Association between metabolic syndrome, diabetes mellitus and prostate cancer risk.

BACKGROUND: The worldwide incidence of diabetes mellitus is rapidly increasing. There is recent interest in the influence of glucose metabolism on oncogenesis. We investigated the role of diabetes mellitus and the metabolic syndrome (MS) on prostate cancer development. METHODS: This study consisted of 11 541 men with coronary heart disease screened to participate in a secondary cardiac prevention trial. MS was defined according to modified NCEP/ATP III criteria. Multivariable regression analysis accounting for competing risks was performed using a modified Cox proportional hazard model in order to assess the association between diabetes, the MS and the subsequent development of prostate cancer. RESULTS: At baseline, subjects were classified into one of the four groups: (1) 6119 (53%) with neither diabetic mellitus nor MS, (2) 3376 (29%) with the MS but without diabetes, (3) 560 (5%) with diabetes mellitus but without MS and (4) 1486 (13%) with both conditions. Median follow-up was 12.7 years (range 0-15.7 years). During follow-up, 459 new cases of prostate cancer were recorded. The age-adjusted hazard ratio (HR) for prostate cancer was reduced in diabetic patients compared with those without diabetes, 0.54 and 95% confidence interval of 0.40-0.73. No significant association was noted between the presence of MS and prostate cancer development. On multivariate analysis, diabetes mellitus continued to protect against the development of prostate cancer, this was more pronounced in the absence of MS (HR=0.43, P=0.01 for diabetes in the absence of MS; HR=0.64, P=0.08 in the presence of MS). CONCLUSIONS: The results of this study indicate an inverse association between type 2 diabetes mellitus and prostate cancer risk.

Off-hours admission for acute stroke is not associated with worse outcome--a nationwide Israeli stroke project.

BACKGROUND AND PURPOSE: Several studies reported worse outcome for stroke patients arriving on weekends. We compared working hours to off-work hours throughout the week as there is lack of experienced staff and special services during off-hours. METHODS: A nationwide stroke survey project on acute stroke was carried out in all acute care hospitals in Israel during 2004, 2007 and 2010 (2-month each). 'On-hours' were defined as regular Israel working hours and the rest, including holidays, were defined as 'off-hours'. The modified Rankin scale (mRS) at discharge was used for the main analysis on outcome. RESULTS: A total of 4827 acute strokes patients were analyzed (2139 arrived on-hours and 2688 during off-hours). 'Off-hours' patients were 1 year younger (mean 70 vs. 71 years in 'on-hours') had lower rates of prior cardiac interventions, but had higher admission blood pressure levels and had more intracerebral hemorrhages (ICH) (11% vs. 8% in 'on-hours' patients, P < 0.001). Death during hospitalization was recorded in 9% of 'off-hours' vs. 6% of 'on-hours' patient (P = 0.004). Controlling for age, blood pressure, stroke type, pre-stroke mRS, admission NIHSS, and thrombolysis, the relative odds of poor outcome (i.e. mRS ≥ 2) amongst 'off-hours' admissions compared to on-hours was 1.09 (95% CI: 0.92-1.30). Odds ratio amongst ischaemic stroke patients was 1.08 (95% CI: 0.88-1.33). CONCLUSIONS: Off-hours stroke admissions were associated with higher short-term mortality rate, probably due to a higher rate of ICH. After controlling for the latter and other potential confounders, 'off-hours' admissions were not different from 'on-hours' with respect to poor outcome.

Increased insulin resistance and risk of incident cerebrovascular events in patients with pre-existing atherothrombotic disease.

