Relation of heart rate parameters during exercise test to sudden death and all-cause mortality in asymptomatic men

Heart rate (HR) profile during exercise predicts all-cause mortality. However, less is known about its relation to sudden (vs nonsudden) death in asymptomatic people. The relation of exercise HR parameters (HR at rest, target HR achievement, HR increase, and HR recovery) with sudden death, coronary heart disease (CHD) death, myocardial infarction, and all-cause mortality was assessed in 12,555 men who participated in MRFIT. Subjects were 35 to 57 years old without clinical CHD, but with higher than average Framingham risk. Trial follow-up was 7 years, and extended follow-up after the trial for all-cause mortality was 25 years. After adjusting for cardiac risk factors, having to stop exercise before achieving 85% of age-specific maximal HR was associated with increased risk of sudden death (hazard ratio 1.8, 95% confidence interval [CI] 1.3 to 2.5, p = 0.001), CHD death (hazard ratio 1.4, 95% CI 1.2 to 1.5, p <0.001), and all-cause mortality (hazard ratio 1.3, 95% CI 1.2 to 1.4, p <0.001). Increased HR at rest (p = 0.001), attenuated HR increase (p = 0.02), delayed HR recovery (p = 0.04), and exercise duration (p <0.0001) were independent predictors of all-cause death in the overall study population and also in the subgroup that achieved target HR. In conclusion, middle-aged men without clinical CHD who stopped exercise before reaching 85% of maximal HR had a higher risk of sudden death. Other exercise HR parameters and exercise duration predicted all-cause mortality.     

Exercise blood pressure and the risk of incident cardiovascular disease (from the Framingham Heart Study)

Exaggerated systolic blood pressure (BP) augmentation with exercise has been associated with impaired endothelial function and cardiovascular risk. However, previous studies were largely restricted to men, did not evaluate diastolic BP, and focused on peak exercise measures, which are influenced by effort and fitness level. The aim of this study was to determine the association of exercise BP responses with risk of incident cardiovascular disease (CVD). BP was assessed during stage 2 of the Bruce protocol and during recovery in 3,045 Framingham Study subjects (mean age 43 years; 53% women). The association between exercise BP and CVD events during 20 years of follow-up was examined using Cox proportional hazards models. In age- and sex-adjusted analyses, exercise systolic and diastolic BP were associated with incident CVD (adjusted hazard ratios [HRs] for top quintile 1.55, 95% confidence interval [CI] 1.18 to 2.04; and 1.77, 95% CI 1.35 to 2.31, respectively, relative to the lower 4 quintiles; p <0.005). After adjustment for BP at rest and conventional risk factors, exercise diastolic BP (HR 1.41, 95% CI 1.01 to 1.95, p = 0.04), but not exercise systolic BP (HR 0.97, 95% CI 0.68 to 1.38, p = 0.86), remained a significant predictor of CVD. Similarly, in recovery responses after exercise, only diastolic BP (HR 1.53, 95% CI 1.08 to 2.18, p = 0.02) predicted incident CVD in multivariable models. In conclusion, in middle-aged adults, diastolic BP during low-intensity exercise and recovery predicted incident CVD. Our findings support the concept that dynamic BP provides incremental information to BP at rest and suggest that exercise diastolic BP may be a better predictor than exercise systolic BP in this age group.     

Chronic kidney disease and risk of incident myocardial infarction and all-cause and cardiovascular disease mortality in middle-aged men and women from the general population.

