Cardiovascular Mortality In Elderly Men Research Articles

PDGF-D gene polymorphism is associated with increased cardiovascular mortality in elderly men.

BackgroundPlatelet-derived growth factor (PDGF) D has been reported to be active in fibroblasts, and in areas of myocardial infarction. In this longitudinal study we evaluated the association between PDGF-D polymorphism and cardiovascular mortality, and attempted to discover whether specific genotype differences regarding risk could be observed, and if gender differences could be seen.MethodsFour hundred seventy-six elderly community participants were included in this study. All participants underwent a clinical examination, echocardiography, and blood sampling including PDGF-D single nucleotide polymorphism (SNP) analyses of the rs974819 A/A, G/A and G/G SNP. The follow-up time was 6.7 years.ResultsNo specific genotype of rs974819 demonstrated increased cardiovascular mortality in the total population, however, the male group with genotypes A/A and G/A demonstrated an increased risk that persisted in a multivariate evaluation where adjustments were made for well-known cardiovascular risk factors (2.7 fold compared with the G/G genotype). No corresponding finding was observed in the female group.ConclusionWe report here for the first time that the genotypes G/A or A/A of the SNP rs974819 near PDGF-D exhibited a 2.7 fold increased cardiovascular mortality risk in males. Corresponding increased risk could not be observed in either the total population and thus not in the female group. However, the sample size is was small and the results should be regarded as hypothesis-generating, and thus more research in the field is recommended.

SP291NON-ESTERIFIED FATTY ACIDS AND CARDIOVASCULAR MORTALITY IN ELDERLY MEN WITH CHRONIC KIDNEY DISEASE

Non-Esterified Fatty Acids and Cardiovascular Mortality in Elderly Men with Chronic Kidney Disease

Nonesterified fatty acids and cardiovascular mortality in elderly men with CKD.

Although nonesterified fatty acids (NEFAs) are essential as energy substrate for the myocardium, an excess of circulating NEFAs can be harmful. This study aimed to assess plausible relationships between serum NEFA and mortality due to cardiovascular disease (CVD) in individuals with CKD. This was a prospective cohort study from the third examination cycle of the Uppsala Longitudinal Study of Adult Men, a population-based survey of 1221 elderly men aged 70-71 years residing in Uppsala, Sweden. Data collection took place during 1991-1995. All participants had measures of kidney function; this study investigated 623 (51.7%) of these patients with manifest CKD (defined as either eGFR<60 ml/min per 1.73 m(2) or urine albumin excretion rate ≥20 µg/min). Follow-up for mortality was done from examination date until death or December 31, 2007. After a median follow-up of 14 years (interquartile range, 8-16.8), associations of NEFAs with mortality (related to all causes, CVD, ischemic heart disease [IHD], or acute myocardial infarction) were ascertained. The median serum NEFA was 14.1 mg/dl (interquartile range, 11.3-17.8). No association was found with measures of kidney function. Diabetes and serum triglycerides were the only multivariate correlates of NEFA. During follow-up, 453 participants died, of which 209 deaths were due to CVD, including 88 IHD deaths, with 41 attributed to acute myocardial infarction (AMI). In fully adjusted covariates, serum NEFA was an independent risk factor for all-cause mortality (hazard ratio [HR] per log2 increase, 1.22; 95% confidence interval [95% CI], 1.00 to 1.48) and CVD-related death (HR, 1.51; 95% CI, 1.15 to 1.99), including both IHD (HR, 1.51; 95% CI, 1.00 to 2.32) and AMI mortality (HR, 2.08; 95% CI, 1.09 to 3.98). Elevated serum NEFA associated with CVD mortality, and particularly with mortality due to AMI, in a homogeneous population of older men with moderate CKD.

Urinary kidney injury molecule-1 and the risk of cardiovascular mortality in elderly men.

