Abstract Background Studies of patients presenting for catheter ablation suggest that premature ventricular contractions (PVCs) are a modifiable risk factor for congestive heart failure (CHF). The ...relationship among PVC frequency, incident CHF, and mortality in the general population remains unknown. Objectives The goal of this study was to determine whether PVC frequency ascertained using a 24-h Holter monitor is a predictor of a decrease in the left ventricular ejection fraction (LVEF), incident CHF, and death in a population-based cohort. Methods We studied 1,139 Cardiovascular Health Study (CHS) participants who were randomly assigned to 24-h ambulatory electrocardiography (Holter) monitoring and who had a normal LVEF and no history of CHF. PVC frequency was quantified using Holter studies, and LVEF was measured from baseline and 5-year echocardiograms. Participants were followed for incident CHF and death. Results Those in the upper quartile versus the lowest quartile of PVC frequency had a multivariable-adjusted, 3-fold greater odds of a 5-year decrease in LVEF (odds ratio OR: 3.10; 95% confidence interval CI: 1.42 to 6.77; p = 0.005), a 48% increased risk of incident CHF (HR: 1.48; 95% CI: 1.08 to 2.04; p = 0.02), and a 31% increased risk of death (HR: 1.31; 95% CI: 1.06 to 1.63; p = 0.01) during a median follow-up of >13 years. Similar statistically significant results were observed for PVCs analyzed as a continuous variable. The specificity for the 15-year risk of CHF exceeded 90% when PVCs included at least 0.7% of ventricular beats. The population-level risk for incident CHF attributed to PVCs was 8.1% (95% CI: 1.2% to 14.9%). Conclusions In a population-based sample, a higher frequency of PVCs was associated with a decrease in LVEF, an increase in incident CHF, and increased mortality. Because of the capacity to prevent PVCs through medical or ablation therapy, PVCs may represent a modifiable risk factor for CHF and death.
Abstract Background and Aims Understanding contributions of lean and fat tissue to cardiovascular and non-cardiovascular mortality may help clarify areas of prevention in older adults. We aimed to ...define distributions of lean and fat tissue in older adults and their contributions to cause-specific mortality. Methods and Results A total of 1335 participants of the Cardiovascular Health Study (CHS) who underwent dual-energy x-ray absorptiometry (DEXA) scans were included. We used principal components analysis (PCA) to define two independent sources of variation in DEXA-derived body composition, corresponding to principal components composed of lean (“lean PC”) and fat (“fat PC”) tissue. We used Cox proportional hazards regression using these PCs to investigate the relationship between body composition with cardiovascular and non-cardiovascular mortality. Mean age was 76.2±4.8 years (56% women) with mean body mass index 27.1±4.4 kg/m2 . A greater lean PC was associated with lower all-cause (HR=0.91, 95% CI 0.84-0.98, P=0.01) and cardiovascular mortality (HR=0.84, 95% CI 0.74-0.95, P=0.005). The lowest quartile of the fat PC (least adiposity) was associated with a greater hazard of all-cause mortality (HR = 1.24, 95% CI 1.04-1.48, P=0.02) relative to fat PCs between the 25th -75th percentile, but the highest quartile did not have a significantly greater hazard (P=0.70). Conclusion Greater lean tissue mass is associated with improved cardiovascular and overall mortality in the elderly. The lowest levels of fat tissue mass are linked with adverse prognosis, but the highest levels show no significant mortality protection. Prevention efforts in the elderly frail may be best targeted toward improvements in lean muscle mass.
Older adults comprise the majority of new-onset heart failure (HF) diagnoses, but traditional risk-factor prediction models have limited accuracy in this population to identify those at highest risk ...for hospitalization or death.
To determine if cardiac troponin T (cTnT) measured by a highly sensitive assay would be detectable in the majority of community-dwelling older adults, and if serial measures were associated with risk of HF hospitalization and cardiovascular death.
A longitudinal nationwide cohort study (Cardiovascular Health Study) of 4221 community-dwelling adults aged 65 years or older without prior HF who had cTnT measured using a highly sensitive assay at baseline (1989-1990) and repeated after 2 to 3 years (n = 2918).
New-onset HF and cardiovascular death were examined through June 2008 with respect to cTnT concentrations, accounting for clinical risk predictors.
