D-dimer and platelet aggregability are related to thrombotic events in patients with peripheral arterial occlusive disease.

AIMS: To evaluate the frequency of arterial thrombotic events in patients with peripheral arterial occlusive disease during 3-5 years of follow-up and to determine whether baseline levels of haemostatic factors were related to the risk of future thrombotic events. METHODS AND RESULTS: One hundred and twenty-three patients, mean age 56 years, with peripheral arterial occlusive disease and intermittent claudication were followed prospectively for an average of 4.2 years. Fibrinogen, prothrombin fragment 1+2, D-dimer, tissue plasminogen activator, plasminogen activator inhibitor type I antigen and activity, plasmin-alpha(2)-antiplasmin complex, beta thromboglobulin and ADP-induced platelet aggregation were measured at the recruitment. Thirty-eight new vascular events (15 fatal) were identified. Age- (and other clinical and laboratory variables) -adjusted relative risks (RR) of thrombotic events were significantly elevated (P<0.05) per higher value of D-dimer (RR: 14.1, 95% CI 1.7;115.8) and platelet aggregation was low (RR: 4.6, 95% CI 1.3;16.3). Diabetes mellitus, cerebrovascular disease, and continuing deterioration of intermittent claudication at the recruitment were also independently associated with risk of thrombotic events in the multiple regression model (RR: 5.2, 95% CI 1.5;17.5; RR: 8.6, 95% CI 2.7;27.4; RR: 2.6, 95% CI 1.2;5.7 respectively). CONCLUSION: Elevated level of D-dimer and low platelet aggregation are independent haemostatic predictors of thrombotic events in patients with peripheral arterial occlusive disease.     

Risk of mortality and cardiovascular disease associated with the ankle-brachial index: Systematic review

OBJECTIVE: To determine the strength and consistency with which a low ankle brachial pressure index (ABI), measured in the general population, is associated with an increased risk of subsequent death and/or cardiovascular events. DESIGN: Systematic review. DATA SOURCES: Medline, Embase, reference lists and grey literature were searched; studies known to experts were also retrieved. MAIN OUTCOME MEASURES: All cause mortality, fatal and non-fatal coronary heart disease and stroke. REVIEW METHODS: Longitudinal studies in which participants were representative of the general population (all ages, either sex) and which used any standard method for measurement and calculation of the ABI. Studies in which participants were selected according to presence of pre-existing disease or were post intervention (e.g. angioplasty or peripheral arterial grafting) were excluded. RESULTS: 11 studies comprising 44,590 subjects from six different countries were included. Despite clinical heterogeneity between studies, the findings were remarkably consistent in demonstrating an increased risk of clinical cardiovascular disease associated with a low ABI. A low ABI (<0.9) was associated with an increased risk of subsequent all cause mortality (pooled RR 1.60, 95% CI 1.32-1.95), cardiovascular mortality (pooled RR 1.96, 95% CI 1.46-2.64), coronary heart disease (pooled RR 1.45, 95% CI 1.08-1.93) and stroke (pooled RR 1.35, 95% CI 1.10-1.65) after adjustment for age, sex, conventional cardiovascular risk factors and prevalent cardiovascular disease. CONCLUSIONS: The ABI may help to identify asymptomatic individuals in the general population who are at increased risk of subsequent cardiovascular events. Evaluation is now required of the potential of incorporating ABI measurement into cardiovascular prevention programmes.     

Fibrin D-dimer and cardiovascular risk

Fibrin D-dimer, the most commonly used clinical assay for detection of coagulation activation and in vivo fibrin formation and lysis in circulating blood, has been associated with risks of cardiovascular diseases in studies published over the past 15 years. This review discusses, in turn, analytic and preanalytic considerations; associations with risk factors; and associations with coronary heart disease, atrial fibrillation, stroke and cerebrovascular disease, peripheral arterial disease, and venous thromboembolism. These associations suggest that activated coagulation and in vivo fibrin formation and lysis may play a role in arterial, intracardiac, and venous thromboembolism. The potential clinical utility of D-dimer in prediction of cardiovascular risk, in indicating patient groups for prophylactic anticoagulation and in monitoring of anticoagulation, requires further study. Harmonization of results from different assays would increase clinical utility.     

C-reactive protein, fibrin D-dimer, and incident ischemic heart disease in the Speedwell study: are inflammation and fibrin turnover linked in pathogenesis?

