Height loss in older men: associations with total mortality and incidence of cardiovascular disease

BACKGROUND: Height declines with age, but the impact of height loss on health outcomes has been little studied. We examined the relationships between height loss over 20 years (starting at middle age) and subsequent total mortality and incidence of coronary heart disease and stroke in older men. METHODS: A prospective study was performed on 4213 men whose height was measured between the ages of 40 and 59 years and again 20 years later between the ages of 60 and 79 years. The men were then followed up for a mean period of 6 years, during which 760 deaths occurred. RESULTS: Height loss correlated significantly with initial age (r = 0.20) and weight loss (r = 0.20). Total mortality risk was higher in men with a height loss of 3 cm or more than in men with a height loss of less than 1 cm (age-adjusted relative risk [RR], 1.64; 95% confidence interval [CI], 1.33-2.03). The excess deaths were largely attributable to cardiovascular and respiratory conditions and other causes but not to cancer. Adjustment for age, established cardiovascular risk factors, lung function, preexisting cardiovascular disease, albumin concentration, self-reported poor or fair health, and weight loss had a modest impact on the increased risk of total mortality (RR, 1.45; 95% CI, 1.15-1.82). The risk of major coronary heart disease events was increased only in men with a height loss of 3 cm or more even after adjustment (adjusted RR, 1.42; 95% CI, 1.02-1.98; > or =3.0 cm vs <3.0 cm); no association was seen with stroke risk. CONCLUSION: Marked height loss (> or =3 cm) in older men is independently associated with an increased risk of all-cause mortality and coronary heart disease.     

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.     

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.     

A population-based study of the long-term risks associated with atrial fibrillation: 20-year follow-up of the Renfrew/Paisley study

PURPOSE: To describe the effect of atrial fibrillation on long-term morbidity and mortality. SUBJECTS AND METHODS: The Renfrew/Paisley Study surveyed 7052 men and 8354 women aged 45-64 years between 1972 and 1976. All hospitalizations and deaths occurring during the subsequent 20 years were analyzed by the presence or absence of atrial fibrillation at baseline. Lone atrial fibrillation was defined in the absence of other cardiovascular signs or symptoms. Cox proportional hazards models were used to adjust for age and cardiovascular conditions. RESULTS: After 20 years, 42 (89%) of the 47 women with atrial fibrillation had a cardiovascular event (death or hospitalization), compared with 2276 (27%) of the 8307 women without this arrhythmia. Among men, 35 (66%) of 53 with atrial fibrillation had an event, compared with 3151 (45%) of 6999 without atrial fibrillation. In women, atrial fibrillation was an independent predictor of cardiovascular events (rate ratio [RR] = 3.0; 95% confidence interval [CI]: 2.1-4.2), fatal or nonfatal strokes (RR = 3.2; 95% CI: 1.0-5.0), and heart failure (RR = 3.4; 95% CI: 1.9-6.2). The rate ratios among men were 1.8 (95% CI: 1.3-2.5) for cardiovascular events, 2.5 (95% CI: 1.3-4.8) for strokes, and 3.4 (95% CI: 1.7-6.8) for heart failure. Atrial fibrillation was an independent predictor of all-cause mortality in women (RR = 2.2; 95% CI: 1.5-3.2) and men (RR = 1.5; 95% CI: 1.2-2.2). However, lone atrial fibrillation (which occurred in 15 subjects) was not associated with a statistically significant increase in either cardiovascular events (RR = 1.5; 95% CI: 0.6-3.6) or mortality (RR = 1.8; 95% CI: 0.9-3.8). CONCLUSIONS: Atrial fibrillation is associated with an increased long-term risk of stroke, heart failure, and all-cause mortality, especially in women.     

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.     