BACKGROUND AND PURPOSE: Diabetes and the metabolic syndrome are known risk factors for ischaemic stroke. Our aim was to examine whether amongst patients with pre-existing atherothrombotic disease, increased insulin resistance is associated with incident cerebrovascular events. METHODS: Patients with stable coronary heart disease included in a secondary prevention trial were followed up for a mean of 6.2 years. Coronary heart disease was documented by a history of myocardial infarction > or =6 months and <5 years before enrollment and/or stable angina pectoris with evidence of ischaemia confirmed by ancillary diagnostic testing. Main exclusion criteria were insulin treated diabetes, hepatic or renal failure, and disabling stroke. Baseline insulin levels were measured in 2938 patients from stored frozen plasma samples and increased insulin resistance assessed using the homeostatic model assessment of insulin resistance (HOMA-IR), categorized into tertiles or quartiles. RESULTS: Crude rates of incident cerebrovascular events rose from 5.0% for HOMA-IR at the bottom tertile to 5.7% at the middle tertile, and 7.0% at the top tertile (P = 0.07). HOMA-IR at the top versus bottom tertile was associated with an unadjusted hazard ratio (HR) of 1.37 (95%CI, 0.94-1.98) and a 1-unit increase in the ln HOMA-IR was associated with a HR of 1.14 (95%CI, 0.97-1.35). In further analyses adjusting for potential confounders, or categorizing baseline HOMA-IR into quartiles, or excluding diabetic patients, we did not identify an increased risk for incident cerebrovascular events conferred by the top category. CONCLUSIONS: Increased insulin resistance did not predict incident cerebrovascular events amongst patients with pre-existing atherothrombotic disease.

Systematically missing confounders in individual participant data meta-analysis of observational cohort studies.

One difficulty in performing meta-analyses of observational cohort studies is that the availability of confounders may vary between cohorts, so that some cohorts provide fully adjusted analyses while others only provide partially adjusted analyses. Commonly, analyses of the association between an exposure and disease either are restricted to cohorts with full confounder information, or use all cohorts but do not fully adjust for confounding. We propose using a bivariate random-effects meta-analysis model to use information from all available cohorts while still adjusting for all the potential confounders. Our method uses both the fully adjusted and the partially adjusted estimated effects in the cohorts with full confounder information, together with an estimate of their within-cohort correlation. The method is applied to estimate the association between fibrinogen level and coronary heart disease incidence using data from 154,012 participants in 31 cohorts

C-reactive protein distribution and correlates among men and women with chronic coronary heart disease.

BACKGROUND: C-reactive protein (CRP) elevated in inflammation is associated with atherosclerotic disease. We describe the distribution of CRP and its association with coronary heart disease (CHD) risk factors in a large CHD patient group. METHODS: This analysis comprises 2,723 male and 256 female CHD patients, included in the Bezafibrate Infarction Prevention (BIP) study. High sensitive CRP levels were determined in frozen plasma samples. RESULTS: CRP distribution, was normalized upon log transformation. Levels among women were higher than in men in the entire group (4.4 vs. 3.5 mg/l) and in each age group. Co-morbidities, smoking, lower education level, and use of cardiovascular drugs, were associated with elevated CRP levels in both sexes. The correlation between CRP and body mass index (BMI), insulin and glucose was stronger among women. The explained variability in CRP level was larger in women (20%) compared to men (13%). Among women, BMI explained 10% of CRP variability, whereas the contribution of each variable among men was significantly smaller. CONCLUSIONS: Among men and women with CHD, CRP level was correlated with traditional risk factors and to a lesser degree to manifestation of CHD. BMI is the main contributor to CRP variability, explained by these factors among women.

Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis.

CONTEXT: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. DATA SOURCES: Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators. STUDY SELECTION: All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded. DATA EXTRACTION: Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias. DATA SYNTHESIS: Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design. CONCLUSIONS: In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.

A prospective study of plasma fibrinogen levels and the risk of stroke among participants in the bezafibrate infarction prevention study.

