Established Heart Failure Risk Factors Research Articles

High Variability of Body Mass Index Is Independently Associated With Incident Heart Failure.

Heart failure (HF) is a serious condition with increasing prevalence, high morbidity, and increased mortality. Obesity is an established risk factor for HF. Fluctuation in body mass index (BMI) has shown a higher risk of cardiovascular outcomes. We investigated the association between BMI variability and incident HF. In the UK Biobank, we established a prospective cohort after excluding participants with prevalent HF or cancer at enrollment. A total of 99 368 White participants with ≥3 BMI measures during >2 years preceding enrollment were included, with a median follow-up of 12.5 years. The within-participant variability of BMI was evaluated using standardized SD and coefficient of variation. The association of BMI variability with incident HF was assessed using Fine and Gray's competing risk model, adjusting for confounding factors and participant-specific rate of BMI change. Higher BMI variability measured in both SD and coefficient of variation was significantly associated with higher risk in HF incidence (SD: hazard ratio [HR], 1.05 [95% CI, 1.03-1.08], P<0.0001; coefficient of variation: HR, 1.07 [95% CI, 1.04-1.10], P<0.0001). Longitudinal health records capture BMI fluctuation, which independently predicts HF incidence.

Association Between Serum 3-Hydroxyisobutyric Acid and Prognosis in Patients With Chronic Heart Failure - An Analysis of the KUNIUMI Registry Chronic Cohort.

Diabetes increases the risk of heart failure (HF). 3-Hydroxyisobutyric acid (3-HIB) is a muscle-derived metabolite reflecting systemic insulin resistance. In this study, we investigated the prognostic impact of 3-HIB in patients with chronic HF.Methods and Results: The KUNIUMI Registry chronic cohort is a community-based cohort study of chronic HF in Awaji Island, Japan. We analyzed the association between serum 3-HIB concentrations and adverse cardiovascular (CV) events in 784 patients from this cohort. Serum 3-HIB concentrations were significantly higher in patients with than without diabetes (P=0.0229) and were positively correlated with several metabolic parameters. According to Kaplan-Meier analysis, rates of CV death and HF hospitalization at 2 years were significantly higher among HF patients without diabetes in the high 3-HIB group (3-HIB concentrations above the median; i.e., >11.30 μmol/L) than in the low 3-HIB group (log-rank P=0.0151 and P=0.0344, respectively). Multivariable Cox proportional hazard models adjusted for established risk factors for HF revealed high 3-HIB as an independent predictor of CV death (hazard ratio [HR] 1.82; 95% confidence interval [CI] 1.16-2.85; P=0.009) and HF hospitalization (HR 1.72; 95% CI 1.17-2.53, P=0.006) in HF patients without diabetes, whereas no such trend was seen in subjects with diabetes. In a community cohort, circulating 3-HIB concentrations were associated with prognosis in chronic HF patients without diabetes.

Abstract P581: Body Mass Index Variability in Relation to Heart Failure and Outcomes

Introduction: Heart failure (HF) is a disease with high morbidity and mortality, and affects an estimated total of 6.2 million HF patients in the US. Obesity is an established risk factor for HF, and fluctuation in body mass index (BMI) has shown a negative effect in health. Hypothesis: We assessed the hypothesis that BMI variability is associated with incident HF. Methods: This study used data from the UK Biobank, which is a prospective cohort study with a median follow-up of 12.5 years. After excluding prevalent HF or cancer at enrollment, a total of 99,368 White participants with ≥ 3 BMI measures from primary care records within &gt; 2 years before and at enrollment were included. The within-participant variability of BMI was evaluated using standard deviation (SD) and coefficient of variation (CV), which were converted to z scores for further analysis. HF prevalence and incidence were ascertained based on in-patient Hospital Episode Statistics using ICD-9 and -10 codes and self-report at enrollment. The association of BMI variability with incident HF was assessed using Fine and Gray's competing risk model, treating death events obtained from the National Death Registry as competing risk. Two multi-variate models were used: Model 1 adjusted for age, sex, smoking history, alcohol consumption, diabetes, hypertension, history of heart attack or stroke, lipids, estimated glomerular filtration rate; Model 2 additionally adjusted for mean BMI across multiple measures per individual. Sex-stratified analyses were also conducted. Results: The cohort was 43% male, with mean age 57.5 (SD 7.8) years. A total of 3,406 incident HF cases were observed during the follow-up. Per SD higher in BMI variability measured in SD and CV were associated with higher risk in HF incidence, with stronger associations observed among females, Figure 1 . Conclusions: BMI fluctuation is linked with HF incidence. Future studies are warranted to explore the mechanisms in changes of BMI such as body composition, and the possible causal pathways leading to HF.

