Menstrual cycle irregularity and risk for future cardiovascular disease

Cross-sectional studies suggest that women who have irregular menstrual cycles and hyperandrogenism may be at increased risk for cardiovascular disease (CVD). However, prospective data are lacking on the relationship between menstrual cycle irregularity and subsequent CVD risk. The objective of this study was to assess prospectively the risk for coronary heart disease (CHD) and stroke associated with a history of irregular menstrual cycles. The study design was a prospective cohort study of 82,439 female nurses who provided information in 1982 on prior menstrual regularity (at ages 20-35 yr) and were followed through 1996 for cardiovascular events. Incident reports of nonfatal myocardial infarction, fatal CHD, and nonfatal and fatal stroke were made. Medical records were reviewed for confirmation. During 14 yr (1,155,915 person-yr) of follow-up, there were 1417 incident cases of CHD and 838 incident cases of stroke, including 471 cases of ischemic stroke. Compared with women reporting a history of very regular menstrual cycles, women reporting usually irregular or very irregular cycles had an increased risk for nonfatal or fatal CHD [age-adjusted relative risks (RR), 1.25 and 1.67, respectively; 95% confidence intervals (CI), 1.07-1.47 and 1.35-2.06, respectively]. Increased risks for CHD associated with prior cycle irregularity remained significant after adjustment for body mass index and several potential confounders. There was a nonsignificant increase in overall stroke risk (RR, 1.30; 95% CI = 0.97-1.74) and in ischemic stroke risk (RR, 1.40; 95% CI = 0.97-2.04) associated with very irregular cycles. Menstrual cycle irregularity may be a marker of metabolic abnormalities predisposing to increased risk for CVD.     

小剂量阿司匹林对心血管病一级预防效果及安全性的系统评价

目的 系统评价小剂量阿司匹林在高危人群中一级预防心血管病的有效性和安全性.方法 计算机检索MEDLINE、EMbase、Cochrane图书馆(2008年第3期)、中国生物医学文献数据库、中国学术期刊全文数据库,同时筛检了纳入文献的参考文献.收集小剂量阿司匹林(75～150 mg)一级预防心血管病的随机对照试验(RCT),2名评价员独立评价文献质量和提取资料,并采用RevMan4.2软件对资料进行荟萃分析.结果 共纳入6个研究(TPT,HOT,PPP,WHS,POPADAD,JPAD),72 466例患者.(1)小剂量阿司匹林总的心血管事件的发生率(RR=0.85,95% CI:0.80～0.92)、卒中发生率(RR=0.87,95% CI:0.77～0.98)、非致死性卒中发生率(RR=0.81,95%CI:0.70～0.95)、短暂脑缺血发作发生率(RR=0.76,95%CI:0.64～0.90)均低于安慰剂(均P＜0.05).(2)小剂量阿司匹林非致死性心肌梗死(RR=0.89,95%CI:0.77～1.02)、心血管性死亡(RR=0.98,95% CI:0.86～1.13)、全因死亡发生率(RR=0.95,95%CI:0.88～1.02)与安慰剂比较,差异无统计学意义(P＞0.05).(3)在老年人群中分析显示,小剂量阿司匹林冠心病的发生率低于安慰剂(RR=0.81,95%CI:0.70～0.94,P＜0.01).(4)在安全性方面,与安慰剂比较,小剂量阿司匹林有出血并发症的风险(RR=1.15,95%CI:1.12～1.18,P＜0.01),而在过敏反应方面差异无统计学意义(P＞0.05).结论 小剂最阿司匹林能降低总的心血管事件、短暂脑缺血发作、卒中、非致死性卒中的发生率;对降低非致死性心肌梗死、心血管性死亡、全因死亡方面效果不明显;在老年人群中小剂量阿司匹林能降低冠心病的发牛率;长期应用无明显过敏反应,但存在出血并发症的风险.     