PURPOSE: Plasma fibrinogen has emerged as an important predictor of cardiovascular disease, but few data are available on its association with stroke. We sought to determine if plasma fibrinogen is a marker of increased risk or a direct causative risk factor for stroke. SUBJECTS AND METHODS: Patients from the Bezafibrate Infarction Prevention Study, a placebo-controlled, randomized clinical trial of secondary prevention of coronary heart disease by lipid modification with bezafibrate retard (400 mg daily), were studied. Plasma fibrinogen levels were measured at baseline and yearly thereafter. Stroke, a prospectively monitored endpoint, was systematically assessed regarding stroke type, subtype, and functional outcome. RESULTS: Mean baseline fibrinogen levels were significantly higher in patients subsequently having a cerebrovascular event (140 strokes, 36 transient ischemic attacks; mean follow-up, 6.2 years) than in patients who did not (375 vs. 349 mg/dL, P <0.0001). Fibrinogen levels did not differ significantly by the type, subtype, or severity of the cerebrovascular event. Risk of ischemic stroke increased from 3.3% in the lowest tertile (baseline fibrinogen <314 mg/dL) to 7.% in the middle tertile (fibrinogen 314 to 373 mg/dL) to 10% in the upper tertile (fibrinogen >373 mg/dL, P <0.001). Adjusting for age, blood pressure, and other covariates, fibrinogen levels in the upper tertile were associated with more than a twofold increase in risk of ischemic stroke compared with in the lowest tertile (hazard ratio = 2.6; 95% confidence interval: 1.5 to 4.3). We did not find fibrinogen change from baseline to be related to subsequent ischemic stroke events. CONCLUSION: Plasma fibrinogen is a strong predictor of, rather than a direct causative factor for, subsequent stroke among patients at increased risk owing to manifest coronary heart disease.

Oral antidiabetic treatment in patients with coronary disease: time-related increased mortality on combined glyburide/metformin therapy over a 7.7-year follow-up.

BACKGROUND: A sulfonylurea--usually glyburide--plus metformin constitute the most widely used oral antihyperglycemic combination in clinical practice. Both medications present undesirable cardiovascular effects. The issue whether the adverse effects of each of these pharmacologic agents may be additive and detrimental to the prognosis for coronary patients has not yet been specifically addressed. HYPOTHESIS: This study was designed to examine the survival in type 2 diabetics with proven coronary artery disease (CAD) receiving a combined glyburide/metformin antihyperglycemic treatment over a long-term follow-up period. METHODS: The study sample comprised 2,275 diabetic patients, aged 45-74 years, with proven CAD, who were screened but not included in the bezafibrate infarction prevention study. In addition, 9,047 nondiabetic patients with CAD represented a reference group. Diabetics were divided into four groups on the basis of their therapeutic regimen: diet alone (n = 990), glyburide (n = 953), metformin (n = 79), and a combination of the latter two (n = 253). RESULTS: The diabetic groups presented similar clinical characteristics upon recruitment. Crude mortality rate after a 7.7-year follow-up was lower in nondiabetics (14 vs. 31.6%, p<0.001). Among diabetics, 720 patients died: 260 on diet (mortality 26.3%), 324 on glyburide (34%), 25 on metformin alone (31.6%), and 111 patients (43.9%) on combined treatment (p<0.000001). Time-related mortality was almost equal for patients on metformin and on combined therapy over an intermediate follow-up period of 4 years (survival rates 0.80 and 0.79, respectively). The group on combined treatment presented the worst prognosis over the long-term follow-up, with a time-related survival rate of 0.59 after 7 years, versus 0.68 and 0.70 for glyburide and metformin, respectively. After adjustment to variables for prognosis, the use of the combined treatment was associated with an increased hazard ratio (HR) for all-cause mortality of 1.53 (95% confidence interval [CI] 1.20-1.96), whereas glyburide and metformin alone yielded HR 1.22 (95% CI 1.02-1.45) and HR 1.26 (95% CI 0.81-1.96), respectively. CONCLUSIONS: We conclude that after a 7.7-year follow-up, monotherapy with either glyburide or metformin in diabetic patients with CAD yielded a similar outcome and was associated with a modest increase in mortality. However, time-related mortality was markedly increased when a combined glyburide/metformin treatment was used.

Are routine arrhythmia inductions necessary in patients with pectoral implantable cardioverter defibrillators?