AIMS: Chronic kidney disease (CKD) was found to be an independent risk factor for all-cause mortality as well as adverse cardiovascular disease (CVD) events in high-risk populations. Findings from population-based studies are scarce and inconsistent. We investigated the gender-specific association of CKD with all-cause mortality, cardiovascular mortality, and incident myocardial infarction (MI) in a population-based cohort. METHODS AND RESULTS: The study was based on 3860 men and 3674 women (aged 45-74 years) who participated in one of the three MONICA Augsburg surveys between 1984 and 1995. CKD was defined by an estimated glomerular filtration rate between 15 and 59 mL/min/1.73 m(2). Hazard ratios (HRs) were estimated from Cox proportional hazard models. In this study, 890 total deaths, 400 CVD deaths, and 321 incident MIs occurred in men up to 31 December 2002; the corresponding numbers in women were 442, 187, and 102. In multivariable analyses, the HR for women with CKD compared to women with preserved renal function was significant for incident MI [HR 1.67; 95% confidence interval (CI) 1.07-2.61] and CVD mortality (HR 1.60; 95% CI 1.17-2.18). In men, CKD was also significantly associated with incident MI (HR 1.51; 95% CI 1.09-2.10) and CVD mortality (HR 1.48; 95% CI 1.15-1.92) after adjustment for common CVD risk factors. In contrast, men and women with CKD had no significant increased risk of all-cause mortality. CONCLUSION: CKD was strongly associated with an increased risk of incident MI and CVD mortality independent from common cardiovascular risk factors in men and women from the general population.     

Mortality in diabetes compared with previous cardiovascular disease: A gender-specific meta-analysis

AimsDiabetes has been described as a cardiovascular disease (CVD) risk equivalent. There is evidence, however, that its impact may differ between women and men. For this reason, our study aimed to obtain gender-specific hazard ratios (HRs) comparing diabetes and CVD patients in terms of all-cause, CVD and coronary heart disease (CHD) mortality.MethodsIndividuals with diabetes (without CVD) and those with CVD (without diabetes) were examined through a systematic review of articles that provided gender-specific HRs for mortality. Searches included Medline, Embase and the Cochrane Library database (from January 1998 to December 2009) and exploded MeSH headings [cardiovascular diseases, risk, epidemiologic studies, case-control studies, cohort studies, mortality, outcome assessment (health care), sex factors, survival analysis and diabetes mellitus, type 2]. Two observers selected and reviewed the studies and hierarchical Bayesian random-effects models were used to combine HRs, thereby accommodating any between-study differences through inclusion of a between-study variance in HRs.ResultsOut of 5425 studies, nine were relevant (0.17%). CVD and CHD mortality in men was lower for diabetes alone (CVD mortality HR: 0.82, 95% CrI: 0.69–0.98; CHD mortality HR: 0.73, 95% CrI: 0.65–0.83). In contrast, rates appeared to be higher in women with diabetes alone (CVD mortality HR: 1.29, 95% CrI: 0.79–2.26; CHD mortality HR: 1.28, 95% CrI: 0.75–2.22), although wide credible intervals precluded any definitive conclusions. All-cause mortality in men was similar for diabetes and previous CVD (HR: 1.02, 95% CrI: 0.93–1.12) whereas, among women, it was at least as high and possibly higher for diabetes alone (HR: 1.25, 95% CrI: 0.89–1.76).ConclusionCompared with previous CVD, diabetes alone leads to lower CVD and CHD mortality risk in men, and similar all-cause mortality. In contrast, although further studies are needed, it is possible that diabetes leads to higher CVD, CHD and all-cause mortality in women.     

Hard drinking water does not protect against cardiovascular disease: new evidence from the British Regional Heart Study.

BACKGROUND: It has been previously suggested that hard drinking water in general, and in particular high calcium and magnesium intake from drinking water, protect against cardiovascular disease. DESIGN: Prospective study of men from 24 British towns, with widely differing levels of hardness in drinking water. METHODS: A total of 7,735 men aged 40-59 years were recruited during 1978-1980. Estimates of town-level water hardness were available and tap water samples, taken from 947 participants who also answered a questionnaire about water consumption, were used to calculate individual calcium and magnesium intakes. Men were followed for incident of major coronary heart disease (CHD) and stroke, and CHD mortality for 25 years. RESULTS: Water hardness varied from 0.27 to 5.28 mmol/l in the 24 towns. A weak inverse association was found between water hardness and incidence of cardiovascular disease (CVD) [hazard ratio (HR), 0.96 per two-fold increase, 95% confidence interval (CI), 0.91-1.01, P=0.08 after adjustment for age and seven established coronary risk factors]. No association was observed with CHD incidence (adjusted HR, 0.99, 95% CI, 0.94-1.04, P=0.62) or mortality (adjusted HR, 0.96, 95% CI, 0.90-1.02, P=0.18). Individual magnesium intake showed a positive, rather than an inverse, association with CHD incidence (adjusted HR, 1.10 per two-fold increase, 95% CI, 1.01-1.20, P=0.045); individual calcium intake was unrelated to CHD or CVD end points. CONCLUSIONS: This study suggests that neither high water hardness, nor high calcium or magnesium intake appreciably protect against CHD or CVD. Initiatives to add calcium and magnesium to desalinated water cannot be justified by these findings.     