A prospective study of maturity-onset diabetes mellitus and risk of coronary heart disease and stroke in women

We examined the relationship of maturity-onset clinical diabetes mellitus with the subsequent incidence of coronary heart disease, stroke, total cardiovascular mortality, and all-cause mortality in a cohort of 116,177 US women who were 30 to 55 years of age and free of known coronary heart disease, stroke, and cancer in 1976. During 8 years of follow-up (889 255 person-years), we identified 338 nonfatal myocardial infarctions, 111 coronary deaths, 259 strokes, 238 cardiovascular deaths, and 1349 deaths from all causes. Diabetes was associated with a markedly increased risk of nonfatal myocardial infarction and fatal coronary heart disease (age-adjusted relative risk [RR] = 6.7; 95% confidence interval [CI], 5.3 to 8.4), ischemic stroke (RR = 5.4; 95% CI, 3.3 to 9.0), total cardiovascular mortality (RR = 6.3; 95% CI, 4.6 to 8.6), and all-cause mortality (RR = 3.0; 95% CI, 2.5 to 3.7). A major independent effect of diabetes persisted in multivariate analyses after simultaneous control for other known coronary risk factors (for these end points, RR [95% CI] = 3.1 [2.3 to 4.2], 3.0 [1.6 to 5.7], 3.0 [1.9 to 4.8], and 1.9 [1.4 to 2.4], respectively). The absolute excess coronary risk due to diabetes was greater in the presence of other risk factors, including cigarette smoking, hypertension, and obesity. These prospective data indicate that maturity-onset clinical diabetes is a strong determinant of coronary heart disease, ischemic stroke, and cardiovascular mortality among middle-aged women. The adverse effect of diabetes is amplified in the presence of other cardiovascular risk factors, many of which are modifiable.     

An overview of the 4 randomized trials of aspirin therapy in the primary prevention of vascular disease

BACKGROUND: In the primary prevention of cardiovascular disease, in contrast to the recommendations of the American College of Chest Physicians and the American Heart Association, the US Food and Drug Administration recently stated that there was insufficient evidence to judge whether aspirin therapy decreases the risk of a first myocardial infarction. OBJECTIVE: To perform an overview of the 4 primary prevention trials of aspirin therapy to obtain the most reliable estimates of the effects of aspirin therapy on various vascular disease end points. METHODS AND RESULTS: These 4 trials included more than 51,000 subjects and 2284 important vascular events. Those assigned to aspirin therapy experienced significant reductions of 32% (95% confidence interval [CI], 21%-41%) for nonfatal myocardial infarction and 13% (95% CI, 5%-19%) for any important vascular event. There were possible small but nonsignificant increases in risks of vascular disease-related death (1%; 95% CI, -12% to 16%) and nonfatal stroke (8%; 95% CI, -12% to 33%). When strokes were subdivided by type, there was no significant effect of aspirin therapy on the risk of ischemic stroke, but, while based on small numbers, there was a 1.7-fold apparent increase (95% CI, 6%-269%) in the risk of hemorrhagic stroke, which did achieve statistical significance. CONCLUSIONS: For the primary prevention of vascular disease, aspirin therapy confers significant beneficial effects on first myocardial infarction and, as a result, on any important vascular event; these effects are clinically important. Whether there is any reduction in vascular disease-related death or stroke associated with treatment remains unclear because of inadequate numbers of events in the primary prevention trials completed to date. More data on hemorrhagic stroke are also needed. In addition, randomized trial data, especially in women but also in men, are needed to help to formulate a rational public health policy for individuals at usual risk. Meanwhile, these data provide evidence for a significant benefit of aspirin therapy in the primary prevention of myocardial infarction.     

Benefits of pravastatin on cardiovascular events and mortality in older patients with coronary heart disease are equal to or exceed those seen in younger patients: Results from the LIPID trial