INTRODUCTION: The value of ventricular arrhythmia inductions as part of routine implantable cardioverter defibrillator (ICD) follow-up in new-generation pectoral ICDs is unknown. METHODS AND RESULTS: We performed a retrospective analysis of a prospectively collected database analyzing data from 153 patients with pectoral ICDs who had routine arrhythmia inductions at predismissal, and 3 months and 1 year after implantation. Routine predismissal ventricular fibrillation (VF) induction yielded important findings in 8.8% of patients, all in patients with implantation defibrillation threshold (DFT) > or = 15 J or with concomitant pacemaker systems. At 3 months and 1 year, routine VF induction yielded important findings in 5.9% and 3.8% of tested patients, respectively, all in patients who had high DFT on prior testing. Ventricular tachycardia (VT) induction at predismissal, and 3 months and 1 year after implantation resulted in programming change in 37.4%, 28.1%, and 13.8% of tested patients, almost all in patients with inducible VT on baseline electrophysiologic study and clinical episodes since implantation. CONCLUSION: Although helpful in identifying potentially important ICD malfunctions, routine arrhythmia inductions during the first year after ICD implantation may not be necessary in all cases. VF inductions have a low yield in patients with previously low DFTs who lack concomitant pacemakers. VT inductions have a low yield in patients without baseline inducible VT and in the absence of clinical events. Definite recommendations regarding patient selection must await larger prospective studies as well as consensus in the medical community about what comprises an acceptable risk justifying avoidance of the costs and inconveniences of routine arrhythmia inductions.

Antihyperglycemic treatment in diabetics with coronary disease: increased metformin-associated mortality over a 5-year follow-up.

Mortality rates are considerably higher in chronic ischemic heart disease (IHD) patients with non-insulin-dependent diabetes mellitus (NIDDM) than in those who are nondiabetics. The relationship between different types of antihyperglycemic pharmacological therapy and mortality rate in this NIDDM population is uncertain. We aimed to examine the survival in NIDDM patients with IHD using various types of oral antidiabetic treatments over a 5-year follow-up period. The study sample comprised 11,440 patients with a previous myocardial infarction and/or stable anginal syndrome, aged 45-74 years, who were screened, but not included in the Bezafibrate Infarction Prevention study. Among them, 9,045 were nondiabetics and 2,395 diabetics. The diabetic patients were divided into four groups on the basis of their therapeutic regimen at screening: diet alone (n = 990), sulfonylureas (n = 1,041), metformin (n = 78) and a combination of a sulfonylurea and metformin (n = 266). All NIDDM groups were similar with regard to age, gender, hypertension, smoking, heart failure, angina and prior myocardial infarction. Crude mortality rate was lower in the nondiabetic group (11.21 vs. 21.8%; p < 0.001). In the diabetic group, mortality was 18.5% for patients on diet alone, 22.5% for those on sulfonylureas, 25.6% for patients on metformin, and 31.6% for the combined sulfonylurea/metformin group (p < 0.01). When analyzing age-adjusted mortality rate and actuarial survival curves, the lowest mortality was found in patients on diet alone and the highest in patients on metformin (alone or in combination with sulfonylureas). After adjustment for variables connected with long-term prognosis, the use of metformin was associated with increased relative risk (RR) for all-cause mortality of 1.42 (95% CI 1.10-1.85), whereas the use of sulfonylureas alone was not [RR 1.11 (95% CI 0.90-1.36)]. NIDDM patients with IHD using metformin, alone or in combination with sulfonylureas, exhibited a significantly increased mortality. Until the results of problem-oriented prospective studies on oral control of NIDDM will be available, alternative therapeutic approaches should be investigated in these patients.

Elevated serum triglyceride levels and long-term mortality in patients with coronary heart disease: the Bezafibrate Infarction Prevention (BIP) Registry.