Plasma levels of C-reactive protein (CRP, a marker of the reactant plasma protein component of the inflammatory response) and of fibrin D-dimer (a marker of cross-linked fibrin turnover) have each been associated in recent studies with the risk of future ischemic heart disease (IHD). Previous experimental studies have shown that fibrin degradation products, including D-dimer, have effects on inflammatory processes and acute-phase protein responses. In the Speedwell Prospective Study, we therefore measured CRP and D-dimer levels in stored plasma samples from 1690 men aged 49 to 67 years who were followed-up for incident IHD for an average of 75+/-4 months (mean+/-SD) and studied their associations with each other, with baseline and incident IHD, and with IHD risk factors. CRP and D-dimer levels were each associated with age, plasma fibrinogen, smoking habit, and baseline evidence of IHD. CRP was associated with D-dimer (r=0.21, P<0.00001). On univariate analyses, both CRP and D-dimer were associated with incident IHD. The incidence of IHD increased with CRP independently of the level of D-dimer (P=0.0002) and also increased with D-dimer independently of the level of CRP (P=0.048). In multivariate analyses, inclusion of D-dimer and conventional risk factors reduced the strength of the association between CRP and incident IHD; likewise, inclusion of CRP and conventional risk factors reduced the strength of the association between D-dimer and incident IHD. We conclude that although these respective markers of inflammation and fibrin turnover show modest association with each other in middle-aged men, they may have additive associations with risk of incident IHD. Further larger studies are required to test this hypothesis.     

Can haemostatic factors predict atherothrombosis?

Thrombosis is “haemostasis in the wrong place”, and there is increasing evidence that haemostatic factors are associated with increased risk of atherothrombotic events. Increasing plasma levels of fibrinogen are associated with increased risks of coronary heart disease, stroke and peripheral arterial disease, and with vascular and nonvascular mortality. However, as with other markers of haemostasis (and of inflammation), their additional predictive value to conventional risk factors is small. Ongoing studies of activation markers of coagulation (e.g. fibrin D-dimer), endothelium (e.g. von Willebrand factor, tissue plasminogen activator antigen) and platelets (mean platelet volume) may provide additional predictive value for atherothrombotic events. However, at present there is no sufficient evidence base for their routine measurement in prediction.     

Factors determining prognosis of patients with stable ischemic heart disease (results of a five years prospective study)

Risk stratification seems to be very important in patients with stable coronary artery disease (CAD). However, the prognostic scales are now available only for the early risk assessment in patients with acute coronary syndromes and in patients undergoing percutaneous coronary interventions. Aim of the study was to assess the frequency of cardiovascular events (CVE) during 5 years of follow-up in patients with stable CAD and to construct a long-term risk prediction model for these patients. 503 patients (mean age 59.4 years) were included in the study. The follow-up period ranged between 3.0 and 7.5 years (mean 5.0 years). Main end points were fatal and non-fatal cardiovascular events: cardiovascular death, acute coronary syndromes, ischemic stroke, transient ischemic attack, peripheral arterial thrombosis, and need for revascularization in any affected vascular area. Total frequency of events was 31.0% (5.7/100 patient years). Independent predictors of events were: severity of angina, three vessel coronary disease, previous myocardial infarction, previous stroke/ transient ischemic attack, peripheral arterial disease, obesity, chronic kidney disease and history of erosive gastritis. The presence of more or equal 3 risk factors was significantly associated with increased frequency of CVE.     

Does claudication affect the development of coronary collaterals?

Atherothrombosis is a generalized disease process that affects large- and medium-diameter arteries throughout the arterial tree. In this study, we aimed to evaluate the correlation between collaterals in different vascular beds. Patients who had undergone digital subtraction angiography for symptomatic lower extremity peripheral arterial disease and coronary angiography after an acute anterior myocardial infarction (MI) were compared with a control group composed of those patients who were hospitalized for acute anterior MI and underwent coronary angiography but had no claudication and had an ankle-brachial index of greater than 0.9 in both legs. In claudicants, stenosis in the left anterior descending artery (LAD) (90.3 ± 17.5 vs 78.6 ± 13.8, P = 0.005) was greater compared with the patients without claudication. The collaterals to the LAD (88% vs 37.5%, P = 0.001) and the collateral grades (1.7 ± 0.7 vs 0.7 ± 0.9, P = 0.001) were higher in the patients with claudication compared with those without claudication. A previous history of angina (52.2% vs 16.3%, P = 0.001), claudication (39.1% vs 4.6%, P = 0.001), and peripheral collaterals (45.7% vs 6.9%, P = 0.001) were higher in the patients with coronary collaterals than in those without. The factors affecting the development of coronary collaterals were claudication [relative risk (RR): 8.8; 95% confidence interval (CI): 2.1–39.8], peripheral collaterals (RR: 1.1; 95% CI: 1.1–1.3), and LAD stenosis (RR: 1.2; 95% CI: 0.03–29.1). Our results suggest that the presence of collateralization or angiogenesis in one vascular bed highly predicts collateralization in another arterial bed.     