Kidney injury molecule-1 (KIM-1) has been suggested as a clinically relevant highly specific biomarker of acute kidney tubular damage. However, community-based data on the association between urinary levels of KIM-1 and the risk for cardiovascular mortality are lacking. This study aimed to investigate the association between urinary KIM-1 and cardiovascular mortality. This was a prospective study, using the community-based Uppsala Longitudinal Study of Adult Men (N=590; mean age 77 years; baseline period, 1997-2001; median follow-up 8.1 years; end of follow-up, 2008). During follow-up, 89 participants died of cardiovascular causes (incidence rate, 2.07 per 100 person-years at risk). Models were adjusted for cardiovascular risk factors (age, systolic BP, diabetes, smoking, body mass index, total cholesterol, HDL cholesterol, antihypertensive treatment, lipid-lowering treatment, aspirin treatment, and history of cardiovascular disease) and for markers of kidney dysfunction and damage (cystatin C-based eGFR and urinary albumin/creatinine ratio). Higher urinary KIM-1/creatinine (from 24-hour urine collections) was associated with a higher risk for cardiovascular mortality (hazard ratio per SD increase, 1.27; 95% confidence interval [95% CI], 1.05 to 1.54; P=0.01). Participants with a combination of high KIM-1/creatinine (upper quintile, ≥175 ng/mmol), low eGFR (≤60 ml/min per 1.73 m(2)), and microalbuminuria/macroalbuminuria (albumin/creatinine ratio≥3 g/mol) had a >8-fold increased risk compared with participants with low KIM-1/creatinine (<175 ng/mmol), normal eGFR (>60 ml/min per 1.73 m(2)), and normoalbuminuria (albumin/creatinine ratio<3 g/mol) (hazard ratio, 8.56; 95% CI, 4.17 to 17.56; P<0.001). These findings suggest that higher urinary KIM-1 may predispose to a higher risk of cardiovascular mortality independently of established cardiovascular risk factors, eGFR, and albuminuria. Additional studies are needed to further assess the utility of measuring KIM-1 in the clinical setting.

The combined contribution of albuminuria and glomerular filtration rate to the prediction of cardiovascular mortality in elderly men

Cardiovascular risk prediction is particularly important in the primary prevention of cardiovascular disease (CVD). Yet, data on whether the combined addition of albuminuria and estimated glomerular filtration rate (eGFR) improves cardiovascular risk prediction in individuals without CVD in the community is scarce. We investigated associations between urinary albumin excretion rate (UAER), cystatin C-based eGFR and cardiovascular mortality in a community-based cohort of elderly men (ULSAM study; n = 1113, mean age 71 years, 208 cardiovascular deaths, median follow-up 12.9 years) with prespecified analyses in participants without CVD (n = 649, 86 cardiovascular deaths). Using multivariable Cox regression, higher UAER and lower eGFR were associated with increased risk for cardiovascular mortality independently of established cardiovascular risk factors in the whole sample and in men without CVD at baseline [subsample without CVD: UAER; hazard ratio (HR) per 1 SD 1.26, 95% confidence interval (CI) 1.05-1.51, P = 0.01; eGFR: HR per 1 SD 0.74, 95% CI 0.59-0.92, P = 0.007]. Analyses of model discrimination, calibration, reclassification and global fit suggested that UAER and eGFR also add relevant prognostic information beyond established cardiovascular risk factors in participants without prevalent CVD. Interestingly, established cutoffs used to diagnose microalbuminuria (UAER > 20 μg/min) and chronic kidney disease Stage 3 (eGFR < 60 mL/min/1.73 m(2)), appeared less suitable for cardiovascular risk prediction [integrated discrimination improvement (IDI) 0.006, P = 0.11], while cutoffs UAER > 6 μg/min and eGFR < 45 mL/min/1.73 m(2) significantly improved IDI (0.047, P < 0.001). UAER and eGFR improved cardiovascular risk prediction beyond established cardiovascular risk factors, suggesting that these kidney biomarkers may be useful in predicting cardiovascular death in elderly men.

Prediction of Mortality Risk in the Elderly

Purpose Ways to predict the risk of cardiovascular (CV) events or all-cause mortality have largely been derived from populations in which old and very old subjects were underrepresented. We set out to estimate the incremental prognostic utility of inflammation and atherosclerosis markers in the prediction of all-cause and CV mortality in elderly men. Methods In a prospective population-based cohort study, conventional CV risk factors were documented in 403 independently living elderly men. C-reactive protein (CRP) and interleukin (IL)-6 levels were measured. Carotid plaques were assessed by ultrasound. Analyses were performed with proportional hazards analyses, and bootstrapping was used for internal validation. Main outcome was CV and all-cause mortality occurring during 4 years of follow-up. Results Increasing tertiles of CRP, IL-6, and number of plaques were independently associated with all-cause and CV mortality. With information on age, carotid plaques, IL-6, and CRP yielded good discriminatory power for all-cause and CV mortality: area under the receiver operating characteristic curve (95% confidence interval), 0.76 (0.70-0.82) and 0.74 (0.68-0.80), respectively. Combined use of only IL-6 and plaque burden allowed identification of subjects with low and high mortality risk. The Framingham PROCAM and a Dutch Risk Function poorly predicted mortality risk, similar or worse than a model using age alone. Conclusion In the old and very old, IL-6 and number of carotid plaques are powerful predictors of mortality risk in the years to come. Conventional risk scores seem to perform unsatisfactorily.