Cardiac troponin T was detectable (≥3.00 pg/mL) in 2794 participants (66.2%). During a median follow-up of 11.8 years, 1279 participants experienced new-onset HF and 1103 cardiovascular deaths occurred, with a greater risk of both end points associated with higher cTnT concentrations. Among those participants with the highest cTnT concentrations (>12.94 pg/mL), there was an incidence rate per 100 person-years of 6.4 (95% confidence interval CI, 5.8-7.2; adjusted hazard ratio aHR, 2.48; 95% CI, 2.04-3.00) for HF and an incidence rate of 4.8 (95% CI, 4.3-5.4; aHR, 2.91; 95% CI, 2.37-3.58) for cardiovascular death compared with participants with undetectable cTnT levels (incidence rate, 1.6; 95% CI, 1.4-1.8 and 1.1; 95% CI, 0.9-1.2 for HF and cardiovascular death, respectively). Among individuals with initially detectable cTnT, a subsequent increase of more than 50% (n = 393, 22%) was associated with a greater risk for HF (aHR, 1.61; 95% CI, 1.32-1.97) and cardiovascular death (aHR, 1.65; 95% CI, 1.35-2.03) and a decrease of more than 50% (n = 247, 14%) was associated with a lower risk for HF (aHR, 0.73; 95% CI, 0.54-0.97) and cardiovascular death (aHR, 0.71; 95% CI, 0.52-0.97) compared with participants with 50% or less change. Addition of baseline cTnT measurements to clinical risk factors was associated with only modest improvement in discrimination, with change in C statistic of 0.015 for HF and 0.013 for cardiovascular death.
In this cohort of older adults without known HF, baseline cTnT levels and changes in cTnT levels measured with a highly sensitive assay were significantly associated with incident HF and cardiovascular death.
This study aimed to determine temporal trends in the incidence of and mortality associated with heart failure (HF) and its subtypes (heart failure with reduced ejection fraction HFrEF and heart rate ...with preserved ejection fraction HFpEF) in the community.
Major shifts in cardiovascular disease risk factor prevalence and advances in therapies may have influenced HF incidence and mortality.
In the FHS (Framingham Heart Study) and CHS (Cardiovascular Health Study), for participants who were ≥60 years of age and free of HF (n = 15,217; 60% women; 2,524 incident HF cases; 115,703 person-years of follow-up), we estimated adjusted incidence rate ratios of HF, HFrEF, and HFpEF from 1990 to 1999 and 2000 to 2009. We compared the cumulative incidence of and mortality associated with HFrEF versus HFpEF within and between decades.
Across the 2 decades, HF incidence rate ratio was similar (p = 0.13). The incidence rate ratio of HFrEF declined (p = 0.0029), whereas HFpEF increased (p < 0.001). Although HFrEF incidence declined more in men than in women, men had a higher incidence of HFrEF than women in each decade (p < 0.001). The incidence of HFpEF significantly increased over time in both men and women (p < 0.001 and p = 0.02, respectively). During follow-up after HF, 1,701 individuals died (67.4%; HFrEF, n = 557 33%; HFpEF, n = 474 29%). There were no significant differences in mortality rates (overall, cardiovascular disease, and noncardiovascular disease) across decades within HF subtypes or between HFrEF and HFpEF within decade.
In several U.S. community–based samples from 1990 to 2009, we observed divergent trends of decreasing HFrEF and increasing HFpEF incidence, with stable overall HF incidence and high risk for mortality. Our findings highlight the need to elucidate factors contributing to these observations.
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Atrial fibrillation (AF) is the most common sustained arrhythmia in the elderly, and shares several risk factors with diastolic dysfunction, including hypertension and advanced age. The purpose of ...this study is to examine diastolic dysfunction as a risk for incident AF.
We examined the association of echocardiographic parameters of diastolic function with the incidence of AF in 4480 participants enrolled in the Cardiovascular Health Study, an ongoing cohort of community-dwelling older adults from four US communities. Participants underwent baseline echocardiography in 1989-1990 and were followed for incident AF on routine follow-up and hospitalizations. After 50 941 person-years of follow-up (median follow-up time 12.1 years), 1219 participants developed AF. In multivariable-adjusted age-stratified Cox models, diastolic echocardiographic parameters were significantly associated with the risk of incident AF. The most significant parameters were the Doppler peak E-wave velocity and left atrial diameter, which demonstrated a positive nonlinear association HR 1.5 (CI 1.3-1.9) and HR 1.7 (CI 1.4-2.1) for highest vs. lowest quintile, respectively, and Doppler A-wave velocity time integral, which displayed a U-shaped relationship with the risk of AF HR 0.7 (CI 0.6-0.9) for middle vs. lowest quintile. Each diastolic parameter displayed a significant association with adjusted NT-proBNP levels, although the nature of the association did not entirely parallel the risk of AF. Further cluster analysis revealed unique patterns of diastolic function that may identify patients at risk for AF.
