Effects of hypertension and type 2 diabetes mellitus on the risk of total cardiovascular events in Japanese patients with hypercholesterolemia: implications from the Japan Lipid Intervention Trial (J-LIT).

Hyperlipidemia, hypertension, and diabetes mellitus (DM) are well-established risk factors for cardiovascular disease. We analyzed the cardiovascular events in hyperlipidemic patients with or without DM who were administered open-labeled simvastatin in groups stratified by blood pressure level using data from the Japan Lipid Intervention Trial (J-LIT). Hyperlipidemic patients with DM (n=6,288) had significantly more cardiovascular events than those without DM (n=33,933). The incidence rates of total cardiovascular events in the Non-DM and DM groups were 15.40 and 25.76 per 1,000 patients for the 6-year period, respectively. The relative risk of total cardiovascular events in the DM vs. the Non-DM group was 1.68, and the relative risk was significantly higher in the DM than in the Non-DM group. The relative risks of total cardiovascular events were significantly higher in DM and Non-DM patients whose systolic blood pressure (SBP) was greater than or equal to 130 mmHg compared to that of Non-DM patients whose SBP was less than 130 mmHg, and in DM and Non-DM patients whose diastolic blood pressure (DBP) was greater than or equal to 80 mmHg compared to that of Non-DM patients whose DBP was less than 80 mmHg. In all groups stratified by SBP and DBP, relative risks of total cardiovascular events were higher in DM patients than in Non-DM patients. For patients with hypercholesterolemia and DM, blood pressure should be strictly controlled in order to prevent both coronary events and stroke. These results are in good agreement with the JNC 7 and the ESH/ESC guidelines for DM patients, which recommended that the SBP and DBP be less than 130 and 80 mmHg, respectively.     

Large-scale cohort study on the relationship between serum lipid concentrations and risk of cerebrovascular disease under low-dose simvastatin in Japanese patients with hypercholesterolemia: sub-analysis of the Japan Lipid Intervention Trial (J-LIT).

BACKGROUND: The Japan Lipid Intervention Trial was a nationwide cohort study of 52,421 hypercholesterolemic patients treated with open-labeled simvastatin for 6 years under standard clinical practices. Cerebrovascular disease (CVD) is one of the leading causes of death in Japan, but the effect of hypercholesterolemia on CVD has not been well established in Japanese patients. This study aimed to determine the relationship between the risk of CVD and serum lipid concentrations during treatment in Japan. METHODS AND RESULTS: Patients were treated with 5-10 mg/day of simvastatin and all, including those who discontinued simvastatin for any reason, had their lipid concentrations and incidence of CVD monitored for 6 years. Data of 41,088 patients were analyzed in this study, excluding those who had a history of coronary heart disease or CVD. The risk of cerebral infarction was higher in patients whose mean total cholesterol concentrations during treatment were > or = 240 mg/dl, low-density lipoprotein cholesterol concentrations > or = 160 mg/dl, triglycerides > or = 150 mg/dl and high-density lipoprotein cholesterol concentrations <40 mg/dl. There was no obvious correlation between cerebral hemorrhage and serum lipid concentrations. CONCLUSION: Improvement of serum lipid concentrations is important for reducing the incidence of cerebral infarction.     

Risk of coronary events in Japanese patients with both hypercholesterolemia and type 2 diabetes mellitus on low-dose simvastatin therapy: implication from Japan Lipid Intervention Trial (J-LIT)

Hypercholesterolemic patients with type 2 diabetes mellitus are at increased risk of coronary heart disease (CHD); however, direct evidence is very limited in Japanese patients. The J-LIT is the first nationwide study conducted to assess the relationship between serum lipid levels and development of coronary events in Japanese hypercholesterolemic patients. We analyzed the coronary events in the J-LIT study subjects by having type 2 diabetes or not. Of the total 41,801 subjects without prior CHD who received open-label simvastatin, 5mg/day, 6554 (male 40.2%, age 57.8+/-7.8) subjects had type 2 diabetes, while 35,247 (male 30.0%, age 57.8+/-7.9) did not. In this analysis, relative coronary event risks based on a 0.26 mmol/l (10mg/dl) increase in low density lipoprotein-cholesterol (LDL-C), were similar between hypercholesterolemic subjects with and without type 2 diabetes (17.3% versus 19.4%). Although all subjects were treated with simvastatin, the subjects with type 2 diabetes have significantly more coronary events compared to the subjects without type 2 diabetes (1.80/1000 and 0.76/1000 patient-years, respectively). Given the results above, to reduce the risk of coronary events in Japanese patients with both hypercholesterolemia and type 2 diabetes, careful and strict cholesterol management is needed in addition to the control of blood glucose.     