The risk of cardiovascular disease mortality associated with microalbuminuria and gross proteinuria in persons with older-onset diabetes mellitus

BACKGROUND: Despite the numerous studies on the relation of albuminuria with increased risk of all-cause mortality in type 2 diabetes mellitus, it remains uncertain whether microalbuminuria and/or gross proteinuria are independent risk factors for cardiovascular mortality. Moreover, the association of albuminuria with cardiovascular mortality in people with type 2 diabetes mellitus has not been well described in US populations. OBJECTIVE: To estimate the relative risks (RRs) for the associations of microalbuminuria and gross proteinuria with cardiovascular disease mortality among persons with older-onset diabetes mellitus. METHODS: We conducted a prospective cohort study of 840 people with older-onset diabetes mellitus who provided urine samples in the 1984-1986 examination of a population-based study of diabetic persons. The presence of microalbuminuria was determined by an agglutination inhibition assay and gross proteinuria by a reagent strip. The main outcome was time to mortality from cardiovascular disease, as determined from death certificates. RESULTS: Of the 840 older-onset diabetic persons, 54.8% had normoalbuminuria, while 24.8% had microalbuminuria and 20.5% had gross proteinuria. During the 12-year follow-up (6127 person-years), we identified 364 deaths from cardiovascular disease. Compared with persons with normoalbuminuria, those with microalbuminuria and gross proteinuria had significantly higher risks of cardiovascular mortality. The RR as controlled for age, sex, glycemic control, insulin use, alcohol intake, physical activity, cardiovascular disease history, antihypertensive use, and retinopathy severity, was 1.84 (95% confidence interval [CI], 1.42-2.40) for those with microalbuminuria and 2.61 (95% CI, 1.99-3.43) for those with gross proteinuria. Further adjustment for other factors did not change the relations we found. When the end point used was mortality from coronary heart disease, stroke, or all causes, the increased risks were significant for both microalbuminuria (adjusted RRs [95% CIs], 1.96 [1.42-2.72], 2.20 [1.29-3.75], and 1.68 [1.35-2.09], respectively) and gross proteinuria (adjusted RRs [95% CIs], 2.73 [1.95-3.81], 2.33 [1.28-4.24], and 2.47 [1.97-3.10], respectively). CONCLUSIONS: Results from our population-based study strongly suggest that both microalbuminuria and gross proteinuria were significantly associated with subsequent mortality from all causes and from cardiovascular, cerebrovascular, and coronary heart diseases. These associations were independent of known cardiovascular risk factors and diabetes-related variables.     

Statins for secondary prevention in elderly patients: a hierarchical bayesian meta-analysis.

OBJECTIVES: This study was designed to determine whether statins reduce all-cause mortality in elderly patients with coronary heart disease. BACKGROUND: Statins continue to be underutilized in elderly patients because evidence has not consistently shown that they reduce mortality. METHODS: We searched 5 electronic databases, the Internet, and conference proceedings to identify relevant trials. In addition, we obtained unpublished data for the elderly patient subgroups from 4 trials and for the secondary prevention subgroup from the PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) trial. Inclusion criteria were randomized allocation to statin or placebo, documented coronary heart disease, > or =50 elderly patients (defined as age > or =65 years), and > or =6 months of follow-up. Data were analyzed with hierarchical Bayesian modeling. RESULTS: We included 9 trials encompassing 19,569 patients with an age range of 65 to 82 years. Pooled rates of all-cause mortality were 15.6% with statins and 18.7% with placebo. We estimated a relative risk reduction of 22% over 5 years (relative risk [RR] 0.78; 95% credible interval [CI] 0.65 to 0.89). Furthermore, statins reduced coronary heart disease mortality by 30% (RR 0.70; 95% CI 0.53 to 0.83), nonfatal myocardial infarction by 26% (RR 0.74; 95% CI 0.60 to 0.89), need for revascularization by 30% (RR 0.70; 95% CI 0.53 to 0.83), and stroke by 25% (RR 0.75; 95% CI 0.56 to 0.94). The posterior median estimate of the number needed to treat to save 1 life was 28 (95% CI 15 to 56). CONCLUSIONS: Statins reduce all-cause mortality in elderly patients and the magnitude of this effect is substantially larger than had been previously estimated.     

Exercise workload, coronary risk evaluation and the risk of cardiovascular and all-cause death in middle-aged men.