Association Between Inflammation, Incident Heart Failure, and Heart Failure Subtypes in Patients With Rheumatoid Arthritis.

In rheumatoid arthritis (RA), there are limited data on risk factors for the clinical heart failure (HF) subtypes of HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). This study examined the association between inflammation and incident HF subtypes in RA. Because inflammation changes over time with disease activity, we hypothesized that the effect of inflammation may be stronger at the 5-year follow-up than at the standard 10-year follow-up from general population studies of cardiovascular risk. We studied an electronic health record (EHR)-based RA cohort with data pre- and post-RA incidence. We applied a validated approach to identify HF and extract ejection fraction to classify HFrEF and HFpEF. Follow-up started from the RA incidence date (index date) to the earliest occurrence of incident HF, death, last EHR encounter, or 10 years. Baseline inflammation was assessed using erythrocyte sedimentation rate or C-reactive protein values. Covariates included demographic characteristics, established HF risk factors, and RA-related factors. We tested the association between baseline inflammation with incident HF and its subtypes using Cox proportional hazards models. We studied 9,087 patients with RA; 8.2% developed HF during 10 years of follow-up. Elevated inflammation was associated with increased risk for HF at both 5- and 10-year follow-ups (hazard ratio [HR] 1.66, 95% confidence interval [95% CI] 1.12-2.46 and HR 1.46, 95% CI 1.13-1.90, respectively), which is also seen for HFpEF at 5 years (HR 1.72, 95% CI 1.09-2.70) and 10 years (HR 1.45, 95% CI 1.07-1.94). HFrEF was not associated with inflammation for either follow-up time. Elevated inflammation early in RA diagnosis was associated with HF; this association was driven by HFpEF and not HFrEF, suggesting a window of opportunity for prevention of HFpEF in RA.

Multi-variable biomarker approach in identifying incident heart failure in chronic kidney disease: results from the Chronic Renal Insufficiency Cohort study.

Heart failure (HF) is one of the leading causes of cardiovascular morbidity and mortality in the ever-growing population of patients with chronic kidney disease (CKD). There is a need to enhance early prediction to initiate treatment in CKD. We sought to study the feasibility of a multi-variable biomarker approach to predict incident HF risk in CKD. We examined 3182 adults enrolled in the Chronic Renal Insufficiency Cohort (CRIC) without prevalent HF who underwent serum/plasma assays for 11 blood biomarkers at baseline visit (B-type natriuretic peptide [BNP], CXC motif chemokine ligand 12, fibrinogen, fractalkine, high-sensitivity C-reactive protein, myeloperoxidase, high-sensitivity troponin T (hsTnT), fibroblast growth factor 23 [FGF23], neutrophil gelatinase-associated lipocalin, fetuin A, aldosterone). The population was randomly divided into derivation (n=1629) and validation (n=1553) cohorts. Biomarkers that were associated with HF after adjustment for established HF risk factors were combined into an overall biomarker score (number of biomarkers above the Youden's index cut-off value). Cox regression was used to explore the predictive role of a biomarker panel to predict incident HF. A total of 411 patients developed incident HF at a median follow-up of 7 years. In the derivation cohort, four biomarkers were associated with HF (BNP, FGF23, fibrinogen, hsTnT). In a model combining all four biomarkers, BNP (hazard ratio [HR] 2.96 [95% confidence interval 2.14-4.09]), FGF23 (HR 1.74 [1.30-2.32]), fibrinogen (HR 2.40 [1.74-3.30]), and hsTnT (HR 2.89 [2.06-4.04]) were associated with incident HF. The incidence of HF increased with the biomarker score, to a similar degree in both derivation and validation cohorts: from 2.0% in score of 0% to 46.6% in score of 4 in the derivation cohort to 2.4% in score of 0% to 43.5% in score of 4 in the validation cohort. A model incorporating biomarkers in addition to clinical factors reclassified risk in 601 (19%) participants (352 [11%] participants to higher risk and 249 [8%] to lower risk) compared with clinical risk model alone (net reclassification improvement of 0.16). A basic panel of four blood biomarkers (BNP, FGF23, fibrinogen, and hsTnT) can be used as a standalone score to predict incident HF in patients with CKD allowing early identification of patients at high-risk for HF. Addition of biomarker score to clinical risk model modestly reclassifies HF risk and slightly improves discrimination.

