% had a serum cholesterol level checked within the last 999 days. Nearly all patients (84%) had two or more risk factors noted. The mean cholesterol level was 5.85 mmol/L (226 mg/dL), with 72% of patients having levels above 5.20 mmol/L (200 mg/dL) and 36.1% having levels above 6.20 mmol/L (240 mg/dL). Of patients who had their cholesterol level checked, 69% (77/111) would require lipoprotein analysis by National Cholesterol Education Program guidelines (cholesterol, greater than or equal to 6.20 mmol/L [greater than or equal to 240 mg/dL] or 5.15 to 6.20 mmol/L [200 to 239 mg/dL] with two or more risk factors), yet only 16% (12/77) had lipoprotein analyses done. Extrapolating from these data, the Denver Veteran Affairs Medical Center, which cares for 28,000 patients, has more than 19,000 patients who would need lipoprotein analysis to meet current guidelines. Full evaluation and subsequent treatment of dyslipidemias in veterans would require tremendous financial and manpower commitments.     

HDL, HDL2, and HDL3 subfractions, and the risk of acute myocardial infarction. A prospective population study in eastern Finnish men

BACKGROUND. We investigated the association of cholesterol concentrations in serum high density lipoprotein (HDL) and its subfractions HDL2 and HDL3 with the risk of acute myocardial infarction in 1,799 randomly selected men 42, 48, 54, or 60 years old. METHODS AND RESULTS. Baseline examinations in the Kuopio Ischaemic Heart Disease Risk Factor Study were done during 1984-1987. In Cox multivariate survival models adjusted for age and examination year, serum HDL cholesterol of less than 1.09 mmol/l (42 mg/dl) was associated with a 3.3-fold risk of acute myocardial infarction (95% confidence intervals [CI], 1.7-6.4), serum HDL2, cholesterol of less than 0.65 mmol/l (25 mg/dl) was associated with a 4.0-fold risk of acute myocardial infarction (95% CI, 1.9-8.3), and serum HDL3 cholesterol of less than 0.40 mmol/l (15 mg/dl) was associated with a 2.0-fold (95% CI, 1.1-4.0) risk of acute myocardial infarction. Adjustments for obesity, ischemic heart disease, other cardiovascular disease, maximal oxygen uptake, systolic blood pressure, antihypertensive medication, serum low density lipoprotein cholesterol, and triglyceride concentrations reduced the excess risks associated with serum HDL, HDL2, and HDL3 cholesterol in the lowest quartiles by 52%, 48%, and 41%, respectively. Additional adjustments for alcohol consumption, cigarettes smoked daily, smoking years, and leisure time energy expenditure reduced these excess risks associated with low HDL, HDL2, and HDL3 cholesterol levels by another 26%, 24% and 21%, respectively. CONCLUSIONS. Our data confirm that both total HDL and HDL2 levels have inverse associations with the risk of acute myocardial infarction and may thus be protective factors in ischemic heart disease, whereas the role of HDL3 remains equivocal.     

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.     

Relationship between urinary cGMP excretion and serum total cholesterol levels in a general population

Hypercholesterolemia impairs endothelial function. However, the critical level of serum total cholesterol at which endothelial dysfunction occurs is unknown at present. We investigated cross-sectionally the correlation between urinary excretion of cyclic guanosine 3',5' monophosphate (cGMP), a second messenger of nitric oxide (NO) and serum total cholesterol concentrations in a general population sample of Japanese men and women. The samples comprised 1541 subjects (788 men and 753 women) aged 40-79 years, who participated in cardiovascular risk surveys between 1997 and 2002 and underwent a 24h urine collection. Urinary excretion of cGMP was measured using a (125)I-labeled cGMP radioimmunoassay and was adjusted for urinary creatinine excretion (nmol/mmol creatinine). The mean urinary cGMP excretion correlated linearly and inversely with serum total cholesterol level: mean cGMP excretion adjusted for age, sex and cardiovascular risk factors was 61.7, 53.6, 50.8, 49.2, 47.3 and 46.4 nmol/mmol for total cholesterol levels <4.14, 4.14-4.64, 4.65-5.16, 5.17-5.68, 5.69-6.20 and > or =6.21 mmol/L, respectively (p=0.007). This relation was more evident among individuals with end-organ damage, among subjects with higher C-reactive protein (CRP) levels and among postmenopausal women. Our data suggest a reduction of NO bioactivity with higher serum total cholesterol levels, even within clinically normal cholesterol levels.     