BACKGROUND: No data exist on exercise workload combined with European Systematic Coronary Risk Evaluation (SCORE) with respect to death from cardiovascular diseases and other causes. We therefore investigated the prognostic significance of risk scores and exercise capacity with respect to cardiovascular diseases. DESIGN: A population-based follow-up study. METHODS: Exercise workload was measured by exercise test with an electrically braked cycle ergometer. The study is based on a random population-based sample of 1639 men (42-60 years) without history of type II diabetes or atherosclerotic cardiovascular disease including coronary heart disease, stroke or claudication. RESULTS: During an average follow-up of 16 years, a total of 304 overall deaths and 116 cardiovascular deaths occurred. Relative risk (RR) was 2.50 [95% confidence intervals (CI): 1.71-3.68, P<0.001] for all-cause death and 2.04 (95% CI: 1.14-3.65, P=0.016) for cardiovascular death among men with exercise capacity less than 162 W as compared with those with exercise capacity over 230 W, after adjustment for risk factors. Independent predictors for all-cause death were European SCORE (for 1% increment, RR: 1.15, 95% CI: 1.10-1.20, P<0.001), exercise workload (for 20 W increment, RR: 0.86, 95% CI: 0.82-0.91, P<0.001), C-reactive protein and alcohol consumption, when adjusted for serum high-density lipoprotein, body mass index, family history of coronary heart disease, exercise-induced ST changes and the use of medications for hypertension, dyslipidemia or aspirin. CONCLUSION: Low exercise workload predicts an especially high risk for death from cardiovascular and any other cause when combined with high risk SCORE.     

Fluvastatin Reduces Cardiac Mortality in Patients with Coronary Heart Disease

PURPOSE: To test the effectiveness of fluvastatin, 40-80 mg, in reducing the occurrence of cardiac and all-cause mortality in patients with coronary heart disease (CHD). METHODS: Meta-analysis of all clinical trials that assessed the effects of fluvastatin in CHD patients on major adverse cardiac events (MACE) as a prespecified endpoint was performed. A pooled analysis of four studies (n = 3525) was performed on an intent-to-treat basis. Clinical endpoints were the incidence, and time to first occurrence, of MACE (cardiac death, nonfatal MI, revascularization), noncardiac death, or all-cause death. Lipid parameters were also analyzed. RESULTS: Fluvastatin treatment significantly prolonged the time to cardiac death (p = 0.0174) and the time to cardiac death or nonfatal MI (p = 0.0055) compared with placebo. Fluvastatin significantly reduced the risk of any MACE (Cox risk ratio [RR], 0.85; 95% confidence interval [CI], 0.73-0.98), cardiac death (RR, 0.53; 95% CI, 0.31-0.90), cardiac death or MI (RR, 0.66; 95% CI, 0.49-0.89), all-cause death (RR, 0.65; 95% CI, 0.45-0.94) and all-cause death or MI (RR, 0.69; 95% CI, 0.53-0.90). Fluvastatin significantly lowered total cholesterol and low-density lipoprotein cholesterol levels and was well tolerated, with no cases of rhabdomyolysis in any of the studies assessed in the meta-analysis. CONCLUSIONS: This meta-analysis demonstrates clear beneficial effects of fluvastatin on cardiac and all-cause mortality in CHD patients, and supports the use of fluvastatin to reduce the incidence of MACE in a wide range of at-risk patients.     

The association between the length of the QT interval and mortality in the Cardiovascular Health Study