Renal function and cardiovascular mortality in elderly men: the role of inflammatory, procoagulant, and endothelial biomarkers

To assess the extent to which inflammatory, procoagulant, and endothelial biomarkers modify the relationship between diminished renal function and cardiovascular mortality. Prospective study of 4029 men aged 60-79 years followed up for a mean period of 6 years, during which 304 cardiovascular deaths occurred. Predicted estimated glomerular filtration rate (eGFR) was used as a measure of renal function. Reduced eGFR was associated with increased prevalence of established cardiovascular risk factors [cardiovascular disease, diabetes, hypertension, left ventricular (LV) hypertrophy, and dyslipidaemia] and higher levels of inflammatory markers [interleukin 6 (IL-6), C-reactive protein], endothelial markers [von Willebrand factor (vWF) and tissue plasminogen activator], activated coagulation markers (fibrin D-dimer), and blood viscosity. Cardiovascular mortality risk increased with decreasing levels of eGFR, particularly among men with eGFR <60 mL/min per 1.73 m(2) even after adjustment for established risk factors (adjusted RR 1.49, 95% CI 1.10, 2.03; <60 vs. > or =70 mL/min per 1.73 m(2)). The association was attenuated after further adjustment for vWF, D-dimer, and IL-6 (adjusted RR 1.34, 95% CI 0.98-1.82). Mild-to-moderate renal insufficiency is associated with significantly increased cardiovascular mortality in elderly men, which is partly explained by the increased prevalence of established risk factors, markers of coagulation, endothelium, and inflammation.

Depressive symptoms as risk factor of cardiovascular mortality in older European men: the Finland, Italy and Netherlands Elderly (FINE) study

Depressive symptoms have been suggested to increase the risk of cardiovascular diseases, but this may reflect reversed causality. We investigated to what extent depressive symptoms are a true risk factor for cardiovascular mortality in elderly men. The Finland, Italy and Netherlands Elderly (FINE) study is a prospective cohort study conducted in Finland, Italy and The Netherlands. Depressive symptoms were measured with the Zung self-rating Depression Scale in 799 elderly men, aged 70-90 years, free from cardiovascular diseases. Using Cox models, hazard ratios (HRs) were calculated for specific cardiovascular mortality endpoints. The analyses were adjusted for potential confounders, stratified on country and repeated after exclusion of men who died from cardiovascular diseases up to 5 years after baseline. During 10-years of follow-up 224 (28%) men died from cardiovascular diseases. The adjusted hazard for a five-point increase in depressive symptoms was 1.15 [95% confidence interval (CI) 1.08-1.23] for cardiovascular mortality. This risk was stronger for mortality from stroke (HR 1.35; 95% CI 1.19-1.53) and heart failure (HR 1.16; 95% CI 1.00-1.35) in comparison with mortality from coronary heart disease (HR 1.08; 95% CI 0.97-1.20) and other degenerative heart diseases (HR 1.06; 95% CI 0.91-1.23). Exclusion of men who died from cardiovascular diseases within 5 years after baseline did not change the strength of the associations. There were no significant differences in HRs between northern and southern Europe. This study provides further and more convincing prospective evidence for depressive symptoms as a risk factor for cardiovascular mortality in elderly men.

A Doppler-derived index of combined left ventricular systolic and diastolic function is an independent predictor of cardiovascular mortality in elderly men

Few studies on echocardiographic and Doppler indices of cardiac function as predictors for cardiovascular mortality have been performed in the general population. The novel myocardial performance index (MPI, also denoted as Tei-Doppler index) has been suggested to reflect both left ventricular (LV) systolic and diastolic function. We investigated whether 10 different echocardiographic and Doppler indices of cardiac function predicted cardiovascular mortality by using a population-based cohort of 583 seventy-year-old men with a mean follow-up time of 6.8 years. In a multivariate Cox proportional hazard analysis for a 1-SD increase including LV ejection fraction, E/A ratio, MPI, and traditional cardiovascular risk factors (previous myocardial infarction, hyperlipidemia, hypertension, diabetes, smoking status, and LV hypertrophy), both ejection fraction (hazard ratio [HR] = 0.59, 95% CI 0.38-0.90, P < .05) and MPI (HR = 2.92, 95% CI 1.71-4.97, P < .0001) were found to be independent predictors for cardiovascular mortality. After excluding subjects with coronary heart disease, only MPI remained a significant predictor (HR = 2.18, 95% CI 1.11-4.27, P < .03, for 1-SD increase), and neither ejection fraction, E/A ratio, nor any of the cardiovascular risk factors remained significant predictors. Myocardial performance index is a predictor for cardiovascular mortality, independent of other measurements of cardiac function and of traditional cardiovascular risk factors in elderly men free from coronary heart disease.

High serum insulin-like growth factor binding protein-1 is associated with increased cardiovascular mortality in elderly men.