北京市首都钢铁公司男工冠心病危险因素前瞻性研究——血压、血清总胆固醇及吸烟与冠心病关系

本文用Cox回归分析首都钢铁公司5 298名男工随访8.38年冠心病发病及其危险因素的研究结果,得出冠心病发病和死亡率随血压和血清总胆固醇水平升高而增加;在胆固醇浓度>5.3mmol/L(200mg/dl)情况下,冠心病危险还随每日吸烟支数增加而增加。     

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.     

Life-style and serum lipids and lipoproteins

In reviewing the trends and influences of life-style in this country on health and disease in the latter half of 20th century, we focused our attention on 4 major habits of smoking, drinking, exercise and diets, and collected data on the Japanese to conduct a meta-analysis of their relationship with serum lipids and lipoproteins, which are the metabolic risk factors most closely related to atherosclerosis. 1) The percentage of smokers was 54.0% in adult males and 14.5% in adult females in 1999. In the data of 7,256 subjects (mean age 47 years) in 16 papers, smoking increased triglycerides by 13 mg/dl (0.15 mmol/L) or in 559 non-drinkers with a mean age of 49 years in 3 papers by 18 mg/dl (0.20 mmol/L), and decreased HDL-cholesterol by 3.5 mg/dl (0.09 mmol/L) with every 20 cigarettes smoked according to the regression equation. 2) As for drinking, the annual ethanol consumption per adult was 8.5L in 1996. The effects of alcohol on serum lipids were analyzed in 27,035 males (mean age 47 years) in 24 studies. Drinking elevated triglycerides by a mean of 10 mg/dl (0.11 mmol/L), and also HDL-cholesterol by 2.5 mg/dl (0.06 mmol/L) per 23 g of alcohol intake (corresponding to 1 go of sake or 1 large bottle of beer). 3) Concerning exercise habit, 25% of males and 21% of females (mean age 47 years) regularly performed exercise such as jogging, swimming, aerobics, and tennis. However, walking was regarded as an easy exercise to be practiced by subjects of all ages. The effects of walking on serum lipids were studied in a total of 46,074 subjects (mean age 47 years) in 8 populations. Triglycerides were significantly lower by 10 mg/dl (0.11 mol/L), and HDL-cholesterol higher by 3 mg/dl (0.08 mmol/L) in those who walked 6,000 or more steps/day than in those who walked less than 2,000 steps/day. The effects of harder exercise like jogging or swimming were analyzed in 2,242 subjects in 14 papers (mean age 44 years). Triglycerides decreased by 10 mg/dl (0.11 mmol/L), and HDL-cholesterol elevated by 5 mg/dl (0.13 mmol/L) with an increase in the exercise intensity by one level of about 300 kcal. In exercise therapy, triglycerides were decreased by a mean of 20 mg/dl (0.23 mmol/L), and HDL cholesterol increased by a mean of 10 mg/dl (0.26 mmol/L) by exercise at a mean heart rate of about 135 bpm, which is equivalent to 50% VO2max for 30 minutes x 3 times/week. 4) In nutritional trends, the mean energy intake in 52 postwar years averaged 2,116+/-84 kcal with no marked changes according to nutritional surveys. However, the percentage of fat in total energy intake was lowest at 7% in 1946, increased thereafter until it exceeded 20% in 1973, and surpassed 25% in 1988. The mean total cholesterol level of the Japanese increased by 28 mg/dl (0.72 mmol/L) in the past 30 years and reached 204 mg/dl (5.28 mmol/L) in a survey in 1990. 5) Concerning dietary habits, total cholesterol was lower by a mean of 13 mg/dl (0.34 mmol/L), triglycerides lower by 40 mg/dl (0.45 mmol/L), and HDL-cholesterol higher by 5 mg/dl (0.13 mmol/L) in the group who ate 7 or more Japanese-style meals in the 9 meals during 3 days than in the group who ate 3 or less Japanese-style meals in the 9 meals. When serum lipids were compared among individuals living in cities (8 groups; 3,613 subjects; mean age 51 years), agricultural villages (13 groups; 5,364 subjects; mean age 51 years), and fishing villages (9 groups; 1,071 subjects; mean age 52 years). Total cholesterol was lower by a mean of 10 mg/dl (0.26 mmol/L) in fishing villages than in cities, and triglycerides lower by a mean of 15 mg/dl (0.17 mmol/L) in fishing villages than in cities and agricultural villages. HDL-cholesterol was 5 mg/dl (0.13 mmol/L) higher in agricultural villages and 3 mg/dl (0.08 mmol/L) higher in fishing villages than in cities. 6) The effects of dietary therapy or guidance were evaluated in 585 subjects (mean age, 53 years) in 12 papers. Total cholesterol was reduced by 20 mg/dl (0.52 mmol/L), triglycerides by a mean of 40 mg/dl (0.45 mmol/L), and HDL-cholesterol was increased by 5 mg/dl (0.13 mmol/L) by restriction of fat intake or restriction of the intake of saturated fat and dietary cholesterol. The results of these meta-analyses are considered to indicate the extent to which abnormalities of serum lipids are caused by a distorted life-style and the extent to which they are improved by correction of the life-style and exercise or dietary therapy. Correction of the life-style as a non-drug therapy may clearly improve hyperlipidemias or hypo-HDL-cholesterolemia so that this approach should be aggressively employed as part of the prevention and treatment for hyperlipidemias.     