Lifestyle and cardiovascular disease in Japan

The aim was to give on overview of the profile of cardiovascular disease, vascular pathology and the relationships between lifestyle and cardiovascular disease in Japanese. Compared with the United States and Europe, the higher mortality from stroke and lower mortality from coronary heart disease constitute a unique cardiovascular profile for Japan. A selective review of population-based pathology, trend and prospective cohort studies was performed to clarify the characteristics of cardiovascular disease and vascular pathology, trends in the incidence and mortality of cardiovascular disease, and the relationships between lifestyle and cardiovascular disease among Japanese adults. Since the 1970s, mortality from coronary heart disease as well as stroke has declined substantially in Japan, probably due to a major decline in blood pressure levels and for men a more recent decline in smoking, in spite of an increase in body mass index and total cholesterol levels. However, the decline in mortality was smaller and plateaued in middle-aged men aged 30-49 in the metropolitan cities of Tokyo and Osaka. The incidence of coronary heart disease has increased among middle-aged men residing in the suburbs of Osaka. As for the associations between lifestyle and cardiovascular disease, higher sodium, lower calcium and lower animal protein content in the diet and for men higher alcohol consumption may account for the higher prevalence of hypertension and higher risk of stroke for Japanese than for western populations. On the other hand, lower saturated fat (meat) and higher n3 polyunsaturated fat (fish) in the Japanese diet may contribute to the lower prevalence of hypercholesterolemia and lower risk of coronary heart disease among Japanese. Japan is unique among developed countries in that coronary heart disease mortality has been low and has continued to decline, while stroke mortality has declined substantially. However, a recent trend for coronary heart disease incidence to increase among urban men is a cause for concern as a potential source of future problems for public health and clinical practice in Japan.     

Primary cardiovascular events and serum lipid levels in elderly Japanese with hypercholesterolemia undergoing 6-year simvastatin treatment: a subanalysis of the Japan lipid intervention trial

OBJECTIVES: To determine the relationship between serum lipid levels and the incidence of coronary events in older Japanese hypercholesterolemic patients without prior coronary heart disease (CHD). DESIGN: Post hoc subanalysis of the results in the Japan Lipid Intervention Trial. SETTING: A large-scale cohort observational study conducted throughout Japan. PARTICIPANTS: Men aged 35 to 70 and postmenopausal women younger than 70 with serum total cholesterol (TC) level of 220 mg/dL or greater treated for 6 years with low-dose simvastatin (52,421 total patients). After exclusion of 5,127 patients because of prior CHD and 4,934 patients because of incomplete data, 42,360 patients were divided into an older (9,860 patients, aged 65-70, mean age 67.1) and younger (32,500 patients, younger than 65, mean age 54.9) group and analyzed. MEASUREMENTS: Fasting serum lipid levels were measured every 6 months. Major coronary events, including fatal or nonfatal myocardial infarction, and sudden cardiac death as the primary endpoint and other cardiovascular diseases, including onset of angina pectoris, cerebrovascular events, and any causes of death, as the secondary endpoints were monitored. RESULTS: Simvastatin treatment in older patients was as safe and effective as in younger patients. Incident rates of major coronary events were 1.30 per 1,000 patient-years in the older group and 0.80 per 1,000 patient-years in the younger group. The incidence of a major coronary event was correlated to serum TC and low-density lipoprotein cholesterol (LDL-C) levels in both groups. The absolute risk of major coronary events in the older group was higher than in the younger group at any level of LDL-C, whereas the relative risk increased by 1.7% with an elevation of each 1 mg/dL LDL-C level in both groups. In the older group, the risk of major coronary events also increased as triglyceride level increased, whereas the risk decreased as high-density lipoprotein cholesterol level increased above 60 md/dL. CONCLUSION: The LDL-C level-dependent increase of relative risk of CHD was similar in elderly and younger patients, whereas the absolute risk at any LDL-C level in elderly patients was higher than in younger patients.     