BACKGROUND: The effect of cholesterol-lowering therapy on death from coronary heart disease in older patients with previous coronary heart disease and average cholesterol levels is uncertain. OBJECTIVE: To compare the relative and absolute effects of pravastatin on cardiovascular disease outcomes in patients with coronary heart disease who are 65 years of age or older with those in patients 31 to 64 years of age. DESIGN: Subgroup analysis of a randomized, placebo-controlled trial. SETTING: 87 centers in Australia and New Zealand. PATIENTS: 3514 patients 65 to 75 years of age, chosen from among 9014 patients with previous myocardial infarction or unstable angina and a baseline plasma cholesterol level of 4.0 to 7.0 mmol/L (155 to 271 mg/dL). INTERVENTION: Pravastatin, 40 mg/d, or placebo. MEASUREMENTS: Major cardiovascular disease events over 6 years. RESULTS: Older patients were at greater risk than younger patients (31 to 64 years of age) for death (20.6% vs. 9.8%), myocardial infarction (11.4% vs. 9.5%), unstable angina (26.7% vs. 23.2%), and stroke (6.7% vs. 3.1%) (all P < 0.001). Pravastatin reduced the risk for all cardiovascular disease events, and similar relative effects were observed in older and younger patients. In patients 65 to 75 years of age, pravastatin therapy reduced mortality by 21% (CI, 7% to 32%), death from coronary heart disease by 24% (CI, 7% to 38%), coronary heart disease death or nonfatal myocardial infarction by 22% (CI, 9% to 34%), myocardial infarction by 26% (CI, 9% to 40%), and stroke by 12% (CI, -15% to 32%). For every 1000 older patients treated over 6 years, pravastatin prevented 45 deaths, 33 myocardial infarctions, 32 unstable angina events, 34 coronary revascularization procedures, 13 strokes, or 133 major cardiovascular events, compared with 22 deaths and 107 major cardiovascular events per 1000 younger patients. Among older patients, the numbers needed to treat were 22 (CI, 17 to 36) to prevent one death from any cause, 35 (CI, 24 to 67) to prevent one death from coronary heart disease, and 21 (CI, 17 to 31) to prevent one coronary heart disease death or nonfatal myocardial infarction. CONCLUSIONS: In older patients with coronary heart disease and average or moderately elevated cholesterol levels, pravastatin therapy reduced the risk for all major cardiovascular events and all-cause mortality. Since older patients are at greater risk than younger patients for these events, the absolute benefit of treatment is significantly greater in older patients.     

Electrocardiographic strain pattern and prediction of cardiovascular morbidity and mortality in hypertensive patients

The ECG strain pattern of lateral ST depression and T-wave inversion is a marker for left ventricular hypertrophy (LVH) and adverse prognosis in population studies. However, whether ECG strain is an independent predictor of cardiovascular (CV) morbidity and mortality in the setting of aggressive antihypertensive therapy is unclear. ECGs were examined at study baseline in 8854 hypertensive patients with ECG LVH who were treated in a blinded manner with atenolol- or losartan-based regimens. Strain was defined by the presence of a downsloping convex ST segment with an inverted asymmetrical T wave opposite to the QRS axis in leads V5 and/or V6 and was present in 971 patients (11.0%). The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study composite end point of CV death or nonfatal myocardial infarction or stroke occurred in 1035 patients (11.7%). In Cox analyses adjusting only for treatment effect, ECG strain was a significant predictor of CV death (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.78 to 2.86), fatal/nonfatal myocardial infarction (HR 2.16, 95% CI 1.67 to 2.80), fatal/nonfatal stroke (HR 1.76, 95% CI 1.39 to 2.21), and the composite CV end point (HR 1.99, 95% CI 1.70 to 2.33). After further adjusting for standard CV risk factors, baseline blood pressure, and severity of ECG LVH, ECG strain remained a significant predictor of CV mortality (HR 1.53, 95% CI 1.18 to 2.00), myocardial infarction (HR 1.55, 95% CI 1.16 to 2.06), and the composite CV end point (HR 1.33, 95% CI 1.11 to 1.59). Thus, ECG strain is a marker of increased CV risk in hypertensive patients in the setting of aggressive blood pressure lowering, independent of baseline severity of ECG LVH.     