PURPOSE: A long QT interval is a risk factor for arrhythmic events and sudden death. Whether moderate QT prolongation is associated with clinical events in community-dwelling elderly patients is uncertain. METHODS: We measured the QT interval in a population-based sample of 5888 men and women at least 65 years of age who were participants in the Cardiovascular Health Study. The association between Bazett's rate-corrected QT (QTc, in ms) and mortality during the subsequent 10 years was evaluated. We stratified participants by the presence or absence of coronary heart disease status at baseline, and adjusted for coronary heart disease risk factors. RESULTS: The rates of all-cause and coronary heart disease mortality were greater in participants with longer QTc intervals. Among participants without known coronary heart disease, those whose QTc interval was >450 ms were at increased risk of all-cause mortality (relative risk [RR] = 1.34; 95% confidence interval [CI]: 1.07 to 1.67) and coronary heart disease mortality (RR = 1.6; 95% CI: 1.0 to 2.5) when compared with participants whose QTc interval was <410 ms. The associations were stronger among those with known coronary heart disease (RR for all-cause mortality = 2.3; 95% CI: 1.6 to 3.3; and RR for coronary heart disease mortality = 2.0; 95% CI: 1.1 to 3.7). CONCLUSIONS: The QT interval from the standard electrocardiograms is of value for identification of elderly persons at increased risk of coronary heart disease and total mortality. A QTc interval >450 ms should prompt clinical evaluation and possible interventions to reduce the risk of coronary events.     

Clinical events in high-risk hypertensive patients randomly assigned to calcium channel blocker versus angiotensin-converting enzyme inhibitor in the antihypertensive and lipid-lowering treatment to prevent heart attack trial

The Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT) provides a unique opportunity to compare the long-term relative safety and efficacy of angiotensin-converting enzyme inhibitor and calcium channel blocker-initiated therapy in older hypertensive individuals. Patients were randomized to amlodipine (n=9048) or lisinopril (n=9054). The primary outcome was combined fatal coronary heart disease or nonfatal myocardial infarction, analyzed by intention-to-treat. Secondary outcomes included all-cause mortality, stroke, combined cardiovascular disease (CVD), end-stage renal disease (ESRD), cancer, and gastrointestinal bleeding. Mean follow-up was 4.9 years. Blood pressure control was similar in nonblacks, but not in blacks. No significant differences were found between treatment groups for the primary outcome, all-cause mortality, ESRD, or cancer. Stroke rates were higher on lisinopril in blacks (RR=1.51, 95% CI 1.22 to 1.86) but not in nonblacks (RR=1.07, 95% CI 0.89 to 1.28), and in women (RR=1.45, 95% CI 1.17 to 1.79), but not in men (RR=1.10, 95% CI 0.92 to 1.31). Rates of combined CVD were higher (RR=1.06, 95% CI 1.00 to 1.12) because of higher rates for strokes, peripheral arterial disease, and angina, which were partly offset by lower rates for heart failure (RR=0.87, 95% CI 0.78 to 0.96) on lisinopril compared with amlodipine. Gastrointestinal bleeds and angioedema were higher on lisinopril. Patients with and without baseline coronary heart disease showed similar outcome patterns. We conclude that in hypertensive patients, the risks for coronary events are similar, but for stroke, combined CVD, gastrointestinal bleeding, and angioedema are higher and for heart failure are lower for lisinopril-based compared with amlodipine-based therapy. Some, but not all, of these differences may be explained by less effective blood pressure control in the lisinopril arm.     

Low-dose aspirin in patients with stable cardiovascular disease: a meta-analysis

Objective

Many recommendations for aspirin in stable cardiovascular disease are based on analyses of all antiplatelet therapies at all dosages and in both stable and unstable patients. Our objective was to evaluate the benefit and risk of low-dose aspirin (50-325 mg/d) in patients with stable cardiovascular disease.

Methods

Secondary prevention trials of low-dose aspirin in patients with stable cardiovascular disease were identified by searches of the MEDLINE database from 1966 to 2006. Six randomized trials were identified that enrolled patients with a prior myocardial infarction (MI) (n = 1), stable angina (n = 1), or stroke/transient ischemic attack (n = 4). A random effects model was used to combine results from individual trials.

Results

Six studies randomized 9853 patients. Aspirin therapy was associated with a significant 21% reduction in the risk of cardiovascular events (nonfatal MI, nonfatal stroke, and cardiovascular death) (95% confidence interval [CI], 0.72-0.88), 26% reduction in the risk of nonfatal MI (95% CI, 0.60-0.91), 25% reduction in the risk of stroke (95% CI, 0.65-0.87), and 13% reduction in the risk of all-cause mortality (95% CI, 0.76-0.98). Patients treated with aspirin were significantly more likely to experience severe bleeding (odds ratio 2.2, 95% CI, 1.4-3.4). Treatment of 1000 patients for an average of 33 months would prevent 33 cardiovascular events, 12 nonfatal MIs, 25 nonfatal strokes, and 14 deaths, and cause 9 major bleeding events. Among those with ischemic heart disease, aspirin was most effective at reducing the risk of nonfatal MI and all-cause mortality; however, among those with cerebrovascular disease, aspirin was most effective at reducing the risk of stroke.