Results of the National Cholesterol Education (NCEP) Program Evaluation ProjecT Utilizing Novel E-Technology (NEPTUNE) II survey and implications for treatment under the recent NCEP Writing Group recommendations

The most recent national survey of compliance with the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) guidelines was completed before ATP III and showed significant underachievement of low-density lipoprotein (LDL) cholesterol goals. The NCEP Evaluation ProjecT Utilizing Novel E-Technology (NEPTUNE) II was a national survey conducted in 2003. Of the 4,885 patients, 67% achieved their LDL cholesterol treatment goal, including 89%, 76%, and 57%, respectively, in the 0 or 1 risk factor, > or = 2 risk factors or coronary heart disease (CHD), and CHD risk equivalent categories. The percentage with triglyceride concentrations > or = 200 mg/dl (2.25 mmol/L) in each risk category who achieved their LDL cholesterol and non-high-density lipoprotein cholesterol goals was 64%, 52%, and 27%, respectively. Patients with diabetes (55%) and other CHD risk equivalents (40%) were less likely to have achieved their LDL cholesterol targets than those with CHD (62%). Of the 1,447 patients with cardiovascular disease, 75% could be classified as very high risk according to the new July 2004 NCEP Writing Group recommendations, and 17.8% of those at very high risk had an LDL cholesterol level of <70 mg/dl (<1.81 mmol/L). In conclusion, these results suggest improved lipid management compared with previous surveys. The largest treatment gaps were found for features new to ATP III as of July 2004, including goal achievement for patients with CHD risk equivalents and for non-high-density lipoprotein cholesterol targets. Most of those (75%) with cardiovascular disease in NEPTUNE II would be considered very high risk and candidates for aggressive therapy to reach the new optional treatment goals.     

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。     

Prevalence of risk factors for coronary heart disease in a mountain community in northern Italy.