Angiotensin-converting enzyme inhibitors in coronary artery disease and preserved left ventricular systolic function: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: This study sought to assess the efficacy of angiotensin-converting enzyme inhibitors (ACEIs) in patients with coronary heart disease and preserved left ventricular (LV) function. BACKGROUND: The ACEIs have been shown to improve outcomes in patients with heart failure and myocardial infarction (MI). However, there is conflicting evidence concerning the benefits of ACEIs in patients with coronary artery disease (CAD) and preserved LV systolic function. METHODS: An extensive search was performed to identify randomized, placebo-controlled trials of ACEI use in patients with CAD and preserved LV systolic function. Of 61 potentially relevant articles screened, 6 trials met the inclusion criteria. They were reviewed to determine cardiovascular mortality, nonfatal MI, all-cause mortality, and revascularization rates. We performed random-effect model meta-analyses and quantified between-studies heterogeneity with I(2). RESULTS: There were 16,772 patients randomized to ACEI and 16,728 patients randomized to placebo. Use of ACEIs was associated with a decrease in cardiovascular mortality (relative risk [RR] 0.83, 95% confidence interval [CI] 0.72 to 0.96, p = 0.01), nonfatal MI (RR 0.84, 95% CI 0.75 to 0.94, p = 0.003), all-cause mortality (RR 0.87, 95% CI 0.81 to 0.94, p = 0.0003), and revascularization rates (RR 0.93, 95% CI 0.87 to 1.00, p = 0.04). There was no significant between-studies heterogeneity. Treatment of 100 patients for an average duration of 4.4 years prevents either of the adverse outcomes (one death, or one nonfatal myocardial infarction, or one cardiovascular death or one coronary revascularization procedure). CONCLUSIONS: The cumulative evidence provided by this meta-analysis shows a modest favorable effect of ACEIs on the outcome of patients with CAD and preserved LV systolic function.     

C-reactive protein and coronary events following percutaneous coronary angioplasty

PURPOSE: We investigated the associations between baseline C-reactive protein levels in patients undergoing percutaneous coronary angioplasty and death, nonfatal myocardial infarction, and repeat revascularization during 14 months of follow-up. METHODS: In a single-center, prospective, cohort study, plasma levels of C-reactive protein were measured in 1458 consecutive patients undergoing elective or urgent coronary angioplasty. Patients were followed at 12 to 14 months for the occurrence of death, nonfatal myocardial infarction, and repeat revascularization. RESULTS: The incidence of death or myocardial infarction was 6.1% (44/716) in patients with an increased C-reactive protein level (>3 mg/L) and 1.5% (11/742) in patients with a normal level (relative risk [RR] = 4.4; 95% confidence interval [CI]: 2.2 to 8.5; P <0.0001). In a multivariate logistic regression model, an increased C-reactive protein level was an independent predictor of death or nonfatal myocardial infarction (RR = 3.6; 95% CI: 1.8 to 7.2; P =0.0001). The incidence of repeat revascularization was similar in patients with or without an increased C-reactive protein level (23% [168/716] vs. 22% [163/742], P = 0.54). Statin therapy at the time of the procedure was associated with a lower mean (+/- SD) C-reactive protein level (5.8 +/- 9.7 mg/L vs. 7.2 +/- 12.1 mg/L, P =0.02), but was not associated with the risk of death, nonfatal myocardial infarction, and repeat revascularization during follow-up. CONCLUSION: An increased C-reactive protein level is an independent prognostic indicator for the occurrence of death or nonfatal myocardial infarction following coronary angioplasty, but is not associated with the need for repeat revascularization.     

Systemic lupus erythematosus and the risk of cardiovascular disease: Results from the nurses' health study

Objective

Systemic lupus erythematosus (SLE) has been associated with an increased risk of cardiovascular disease. However, prospective population‐based data addressing this association have been lacking.

Methods

We conducted a prospective cohort study among 119,332 women participating in the Nurses' Health Study who were free of cardiovascular disease and SLE at baseline in 1976. Incident SLE was confirmed by medical record review. Cardiovascular events included fatal and nonfatal myocardial infarction, stroke, coronary artery bypass grafting, and angioplasty. The relative risk (RR) of cardiovascular events among participants with SLE as compared with those without SLE was estimated using Cox proportional hazards models.

Results

Over 28 years of followup (2.9 million person‐years), 8,169 cardiovascular events occurred and 148 women developed incident SLE. The mean age at SLE diagnosis was 52.6 years, and 20 participants with SLE developed a subsequent cardiovascular event. After adjusting for potential confounding factors, including age, race, cardiovascular risk factors, and medication use, the RR of a cardiovascular event in women with SLE compared with those without SLE was 2.26 (95% confidence interval [95% CI] 1.45–3.52). When end points were analyzed separately, the RR for coronary heart disease was 2.25 (95% CI 1.37–3.69) and the RR for stroke was 2.29 (95% CI 0.85–6.15).

Conclusion

In this prospective population‐based study, we found a statistically significant >2‐fold increased risk of cardiovascular disease among participants with SLE. The risk was not as high as has been previously reported, which may have been due to the relatively high age at diagnosis of SLE in this cohort.     