In a community-based population of older adults, echocardiographic measures of diastolic function are significantly associated with an increased risk of AF.
Lifetime risk of heart failure has been estimated to range from 20% to 46% in diverse sex and race groups. However, lifetime risk estimates for the 2 HF phenotypes, HF with preserved ejection ...fraction (HFpEF) and HF with reduced ejection fraction (HFrEF), are not known.
Participant-level data from 2 large prospective cohort studies, the CHS (Cardiovascular Health Study) and MESA (Multiethnic Study of Atherosclerosis), were pooled, excluding individuals with prevalent HF at baseline. Remaining lifetime risk estimates for HFpEF (EF ≥45%) and HFrEF (EF <45%) were determined at different index ages with the use of a modified Kaplan-Meier method with mortality and the other HF subtype as competing risks.
We included 12 417 participants >45 years of age (22.2% blacks, 44.8% men) who were followed up for median duration of 11.6 years with 2178 overall incident HF events with 561 HFrEF events and 726 HFpEF events. At the index age of 45 years, the lifetime risk for any HF through 90 years of age was higher in men than women (27.4% versus 23.8%). Among HF subtypes, the lifetime risk for HFrEF was higher in men than women (10.6% versus 5.8%). In contrast, the lifetime risk for HFpEF was similar in men and women. In race-stratified analyses, lifetime risk for overall HF was higher in nonblacks than blacks (25.9% versus 22.4%). Among HF subtypes, the lifetime risk for HFpEF was higher in nonblacks than blacks (11.2% versus 7.7%), whereas that for HFrEF was similar across the 2 groups. Among participants with antecedent myocardial infarction before HF diagnosis, the remaining lifetime risks for HFpEF and HFrEF were up to 2.5-fold and 4-fold higher, respectively, compared with those without antecedent myocardial infarction.
Lifetime risks for HFpEF and HFrEF vary by sex, race, and history of antecedent myocardial infarction. These insights into the distribution of HF risk and its subtypes could inform the development of targeted strategies to improve population-level HF prevention and control.
The purpose of this study was to examine the prevalence of abnormalities in cardiac structure and function present in patients with heart failure and a preserved ejection fraction (HFPEF) and to ...determine whether these alterations in structure and function were associated with cardiovascular morbidity and mortality.
The Irbesartan in HFPEF trial (I-PRESERVE) enrolled 4128 patients; echocardiographic determination of left ventricular (LV) volume, mass, left atrial (LA) size, systolic function, and diastolic function were made at baseline in 745 patients. The primary end point was death or protocol-specific cardiovascular hospitalization. A secondary end point was the composite of heart failure death or heart failure hospitalization. Associations between baseline structure and function and patient outcomes were examined using univariate and multivariable Cox proportional hazard analyses. In this substudy, LV hypertrophy or concentric remodeling was present in 59%, LA enlargement was present in 66%, and diastolic dysfunction was present in 69% of the patients. Multivariable analyses controlling for 7 clinical variables (including log N-terminal pro-B-type natriuretic peptide) indicated that increased LV mass, mass/volume ratio, and LA size were independently associated with an increased risk of both primary and heart failure events (all P<0.05).
Left ventricular hypertrophy or concentric remodeling, LA enlargement, and diastolic dysfunction were present in the majority of patients with HFPEF. Left ventricular mass and LA size were independently associated with an increased risk of morbidity and mortality. The presence of structural remodeling and diastolic dysfunction may be useful additions to diagnostic criteria and provide important prognostic insights in patients with HFPEF.
Valvular heart diseases are not usually regarded as a major public-health problem. Our aim was to assess their prevalence and effect on overall survival in the general population.
We pooled ...population-based studies to obtain data for 11 911 randomly selected adults from the general population who had been assessed prospectively with echocardiography. We also analysed data from a community study of 16 501 adults who had been assessed by clinically indicated echocardiography.