BACKGROUND: The association between elevated blood triglyceride levels and subsequent mortality risk in patients with established coronary heart disease (CHD) has been investigated rarely. The aim of the present study was to investigate this association. METHODS AND RESULTS: We evaluated mortality over a mean follow-up time of 5. 1 years among 9033 male and 2499 female CHD patients who were screened for participation in the Bezafibrate Infarction Prevention (BIP) Study. A stepwise increase in mortality with increasing serum triglyceride levels was observed in patients with desirable or elevated serum total cholesterol levels and in patients with either desirable or abnormally low HDL cholesterol levels. Multivariate adjustment for factors other than HDL cholesterol yielded a slightly increased adjusted mortality risk with a 1-natural-log-unit elevation of triglyceride levels in men (hazard ratio [HR] 1.14, 95% CI 1.00 to 1.30) and women (HR 1.37, 95% CI 1.04 to 1.88). Excess covariate-adjusted risk was noted among patients with elevated total and LDL cholesterol and in women with HDL cholesterol levels >45 mg/dL. After additional adjustment for HDL cholesterol, the risk of mortality with a 1-natural-log-unit elevation of triglycerides declined in men (HR 1.09, 95% CI 0.94 to 1.26) and in women (HR 1.10, 95% CI 0.80 to 1.50). A trend for increased mortality risk remained in patients with elevated total and LDL cholesterol and in women with HDL cholesterol >45 mg/dL. CONCLUSIONS: Elevated triglyceride levels were associated with a small, independent increased mortality risk in CHD patients. This risk may be increased among subgroups of patients with elevated total cholesterol and LDL cholesterol levels.

Effect of beta-blocker therapy in patients with coronary artery disease in New York Heart Association classes II and III. The Bezafibrate Infarction Prevention (BIP) Study Group.

The aim of the study was to investigate the effect of beta-blocker treatment on a large cohort of patients with coronary artery disease in functional classes II and III according to the New York Heart Association (NYHA) classification. Among 11,575 patients with coronary artery disease screened for participation, but not included in the Bezafibrate Infarction Prevention (BIP) study, 3,225 (28%) were in NYHA classes II and III. In the latter group of patients we compared the prognosis of 1,109 (34%) treated with beta blockers with 2,116 counterparts not receiving beta-blocker therapy. After a mean follow-up of 4 years, all-cause and cardiac mortality rates were significantly lower among beta-blocker users, 9% and 5%, respectively, than among beta-blocker nonusers, 17% and 11%, respectively (p <0.01 for both). After multivariate adjustment, treatment with beta blockers was associated with a lower all-cause mortality risk (hazards ratio [HR] 0.62, 95% confidence interval [CI] 0.49 to 0.78), and a lower cardiac mortality risk (HR = 0.61, 95% CI 0.45 to 0.83) than was no treatment with a beta blocker. Lower total mortality risk was noted among patients in NYHA class II (HR 0.63, 95% CI 0.48 to 0.82) and in NYHA class III (HR 0.57, 95% CI 0.37 to 0.87) as well as in patients with (HR 0.62, 95% CI 0.48 to 0.81) or without (HR 0.70, 95% CI 0.45 to 1.09) a previous myocardial infarction. We conclude that beta-blocker therapy in coronary patients in NYHA classes II or III is safe and associated with a lower risk for all-cause and cardiac mortality.

Long-term prognosis of women after myocardial infarction. SPRINT Study Group. Secondary Prevention Reinfarction Israeli Nifedipine Trial.