Inflammatory markers and long-term risk of ischemic heart disease in men A 13-year follow-up of the Quebec Cardiovascular Study

We tested the hypothesis that elevated plasma interleukin-6 (IL-6), C-reactive protein (CRP) and fibrinogen concentrations are independent risk factors and interact in increasing the long-term risk of ischemic heart disease (IHD) in men. A total of 1982 IHD-free men from the Quebec Cardiovascular Study were followed over a period of 13 years during which 210 first fatal IHD events and non-fatal myocardial infarctions were recorded. Increased CRP levels (4th versus 1st quartile) were not associated with an increased risk of IHD after adjustment for non-lipid risk factors (age, body mass index, systolic blood pressure, diabetes, smoking and medication use at baseline), lipid risk factors (LDL and HDL cholesterol and triglyceride levels) and for IL-6 and fibrinogen (RR=0.70, 95% CI=0.43-1.13). High plasma IL-6 levels (4th versus 1st quartile) were associated with a 70% greater risk of IHD independent of confounding risk factors and of the other 2 inflammatory markers (RR=1.71, 95% CI=1.07-2.75). The relationship between high fibrinogen levels (4th versus 1st quartile) and IHD risk was borderline significant in multivariate analyses (RR=1.53, 95% CI=0.97-2.43). An inflammation score based on plasma IL-6 and fibrinogen levels improved the IHD risk predictive value of a multivariate model of traditional risk factors (p=0.03). Including plasma CRP levels into the inflammatory score provided no additional predictive value. In conclusion, elevated plasma IL-6 concentrations are more strongly related to IHD risk than CRP and fibrinogen. An inflammation score based on high plasma IL-6 and fibrinogen levels used in combination with traditional risk factors may improve our ability to adequately identify high risk individuals.     

The role of haematological factors in diabetic peripheral arterial disease: the Edinburgh Artery Study

The relationship between haematological factors and peripheral arterial disease (PAD) among diabetics has not been widely examined. 1592 men and women aged 55-74 years were selected from the general population. They underwent an assessment for PAD and a glucose tolerance test. 288 subjects (18.7%) were identified as having diabetes or impaired glucose tolerance (IGT). Among the diabetes/IGT group, median levels of fibrinogen, von Willebrand factor (VWF), tissue plasminogen activator (t-PA), fibrin D-dimer and plasma viscosity were higher in subjects with PAD than those without PAD (P 相似文献   

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.     

Diuretic versus alpha-blocker as first-step antihypertensive therapy: final results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, double-blind, active, controlled clinical trial conducted to determine whether newer antihypertensive agents, including doxazosin, an alpha-blocker, differ from chlorthalidone, a diuretic, with respect to coronary heart disease (CHD) and other cardiovascular disease (CVD) events in hypertensive patients at high risk of CHD. In February 2000, the doxazosin treatment arm was discontinued, and findings through December 1999 were reported. This report includes an additional 9232 participant-years and 939 CVD events. At 623 clinical centers, patients (aged >or=55 years) with hypertension and at least 1 other CHD risk factor were randomly assigned to either chlorthalidone or doxazosin. The primary outcome measure was the combined occurrence of fatal CHD or nonfatal myocardial infarction (MI), analyzed by intent to treat; prespecified secondary outcome measures included all-cause mortality, stroke, combined CHD (fatal CHD, nonfatal MI, hospitalized angina, and coronary revascularization), and combined CVD (combined CHD, stroke, angina treated outside the hospital, heart failure, and peripheral arterial disease). Mean follow-up was 3.2 years. There was no difference in primary outcome between the arms (relative risk [RR], 1.02; 95% confidence interval [CI], 0.92 to 1.15). All-cause mortality also did not differ (RR, 1.03; 95% CI, 0.94 to 1.13). However, the doxazosin arm compared with the chlorthalidone arm had a higher risk of stroke (RR, 1.26; 95% CI, 1.10 to 1.46) and combined CVD (RR 1.20; 95% CI, 1.13 to 1.27). These findings confirm the superiority of diuretic-based over alpha-blocker-based antihypertensive treatment for the prevention of CVD.     