In the general population group, moderate or severe valve disease was identified in 615 adults. There was no difference in the frequency of such diseases between men and women (p=0·90). Prevalence increased with age, from 0·7% (95% CI 0·5–1·0) in 18–44 year olds to 13·3% (11·7–15·0) in the 75 years and older group (p<0·0001). The national prevalence of valve disease, corrected for age and sex distribution from the US 2000 population, is 2·5% (2·2–2·7). In the community group, valve disease was diagnosed in 1505 (1·8% adjusted) adults and frequency increased considerably with age, from 0·3% (0·2–0·3) of the 18–44 year olds to 11·7% (11·0–12·5) of those aged 75 years and older, but was diagnosed less often in women than in men (odds ratio 0·90, 0·81–1·01; p=0·07). The adjusted mortality risk ratio associated with valve disease was 1·36 (1·15–1·62; p=0·0005) in the population and 1·75 (1·61–1·90; p<0·0001) in the community.
Moderate or severe valvular diseases are notably common in this population and increase with age. In the community, women are less often diagnosed than are men, which could indicate an important imbalance in view of the associated lower survival. Valve diseases thus represent an important public-health problem.
In patients with heart failure and preserved ejection fraction, little is known about the characteristics of, and outcomes in, those with and without diabetes mellitus.
We examined clinical and ...echocardiographic characteristics and outcomes in the I-Preserve trial (Irbesartan in Heart Failure With Preserved Ejection Fraction) according to history of diabetes mellitus. Cox regression models were used to estimate hazard ratios for cardiovascular outcomes adjusted for known predictors, including age, sex, natriuretic peptides, and comorbidity. Echocardiographic data were available in 745 patients and were additionally adjusted for in supplementary analyses.
Overall, 1134 of 4128 patients (27%) had diabetes mellitus. Compared with those without diabetes mellitus, they were more likely to have a history of myocardial infarction (28% versus 22%), higher body mass index (31 versus 29 kg/m
), worse Minnesota Living With Heart Failure score (48 versus 40), higher median N-terminal pro-B-type natriuretic peptide concentration (403 versus 320 pg/mL; all
<0.01), more signs of congestion, but no significant difference in left ventricular ejection fraction. Patients with diabetes mellitus had a greater left ventricular mass and left atrial area than patients without diabetes mellitus. Doppler E-wave velocity (86 versus 76 cm/s;
<0.0001) and the E/e' ratio (11.7 versus 10.4;
=0.010) were higher in patients with diabetes mellitus. Over a median follow-up of 4.1 years, cardiovascular death or heart failure hospitalization occurred in 34% of patients with diabetes mellitus versus 22% of those without diabetes mellitus (adjusted hazard ratio, 1.75; 95% confidence interval, 1.49-2.05), and 28% versus 19% of patients with and without diabetes mellitus died (adjusted hazard ratio, 1.59; confidence interval, 1.33-1.91).
In heart failure with preserved ejection fraction, patients with diabetes mellitus have more signs of congestion, worse quality of life, higher N-terminal pro-B-type natriuretic peptide levels, and a poorer prognosis. They also display greater structural and functional echocardiographic abnormalities. Further investigation is needed to determine the mediators of the adverse impact of diabetes mellitus on outcomes in heart failure with preserved ejection fraction and whether they are modifiable.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00095238.
The left atrium enlarges in association with many factors, including aging, atrial fibrillation, hypertension, diastolic dysfunction, and heart failure (HF) with low ejection fraction. However, left ...atrial (LA) volume, geometry, and emptying have not been compared between diastolic and systolic HF, nor has the association of LA volume for new HF been determined in older subjects, many of whom have normal ejection fraction. We used echocardiography to measure the LA volume, geometry, and emptying in 851 community-dwelling subjects ≥65 years of age, including 180 with HF at baseline and 255 participants who subsequently developed HF. The LA volume, area, and linear dimensions were higher in the prevalent and incident HF groups than in controls and did not differ between those with systolic versus diastolic HF, independent of co-morbidities and Doppler measures of diastolic function. The fractional area change was associated with prevalent, but not incident, HF. In conclusion, in population-based older subjects, the LA size is increased and LA emptying decreased in patients with either systolic or diastolic HF. LA size is associated with the new development of HF. These findings highlight the important role of the left atrium in HF, with or without a decreased ejection fraction.
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