We performed a population survey in the Valle Sabbia mountain community, a highly industrialized area in the province of Brescia, in northern Italy, in order to estimate the prevalence of the main risk factors for coronary heart disease (CHD) among middle-aged men and women. A random sample of 1497 subjects (747 males) aged 40-59 were interviewed and underwent a physical examination. A blood sample was also taken to test total serum cholesterol. Personal histories of hypertension and CHD were given by 20.3 and 4.6% of men, and by 23 and 2.4% of women, respectively. A personal history of diabetes mellitus was reported by 5.2% of men and 4% of women. The mean values of systolic and diastolic blood pressure (SBP and DBP), total cholesterol, number of cigarettes smoked per day and BMI were, respectively: 135.1 and 84.1 mmHg, 219.2 mg/dl, 10.2 cig/day and 26.2 in men, and 136.8 and 83.9 mmHg, 214.3 mg/dl, 2.4 cig/day and 25.1 in women. Among men, 45.0% had SBP > or = 140 or DBP > or = 90, 32.3% had total cholesterol > or = 240 mg/dl, 29.3% were current smokers and 60.7% had a BMI higher than 25. Among women, 48.7% had SBP > or = 140 or DBP > or = 90, 26.0% had total cholesterol > or = 240 mg/dl, 16.8% were current smokers and 44.3% had a BMI higher than 25. When considering the prevalence of high SBP or DBP, high total cholesterol or cigarette smoking, 72.3% of men and 67.7% of women had at least one of the main risk factors for CHD, usually higher values of SBP or DBP, whereas 29.3% of men and 21.2% of women had two or more factors. Overall, prevalences of the most common CHD risk factors in this community were similar to those found in other surveys carried out in Italy in the last decade.     

A multinational study of the effects of low-dose pravastatin in patients with non-insulin-dependent diabetes mellitus and hypercholesterolemia

This multinational, 16-week, randomized, doubleblind, placebo-controlled study evaluated the efficacy and safety of low-dose pravastatin in 325 patients with non-insulindependent diabetes mellitus (NIDDM) and hypercholesterolemia [serum total cholesterol concentrations of 5.2-7.8 mmol/1 (200 to 300 mg/dl)]. Patients were randomized to receive pravastatin 10 mg or matching placebo with doubling of the dose after 8 weeks if predefined target levels for total cholesterol [(i.e., < 5.2 mmol/1 (200 mg/dl) or > 15% decrease from baseline] had not been achieved. At Week 16, pravastatin-treated patients showed a 21.4% decrease in serum low-density lipoprotein cholesterol (LDL-C) and a 13.5% reduction in serum total cholesterol (TC) concentrations (p < 0.001 compared with placebo). Levels of triglycerides (TG) were reduced 9.6% during pravastatin treatment (p < 0.05 compared with placebo) while high-density lipoprotein cholesterol (HDL-C) levels were increased 4.4% (p =NS). Adverse events and laboratory test abnormalities were similar among patients treated with pravastatin or placebo. Glycosylated hemoglobin (HbA₁C) levels remained unchanged. The results of this study demonstrate that low-dose pravastatin is effective and well tolerated for lowering elevated cholesterol concentrations during short-term treatment of patients with NIDDM and hypercholesterolemia.     

Effect of pravastatin on cardiovascular events in women after myocardial infarction: the Cholesterol and Recurrent Events (CARE) trial

Objectives. We sought to determine the effect of pravastatin on recurrent cardiovascular events in women with average cholesterol levels after myocardial infarction (MI).Background. Little information is available on the effectiveness of lipid lowering in secondary prevention of coronary heart disease (CHD) in women; in particular, those with CHD and average cholesterol levels.Methods. In the Cholesterol and Recurrent Events (CARE) trial, 576 postmenopausal women, between 3 and 20 months after MI, with a total cholesterol level <240 mg/dl and a low density lipoprotein cholesterol level 115 to 174 mg/dl, were randomized to receive pravastatin 40 mg/day or matching placebo for a median follow-up period of 5 years. The main outcome measures were combined coronary events (coronary death, nonfatal MI, percutaneous transluminal coronary angioplasty [PTCA] or coronary artery bypass graft surgery [CABG]), the primary trial end point (coronary death or nonfatal MI) and stroke.Results. Women treated with pravastatin had a risk reduction of 43% for the primary end point (p = 0.035), 46% for combined coronary events (p = 0.001), 48% for PTCA (p = 0.025), 40% for CABG (p = 0.14) and 56% for stroke (p = 0.07). The 3,583 men in the CARE trial also showed a reduction in risk, but the magnitude tended to be less. Pravastatin improved plasma lipids similarly in men and women. There were no differences in risk of coronary events in the placebo group between men and women. Minor differences between men and women were present in baseline characteristics and treatment for MI, in general, conferring a higher risk status and a lower incidence of CABG in the women.Conclusions. Pravastatin led to significant early reduction of a wide range of cardiovascular events in post-MI women with average cholesterol levels.