Effect of aspirin on mortality in the primary prevention of cardiovascular disease

Objective

The lack of a mortality benefit of aspirin in prior meta-analyses of primary prevention trials of cardiovascular disease has contributed to uncertainty about the balance of benefits and risks of aspirin in primary prevention. We performed an updated meta-analysis of randomized controlled trials of aspirin to obtain best estimates of the effect of aspirin on mortality in primary prevention.

Methods

Eligible articles were identified by searches of electronic databases and reference lists. Outcomes of interest were all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, and bleeding. Data were pooled from individual trials using the DerSimonian-Laird random-effects model, and results are presented as relative risk (RR) and 95% confidence intervals (CIs).

Results

Nine randomized controlled trials enrolling 100,076 participants were included. Aspirin reduced all-cause mortality (RR 0.94; 95% CI, 0.88-1.00), myocardial infarction (RR 0.83; 95% CI, 0.69-1.00), ischemic stroke (RR 0.86; 95% CI, 0.75-0.98), and the composite of myocardial infarction, stroke, or cardiovascular death (RR 0.88; 95% CI, 0.83-0.94), but did not reduce cardiovascular mortality (RR 0.96; 95% CI, 0.84-1.09). Aspirin increased the risk of hemorrhagic stroke (RR 1.36; 95% CI, 1.01-1.82), major bleeding (RR 1.66; 95% CI, 1.41-1.95), and gastrointestinal bleeding (RR 1.37; 95% CI, 1.15-1.62). A lack of availability of patient-level data precluded exploration of benefits and risks of aspirin in key subgroups.

Conclusion

Aspirin prevents deaths, myocardial infarction, and ischemic stroke, and increases hemorrhagic stroke and major bleeding when used in the primary prevention of cardiovascular disease.     

Aspirin in the treatment and prevention of cardiovascular disease

Randomized trials of aspirin have been conducted in three main populations: patients with evolving acute myocardial infarction (MI), patients with a history of cardiovascular disease and apparently healthy subjects. Initiating aspirin therapy within 24 h after the onset of symptoms of an acute MI results in conclusive reductions in the risk of nonfatal reinfarction, nonfatal stroke and total cardiovascular death. In a wide range of patients with prior occlusive cardiovascular disease, aspirin reduces the risks of nonfatal MI, nonfatal stroke and vascular death. In primary prevention trials, aspirin has been shown to reduce the risk of a first MI in men; limited data make it difficult to draw conclusions regarding its effect on stroke and total cardiovascular death. Randomized data from studies in women and other populations are lacking. Until more data are available, the decision to use aspirin in primary prevention should be based on the clinical judgment of the physician and it should be used as an adjunct in the management of other cardiovascular disease risk factors.     

Long-Acting Calcium Antagonists in Patients with Coronary Artery Disease: A Meta-Analysis

Background

The use of calcium channel blockers (CCBs) in patients with coronary artery disease remains controversial, with reports of increased risk of myocardial infarction and all-cause mortality. Short-acting CCBs have an unfavorable hemodynamic profile. The role of long-acting CCBs in patients with coronary artery disease is unknown.

Methods

MEDLINE/CENTRAL/EMBASE database were searched from 1966 to August 2008 for randomized controlled trials of long-acting CCBs in patients with coronary artery disease with follow-up for at least 1 year. We extracted from the studies the baseline characteristics and 6 outcomes: all-cause mortality, cardiovascular mortality, nonfatal myocardial infarction, stroke, angina pectoris, and heart failure.

Results

Of the 100 randomized controlled trials of CCBs in patients with coronary artery disease, 15 studies evaluating 47,694 patients fulfilled our inclusion criteria. When compared with the comparison group (including placebo), CCBs were not associated with an increased risk of all-cause mortality (relative risk [RR] 0.99; 95% confidence interval [CI], 0.94-1.05), cardiovascular mortality (RR 1.03; 95% CI, 0.95-1.11), nonfatal myocardial infarction (RR 0.96; 95% CI, 0.87-1.06), or heart failure (RR 0.86; 95% CI, 0.71-1.05), and with a 21% reduction in the risk of stroke (95% CI, 0.70-0.89) and 18% reduction in the risk of angina pectoris (95% CI, 0.72-0.94). When compared with placebo, CCBs resulted in a 28% reduction in the risk of heart failure (95% CI, 0.73-0.92). The results were similar for both dihydropyridines and nondihydropyridine CCBs.