Self-reported habitual snoring and risk of cardiovascular disease and all-cause mortality

Objective

Inconsistent findings have reported the association between self-reported habitual snoring and risk of cardiovascular disease (CVD) and all-cause mortality. We conducted a meta-analysis to investigate whether self-reported habitual snoring was an independent predictor for CVD and all-cause mortality using prospective observational studies.

Methods

Electronic literature databases (PubMed, Medline, Embase, Cochrane Library, Wanfang database, and China National Knowledge Infrastructure) were searched for publications prior to September 2013. Only prospective studies evaluating baseline habitual snoring and subsequent risk of CVD and all-cause mortality were selected. Pooled adjust hazard risk (HR) and corresponding 95% confidence intervals (CI) were calculated for categorical risk estimates.

Results

Eight studies with 65,037 subjects were analyzed. Pooled adjust HR was 1.26 (95% CI 0.98–1.62) for CVD, 1.15 (95% CI 1.05–1.27) for coronary heart disease (CHD), and 1.26 (95% CI 1.11–1.43) for stroke comparing habitual snoring to non-snorers. Pooled adjust HR was 0.98 (95% CI 0.78–1.23) for all-cause mortality in a random effect model comparing habitual snoring to non-snorers. Habitual snoring appeared to increase greater stroke risk among men (HR 1.54; 95% CI: 1.09–2.17) than those in women (HR 1.22; 95% CI: 1.05–1.41).

Conclusions

Self-reported habitual snoring is a mild but statistically significant risk factor for stroke and CHD, but not for CVD and all-cause mortality. However, whether the risk is attributable to obstructive sleep apnea syndrome or snoring alone remains controversial.     

Heart rate response during exercise test and cardiovascular mortality in middle-aged men.

AIMS: The objective is to study whether a heart rate (HR) response during exercise test independently predicts cardiovascular disease (CVD) mortality. METHODS AND RESULTS: The subjects were a representative sample of 1378 men, 42-61 years of age, from eastern Finland with neither prior coronary heart disease (CHD) nor use of beta-blockers at baseline. HR was measured at rest and during a maximal, symptom-limited exercise test at 20, 40, 60, 80, and 100% of maximal workload. During an average follow-up of 11.4 years, there were 56 deaths due to CVD. The slope of HR increase during exercise test was steeper in survivors when compared with those who died due to CVD during follow-up (P<0.001), and the difference in the steepness of HR slope between the groups was the strongest at interval 40-100% (P<0.001). In Cox-multivariable models, maximal HR-HR at 40% workload as a continuous variable was inversely associated with CVD (P=0.04), CHD (P=0.004), and all-cause (P=0.002) mortality after adjustment for known risk factors for CVD death. CONCLUSION: By considering an HR response throughout an exercise test, we found that a blunted HR increase at 40-100% of maximal workload was associated with increased CVD mortality.     

Plasma renin and risk of cardiovascular disease and mortality: the Framingham Heart Study.