Conclusion

In patients with stable cardiovascular disease, low-dose aspirin therapy reduces the incidence of adverse cardiovascular events and all-cause mortality, and increases the risk of severe bleeding.     

Usefulness of noninvasive estimate of pulmonary vascular resistance to predict mortality, heart failure, and adverse cardiovascular events in Patients With stable coronary artery disease (from the Heart and Soul Study)

Pulmonary vascular resistance (PVR) is an important hemodynamic variable that affects prognosis and therapy in a wide range of cardiovascular and pulmonary conditions. We sought to determine whether a noninvasive estimate of PVR predicts adverse outcomes in patients with stable coronary artery disease. Using Doppler echocardiography we measured the estimated PVR (defined as the ratio of the tricuspid regurgitant velocity [TRV] to the velocity-time integral [VTI] of the right ventricular outflow tract [RVOT]) in 795 ambulatory patients with stable coronary artery disease. Participants were categorized by quartiles of the TRV/VTI RVOT ratio. Hazard ratios (HRs) and 95% confidence intervals were calculated for all-cause mortality, heart failure hospitalization, and adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or stroke). After 4.3 years of follow-up there were 161 deaths, 44 deaths from cardiovascular causes, 103 heart failure hospitalizations, and 120 adverse cardiovascular events. Compared with patients in the lowest TRV/VTI RVOT quartile, those in the highest quartile were at increased risk of all-cause mortality (unadjusted HR 1.8, 95% confidence interval 1.3 to 2.5), heart failure hospitalization (unadjusted HR 2.9, 95% confidence interval 2.0 to 4.3), and adverse cardiovascular events (unadjusted HR 2.0, 95% confidence interval 1.4 to 2.9). After multivariate adjustment, patients in the highest quartile were at increased risk of heart failure hospitalizations (adjusted HR 2.5, 95% confidence interval 1.3 to 4.7). In conclusion, a noninvasive estimate of PVR (TRV/VTI RVOT ratio) predicts mortality, heart failure hospitalization, and adverse cardiovascular events in patients with stable coronary artery disease.     

Proteinuria as a risk factor for cardiovascular disease and mortality in older people: a prospective study

BACKGROUND: The prognostic significance of proteinuria in older people is not well defined. We examined the associations between proteinuria and incident coronary heart disease, cardiovascular mortality, and all-cause mortality in older people.SUBJECTS AND METHODS: Casual dipstick proteinuria was determined in 1,045 men (mean [+/- SD] age 68 +/- 7 years) and 1,541 women (mean age 69 +/- 7 years) attending the 15th biennial examination of the Framingham Heart Study. Participants were divided by grade of proteinuria: none (85.3%), trace (10.2%), and greater-than-trace (4.5%). Cox proportional hazards analyses were used to determine the relations of baseline proteinuria to the specified outcomes, adjusting for other risk factors, including serum creatinine level.RESULTS: During 17 years of follow-up, there were 455 coronary heart disease events, 412 cardiovascular disease deaths, and 1,214 deaths. In men, baseline proteinuria was associated with all-cause mortality (hazards ratio [HR] = 1.3, 95% confidence interval [CI] 1.0 to 1.7 for trace proteinuria; HR = 1.3, 95% CI 1.0 to 1.8 for greater-than-trace proteinuria; P for trend = 0.02). In women, trace proteinuria was associated with cardiovascular disease death (HR = 1. 6, 95% CI 1.1 to 2.4), and all-cause mortality (HR = 1.4, 95% CI 1.1 to 1.7).CONCLUSION: Proteinuria is a significant, although relatively weak, risk factor for all-cause mortality in men and women, and for cardiovascular disease mortality in women.     