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.     

Development and progression of atherosclerotic disease in relation to insulin resistance and hyperinsulinemia.

It is unclear whether the role of insulin resistance in the development of atherosclerotic cardiovascular disease is similar in populations in which the incidence of atherosclerotic diseases significantly differs from that in Western countries. The aim of this study was to determine the relationship between insulin resistance and the development of cardiovascular disease in the Japanese population. We conducted 75 g-oral glucose tolerance tests (OGTTs) on 1,928 inhabitants of two towns in Hokkaido, Japan. Subjects using antihypertensive agents and known diabetic patients were excluded from the study. Data from the remaining 1,227 subjects (540 males and 687 females; mean age 56.0 +/- 10.8 years) were used for the analysis, and 1,051 subjects were seen in a follow-up care setting for a period of 8 years. The presence of insulin resistance was defined according to the guidelines reported our previous study: insulin levels of 64.0 mU/l or higher 2 h after the 75 g-OGTT. The insulin-resistant (IR) group had several risk factors such as hypertension, diabetes, treated or untreated hypercholesterolemia, hypertriglyceridemia, low high-density-lipoprotein (HDL) cholesterol levels, and obesity. During the follow-up period of 8 years, the incidence of coronary artery disease, which was adjusted for age, body mass index, sex, systolic blood pressure, fasting plasma glucose, total cholesterol, triglyceride, and HDL cholesterol was significantly (3.2 times) higher in the IR group than in the insulin non-resistant group. The results suggested that insulin resistance is an independent risk factor for coronary artery disease in Japanese subjects, as has also been demonstrated in the case of individuals in Europe and USA.     

Anti-inflammatory effects of simvastatin in subjects with hypercholesterolemia

AIMS: Beneficial effects of statins in preventing cardiovascular events may depend, at least in part, on their anti-inflammatory action. The aim of the study was to assess the influence of simvastatin and aspirin on serum levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in hypercholesterolemic subjects. METHODS AND RESULTS: In 33 asymptomatic men with total cholesterol (TC) >6.5 mmol l(-1) and in 25 men with coronary heart disease and borderline-high cholesterol levels (between 5.2 and 6.5 mmol l(-1)) chronically treated with low-dose aspirin (75 mg/d), serum levels of CRP, TNF-alpha, IL-6, and IL-8 were determined before and after a 3-month simvastatin therapy (20-40 mg daily). In the former group, these markers of inflammation were also measured before and after a 2-week treatment with aspirin (300 mg/d), implemented prior to and in combination with simvastatin. A distinct reduction of CRP and TNF-alpha was found in both groups; IL-6 levels were decreased only in subjects with marked hypercholesterolemia. Aspirin had no effect on the anti-inflammatory action of simvastatin. CONCLUSIONS: In men with hypercholesterolemia simvastatin treatment lowers serum levels of CRP and proinflammatory cytokines. Low-dose aspirin does not add to the anti-inflammatory action of simvastatin.     

Effects of simvastatin treatment on sICAM-1 and sE-selectin levels in hypercholesterolemic subjects

This study was performed to determine whether the levels of soluble intercellular adhesion molecule-1 (sICAM-l) and soluble endothelial molecule-1 (sE-selectin) were elevated in subjects with hypercholesterolemia who presented with no other risk factors or evidence of atherosclerosis. The effects of administration of an HMG-CoA reductase inhibitor on the serum levels of these molecules were also examined. Forty hypercholesterolemic subjects (HCh) (19 males and 21 females), without hypertension or cardiovascular disease, received placebo for 4 weeks. The patients were then randomized in two groups; 20 of them (simvastatin group) were treated with simvastatin (20 mg/day) and the other 20 (placebo group) continued placebo administration. After 12 and 24 weeks of either simvastatin or placebo treatment, sICAM-1 and sE-selectin levels were measured. The same parameters were measured in 20 control subjects (C) with normal cholesterol levels, matched for sex and age. HCh had sICAM-1 basal values higher than C (352.4+/-57.9 ng/ml versus 114.9+/-89.6 ng/ml; P<0.001); however, sE-selectin basal values were not different in the two groups. No correlation was observed between HCh sICAM-1 levels and cholesterol levels (total and low-density lipoprotein). Furthermore, cholesterol-lowering treatment with simvastatin did not significantly diminish sICAM-1 levels. Our findings would support the hypothesis that patients with isolated hypercholesterolemia and without clinical atherosclerosis may be silent carriers of arterial subendothelial inflammation, expressed as an increase of sICAM-1.     