Endothelial dysfunction and the risk of heart failure in a community-based study: the Multi-Ethnic Study of Atherosclerosis.

AimsWe aimed to investigate the association between endothelial dysfunction, assessed by brachial flow‐mediated dilation (FMD), and the incidence of heart failure (HF) in the community‐based Multi‐Ethnic Study of Atherosclerosis.Methods and resultsBrachial artery FMD was measured in a nested case‐cohort sample including 3496 of 6814 Multi‐Ethnic Study of Atherosclerosis participants without prevalent cardiovascular disease (mean age 61 years, 50% women). Multivariable probability‐weighted Cox proportional hazards analysis was used to examine the association between FMD and incident HF. We also investigated the association between FMD and HF with reduced vs. preserved ejection fraction [HFrEF (left ventricular ejection fraction <45%) vs. HFpEF (left ventricular ejection fraction ≥45%)]. During follow‐up (median 12 years), 149 participants developed incident HF (incidence rate 3.7 events per 1000 person years). There were 56 HFrEF and 69 HFpEF events (incidence rates 1.4 and 1.7 events per 1000 person years, respectively). In multivariable models adjusted for established HF risk factors (age, sex, race/ethnicity, body mass index, systolic blood pressure, antihypertensive treatment, heart rate, diabetes mellitus, history of myocardial infarction, current smoker, and former smoker status), individuals in the highest quartile of FMD (reflecting better endothelial function) had a lower HF risk compared with individuals in the lowest quartile [hazard ratio 0.53, 95% confidence interval (CI) 0.31–0.95]. Lower risk according to higher FMD was particularly evident for HFrEF, but not for HFpEF (hazard ratio per standard deviation increase 0.79, 95% CI 0.64–0.97 vs. 0.99, 95% CI 0.78–1.26, respectively). Results remained similar after adjustment for baseline natriuretic peptide levels. The addition of FMD to established HF risk factors generally rendered no or only modest improvement in C‐statistics [C‐statistics for model with established HF risk factors: 0.774, and with the addition of FMD: 0.776 (delta C 0.002, 95% confidence interval −0.002 to 0.006)].ConclusionsEndothelial dysfunction was independently associated with HF in this community cohort, suggesting a pathophysiological contribution of endothelial function to the development of HF, in particular HFrEF. However, the value of FMD measurements for HF risk prediction seems limited.

Prevalence and determinants of the precursor stages of heart failure: results from the population-based STAAB cohort study.