Conclusions

In patients with coronary artery disease, long-acting CCBs (either dihydropyridines or nondihydropyridines), were associated with a reduction in the risk of stroke, angina pectoris, and heart failure, with similar outcomes for other cardiovascular events as the comparison group.     

Ankle-arm index as a predictor of cardiovascular disease and mortality in the Cardiovascular Health Study. The Cardiovascular Health Study Group

Peripheral arterial disease (PAD) in the legs, measured noninvasively by the ankle-arm index (AAI) is associated with clinically manifest cardiovascular disease (CVD) and its risk factors. To determine risk of total mortality, coronary heart disease, or stroke mortality and incident versus recurrent CVD associated with a low AAI, we examined the relationship of the AAI to subsequent CVD events in 5888 older adults with and without CVD. The AAI was measured in 5888 participants >/=65 years old at the baseline examination of the Cardiovascular Health Study. All participants had a detailed assessment of prevalent CVD and were contacted every 6 months for total mortality and CVD events (including CVD mortality, fatal and nonfatal myocardial infarction, congestive heart failure, angina, stroke, and hospitalized PAD). The crude mortality rate at 6 years was highest (32.3%) in those participants with prevalent CVD and a low AAI (P<0.9), and it was lowest in those with neither of these findings (8.7%, P<0.01). Similar patterns emerged from analysis of recurrent CVD and incident CVD. The risk for incident congestive heart failure (relative risk [RR]=1.61) and for total mortality (RR=1.62) in those without CVD at baseline but with a low AAI remained significantly elevated after adjustment for cardiovascular risk factors. Hospitalized PAD events occurred months to years after the AAI was measured, with an adjusted RR of 5.55 (95% CI, 3.08 to 9.98) in those at risk for incident events. A statistically significant decline in survival was seen at each 0.1 decrement in the AAI. An AAI of <0.9 is an independent risk factor for incident CVD, recurrent CVD, and mortality in this group of older adults in the Cardiovascular Health Study.     

Metabolic syndrome as a cardiovascular risk factor in patients with type 2 diabetes

INTRODUCTION AND OBJECTIVES: To assess the cardiovascular risk associated with the presence of metabolic syndrome in patients with type 2 diabetes.Patients and method. Prospective cohort study of patients with type 2 diabetes. The baseline presence of components of metabolic syndrome as defined by the World Health Organization was determined. The main dependent variable was a combination of coronary events (onset angina, fatal or nonfatal myocardial infarction) and cerebrovascular events (transient ischemic attack, fatal or nonfatal stroke and lower limb amputation). Secondary end points were coronary events and stroke. We calculated the predictive power of the presence of metabolic syndrome and of different numbers of its component features. RESULTS: 318 patients were included. Mean duration of follow-up was 4.6 years (SD 1.5 years). The prevalence of metabolic syndrome was 77.0%. The rates of cardiovascular events, coronary events and stroke, expressed per 1000 patient-years, were 14.0, 5.6, and 8.4 respectively in patients without metabolic syndrome, and 33.3, 20.7, and 11.7 respectively in patients with metabolic syndrome (P=.058 cardiovascular events; P=.05 coronary events). In the multivariate analysis, the simultaneous presence of all four metabolic syndrome components significantly increased the global cardiovascular disease risk (RR=5.0; 95% CI, 1.6-15.9; P=.006) and the risk of coronary heart disease (RR=7.4; 95% CI, 1.3-41.1; P=.02), but not the risk of stroke. CONCLUSIONS: The simultaneous presence of all four metabolic syndrome components is associated with an increase in the risk of cardiovascular events in patients with type 2 diabetes.     

Hypertension as a risk factor for cardiovascular morbidity and mortality in an elderly German population; the prospective STEPHY II study. Starnberg Study on Epidemiology of Parkinsonism and Hypertension in the Elderly.