Effect of statins on mortality and cardiovascular events in elderly high-risk persons

Review of: MRC/BHF Heart Protection Study of Cholesterol Lowering with Simvastatin in 20,536 High‐Risk Individuals: a Randomized Placebo‐Controlled Trial. Lancet 2002;360:7–22. PURPOSE: To determine the effect of simvastatin 40 mg daily versus placebo on all‐cause mortality and cardiovascular events in high‐risk persons with serum total cholesterol levels of 135 mg/dL or greater. BACKGROUND: Pooled data from three secondary prevention trials of patients with coronary artery disease (CAD) and two primary prevention studies showed that treatment of hypercholesterolemia with statins caused a 31% reduction in major coronary events (95% confidence interval (CI) = 26–36%) and a 21% reduction in all‐cause mortality (95% CI = 14–28%). 1 The secondary prevention trials included 4,444 persons (23% aged 65–70) treated with simvastatin in the Scandinavian Simvastatin Survival Study, 2 , 3 4,159 persons (31% aged 65–75) treated with pravastatin in the Cholesterol and Recurrent Events Trial, 4 - 6 and 9,014 persons (39% aged 65–75) treated with pravastatin in the long‐term Intervention with Pravastatin in Ischaemic Disease Trial. 7 The two primary prevention studies included 6,595 middle‐aged men up to 64 years of age treated with pravastatin in the West of Scotland Coronary Prevention Study 8 and 6,605 persons (22% aged 65–73) treated with lovastatin in the Air Force/Texas Coronary Atherosclerosis Prevention Study. 9 The absolute risk reduction in major coronary events per 1,000 persons treated in these five studies was 33 (13–52) for women versus 37 (29–44) for men and 44 (30–58) for persons aged 65 and older versus 32 (24–40) for younger persons. 1 METHODS: The Heart Protection Study included 20,536 persons (15,454 men and 5,082 women) aged 40 to 80 (5,806 aged 70–80) with serum total cholesterol of 135 mg/dL or greater and prior myocardial infarction (MI) (8,510 persons), other CAD (4,876 persons), or no CAD (7,150 persons). Of the 7,150 participants without CAD, 1,820 had cerebrovascular disease, 2,701 had peripheral arterial disease (PAD), and 3,982 had diabetes mellitus. Although treated hypertension was present in 8,457 persons, only 237 persons were included on the basis of hypertension alone. Patients were randomized to simvastatin 40 mg daily or double‐blind placebo. Mean follow‐up was 5 years. Average compliance was 85% for the simvastatin‐treated group, and 17% of the placebo group took a statin during the 5‐year study. RESULTS: During the 5‐year study, simvastatin reduced serum total cholesterol 46 mg/dL, serum low‐density lipoprotein (LDL) cholesterol 39 mg/dL, and serum triglycerides 12 mg/dL and increased serum high‐density lipoprotein (HDL) cholesterol 1 mg/dL Simvastatin caused a 13% reduction in all‐cause mortality (95% CI = 6–19%), a 17% reduction in any vascular death (95% CI = 9–25%), a 27% reduction in major coronary events (95% CI = 21–33%), a 25% reduction in any stroke (95% CI = 15–34%), a 24% reduction in coronary or noncoronary revascularization (95% CI = 17–30%), and a 24% reduction in any major vascular event (95% CI = 19–28%). Simvastatin significantly reduced the first major vascular event in patients with MI, other CAD, or no CAD; in patients with cerebrovascular disease, PAD, diabetes mellitus, treated hypertension, or no hypertension; in men and in women; in patients aged 40 to 64, 65 to 69, and 70 to 80; in patients with low or high serum total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides; in smokers and nonsmokers; and in patients treated with and without aspirin, beta blockers, and angiotensin‐converting enzyme inhibitors. In the 3,500 persons with an initial serum LDL cholesterol of less than 100 mg/dL, reduction of serum LDL cholesterol from 97 mg/dL to 65 mg/dL by simvastatin caused a similar reduction in risk, as did treating patients with higher serum LDL cholesterol levels. Five years of simvastatin therapy prevented MI, stroke, and revascularization in 70 to 100 per 1,000 treated patients. CONCLUSION: In patients with serum total cholesterol of 135 mg/dL or higher at high risk for vascular events, simvastatin 40 mg daily significantly reduced all‐cause mortality, vascular death, major coronary events, coronary or noncoronary revascularization, and any major vascular event regardless of initial levels of serum lipids, age, or gender.     