Women sustaining myocardial infarction fare worse than men during hospitalization. Reports on long-term survival in women surviving an acute myocardial infarction are controversial. The Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT) registry includes 5,839 consecutive myocardial infarction patients who were hospitalized in 13 coronary care units in Israel between 1981 and 1983. The authors examined sex differences in the long-term survival of 4,808 hospital survivors (1,120 women and 3,688 men). Women exhibited a significantly poorer long-term survival than men. After age adjustment, differences between men and women decreased, leaving a survival probability difference of 11% at the end of 12 years of follow-up. In a subgroup analysis, women exhibited poorer survival than men in a comparison of patients with and without periinfarction congestive heart failure or a history of myocardial infarction preceding the index infarction. The multivariate adjusted hazard ratios associated with female sex in diabetic and nondiabetic patients were 1.46 and 1.13, respectively. In conclusion, a cumulative survival disadvantage for women in comparison with men is still evident after 12 years of follow-up. The mortality difference is diminished but not erased after age adjustment or multivariate adjustment for confounders. The authors' results are compatible with a hypothesis that the main factor underlying the increased long-term mortality in women after myocardial infarction, besides older age, is diabetes mellitus.

Low total cholesterol is associated with high total mortality in patients with coronary heart disease. The Bezafibrate Infarction Prevention (BIP) Study Group.

The present non-intervention screening study was undertaken to explore the relationships between pre-existing low total cholesterol and all-cause mortality. Eleven thousand, five hundred and sixty-three patients with coronary heart disease who attended a screening visit but were not included in the Bezafibrate Infarction Prevention study were followed-up for a mean of 3.3 years after determination of baseline total cholesterol. Five hundred and ninety-five (5%) of this largely unselected population who had total cholesterol levels < or = 160 mg.dl-1 formed the study population. The remaining 10968 patients acted as controls. The relative risk of all-cause mortality among patients with low cholesterol compared to others was 1.49 (95% CI: 1.16-1.91). The relative risk of non-cardiac death was 2.27 times higher in the low cholesterol group than in the controls (95% CI: 1.49-3.45), whereas the risk of cardiac death was the same in both groups (relative risk 1.09; 95% CI: 0.76-1.56). The most frequent cause of non-cardiac death associated with low total cholesterol was cancer. These results in patients with coronary heart disease add weight to previous studies associating low total cholesterol with an increased risk of non-cardiac death. However, a longer follow-up of this cohort of patients is necessary in order to clarify this association.

Effect of aspirin on mortality in women with symptomatic or silent myocardial ischemia. Israeli BIP Study Group.

The benefit of aspirin therapy among women with coronary artery disease (CAD) is not well established. Previous studies have shown conflicting results among women. Data from 2,418 women with CAD screened for participation in the ongoing Bezafibrate Infarction Prevention (BIP) study were analyzed: 45% reported aspirin therapy. Baseline characteristics were similar in both groups. Cardiovascular mortality at 3.1 +/- 0.9 years of follow-up was 2.7% in the aspirin treated group versus 5.1% in the non-aspirin-treated women (p = 0.002). All cause mortality was 5.1% and 9.1%, respectively (p = 0.0001). Treatment with aspirin emerged as an independent predictor of reduced cardiovascular (RR = 0.61, 95% confidence interval [CI] 0.38 to 0.97) and all cause (RR = 0.66, 95% CI 0.47 to 0.93) mortality after multiple adjustment for possible confounders such as age, history of myocardial infarction, systemic hypertension, diabetes mellitus, peripheral vascular disease, current smoking, New York Heart Association classification, and concomitant treatment with digitalis. Women who benefited the most from aspirin therapy were older, diabetic, symptomatic, or had a previous myocardial infarction. Thus, treatment with aspirin was associated with reduced mortality among women with CAD. This study suggests that women with CAD should be treated with aspirin, unless specific contraindications exist.

Fibrinogen is a predictor of mortality in coronary heart disease patients. The Bezafibrate Infarction Prevention (BIP) Study Group.