Common paraoxonase gene variants, mortality risk and fatal cardiovascular events in elderly subjects

Recent studies indicate that the enzyme paraoxonase may be an important modulator of cardiovascular disease risk because of its ability to protect LDL from oxidation. We tested for association between two functional variants of the paraoxonase gene (Met-55/Leu and Gln-192/Arg) and both all-cause mortality and fatal cardiovascular disease. This was done within a population-based study among subjects aged 85 years and over in a cross-sectional and a prospective design. In the cross-sectional analysis, the distribution of both paraoxonase genotypes was found to be similar in the subset of 364 elderly subjects who were born in Leiden, The Netherlands, as compared with 250 young subjects whose families originated from the same geographical region. The polymorphisms were in strong linkage disequilibrium (P<0.00001) and the frequency of the haplotype carrying both risk alleles was not lower in the elderly than in the young (0.313 vs. 0.284). The complete cohort of 666 elderly subjects was followed over 10 years. The risk of all-cause and cardiovascular mortality was not increased in elderly subjects with the paraoxonase Leu/Leu (RR, 1.1 [95% CI, 0.9-1.5] and 1.3 [95% CI, 0.8-2.0], respectively) or the Arg/Arg genotype (RR, 0. 9 [95% CI, 0.7-1.2] and 0.7 [95% CI, 0.4-1.3], respectively). In a subset of patients with diabetes, the all-cause mortality risk was elevated in Arg/Arg carriers (RR, 2.1 [95% CI, 0.8-5.8]) but this did not reach statistical significance. Analysis of genotype combinations did not yield significant associations with mortality. The paraoxonase gene variants, previously associated with coronary artery disease, are thus not likely to have a major effect on the risk of fatal cardiovascular disease in the population at large. Adverse effects of the gene variants might be observed in subjects exposed to factors that enhance oxidative stress such as diabetes.     

Mortality and morbidity during and after the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial

A randomized, double-blind, active-controlled, multicenter trial assigned 32,804 participants aged 55 years and older with hypertension and ≥ 1 other coronary heart disease risk factors to receive chlorthalidone (n=15,002), amlodipine (n=8898), or lisinopril (n=8904) for 4 to 8 years, when double-blinded therapy was discontinued. Passive surveillance continued for a total follow-up of 8 to 13 years using national administrative databases to ascertain deaths and hospitalizations. During the post-trial period, fatal outcomes and nonfatal outcomes were available for 98% and 65% of participants, respectively, due to lack of access to administrative databases for the remainder. This paper assesses whether mortality and morbidity differences persisted or new differences developed during the extended follow-up. Primary outcome was cardiovascular mortality and secondary outcomes were mortality, stroke, coronary heart disease, heart failure, cardiovascular disease, and end-stage renal disease. For the post-trial period, data are not available on medications or blood pressure levels. No significant differences (P<.05) appeared in cardiovascular mortality for amlodipine (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.93-1.06) or lisinopril (HR, 0.97; CI, 0.90-1.03), each compared with chlorthalidone. The only significant differences in secondary outcomes were for heart failure, which was higher with amlodipine (HR, 1.12; CI, 1.02-1.22), and stroke mortality, which was higher with lisinopril (HR, 1.20; CI, 1.01-1.41), each compared with chlorthalidone. Similar to the previously reported in-trial result, there was a significant treatment-by-race interaction for cardiovascular disease for lisinopril vs chlorthalidone. Black participants had higher risk than non-black participants taking lisinopril compared with chlorthalidone. After accounting for multiple comparisons, none of these results were significant. These findings suggest that neither calcium channel blockers nor angiotensin-converting enzyme inhibitors are superior to diuretics for the long-term prevention of major cardiovascular complications of hypertension.     

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.     