AIM: To prospectively study the relationship between blood pressure levels and subsequent cardiovascular morbidity and mortality in a population aged 65 years and older. METHODS: Participants of the 1992 baseline survey of the population-based Starnberg Study on Epidemiology of Parkinsonism and Hypertension in the Elderly (STEPHY, 394 men and 588 women above age 65) were followed up for 3 years. Total mortality was assessed by official death data. Cardiovascular morbidity, that is, the occurrence of non-fatal events (new cases of acute myocardial infarction, angina pectoris, stroke, and heart failure) could be assessed in 681 of the 863 survivors by a second interview and analysis of general practitioners' records. The mortality and morbidity risks were compared for hypertensives (baseline blood pressure > or = 160/95 mmHg or antihypertensive treatment) and non-hypertensives. RESULTS: During follow-up a total of 55 men and 64 women died resulting in a 2.7-year cumulative mortality in this population of 12%. Mortality was higher in men (14%) than in women (11%). Hypertensives had no increased risk of death compared to non-hypertensives (adjusted relative risk (RR)=0. 92; 95% CI: 0.48-1.76 for men and RR=1.36; 95% CI 0.67-2.78 for women). This was confirmed in age-stratified analyses. However, among survivors hypertension was associated with a significantly higher occurrence of non-fatal cardiovascular events. After controlling for potentially confounding baseline conditions, the relative risk for any event (RR=1.44; 95% CI: 1.04-2.0) and, in particular, of acute myocardial infarction (RR=5.5; 95% CI: 1.6-18. 7) was raised among hypertensives. Higher rates for angina pectoris (RR=1.4; 95% CI: 0.9-2.4) and heart failure (RR 1.7; 95% CI: 0.9-2. 9) were of borderline significance. Positive risk associations were confined to the age group 65 to 75 years and not detected at higher ages. CONCLUSION: This study demonstrates for a Central European population older than 65 years the impact of hypertension as a risk factor for cardiovascular and cerebrovascular morbidity. To address the issue that risk of death showed no significant relationship to blood pressure, a longer follow-up period might be necessary.     

Lipoprotein (a) and development of intermittent claudication and major cardiovascular events in men and women: the Edinburgh Artery Study.

Lipoprotein (a) may be an important risk factor for atherosclerosis. It is widely accepted that lipoprotein (a) levels are raised in patients with coronary heart disease, but there is some doubt about the causality of the relationship. In addition, little is known about the relationship between lipoprotein (a) and either stroke or peripheral arterial disease, nor about the role of lipoprotein (a) in women. Subjects aged 55-74 years (n=1592) were selected at random from 11 general practices in Edinburgh, Scotland and followed up for 5 years. The incidences of myocardial infarction, intermittent claudication and stroke were 13.4, 9.4 and 3.7%, respectively. Raised lipoprotein (a) levels at baseline were associated with an increased risk (95% confidence interval) of myocardial infarction RR 1.15 (1.00, 1.32), intermittent claudication RR 1.32 (1.10, 1.57) but not significantly for stroke RR 1.24 (0.93, 1.64). This increased risk persisted for intermittent claudication after adjustment for baseline cardiovascular disease and other risk factors RR 1.20 (1.00, 1.43), but for myocardial infarction became non-significant RR 1.06 (0.91, 1.23). The risk of disease associated with raised lipoprotein (a) was slightly higher in women than in men, especially for intermittent claudication (men RR 1.09 (0.87, 1.36) compared to women RR 1.37 (1.01, 1.87)). In conclusion, we found that lipoprotein (a) was an independent predictor of cardiovascular events in both sexes. The association between lipoprotein (a) and cardiovascular events may have been stronger in women than in men, and for peripheral arterial disease than myocardial infarction and stroke.     

Sexual activity with and without the use of sildenafil: risk of cardiovascular events in patients with heart disease.