Results of epidemiological studies have indicated that fibrinogen is an important primary cardiovascular risk factor. The role of fibrinogen as a predictor of mortality in coronary heart disease (CHD) patients is unclear. We investigated the association between fibrinogen and mortality in a large cohort of CHD patients screened for participation in a secondary prevention clinical trial. Of the total investigated, 3092 men who were not included in the trial and for whom vital status was known were followed up for a mean period of 3.2 years. In 54.4% of the 111 men who died, mortality was attributed to CHD. Mean baseline plasma fibrinogen levels were 29.4 mg/dL higher in patients who died than in the survivors. All-cause and CHD mortality rates increased with increasing fibrinogen levels. This relationship was also demonstrated within categories of the primary variables predicting mortality in these patients. The contribution of fibrinogen to CHD and all-cause mortality was assessed by multivariate analysis adjusting for age, CHD severity, and comorbidity. Risk of CHD and all-cause mortality for patients in the highest fibrinogen tertile were 1.67 and 1.75, respectively, relative to patients in the lowest tertile, and an increase of about 1 SD of plasma fibrinogen level (75 mg/dL) was found to increase risk of CHD and all-cause mortality 29% and 31%, respectively. These results indicate clearly that fibrinogen level is associated with significantly increased mortality in CHD patients. Implementation of a standardized measuring method is required to allow assessment of risk in CHD patients on the basis of fibrinogen levels.

Plasma fibrinogen levels and their correlates in 6457 coronary heart disease patients. The Bezafibrate Infarction Prevention (BIP) Study.

The association between fibrinogen measured in healthy individuals and subsequent development of ischemic heart disease is well established, but studies reporting fibrinogen levels in coronary heart disease patients are scarce. Plasma fibrinogen was determined for 5729 men and 728 women (aged 45 to 74) with established coronary heart disease, screened for participation in the Bezafibrate Infarction Prevention study, with the following lipid profile at the time of the first screening visit: total serum cholesterol < or = 270 mg/dl, high density lipoprotein cholesterol < or = 45 mg/dl and triglyceride < or = 300 mg/dl. Increased age was associated with augmented plasma fibrinogen values. Age-adjusted fibrinogen levels were higher in women than in men. A direct association was found between mean fibrinogen levels and low density lipoprotein cholesterol. On the other hand, the correlation with high density lipoprotein cholesterol was inverse. Fibrinogen was also associated with body mass index, behavioral variables and severity of coronary heart disease. In a multivariable linear regression analysis performed, risk factors considered explained merely 6 and 4% of fibrinogen variation for men and women, respectively. Therefore, most of the fibrinogen level variability in coronary heart disease patients is accounted for by factors that remain to be established by further research.

Asymptomatic hyperglycemia in coronary heart disease: frequency and associated lipid and lipoprotein levels in the bezafibrate infarction prevention (BIP) register. The BIP Study Group.

BACKGROUND: The lipid profile of patients with type-II diabetes is characterized by low levels of high-density lipoprotein cholesterol, hypertriglyceridemia, and increased levels of lipoprotein (a), all of which may affect the prognosis in patients with atherosclerotic cardiovascular disease. This study aimed to assess the prevalence of asymptomatic hyperglycemia and the associated lipid profile in a large group of patients with documented coronary heart disease. METHODS: From February 1990 to October 1992, 14,326 patients aged 45-74 years with documented coronary heart disease (a history of myocardial infarction or angina pectoris) were screened for inclusion in a secondary prevention study using bezafibrate retard. All screened patients underwent a medical examination and a blood test after fasting for 14 h. Asymptomatic hyperglycemia was defined as a fasting blood glucose level of 140 mg/dl or above in patients with no previous history of diabetes mellitus. RESULTS: The prevalence of asymptomatic hyperglycemia was 4%, with no differences between the sexes or age groups. Total cholesterol and triglyceride levels were significantly higher and the high-density lipoprotein cholesterol level significantly lower in asymptomatic hyperglycemic than in normoglycemic patients. After multiple adjustments, the relative risk of death was 1.75 and 1.71 in patients with diabetes or asymptomatic hyperglycemia compared with those with no glycemic disorders. CONCLUSION: Asymptomatic hyperglycemia was detected in 4% of patients with ischemic heart disease. The lipid profile in these 4% resembles that of patients with confirmed diabetes, and their morbidity and mortality may therefore be higher than that of normoglycemic patients. Repeated assessment of glucose levels in patients with coronary heart disease is mandatory.