AIMS: Previous studies relating plasma renin to cardiovascular disease (CVD) and mortality yielded conflicting results. We related plasma renin to incidence of CVD and mortality in 3408 individuals (mean age 59; 53% women) and in a hypertensive subset (n = 1413). METHODS AND RESULTS: On follow-up (mean 7.1 years), 176 participants (122 hypertensives) developed CVD and 215 individuals (127 hypertensives) died. Overall, log-renin was associated with mortality [multivariable-adjusted hazards ratio (HR) per SD increment: in whole sample, 1.14, 95% confidence interval (CI) 1.00-1.30, P = 0.046; hypertensives, 1.16, 95% CI 1.00-1.35, P = 0.046], but relations varied over time (P < 0.02). Log-renin was associated with mortality at 2.5 years of follow-up (HR per SD increment: whole sample at 2.5 years, 1.23, 95% CI 1.04-1.45; hypertensives at 2 years, 1.28, 95% CI 1.06-1.54), but not during longer follow-up (HR per SD increment at 5 years: whole sample, 1.02, 95% CI 0.80-1.29; hypertensives, 0.98, 95% CI 0.74-1.30). The time-dependent relation of renin and mortality risk was maintained upon excluding participants with prevalent CVD. Renin was not associated with CVD incidence (HR per SD increment log-renin: whole sample, 0.99, 95% CI 0.85-1.14; hypertensives, 0.96, 95% CI 0.82-1.12). CONCLUSION: Higher plasma renin was associated with greater short-term mortality but not with CVD incidence in the community.     

Heart rate variability in long-term risk assessment in middle-aged women with coronary heart disease: The Stockholm Female Coronary Risk Study

OBJECTIVES: Low heart rate variability (HRV) is associated with poor prognosis after acute coronary events in men. In women, the prognostic impact is not well documented. The objective of this study was to assess the long-term predictive power of HRV on mortality amongst middle-aged women with coronary heart disease (CHD). DESIGN, SETTINGS AND SUBJECTS: Consecutive women below 65 years hospitalized for an acute coronary syndrome during a 3-year period in Stockholm were examined for cardiovascular prognostic factors including HRV, and followed for a median of 9 years. An ambulatory 24-h electrocardiograph was recorded during normal activities, 3-6 months after hospitalization. SDNN index (mean of the standard deviations of all normal to normal intervals for all 5-min segments of the entire recording) and the following frequency domain parameters were assessed: total power, high-frequency (HF) power, low-frequency (LF) power, very-low frequency (VLF) power and LF/HF ratio. Using Cox proportional hazards regression, the hazard ratios (HR) for each 25% decrease of the HRV parameters were assessed. RESULTS: After controlling for the independent, significant predictors of mortality amongst the clinical variables, the following HRV parameters were found to be significant predictors of all-cause mortality: SDNN index [HR 1.56, 95% confidence intervals (CI) 1.19-2.05], total power (HR 1.21, 95% CI 1.08-1.35), VLF power (HR 1.22, 95% CI 1.09-1.36), LF power (HR 1.18 95%, CI 1.07-1.30) and HF power (HR 1.18, 95% CI 1.05-1.33). The results were essentially the same when cardiovascular mortality was used as end-points. The HRV parameters were stronger predictors of mortality in the first 5 years following the index event. CONCLUSION: Low HRV is a predictor of long-term mortality amongst middle-aged women with CHD when measured 3-6 months after hospitalization for an acute coronary syndrome, even after controlling for established clinical prognostic markers.     

Sustained Physical Activity,Not Weight Loss,Associated With Improved Survival in Coronary Heart Disease

Background

Individuals with coronary heart disease (CHD) are recommended to be physically active and to maintain a healthy weight. There is a lack of data on how long-term changes in body mass index (BMI) and physical activity (PA) relate to mortality in this population.

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.     

Body mass index, physical inactivity and low level of physical fitness as determinants of all-cause and cardiovascular disease mortality--16 y follow-up of middle-aged and elderly men and women