Prevention of heart failure relies on the early identification and control of risk factors. We aimed to identify the frequency and characteristics of individuals at risk of heart failure in the general population. We report cross-sectional data from the prospective Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) cohort study investigating a representative sample of residents of Würzburg, Germany. Sampling was stratified 1:1 for sex and 10:27:27:27:10 for age groups of 30-39/40-49/50-59/60-69/70-79 years. Heart failure precursor stages were defined according to American College of Cardiology/American Heart Association: stage A (risk factors for heart failure), stage B (asymptomatic cardiac dysfunction). The main results were internally validated in the second half of the participants. The derivation sample comprised 2473 participants (51% women) with a distribution of 10%/28%/25%/27%/10% in respective age groups. Stages A and B were prevalent in 42% and 17% of subjects, respectively. Of stage B subjects, 31% had no risk factor qualifying for stage A (group 'B-not-A'). Compared to individuals in stage B with A criteria, B-not-A were younger, more often women, and had left ventricular dilation as the predominant B qualifying criterion (all P < 0.001). These results were confirmed in the validation sample (n = 2492). We identified a hitherto undescribed group of asymptomatic individuals with cardiac dysfunction predisposing to heart failure, who lacked established heart failure risk factors and therefore would have been missed by conventional primary prevention. Further studies need to replicate this finding in independent cohorts and characterise their genetic and -omic profile and the inception of clinically overt heart failure in subjects of group B-not-A.

The metabolites urobilin and sphingomyelin (30:1) are associated with incident heart failure in the general population.

AimsWe aimed to investigate whether metabolomic profiling of blood can lead to novel insights into heart failure pathogenesis or improved risk prediction.Methods and resultsMass spectrometry‐based metabolomic profiling was performed in plasma or serum samples from three community‐based cohorts without heart failure at baseline (total n = 3924; 341 incident heart failure events; median follow‐up ranging from 4.6 to 13.9 years). Cox proportional hazard models were applied to assess the association of each of the 206 identified metabolites with incident heart failure in the discovery cohorts Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) (n = 920) and Uppsala Longitudinal Study of Adult Men (ULSAM) (n = 1121). Replication was undertaken in the independent cohort TwinGene (n = 1797). We also assessed whether metabolites could improve the prediction of heart failure beyond established risk factors (age, sex, body mass index, low‐density and high‐density lipoprotein cholesterol, triglycerides, lipid medication, diabetes, systolic and diastolic blood pressure, blood pressure medication, glomerular filtration rate, smoking status, and myocardial infarction prior to or during follow‐up). Higher circulating urobilin and lower sphingomyelin (30:1) were associated with incident heart failure in age‐adjusted and sex‐adjusted models in the discovery and replication sample. The hazard ratio for urobilin in the replication cohort was estimated to 1.29 per standard deviation unit, 95% confidence interval (CI 1.03–1.63), and for sphingomyelin (30:1) to 0.72 (95% CI 0.58–0.89). Results remained similar after further adjustment for established heart failure risk factors in meta‐analyses of all three cohorts. Urobilin concentrations were inversely associated with left ventricular ejection fraction at baseline in the PIVUS cohort (β = −0.70, 95% CI −1.03 to −0.38). No major improvement in risk prediction was observed when adding the top 2 metabolites (C‐index 0.787, 95% CI 0.752–0.823) or nine Lasso‐selected metabolites (0.790, 95% CI 0.754–0.826) to a modified Atherosclerosis Risk in Communities heart failure risk score model (0.780, 95% CI 0.745–0.816).ConclusionsOur metabolomic profiling of three community‐based cohorts study identified associations of circulating levels of the haem breakdown product urobilin, and sphingomyelin (30:1), a cell membrane component involved in signal transduction and apoptosis, with incident heart failure.