Insulin-like growth factor binding protein-1 (IGFBP-1) has been implicated in the development of cardiovascular disease, but it is not known whether IGFBP-1 is related to cardiovascular mortality. We examined the relation of circulating IGFBP-1 to death from coronary heart disease, cardiovascular disease, and all causes in a cohort study consisting of 622 men aged 65 - 84 years, at baseline in 1984. Fasting serum IGFBP-1 and other risk factors were measured in 1984 and 1989. Cardiovascular events for those who died between 1984 and 1995 were analyzed, and cardiovascular diagnoses were coded centrally according to standardized procedures. Of the 622 men, 358 died between 1984 and 1995; 160 deaths were due to cardiovascular causes, 113 of which were coronary deaths. High fasting serum IGFBP-1 concentration (> 75 percentile) in 1984 was associated with increased five-year total mortality (OR 2.05, 95 % CI 1.41 - 2.99; p < 0.0002), cardiovascular mortality (OR 2.20, 95 % CI 1.37 - 3.50; p < 0.0009) and coronary heart disease mortality (OR 2.29, 95 % CI 1.35 - 3.88; p < 0.002). After adjustment for age, high serum IGFBP-1 concentrations still carried an increased risk of total mortality due to (OR 1.73, 95 % CI 1.16 - 2.59; p < 0.007), cardiovascular (OR 1.91 95 % CI 1.18 - 3.09; p < 0.008) and coronary heart disease (OR 2.02. 95 % CI 1.18 - 3.47; p < 0.01). In conclusion, high fasting serum IGFBP-1 is related to increased five-year total and cardiovascular mortality in elderly men.

Bone mineral density at the hip predicts mortality in elderly men.

Low bone density as assessed by calcaneal ultrasound has been associated with mortality in elderly men and women. We examined the relationship between bone density measured at the hip and all cause and cardiovascular mortality in elderly men. Men aged 65-76 years from the general community were recruited from general practices in Cambridge between 1991 and 1995. At baseline survey, data collection included health questionnaires, measures of anthropometry and cardiovascular risk factors, as well as bone mineral density (BMD) measured using dual energy X-ray absorptiometry. All men have been followed up for vital status up to December 1999. BMD was significantly inversely related to mortality from all causes and cardiovascular disease, with decreasing rates with increasing bone density quartile, and an approximate halving of risk between the bottom and top quartile (p < 0.002, test for trend all causes and p < 0.025, test for trend for cardiovascular deaths). In multivariate analyses using the Cox proportional hazards model, an increase of 1 standard deviation (0.144 g/cm2) in total hip bone density was significantly associated with an age-adjusted 0.77 relative risk (95% CI 0.66-0.91) for all-cause mortality and 0.76 relative risk (95% CI 0.62-0.93) for cardiovascular disease mortality. The association remained significant after adjusting for age, body mass index, cigarette smoking status, serum cholesterol, systolic blood pressure, past history of heart attack, stroke or cancer and other lifestyle factors which included use of alcohol, physical activity and general health status. Low bone density at the hip is thus a strong and independent predictor of all-cause and cardiovascular mortality in older men.

Need for a Revision of the Normal Limits of Resting Heart Rate

The current definition of sinus tachycardia is a heart rate >100 beats per minute (bpm).1 This limit was set arbitrarily when heart rate was not yet regarded as a risk factor for cardiovascular disease, probably with the main purpose of distinguishing between a disease state (fever, thyrotoxicosis, anemia, congestive heart failure, etc) and a normal condition. In recent years, interest has been aroused by the awareness that fast heart rate is a potent precursor of hypertension, atherosclerosis, and their sequelae.2 3 4 5 6 7 8 9 10 In addition, many leading epidemiological studies have shown that tachycardia is associated with an increased risk of death from cardiovascular and noncardiovascular causes. This relationship has been found in general populations,3 4 5 6 7 in elderly individuals,9 and in hypertensive cohorts.10 In all of these studies, the heart rate value above that in which a significant increase in risk was observed was below the 100 bpm threshold (Table 1⇓). Only in the study by Levy et al3 was tachycardia defined as a heart rate >99 bpm, but in that study the cutoff between normal and high heart rate was chosen arbitrarily, and the highest heart rate value measured during the examination was taken to define the subject’s heart rate. In all the other studies, the threshold level between normal and fast heart rate was between 79 and 90 bpm. View this table: Table 1. Heart Rate Values Above Which a Significant Increase in Risk Was Found: Data From 9 Epidemiological Studies The normalcy limits of a clinical variable can be established according to different criteria. For many parameters, such as most biochemical indexes, the 95% confidence interval is calculated to identify the upper normal limit of the variable. This statistical approach does not appear suitable for those clinical variables …