Hypercholesterolemia. The evidence supports use of statins

Using statins to treat older men and women with coronary artery disease (CAD) and hypercholesterolemia reduces the risk of all-cause mortality, cardiovascular mortality, coronary events, coronary revascularization, stroke, Intermittent claudication, and congestive heart failure. The target serum low-density lipoprotein (LDL) cholesterol level is < 100 mg in older patients with CAD, prior stroke, peripheral arterial disease, extracranial carotid arterial disease, abdominal aortic aneurysm, diabetes meilitus, and the metabolic syndrome. Statins are also effective in reducing cardiovascular events in older persons with hypercholesterolemia without cardiovascular disease. Consider using statins in older persons without cardiovascular disease but with a serum LDL cholesterol > or = 130 mg/dL, or a serum high-density lipoprotein cholesterol < 50 mg/dL. Data from the Heart Protection Study favor treating patients at high risk for vascular events with statins regardless of age or initial serum lipids.     

Explanation for the Japanese paradox: prevention of increase in coronary heart disease and reduction in stroke

Japan's age-adjusted rate for mortality from stroke increased after the Second World War until 1965 and then showed a significant decline until 1990; however, the age-adjusted rate for mortality from all heart disease and coronary heart disease (CHD) increased until 1970 and then declined slowly. A puzzling question is why the rate of mortality from CHD declined in spite of an increase in serum total cholesterol level following an increase in fat consumption. It was confirmed that CHD incidence was far lower in several Japanese populations compared to Western countries in the " Monitoring Trends and Determinants in Cardiovascular Disease " (MONICA) project; therefore, the lower CHD mortality in Japan stems from the lower CHD incidence. CHD risk factors based on epidemiologic cohort studies in Japan were no different from those of other industrialized countries: hypertension, hypercholesterolemia, smoking and diabetes mellitus (DM). So, how can we explain this phenomenon?There are three possible explanations. One is the decline in population blood pressure level and the prevalence of hypertension during the years 1965-1990; the second is the decline in smoking rate in men and women; the third is that the serum total cholesterol level for middle-aged and elderly populations remains 5-15 mg/dL lower than that of the US elderly counterpart, although men aged 40-49 in Japan and the US had similar serum total cholesterol levels. It was also noted that elderly people in Japan, as observed in the Seven Countries Study, had far lower serum total cholesterol levels in midlife, i.e., around 160 mg/dL in the 1960s. This was not the case for elderly in the US where a higher serum total cholesterol level was observed in midlife. In conclusion, the lower serum cholesterol level in the past of Japanese middle-aged and elderly people compared to Western counterparts helps to maintain the low CHD incidence and mortality supported by the declining trend in blood pressure level and smoking rate for both men and women.     

Complement C3 and C4 in plasma and incidence of myocardial infarction and stroke: a population-based cohort study.

BACKGROUND: Complement factor C3 and C4 have been associated with atherosclerosis and cardiovascular risk factors. This study explored whether plasma levels of C3 and C4 are risk factors for the incidence of cardiovascular disease (CVD). DESIGN: A population-based prospective study of 5850 initially healthy men, 28-61 years old at baseline. METHODS: Plasma levels of C3 and C4 were analysed at the baseline examination. The incidence of coronary events (i.e. fatal or non-fatal myocardial infarction), ischaemic stroke and cardiovascular events (i.e. myocardial infarction, ischaemic stroke or cardiovascular death) was studied over 18 years of follow-up. RESULTS: Adjusted for age, C3 in the fourth quartile (versus the first quartile) was associated with an increased incidence of coronary events [relative risk (RR) 1.54, 95% confidence interval (CI) 1.2-1.9], cardiovascular events (RR 1.56, 95% CI 1.3-1.9), and non-significantly with the incidence of ischaemic stroke (RR 1.31, 95% CI 0.89-1.8). However, after adjustments for smoking, body mass index (BMI), cholesterol, diabetes and systolic blood pressure, these relationships were completely attenuated and non-significant. The relationships were similar for C4 concentrations within the normal range. However, for men with C4 in the top 10% of the distribution (>0.34 g/l), a significantly increased incidence of coronary events was found, which persisted after adjustments for risk factors. CONCLUSION: C3 and C4 show substantial correlations with cardiovascular risk factors, including blood pressure, BMI, and lipids. This relationship accounts for the increased incidence of CVD in men with high C3 levels. However, very high C4 levels may be associated with the incidence of CVD, independently of traditional cardiovascular risk factors.     