OBJECTIVE: To investigate the independent associations and the possible interaction of body mass index (BMI), leisure time physical activity (LTPA) and perceived physical fitness and functional capability with the risk of mortality. DESIGN: Prospective 16y follow-up study. SUBJECTS: A regionally representative cohort of 35-63-y-old Finnish men (n= 1,090) and women (n= 1,122). MEASUREMENTS: All-cause, cardiovascular disease (CVD) and coronary heart disease (CHD) mortality were derived from the national census data until the end of September 1996 while the initial levels of BMI, LTPA, physical fitness and function were determined from self-administered questionnaires. RESULTS: After adjustment for age, marital and employment status, perceived health status, smoking and alcohol consumption, the Cox proportional hazards model showed that BMI was not associated with the risk of death among the men or the women. Compared with the most active subjects the men and women with no weekly vigorous activity had relative risks of 1.61 (95% confidence interval, CI, 0.98-2.64) and 4.68 (95% CI, 1.41-15.57), respectively, for CVD mortality, and for the men there was a relative risk of 1.66 (95% CI, 0.92-2.99) for CHD mortality. When compared with the men who perceived their fitness as better than their age-mates, the men with the 'worse' assessment had a relative risk of 3.29 (95% CI, 1.80-6.02) for all-cause mortality and 4.37 (95% CI, 1.80-10.6) for CVD mortality. Men with at least some difficulty in walking a distance of 2 km had a relative risk of 1.62 (95% CI, 1.05-2.50) for all-cause mortality when compared with those who had no functional difficulties. In addition, in the comparison with subjects with no functional difficulties, the men and women who had some difficulty climbing several flights of stairs had relative risks of 1.47 (95% CI, 0.97-2.23) and 2.39 (95% CI, 1.25-4.60) for all-cause mortality, respectively. For CVD mortality the relative risks were 1.85 (95% CI, 1.04-3.30) and 3.38 (1.22-9.41), respectively. CONCLUSIONS: Although BMI did not prove to be an independent risk factor for mortality from CVD, CHD or from all causes combined, perceived physical fitness and functional capability did. An increase in LTPA seems to have a similar beneficial effect on the mortality risk of obese and nonobese men and women, and the effect also seems to be similar for fit and unfit subjects.     

Erratum to “The growing interest of fibrin imaging in atherosclerosis” [Atherosclerosis 222 (1) (2012) 22–25]

ObjectiveHigh-density lipoprotein cholesterol (HDL) and physical fitness (PF) have both been shown to predict cardiovascular disease (CVD), particularly coronary heart disease (CHD). Increased PF is associated with increased HDL and may partly explain the benefit of HDL. We tested the hypothesis that PF influences the prognostic impact of HDL for CHD and also for CHD-, CVD- and all-cause death.MethodsHDL was measured 1979–1982 in 1357 healthy men aged 44–69 years followed up to 28 years. PF was measured using bicycle exercise test. Hazard ratios (HRs) adjusted for age, smoking, systolic blood pressure, and total cholesterol and further for PF between HDL quartiles were calculated using Cox proportional survival model.ResultsThe highest HDL quartile was associated with lower risk of CHD (HR: 0.57, 95% confidence interval [CI]: 0.43–0.74), fatal CHD (HR: 0.56, CI: 0.36–0.86), fatal CVD (HR: 0.64, CI: 0.46–0.88) and all-cause death (HR: 0.80, CI: 0.65–0.99) compared to the lowest quartile. Adjustments for PF or changes in PF over 8.6 years did not change the results except for all-cause death, which was not significantly different between HDL quartiles. We found no interaction between HDL and PF.ConclusionsHDL is a strong predictor of long term risk of CHD, fatal CHD and fatal CVD in healthy middle-aged men. Physical fitness or its changes had no impact on the ability of HDL to predict CHD.     

Increased serum levels of advanced glycation endproducts predict total, cardiovascular and coronary mortality in women with type 2 diabetes: a population-based 18 year follow-up study

Aims/hypothesis AGEs, modification products formed by glycation or glycoxidation of proteins and lipids, have been linked to premature atherosclerosis in patients with diabetes. We investigated whether increased serum levels of AGEs predict total, cardiovascular (CVD) or CHD mortality in a population-based study. Subjects and methods Serum levels of AGEs were determined by immunoassay in a random sample of 874 Finnish diabetic study participants (488 men, 386 women), aged 45–64 years. These participants were followed for 18 years for total, CVD and CHD mortality. Results Multivariate Cox regression models revealed that serum levels of AGEs were significantly associated with total (p = 0.002) and CVD mortality (p = 0.021) in women, but not in men. Serum levels of AGEs in the highest sex-specific quartile predicted all-cause (hazards ratio [HR] 1.51; 95% confidence intervals [CI], 1.14–1.99; p = 0.004), CVD (HR 1.56; 95% CI 1.12–2.19; p = 0.009), and CHD (HR 1.68; 95% CI 1.11–2.52; p = 0.013) mortality in women, even after adjustment for confounding factors, including high-sensitivity C-reactive protein. Conclusions/interpretation Increased serum levels of AGEs predict total and CVD mortality in women with type 2 diabetes. B. K. Kilhovd and A. Juutilainen contributed equally to this study.     