The predictive value of cardiorespiratory fitness for cardiovascular events in men with various risk profiles: a prospective population-based cohort study.

AIMS: Few data exist to show if the prognostic value of peak exercise oxygen consumption (VO2peak) for fatal and non-fatal coronary events is different among men with low and high pre-test probability for cardiovascular disease (CVD). Our objective was to determine whether VO2peak could predict fatal and non-fatal cardiac events in 2361 men aged 42-60 years with and without conventional risk predictors of CVD or with documented CVD during a 13-year follow-up. METHODS AND RESULTS: Maximal oxygen consumption (ml/kg/min) was measured directly by using respiratory gas exchange in a cycle ergometer exercise test. Of 204 CVD deaths, 153 were due to coronary disease and 51 were due to other CVDs. A total of 323 non-fatal coronary events occurred during the follow-up. One metabolic equivalent (MET) increment in VO2peak was related to a decreased risk of coronary death in both healthy (RR=0.82, 95% CI 0.66-0.99) and unhealthy (RR=0.72, 95% CI 0.63-0.82) men. VO2peak was predictive of non-fatal and fatal cardiac events among men with or without known risk factors. In subjects with or without common risk factors, one MET increment amounted to an average decrease of 17-29% in non-fatal and 28-51% in fatal cardiac events, after adjustment for age. VO2peak and smoking represented two strongest independent and consistent risk predictors. CONCLUSIONS: VO2peak can be used as a very powerful predictor of future fatal cardiac events beyond that predicted by many conventional risk factors. On the prognostic consideration, unfit men with unfavourable risk profiles or underlying chronic disease are the risk groups that will benefit most from preventive measures.     

Carotid intima-media thickness and the risk of new vascular events in patients with manifest atherosclerotic disease: the SMART study.

AIMS: Carotid intima-media thickness (CIMT) is an independent predictor of vascular events in the general population. Currently, little is known about the relationship between CIMT and new vascular events in patients with manifest arterial disease. We aimed to assess the strength of this relationship. METHODS AND RESULTS: The study was performed in the first consecutive 2374 patients with manifest arterial disease enrolled in the cohort study SMART (Second Manifestations of ARTerial disease), a cohort study among patients with manifest arterial disease or cardiovascular risk factors. Common CIMT was measured at baseline in both carotid arteries. Vascular events were vascular death, non-fatal myocardial infarction, or stroke, whichever occurred first. Adjusted for age and sex, an increase in common CIMT of 1 SD ( approximately 0.32 mm) was associated with the occurrence of vascular events [hazard ratio (HR) 1.18; 95% confidence interval (95% CI) 1.04-1.32]. Increasing CIMT was most strongly related to ischaemic stroke incidence (HR 1.35; 95% CI 1.16-1.59). Results were similar in the 2177 patients without large common carotid plaques (CIMT <2 mm at all measurements sites). The findings were similar after additional adjustment for risk factors of CIMT and vascular risk. CONCLUSION: Common CIMT is associated with the occurrence of new vascular events, mostly for ischaemic stroke, in patients with manifest arterial disease. This relation does not appear to depend on the presence of plaques.     

Prognostic value of treadmill exercise echocardiography

INTRODUCTION AND OBJECTIVES: Exercise echocardiography (EE) is useful for diagnosing coronary disease, but little is known about its value for risk stratification. We aimed to determine: a) whether data from EE supplemented clinical data and data from exercise testing and resting echocardiography in predicting cardiac events; and b)whether the number and location of abnormal regions and their responses to exercise influenced risk stratification. PATIENTS AND METHOD: The 2,436 patients referred for EE were followed up for 2.1+/-1.5 years. Some 120 serious cardiovascular events (i.e., non-fatal myocardial infarction or cardiovascular death) occurred before revascularization. RESULTS: In 1203 patients (49%), EE gave abnormal results. There were 89 events in patients with an abnormal result (7.3%) and 31 in those with a normal result (2.5%; P<.0001). Multivariate analysis of clinical data, and data from exercise testing, resting echocardiography, and EE showed that male sex (RR=1.7; 95% CI, 1.1-2.8; P=.02), metabolic equivalents or METs (RR=0.9; 95% CI, 0.86-0.98; P=.01), peak heart rate x blood pressure (RR= 0.9;95% CI, 0.9; P=.002), resting wall motion score index (RR=2.5; 95% CI, 1.5-4.1; P<.0001), and number of abnormal regions at peak exercise (RR=1.4; 95% CI, 1.2-1.7; P<.0001) were independently associated with the risk of a serious event (final model chi2, 170; incremental P<.0001). The same variables, excluding sex, were independently associated with cardiovascular death (final model chi2, 169; incremental P=.01). CONCLUSIONS: Exercise echocardiography supplements clinical data and data from exercise testing and resting echocardiography in patients with known or suspected coronary artery disease.     