中国11省市队列人群危险因素与不同类型心血管病发病危险的比较

目的描述在中国35—64岁人群中,不同类型心血管病（包括急性冠心病事件、急性缺血性脑卒中和出血性脑卒中事件）发病的特点。比较传统心血管病危险因素与冠心病和脑卒中（急性缺血性脑卒中和出血性脑卒中事件）发病危险的关系。方法以中国多省市前瞻性队列研究的数据为基础,该队列由1992年建立的11省市35～64岁27249人和1996年到1999年又加入的3129人所组成,共30378人。本研究基线危险因素水平和1992--2003年期间发生的心血管病（包括冠心病和脑卒中）事件的关系进行分析。结果（1）急性冠心病事件、急性缺血性脑卒中事件和急性出血性脑卒中事件的累积人年发病率分别为114／100000、209／100000和73／100000。（2）随访期间发生心血管病的亚组人群基线时有84％～89％的人伴有1个或1个以上的心血管病危险因素,高于无心血管病的亚组人群（64．7％,P〈0．01）。（3）危险因素对不同类型心血管病发病的影响及作用强度有所差别：对冠心病发病危险的影响因素根据强度依次为高血压、吸烟、高胆固醇血症和低高密度脂蛋白胆固醇血症;对缺血性脑卒中发病危险的影响因素依次为高血压、糖尿病、低高密度脂蛋白胆固醇血症、吸烟和肥胖;对出血性脑卒中发病危险的独立影响因素只有高血压。结论在心血管病的主要危险因素中,不同的危险因素对不同类型的心血管病发病危险的作用存在差别。我国人群不同危险因素的变化趋势将影响不同类型心血管。     

Predicting Coronary Heart Disease and Stroke: The FINRISK Calculator

The FINRISK risk calculator predicts 10-year risk for coronary heart disease, stroke incidence, and their combination. The model is based on 10-year cohort follow-up from 3 different cohorts in 1982, 1987, and 1992 from a random population sample in 3 areas in Finland. Coronary heart disease, stroke, and their combination are predicted by smoking, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, diabetes, and family history. The Internet-based calculator is commonly used in Finland in health services to assess the need for hypertension and hypercholesterolemia treatment and is used also in patients' counseling.     

Lovastatin and simvastatin prevention studies

There is substantial evidence that drug treatment of hypercholesterolemia in patients without known coronary artery disease (CAD) can reduce fatal and nonfatal CAD events. Two trials, the Lipid Research Clinics Coronary Primary Prevention Trial and the Helsinki Heart Study used cholestyramine and gemfibrozil, respectively, to alter lipoprotein levels; their demonstrated efficacy and safety have led to their widespread use in hyperlipidemic patients. Recently, a new class of hypolipidemic agents has been shown to be extremely effective in lowering total and low-density lipoprotein cholesterol levels. These drugs, including lovastatin and simvastatin, competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme of intracellular cholesterol synthesis. Results of safety and efficacy studies suggest that they may be valuable first-line treatment options for high-risk hypercholesterolemic patients. Two long-term clinical trials are planned with lovastatin and simvastatin. In the United States, lovastatin will be used in a double-blind, placebo-controlled, primary prevention trial involving 8,000 patients without clinical evidence of CAD, slight to moderate elevations of total cholesterol, and low- and high-density lipoprotein cholesterol to establish whether 5 years of treatment will decrease the rate of fatal CAD or nonfatal myocardial infarction. A Scandinavian study of 4,000 patients with ischemic heart disease and hypercholesterolemia will determine if simvastatin will improve total survival and reduce fatal or nonfatal myocardial infarction and sudden death for at least 3 years. These study designs will be discussed and compared with other studies, and the expected impact on CAD event rates presented.     