Interplay of Coronary Artery Calcium and Risk Factors for Predicting CVD/CHD Mortality: The CAC Consortium

ObjectivesThis study sought to evaluate the association and burden of coronary artery calcium (CAC) with long-term, cause-specific mortality across the spectrum of baseline risk.BackgroundAlthough CAC is a known predictor of short-term, all-cause mortality, data on long-term and cause-specific mortality are inadequate.MethodsThe CAC Consortium cohort is a multicenter cohort of 66,636 participants without coronary heart disease (CHD) who underwent CAC testing. The following risk factors (RFs) were considered: 1) current cigarette smoking; 2) dyslipidemia; 3) diabetes mellitus; 4) hypertension; and 5) family history of CHD.ResultsDuring the 12.5-years median follow-up, 3,158 (4.7%) deaths occurred; 32% were cardiovascular disease (CVD) deaths. Participants with CAC scores ≥400 had a significantly increased risk for CHD and CVD mortality (hazard ratio [HR]: 5.44; 95% confidence interval [CI]: 3.88 to 7.62; and HR: 4.15; 95% CI: 3.29 to 5.22, respectively) compared with CAC of 0. Participants with ≥3 RFs had a smaller increased risk for CHD and CVD mortality (HR: 2.09; 95% CI: 1.52 to 2.85; and HR: 1.84; 95% CI: 1.46 to 2.31, respectively) compared with those without RFs. Across RF strata, CAC added prognostic information. For example, participants without RFs but with CAC ≥400 had significantly higher all-cause, non-CVD, CVD, and CHD mortality rates compared with participants with ≥3 RFs and CAC of 0.ConclusionsAcross the spectrum of RF burden, a higher CAC score was strongly associated with long-term, all-cause mortality and a greater proportion of deaths due to CVD and CHD. Absence of CAC identified people with a low risk over 12 years of follow-up, with most deaths being non-CVD in nature, regardless of RF burden.     

Depression as an antecedent to heart disease among women and men in the NHANES I study. National Health and Nutrition Examination Survey

BACKGROUND: Depression predicts morbidity and mortality among individuals who have coronary heart disease (CHD), and there is increasing evidence that depression may also act as an antecedent to CHD. The studies that have reported a relationship between depression and CHD incidence or mortality either were restricted to men only or analyzed women and men together. The present investigation was conducted to evaluate the differential effect depression may have on CHD incidence and mortality in women and men. RESEARCH METHODS: We analyzed data from 5007 women and 2886 men enrolled in the first National Health and Nutrition Examination Survey (NHANES I) who were free of CHD at the 1982-1984 interview and who had completed the Center for Epidemiologic Studies Depression Scale (CES-D). Participants were evaluated from the 1982 interview date either until the end of the study (1992 interview date) or until the occurrence of a CHD event. Using CHD incidence and CHD mortality (International Classification of Disease, Ninth Revision, codes 410-414) as the outcome variables, Cox proportional hazards regression models were developed to evaluate the relative risk (RR) of CHD incidence and mortality in the depressed women and men separately, controlling for standard CHD risk factors. RESULTS: The women experienced 187 nonfatal and 137 fatal events, compared with 187 nonfatal and 129 fatal events among the men. The adjusted RR of CHD incidence among depressed women was 1.73 (95% confidence internal [CI], 1.11-2.68) compared with nondepressed women. Depression had no effect on CHD mortality in the women (RR, 0.74; 95% CI, 0.40-1.48). The adjusted RR of CHD incidence among depressed men was 1.71 (95% CI, 1.14-2.56) compared with nondepressed men. Depressed men also had an increased risk of CHD mortality compared with their nondepressed counterparts, with an adjusted RR of 2.34 (95% CI, 1.54-3.56). CONCLUSIONS: In this sample, while controlling for possible confounding factors, depression was associated with an increased risk of CHD incidence in both men and women, as well as CHD mortality in men. Depression had no effect on CHD mortality in women.     