Circulating endostatin and the incidence of heart failure

Objective. Circulating levels of endostatin are elevated in many underlying conditions leading to heart failure such as hypertension, diabetes, chronic kidney disease and ischemic heart disease. Yet, the association between endostatin and the incidence of heart failure has not been reported previously in the community. Design. We investigated the longitudinal association between serum endostatin levels and incident heart failure in two community-based cohorts of elderly: Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, n = 966; mean age 70 years, 51% women, 81 events, mean follow-up 10 years) and Uppsala Longitudinal Study of Adult Men (ULSAM, n = 747 men; mean age 78 years, 98 heart failure events, mean follow-up 8 years). We also investigated the cross-sectional association between endostatin and echocardiographic left ventricular systolic function and diastolic function (ejection fraction and E/A-ratio, respectively). Results. Higher serum endostatin was associated with an increased risk for heart failure in both cohorts after adjustment for established heart failure risk factors, glomerular filtration rate and N-terminal pro-brain natriuretic peptide (NT-proBNP) (PIVUS: multivariable hazard ratio (HR) per 1-standard deviation (SD) increase, HR 1.46 (95%CI, 1.17-1.82, p < .001); ULSAM: HR 1.29 (95%CI, 1.00-1.68, p < .05). In cross-sectional analyses at baseline, higher endostatin was significantly associated with both worsened left ventricular systolic and diastolic function in both cohorts. Conclusion Higher serum endostatin was associated with left ventricular dysfunction and an increased heart failure risk in two community-based cohorts of elderly. Our findings encourage further experimental studies that investigate the role of endostatin in the development of heart failure.

Body Mass Index and Cardiorespiratory Fitness in Mid-Life and Risk of Heart Failure Hospitalization in Older Age: Findings From the Cooper Center Longitudinal Study

ObjectivesThis study evaluated the contributions of obesity and changes in body mass index (BMI) in mid-life to long-term heart failure (HF) risk independent of cardiorespiratory fitness (CRF) levels. BackgroundObesity and low CRF are well-established risk factors for HF. However, given the inverse association between CRF and obesity, the independent contributions of BMI toward HF risk are not fully understood. MethodsWe included 19,485 participants from the Cooper Center Longitudinal Study who survived to receive Medicare coverage, from 1999 to 2009. CRF was estimated in metabolic equivalents (METS) according to Balke treadmill time. Associations of BMI and BMI change with HF hospitalization after age 65 were assessed by applying a proportional hazards recurrent events model to the failure time data. ResultsAfter 127,110 person-years of follow-up, we observed 1,038 HF hospitalization events. Higher mid-life BMI was significantly associated with greater risk of HF hospitalization after adjusting for established HF risk factors (hazard ratio [HR]: 1.19; 95% confidence interval [CI]: 1.12 to 1.26 per 3 kg/m2 higher BMI). This association was attenuated after adjusting for CRF (HR: 1.10; 95% CI: 1.03 to 1.17 per 3 kg/m2 higher BMI). CRF accounted for 47% of the HF risk associated with BMI. BMI change was not significantly associated with risk of HF in older age after adjustment for CRF change. ConclusionsHigher BMI-associated risk of HF is explained largely by differences in CRF levels. Furthermore, BMI change is not significantly associated with HF risk after adjusting for CRF changes. These findings highlight the importance of CRF in mediating BMI-associated HF risk.

Lung function and airway obstruction: associations with circulating markers of cardiac function and incident heart failure in older men—the British Regional Heart Study

AimsThe association between lung function and cardiac markers and heart failure (HF) has been little studied in the general older population. We have examined the association between lung function and...

Abstract 19277: Late Systolic Central Hypertension as a Predictor of Incident Heart Failure: the Multi-Ethnic Study of Atherosclerosis

Background: Experimental studies demonstrate that high aortic pressure in late systole relative to early systole, causes greater myocardial remodeling and dysfunction, for any given absolute peak systolic pressure. Methods: We tested the hypothesis that late systolic hypertension, defined as the ratio of late (last 1/3 of systole) to early (first 2/3 of systole) pressure-time integrals (PTI) of the aortic pressure waveform, independently predicts incident heart failure (HF) in the general population. Aortic pressure waveforms were derived from a generalized transfer function applied to the radial pressure waveform recorded non-invasively from 6,124 adults. The late/early systolic PTI ratio (L/ESPTI) was assessed as a predictor of incident heart failure (HF) during median 8.5 years of follow-up. Results: The L/ESPTI was predictive of incident HF (hazard ratio per 1% increase=1.22; 95%CI=1.15-1.29; P&lt;0.0001) even after adjustment for established risk factors for HF (HR=1.23; 95%CI=1.14-1.32: P&lt;0.0001). In a multivariate model that included brachial systolic and diastolic blood pressure and other standard risk factors of HF, L/ESPTI was the modifiable factor associated with the greatest improvements in model performance. A high L/ESPTI was more predictive of HF than the presence of hypertension. After adjustment for each other and various predictors of HF, the HR associated with hypertension was 1.39 (95%CI=0.86-2.23; P=0.18) whereas the HR associated with a high L/E was 2.31 (95%CI=1.52-3.49; P&lt;0.0001). Cumulative hazard curves for HF among participants stratified according to the presence or absence of hypertension (prevalence=45%) or a high L/ESPTI (set empirically to an identical prevalence of 45% based on E/LSPTI) are shown in the figure. Conclusions: Independently of the absolute level of peak pressure, late systolic hypertension is strongly associated with incident HF in the general population.