Influenza Vaccination as Prevention Therapy for Stable Coronary Artery Disease and Acute Coronary Syndrome: A Meta-Analysis of Randomized Trials

BackgroundInfluenza can cause a significant burden on patients with coronary artery disease. This meta-analysis assessed the effectiveness of influenza vaccination in patients with acute coronary syndrome and stable coronary artery disease.MethodsWe searched the Cochrane Controlled Register of Trials (CENTRAL), Embase, MEDLINE, www.ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform from inception to September 2021. Estimates were summarized using the Mantel-Haenzel method and a random-effects model. To assess heterogeneity the I² statistic was used.ResultsFive randomized trials, comprising 4187 patients, were included, 2 of which included patients with acute coronary syndrome and 3 that included patients with stable coronary artery disease and acute coronary syndrome. Influenza vaccination significantly reduced the risk for all-cause mortality (relative risk [RR] = 0.56; 95% confidence interval [CI], 0.38-0.84), cardiovascular mortality (RR = 0.54; 95% CI, 0.37-0.80), major acute cardiovascular events (RR = 0.66; 95% CI, 0.49-0.88), and acute coronary syndrome (RR = 0.63; 95% CI, 0.44-0.89). On subgroup analysis, influenza vaccination remained effective for these outcomes in acute coronary syndrome but did not meet statistical significance in coronary artery disease. Furthermore, influenza vaccination did not reduce the risk for revascularization (RR = 0.89; 95% CI, 0.54-1.45), stroke or transient ischemic attack (RR = 0.85; 95% CI, 0.31-2.32), or heart failure hospitalization (RR = 0.91; 95% CI, 0.21-4.00).ConclusionsInfluenza vaccine is a cheap and effective intervention to reduce the risk for all-cause mortality, cardiovascular mortality, major acute cardiovascular events, and acute coronary syndrome among coronary artery disease patients, especially in those with acute coronary syndrome.     

Serum uric acid as a risk factor of all-cause mortality and cardiovascular events among type 2 diabetes population: Meta-analysis of correlational evidence

AimsTo explore the association between serum uric acid (SUA) level and the risk of cardiovascular complications and all-cause mortality rates among individuals with type 2 diabetes.MethodsWeb of Science and PubMed database were searched for studies reported associations between SUA level and cardiovascular complications and all-cause mortality among individuals with type 2 diabetes. Hazard ratios (HRs) were independently extracted by two investigators and synthesized through meta-analysis across selected studies.Results6 (n = 11,750 patients), 4 (n = 3044 patients) and 2 studies (n = 7792 patients) were identified reporting associations between SUA level and all-cause mortality, coronary heart disease (CHD) and stroke respectively. HR for all-cause mortality, CHD, and stroke per 59 μmol/l increase was 1.06 (95% CI: 1.03, 1.09), 1.09 (95% CI: 0.94, 1.26) and 1.19 (95% CI: 1.08, 1.31), respectively.ConclusionsOverall, the SUA level was associated with a higher risk of all-cause mortality and stroke. We found no significant association between SUA level and CHD among type 2 diabetes population.     

Renal function and attributable risk of death and cardiovascular hospitalization in participants with diabetes from a registry-based cohort

AimsTo estimate the attributable risk of renal function on all-cause mortality and cardiovascular hospitalization in patients with diabetes.MethodsA prospective cohort study in 19,469 adults with diabetes, free of cardiovascular disease, attending primary care in Spain (2008–2011). The estimated glomerular filtration rate (eGFR) and other variables were collected and patients were followed to the first hospitalization for coronary or stroke event, or death, until the end of 2012. The cumulative incidence of the study endpoints by eGFR categories was graphically displayed and adjusted population attributable risks (PARs) for low eGFR was calculated.ResultsMean follow-up was 3.2 years and 506 deaths and 1720 hospitalizations were recorded. The cumulative risk for the individual events increased as eGFR levels decreased. The PAR associated with having an eGFR of 60 mL/min/1.73 m² or less was 11.4% (95% CI 4.8–18.3) for all-cause mortality, 9.2% (95% CI 5.3–13.4) for coronary heart disease, and 2.6% (95% CI ?1.8 to 7.4) for stroke.ConclusionsReduced eGFR levels were associated with a larger proportion of avoidable deaths and cardiovascular hospitalizations in people with diabetes compared to previously reported results in people with other cardiovascular risk factors.