Serum uric acid for short-term prediction of cardiovascular disease incidence in the Gubbio population Study

OBJECTIVE: The Gubbio Study is an Italian population study measuring risk factors for and incidence of major cardiovascular diseases. This analysis investigates the association of serum uric acid with the incidence of coronary and cardiovascular events. METHODS: A population sample of 2469 men and women aged 35-74 years, free from major cardiovascular diseases and in whom serum uric acid was measured in 1983 along with other standard risk factors, were followed up for 6 years and the incidence of coronary heart disease (CHD) and all cardiovascular atherosclerotic (CVD) events, both fatal and non-fatal, was computed. Proportional hazards models were used for the prediction of these events. RESULTS: In six years 61 CHD hard criteria, 109 CHD any criterion and 149 CVD events were recorded. Age-adjusted rates per 1000 of the 3 event categories were computed in sex-specific quintiles (Q) of serum uric acid with 428 +/- 76 (Q5) and 198 +/- 42 (Q1) micromol/l, respectively. Although higher rates were seen in Q5 as compared to Q1 for all three first event categories considered (relative risks 6.2, 3.6 and 3.7, respectively), a statistically significant trend was seen only for CVD all criteria (t = 3.63, p < 0.036). These trends were borderline significant for CHD any criterion (t = 2.92, p < 0.06) and not significant for CHD hard criteria (t = 2.23, p < 0.11). In multivariate models, adjusted for 8 other risk factors, serum uric acid showed a statistically significant contribution to predict CVD incidence [relative risk (RR) for 92 micromol/l difference of 1.24 with 95% confidence intervals (CI) 1.05-1.45], whereas the statistical contribution to predict CHD any criterion (RR = 1.19 with CI 0.98-1.45) and CHD hard criteria (RR = 1.20 with CI 0.93-1.55) was not significant. Diuretic treatment and blood urea, as further confounders, were positively and significantly related to event incidence (RR ranging from 1.21 to 2.00) but serum uric acid maintained its independent and statistically significant role in the prediction of CVD events (RR = 1.18 with CI 1.00-1.39). Presence of specific treatments to lower serum uric acid levels (in 1.13% of the population), tested as final confounders, was not statistically contributory. CONCLUSIONS: Increased serum uric acid levels are independently and significantly associated with risk of CVD events in the 6-year follow-up of the Gubbio Study. Longer follow-up is needed before the contributory role of serum uric acid can be properly assessed to explain CHD incidence.     

Exercise-induced silent myocardial ischemia and coronary morbidity and mortality in middle-aged men.

OBJECTIVES: We investigated the prognostic significance of exercise-induced silent myocardial ischemia in both high and low risk men with no prior coronary heart disease (CHD). BACKGROUND: Silent ischemia predicts future coronary events in patients with CHD, but there is little evidence of its prognostic significance in subjects free of CHD. METHODS: We investigated the association of silent ischemia, as defined by ST depression during and after maximal symptom-limited exercise test, with coronary risk in a population-based sample of men with no prior CHD followed for 10 years on average. RESULTS: Silent ischemia during exercise was associated with a 5.9-fold (95% CI 2.3 to 11.8) CHD mortality in smokers, 3.8-fold (95% CI 1.9 to 7.9) in hypercholesterolemic men and 4.7-fold (95% CI 2.4 to 9.1) in hypertensive men adjusting for other risk factors. The respective relative risks (RRs) of any acute coronary event were 3.0 (95% CI 1.7 to 5.1), 1.9 (95% CI 1.2 to 3.1) and 2.2 (95% CI 1.4 to 3.5). These associations were weaker in men without these risk factors. Furthermore, silent ischemia after exercise was a stronger predictor for the risk of acute coronary events and CHD death in smokers and in hypercholesterolemic and hypertensive men than in men without risk factors. CONCLUSIONS: Exercise-induced silent myocardial ischemia was a strong predictor of CHD in men with any conventional risk factor, emphasizing the importance of exercise testing to identify asymptomatic high risk men who could benefit from risk reduction and preventive measures.     