Cholesterol 2001. Rationale for lipid-lowering in older patients with or without CAD

Statin treatment of men and women age > or = 50 with coronary artery disease (CAD) and hypercholesterolemia reduces the risk of all-cause mortality, cardiovascular mortality, coronary events, coronary revascularization, stroke, and intermittent claudication. The target serum low-density lipoprotein (LDL) cholesterol level is < 100 mg/dL in older patients with CAD, prior stroke, peripheral arterial disease, or extracranial carotid arterial disease and serum LDL cholesterol > 125 mg/dL despite diet therapy. Statins are also effective in reducing cardiovascular events in older persons with hypercholesterolemia but without cardiovascular disease. Consider using statins in patients age 50 to 80 without cardiovascular disease, serum LDL cholesterol > 130 mg/dL, and serum high-density lipoprotein (HDL) cholesterol < 50 mg/dL.     

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.     

性别对高血压前期患者心脑血管疾病的影响

目的 探讨不同性别对高血压前期患者的脑、冠状动脉粥样硬化的影响。方法 收集心内科行冠脉造影检查（CAG）发现冠状动脉狭窄程度在30%~70%,仅接受药物治疗未行经皮冠脉介入（PCI）治疗的高血压前期患者243例,年龄在45~75岁,根据性别分为男性组140例和女性组103例,比较两组的临床特点、住院及访随期间用药情况,比较两组患者的高血压及心血管疾病（急性心肌梗死、缺血性脑卒中）发生情况。采用Cox多因素回归分析探讨年龄、性别、血脂等危险因素与高血压前期进展为高血压及心血管疾病发生的相关性。结果 两组患者基线资料比较,女性组的年龄显著高于男性组〔(61±7)岁 vs.(59±7)岁,P<0.01〕,女性的血脂（总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇）水平也显著高于男性患者（均P<0.01）,但是男性患者的血肌酐值、左室舒张期内径及具有吸烟、饮酒史的比例显著高于女性患者（均P<0.01）。经3.1~8.7(中位数4.5）年的随访后发现高血压前期患者中男性组有71人(50.7%)进展为高血压,而女性组有52人(50.5%)进展为高血压,两组差异无统计学意义。心血管疾病方面,两组共计有72名患者发生急性心肌梗死,其中男性组心肌梗死发生率显著高于女性组（37.1% vs. 19.4%,P<0.01）,而女性组缺血性卒中发生率显著高于男性组（11.6% vs. 4.3%,P<0.05）,高盐饮食的亚组中男性组35人发生急性心肌梗死,女性组仅13人,其男性的心肌梗死发生率高于女性组（50.7% vs. 25.5%,P<0.01）。为进一步探讨高血压及心血管疾病的危险因素,采用Cox多因素回归分析后发现,在高血压前期人群中,高盐饮食为高血压及心血管疾病独立的危险因素,高盐饮食为男性心血管疾病发生独立的危险因素（均P<0.05）。结论 在高血压前期人群中,高盐饮食会加重高血压及心血管疾病的发生及进展,尤其是男性患者,男性高血压前期人群发生急性心肌梗死危险更高,而女性组中缺血性卒中发生率更高。     

中国多省市心血管病趋势及决定因素的人群监测(中国MONICA方案)Ⅲ.危险因素水平与心血管病的联系

目的探讨我国人群心血管病事件发病率和死亡率与危险因素强度和结构之间的联系。方法对中国ＭＯＮＩＣＡ方案１０年心血管病监测有关资料进行单因素相关及多因素回归分析。结果（１）血清胆固醇水平是冠心病事件发病率的显著预测因素，但对冠心病死亡率无明显预测作用；（２）舒张压水平是脑卒中事件发病率和死亡率的显著预测因素；（３）采用多元回归建立的预测模型效果不尽理想；（４）人群危险因素水平趋势与疾病率趋势无显著一致性。结论中国ＭＯＮＩＣＡ方案生态学研究结果较客观地揭示了危险因素水平与心血管病事件率之间的联系，但在探讨前者对后者的预测作用方面有较大局限性。