The data in the literature on the relationship between sexual activity, with and without the use of sildenafil, and the occurrence of cardiovascular events (ventricular arrhythmias, nonfatal myocardial infarction, stroke and death) have been reviewed in patients with heart disease. To date, only patients with ischemic heart disease (IHD) have been investigated. The prevalence of premature ventricular beats during sexual intercourse is similar to that observed during other daily activities. Therefore, sexual activity does not seem to have a relevant arrhythmogenic effect. The incidence of sustained ventricular tachycardia during sexual intercourse in unknown. The relative risk of nonfatal myocardial infarction is 2.7 in males and 1.3 in females; however, the absolute risk appears extremely low and is similar in normal subjects and in patients with and without IHD. The risk appears to be restricted to the 2-hour time period after sexual intercourse. The incidence of stroke during sexual intercourse appears very low, but clear data are lacking. The incidence of death during sexual activity is unknown; the few available data suggest that it is very low. Extramarital sexual intercourse seems to increase the risk of death. The incidence of cardiovascular events after sildenafil administration has been investigated in placebo-controlled studies in patients with IHD. The incidence of nonfatal myocardial infarction, stroke and death did not significantly differ between sildenafil-treated and placebo-treated patients; therefore, sildenafil does not appear contraindicated in subjects with IHD. However, the drug should be administered with caution in patients with recent myocardial infarction or stroke, in those with active coronary ischemia and in patients with episodes of heart failure. The drug is absolutely contraindicated in patients using nitrates.     

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.     

Haemostatic factors and prediction of ischaemic heart disease and stroke in claudicants

Thrombotic risk factors may be important in determining cardiovascular outcome in patients with symptomatic peripheral arterial disease. A cohort study with a 6-year follow-up period was established to determine the relationships between haemostatic and rheological factors and incident ischaemic heart disease (IHD) and stroke events in patients with peripheral arterial disease. A consecutive series of 607 patients with intermittent claudication was examined between 1989 and 1990 at the Peripheral Vascular Clinic, Royal Infirmary of Edinburgh. Main outcome measures were combined fatal and non-fatal stroke, non-fatal myocardial infarction (MI), coronary death and total coronary events. A total of 210 patients died during follow-up. 203 patients did not experience a vascular event or deterioration of limb ischaemia. Median levels of fibrinogen, von Willebrand factor (VWF), tissue plasminogen activator (t-PA) antigen, fibrin D-dimer and whole blood viscosity were significantly higher in those who experienced an event compared with those who did not. After adjusting for age and sex, fibrin D-dimer was significantly associated with risk of non-fatal myocardial infarction (RR 1.50, 95% CI 1.09–2.06, P 0.01). Both fibrinogen and fibrin D-dimer were associated with risk of total coronary events (P 0.05). The risk of stroke was related to baseline levels of t-PA antigen (RR 1.87, 95% CI 1.04–3.34, P 0.05) and whole blood viscosity (RR 1.33, 95% CI 1.07–1.65, P 0.01). All the relationships became weaker and statistically non-significant after further adjustment for cigarette smoking, systolic blood pressure, glucose and baseline IHD. The associations of these factors to IHD and stroke may therefore be partly related to cardiovascular risk factors, but are likely to be important in the pathogenesis of future atherothrombotic events in subjects with peripheral arterial disease.     

Randomized trials of vitamin E in the treatment and prevention of cardiovascular disease

BACKGROUND: Observational epidemiological studies consistently show that individuals who choose to take high amounts of vitamin E through diet or supplements experience cardiovascular benefits, for which basic research provides plausible mechanisms. However, because the size of the postulated benefit is small to moderate, the confounding inherent in observational studies is as great as the effect size. Before the availability of randomized evidence, about 1 in 4 adults was taking vitamin E supplements in the United States. METHODS: We conducted a computerized search of the English-language literature from 1990 to the present and found 7 large-scale randomized trials of the effectiveness vitamin E in the treatment and prevention of cardiovascular disease. Data were available on myocardial infarction, stroke, or cardiovascular death. RESULTS: Six of the 7 trials showed no significant effect of vitamin E on cardiovascular disease. In an overview, vitamin E had neither a statistically significant nor a clinically important effect on any important cardiovascular event (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.94-1.03) or its components: nonfatal myocardial infarction (OR, 1.00; 95% CI, 0.92-1.09), nonfatal stroke (OR, 1.03; 95% CI, 0.93-1.14), or cardiovascular death (OR, 1.00; 95% CI, 0.94-1.05). CONCLUSIONS: The ORs and CIs provide strong support for a lack of statistically significant or clinically important effects of vitamin E on cardiovascular disease. The use of agents of proven lack of benefit, especially those easily available over the counter, may contribute to underuse of agents of proven benefit and failure to adopt healthy lifestyles.