Red blood cell count in short-term prediction of cardiovascular disease incidence in the Gubbio population study

OBJECTIVE: The Gubbio Study is an Italian population study measuring risk factors and incidence for major cardiovascular diseases.This analysis investigates the association between red blood cell (RBC) count, after preliminarily taking into account haematocrit, and incidence of coronary and cardiovascular events. METHODS: A population sample of 2,469 men and women aged 35-74 years, free from major cardiovascular diseases and in whom RBC count and haematocrit were measured in 1983 along with other standard risk factors, were followed up for 6 years and incidence was estimated for both fatal and non-fatal coronary heart disease (CHD) and all cardiovascular atherosclerotic (CVD) events. Proportional hazards models were solved for the prediction of these events. RESULTS: In six years 61 CHD hard criteria, 109 CHD any criterion and 149 CVD events were recorded. Preliminarily, both haematocrit and RBC count, two highly correlated variables, were studied to predict CVD events; however, haematocrit did not contribute multivariately, in the overall population and separately in men and women. Age-adjusted rates per 1,000 of the 3 event categories were computed in sex-specific RBC count quintiles (Q) and a difference was observed between Q5 and Q1 (with 5.21 +/- 0.31 and 4.18 +/- 0.23 x 10(6) per microl, respectively) for CHD any criterion (p < 0.07) and CVD (p < 0.05). P on trends was < 0.05 for both end-points. In multivariate models, adjusted for 7 other risk factors, RBC count contributed a weak statistical significance to predict CVD incidence [relative risk (RR) for a 0.5 x 10(6) per microl difference 1.23 with 95% confidence intervals (CI) 1.00- 1.51], whereas its contribution to predict CHD any criterion (RR = 1.19 with CI 0.93- 1.51) and CHD hard criteria (RR = 1.15 with Cl 0.83-1.58) was not statistically significant. Inclusion of blood glucose and presence of diuretics (11.33% of the population) as possible confounders had no major effect although the latter were, as expected, a significant risk factor (RR = 1.90 with Cl 1.28-2.82) which further diluted the CVD predictive role of RBC count (RR = 1.22 with CI 0.99- 1.50). CONCLUSIONS: Increased RBC count is independently (yet weakly) associated with risk of CVD events in the 6-year follow-up of the Gubbio Study. Longer follow-up is needed before the contributory role of RBC count can be properly assessed to explain CHD incidence.     

Long-term prognostic value of resting heart rate in subjects with prehypertension

BACKGROUND: Increased resting heart rate increases cardiovascular risk in individuals with hypertension. The extent to which such risk extends to people with prehypertension is not known. The purpose of this study was to determine whether elevated resting heart rate contributes to increased coronary heart disease (CHD) risk in people with prehypertension. METHODS: The cohort for the current study consisted of 3275 persons from the Atherosclerosis Risk in Communities (ARIC) study, 45 to 64 years old in 1986 to 1989, with a mean follow-up of 10.1 years. The primary outcomes were CHD and all-cause mortality. RESULTS: Individuals with prehypertension and elevated resting heart rate had 50% higher all-cause mortality than people with prehypertension and lower resting heart rate (hazard ratio [HR] 1.50, 95% confidence interval [CI] 1.0-2.15), which was essentially unchanged after controlling for age, ethnicity, gender, diabetes, smoking status, LDL-cholesterol, exercise, and use of antilipemic agents (P < .01). Similarly, in unadjusted analyses, CHD risk was 49% higher for people with increased heart rate (HR 1.49, 95% CI 1.03-2.14). In adjusted analyses, elevated resting heart rate remained a factor in increased risk of CHD in women (adjusted HR 2.18, 95% CI 1.08-4.42), but not in men. CONCLUSIONS: Resting heart rate is an easily accessible tool that may be helpful for stratifying CHD and mortality risk in people with prehypertension.