Fasting Plasma Glucose and Incident Heart Failure Risk: A Population-Based Cohort Study and New Meta-analysis

BackgroundThere remains uncertainty regarding the association between fasting plasma glucose (FPG) and risk of heart failure (HF) in individuals without a history of diabetes. Methods and ResultsWe assessed the association between FPG and HF risk in a population-based cohort of 1,740 men aged 42-61 years who were free from HF or diabetes at baseline. During a mean follow-up of 20.4 years, 146 participants developed HF. In age-adjusted analysis, the hazard ratio (HR) for HF per 1 mmol/L increase in FPG was 1.34 (95% confidence interval 1.22–1.48). This association persisted after adjusting for established HF risk factors: HR 1.27, 95% confidence interval 1.14–1.42. The findings remained consistent across several clinical subgroups and in analyses excluding incident coronary heart disease or diabetes during follow-up. In a meta-analysis of 10 prospective studies involving 4,213 incident HF cases, the HR for HF per 1 mmol/L increase in FPG level was 1.11 (95% confidence interval 1.04–1.17), with evidence of heterogeneity between studies (I2 = 79%; 95% confidence interval 63%–89%; P < .001). The corresponding HR was 1.12 (95% confidence interval 1.08–1.18) on exclusion of the single study that accounted for the heterogeneity. ConclusionsThere exists a positive, continuous, and independent association between FPG and risk for HF. Studies are warranted to evaluate the causal relevance of these findings.

Abstract P027: Fasting Glucose And Risk Of Heart Failure

Background: There remains uncertainty regarding the association between fasting glucose (FG) and the risk of heart failure (HF) in individuals without a history of diabetes. Methods and Results: We assessed the association between FG and HF risk in a population-based cohort of 1,740 men aged 42-61 years free from HF or diabetes at baseline. Additionally, we performed a meta-analysis of relevant prospective studies identified from MEDLINE, EMBASE, and Web of Science databases. During a mean follow-up of 20.4 years, 146 participants developed HF (4.1 cases per 1000 person-years). In models adjusted for age, the hazard ratio (HR) for HF per 1 mmol/L increase in FG was 1.34 (95% confidence interval [CI], 1.22, 1.48). This association persisted after adjustment for established HF risk factors (HR 1.27, 95% CI 1.14, 1.42). Compared with FG&lt; 5.6 mmol/L, there was an increased risk amongst those with FG 5.6-6.9 mmol/L (HR 1.24, 95% CI 0.82, 1.88) and ≥ 7.0 mmol/L (HR 3.25, 95% CI 1.50, 7.08). HRs remained consistent across several clinical subgroups. In a meta-analysis of 10 prospective studies (Figure 1) involving a total of 4,213 incident HF cases, the HR for HF per 1 mmol/L increase in FG level was 1.11 (95% CI 1.04, 1.17), consistent with a linear dose-response relationship with evidence of heterogeneity between studies (I2=79%, 63-89%; P&lt;0.001). Conclusions: A positive, continuous, and independent association exists between FG and risk for HF. Further studies are needed to evaluate the causal relevance of these findings.