Smoking raises the risk of total and ischemic strokes in hypertensive men.

To examine the relation between cigarette smoking and risk of stroke and coronary heart disease among Japanese, we conducted a 14-year prospective study of 3,626 men aged 40-69, initially free from history of stroke and coronary heart disease. We identified 257 strokes (75 hemorrhagic and 173 ischemic strokes) and 100 coronary heart disease events. When we adjusted for age and other cardiovascular risk factors, a significant excess risk among current smokers of > 20 cigarettes/day vs. never-smokers was found for total stroke (relative risk (RR) = 1.6 (95% confidence interval (CI), 1.1-2.4)). The excess risk of total stroke was particularly evident among hypertensives (RR = 2.3 (1.2-4.4)). The multivariate RR of ischemic stroke was 1.6 (1.0-2.5) for total subjects, and 2.2 (1.0-5.0) among hypertensives. Significant excess risks among current smokers of > 20 cigarettes/day vs. never-smokers were also found for coronary heart disease (RR = 4.6 (1.6-12.9)) and total cardiovascular disease (1.9 (1.3-2.7)). The estimated proportion of the events attributable to current smoking was 30 (95% CI, 11-44)% for total stroke and 34 (5-54)% for coronary heart disease. In conclusion, current smoking of > 20 cigarettes per day increased the risk of both total stroke and ischemic stroke among Japanese middle-aged men, and particularly among middle-aged hypertensive men.     

Elevated plasma tissue plasminogen activator and anti-THP-1 antibodies are independently associated with decreased graft survival in cardiac transplant recipients.

Hemostatic and immunologic factors have been implicated in future cardiac events in patients with coronary artery disease. The role of these factors and their interaction is less established in cardiac transplant recipients. We sought to characterize the role of these factors in these patients. Cardiac transplant patients who presented for surveillance coronary angiography and/or endomyocardial biopsy were eligible for enrollment. Ninety-nine consecutive patients were enrolled. Plasma levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1, von Willebrand factor, fibrin D-dimer, and anti-t-PA antibody were determined by enzyme-linked immunosorbent assays. Anti-THP-1 cell antibodies directed against a monocytic leukemia cell line were detected by incubating patient plasma with THP-1 cells. Bound antibody was detected using goat peroxidase-labeled immunoglobulin G directed against human immunoglobulins. Lipids were measured by enzymatic methods. Multivariate analysis identified the presence of anti-THP-1 cell antibodies (risk ratio 4.41, p = 0.002), t-PA antigen (risk ratio 1.10, p = 0.033), donor age 20 to 26 years (risk ratio 8.83, p = 0.042), and donor age >36 years (risk ratio 15.53, p = 0.009) as predictors of allograft failure. Altered hemostatic function, as demonstrated by elevated plasma t-PA antigen levels, is predictive of subsequent allograft failure in cardiac transplant recipients. In addition, the presence of anti-THP-1 cell antibodies in these patients is predictive of allograft failure.     

Platelet reactivity-adjusted antiplatelet therapy in patients with percutaneous coronary intervention: a meta-analysis of randomized controlled trials