Cardiorespiratory fitness and risk of heart failure: a population‐based follow‐up study

To examine the relationship between cardiorespiratory fitness (CRF) and risk of incident heart failure (HF). Cardiorespiratory fitness, as measured by maximal oxygen uptake (VO2 max), was assessed at baseline in a prospective cohort of 1873 men aged 42-61 years without HF or chronic respiratory disease. During a mean follow-up of 20.4 years, 152 incident HF events were recorded. Within-person variability was calculated using data from repeat measurements taken 11 years apart. The age-adjusted hazard ratio (HR) per unit increase (1 mL/kg/min of VO2 max) in CRF was 0.89 [95% confidence interval (CI) 0.86-0.93], which was minimally attenuated to 0.94 (95% CI 0.90-0.98) after further adjustment for established HF risk factors (body mass index, systolic blood pressure, history of cardiovascular disease, diabetes, heart rate, and LV hypertrophy) and incident coronary events as a time-varying covariate. In a comparison of extreme quartiles of CRF levels (VO2 max ≥35.4 vs. ≤25.7 mL/kg/min), the corresponding HRs were 0.27 (0.15-0.50) and 0.48 (0.25-0.92), respectively. Each 1 MET (metabolic equivalent of oxygen consumption) increment in CRF was associated with a 21% (7-33%) reduction in multivariable adjusted risk of HF. Addition of CRF to a HF risk prediction model containing established risk factors did not significantly improve risk discrimination (C-index change = 0.0164, P = 0.07). In this Finnish population, there is a strong, inverse, and independent association between long-term CRF and HF risk, consistent with a dose-response relationship. The protective effect of CRF on HF risk warrants further evaluation.

Inequalities in heart failure in older men: prospective associations between socioeconomic measures and heart failure incidence in a 10-year follow-up study

Socioeconomic position has been linked to incident heart failure (HF), but the underlying mechanisms are unclear. We examined the association of socioeconomic measures with incident HF in older adults and examined possible underlying pathways. A socially representative cohort of men aged 60-79 years in 1998-2000 from 24 British towns was followed-up for 10 years for incident HF. Adult socioeconomic position was based on a cumulative score, including occupation, education, housing tenure, pension, and amenities. Childhood socioeconomic measures included father's occupational social class and household amenities. Prevalent myocardial infarction and HF cases were excluded. Among 3836 men, 229 incident cases of HF occurred over 10 years. Heart failure risk increased with an increasing score of adverse adult socioeconomic measures (P for trend = < 0.0001). Compared with men with a score of 0, the hazard ratio for men with a score of ≥ 4 was 2.19 (95% confidence interval, CI, 1.34-3.55), which was attenuated to 1.87 (95% CI 1.12-3.11) after adjusting for systolic blood pressure, body mass index, smoking, HDL-cholesterol, diabetes, and lung function. Adjustment for left ventricular hypertrophy, atrial fibrillation, heart rate, and renal function made little difference. Further adjustment for C-reactive protein, von Willebrand Factor, N-terminal pro-brain natriuretic peptide, and plasma vitamin C also made little difference to the hazard ratio [1.89 (95% CI 1.10-3.24)]. Heart failure risk did not vary by childhood socioeconomic measures. Heart failure risk in older men was greater in the most deprived socioeconomic groups, which was only partly explained by established risk factors for HF. Novel risk factors contribute little to the associated risk.

Plasma phospholipid saturated fatty acids and heart failure risk in the physicians' health study

Previous studies have suggested that some plasma phospholipid saturated fatty acids (SFA) are associated with an increased risk of coronary heart disease and hypertension, major risk factors for heart failure (HF). However, little is known about the association between SFA and HF. This study examines associations of individual plasma phospholipid SFA with HF risk in US male physicians. The current ancillary study used a prospective nested matched case-control design to select 788 cases of incident HF and 788 controls. Plasma phospholipid SFAs were measured using gas chromatography. HF was self-reported on follow-up questionnaires and validated by review of medical records in a subsample. We used conditional logistic regression to estimate relative risks. Mean age was 58.7±8.0 years. One standard deviation higher plasma phospholipid 16:0 was associated with an odds ratio (95% CI) of 1.20 (1.04, 1.38) controlling for established HF risk factors and other SFAs (p=0.042). However, this association was not significant after Bonferroni correction (p>0.008). We did not observe associations between other SFAs (14:0, 15:0, 18:0, 20:0, or 22:0) and HF risk (all p for trend>0.05). Our data suggested no association between plasma phospholipid SFAs and HF in US male physicians.