Numerous number of evidences show that high on-treatment platelet reactivity is a well-known risk factor for adverse events in patients after percutaneous coronary intervention (PCI). Controversial situations still exist regarding the effectiveness of tailoring antiplatelet therapy according to platelet function monitoring. The PubMed, Embase, and Cochrane Central databases were searched for randomized trials comparing platelet reactivity-adjusted antiplatelet therapy with conventional antiplatelet therapy in patients undergoing PCI. The primary end point was all-cause mortality, major adverse cardiac events (MACE) including cardiovascular (CV) death, nonfatal myocardial infarction (MI), definite/probable stent thrombosis (ST), revascularization, and stroke or transient ischemic attack (TIA). The safety end point was defined as major bleeding events. We derived pooled risk ratios (RRs) with fixed-effect models. Six studies enrolling 6347 patients were included. Compared with conventional treatment, tailoring antiplatelet failed to reduce all-cause mortality (RR: 0.89, 95% confidence interval [CI]: 0.63–1.24, P = 0.48), MACE (RR: 1.02, 95% CI: 0.92–1.14, P = 0.69), MI (RR: 1.07, 95% CI: 0.95–1.21, P = 0.24), CV death (RR: 0.69, 95% CI: 0.40–1.19, P = 0.09), ST (RR: 0.83, 95% CI: 0.50–1.38, P = 0.23), stroke or TIA (RR: 1.08, 95% CI: 0.55–2.12, P = 0.83), revascularization (RR: 0.96, 95% CI: 0.69–1.33, P = 0.79), and major bleeding events (RR: 0.79, 95% CI: 0.53–1.17, P = 0.24).

Compared with traditional antiplatelet treatment, tailoring antiplatelet therapy according to platelet reactivity testing failed to reduce all-cause mortality, MACE, and major bleeding events in patients undergoing PCI.     

Exercise workload, cardiovascular risk factor evaluation and the risk of stroke in middle-aged men

Objective. We investigated the prognostic significance of risk scores and exercise workload with respect to stroke. Background. There are no data on exercise workload combined with European Systematic Coronary Risk Evaluation (SCORE) in the prediction of stroke. Methods. Exercise workload was measured by exercise test with an electrically braked cycle ergometer performed at baseline. The study is based on a random population‐based sample of 1639 men (42–60 years) without history of type 2 diabetes or atherosclerotic cardiovascular disease including coronary heart disease, stroke or claudication. Results. During an average follow‐up of 16 years, a total of 97 strokes occurred, of which 71 were ischaemic strokes. Independent predictors for all strokes were European SCORE [for 1% increment, relative risk (RR): 1.12, 95% CI: 1.02 to 1.22, P = 0.017), maximal workload (for 20 W increment, RR: 0.87, 95% CI: 0.80 to 0.95, P = 0.003) and body mass index (for 5 kg m^?2 increment, RR: 1.08, 95% CI: 1.03 to 1.14, P = 0.004), when adjusted for serum HDL, alcohol consumption, C‐reactive protein, family history of coronary heart disease, exercise‐induced ST changes and the use of medications for hypertension, dyslipidaemia or aspirin. The risk was 2.54‐fold (95% CI: 1.27–5.09, P = 0.008) for any strokes and 4.43‐fold (95% CI 1.69–11.78, P = 0.003) for ischaemic strokes amongst men with exercise capacity less than 162 W when compared with those with high exercise capacity over 230 W, after adjustment for risk factors. Conclusions. Low exercise workload predicts an especially high risk for stroke in the presence of high risk SCORE.     

Fluvastatin reduces the 4-year cardiac risk in patients with multivessel disease

BACKGROUND: To evaluate the impact of the extent of coronary disease (single- or multivessel) and of fluvastatin treatment on the incidence of long-term cardiac atherosclerotic complications in the Lescol Intervention Prevention Study (LIPS). METHODS: A total of 1063 patients with single-vessel disease and 614 patients with multivessel disease were randomized to receive fluvastatin (40 mg bid) or placebo for at least 3 years following a first successful percutaneous coronary intervention. The incidence of cardiac atherosclerotic events (cardiac death, non-fatal myocardial infarction, and coronary re-interventions not related to restenosis) was evaluated. RESULTS: Patients with multivessel disease tended to be older and presented a higher prevalence of associated risk factors and cardiovascular antecedents. The presence of multivessel disease markedly increased the risk of cardiac atherosclerotic events compared with single-vessel disease among patients allocated to placebo (RR 1.67 [95% CI: 1.24-2.25]; p<0.001). In patients treated with fluvastatin, however, no significant differences in long-term outcomes were observed between patients with multivessel disease and patients single-vessel disease (RR 1.28 [95% CI: 0.90-1.81]; p=0.2). CONCLUSIONS: Multivessel coronary disease impaired the 4-year outcomes after percutaneous intervention. However, the hazardous effect of multivessel disease was significantly reduced by long-term fluvastatin treatment.     

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.