Cardiac Dysfunction and Noncardiac Dysfunction as Precursors of Heart Failure With Reduced and Preserved Ejection Fraction in the Community

Heart failure (HF) is a clinical syndrome characterized by signs and symptoms involving multiple organ systems. Longitudinal data demonstrating that asymptomatic cardiac dysfunction precedes overt HF are scarce, and the contribution of noncardiac dysfunction to HF progression is unclear. We hypothesized that subclinical cardiac and noncardiac organ dysfunction would accelerate the manifestation of HF. We studied 1038 participants of the Framingham Heart Study original cohort (mean age, 76±5 years; 39% men) with routine assessment of left ventricular systolic and diastolic function. Major noncardiac organ systems were assessed with the use of serum creatinine (renal), serum albumin (hepatic), ratio of forced expiratory volume in 1 second to forced vital capacity (FEV(1):FVC ratio; pulmonary), hemoglobin concentration (hematologic/oxygen-carrying capacity), and white blood cell count (systemic inflammation). On follow-up (mean, 11 years), there were 248 incident HF events (146 in women). After adjustment for established HF risk factors, antecedent left ventricular systolic dysfunction (hazard ratio, 2.33; 95% confidence interval, 1.43 to 3.78) and diastolic dysfunction (hazard ratio, 1.32; 95% confidence interval, 1.01 to 1.71) were associated with increased HF risk. After adjustment for cardiac dysfunction, higher serum creatinine, lower FEV1:FVC ratios, and lower hemoglobin concentrations were associated with increased HF risk (all P<0.05); serum albumin and white blood cell count were not. Subclinical dysfunction in each noncardiac organ system was associated with a 30% increased risk of HF (P=0.013). Antecedent cardiac dysfunction and noncardiac organ dysfunction are associated with increased incidence of HF, supporting the notion that HF is a progressive syndrome and underscoring the importance of noncardiac factors in its occurrence.

Plasma parathyroid hormone and risk of congestive heart failure in the community

In experimental studies parathyroid hormone (PTH) has been associated with underlying causes of heart failure (HF) such as atherosclerosis, left ventricular hypertrophy, and myocardial fibrosis. Individuals with increased levels of PTH, such as primary or secondary hyperparathyroidism patients, have increased risk of ischaemic heart disease and HF. Moreover, increasing PTH is associated with worse prognosis in patients with overt HF. However, the association between PTH and the development HF in the community has not been reported. In a prospective, community-based study of 864 elderly men without HF or valvular disease at baseline (mean age 71 years, the ULSAM study) the association between plasma (P)-PTH and HF hospitalization was investigated adjusted for established HF risk factors (myocardial infarction, hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking, and hypercholesterolaemia) and variables reflecting mineral metabolism (S-calcium, S-phosphate, P-vitamin D, S-albumin, dietary calcium and vitamin D intake, physical activity, glomerular filtration rate, and blood draw season). During follow-up (median 8 years), 75 individuals were hospitalized due to HF. In multivariable Cox-regression analyses, higher P-PTH was associated with increased HF hospitalization (hazard ratio for 1-SD increase of PTH, 1.41, 95% CI 1.12-1.77, P = 0.003). Parathyroid hormone also predicted hospitalization in participants without apparent ischaemic HF and in participants with normal P-PTH. In a large community-based sample of elderly men, PTH predicted HF hospitalizations, also after accounting for established risk factors and mineral metabolism variables. Our data suggest a role for PTH in the development of HF even in the absence of overt hyperparathyroidism.

Influence of Life-Course Socioeconomic Position on Incident Heart Failure in Blacks and Whites: The Atherosclerosis Risk in Communities Study

The influence of early-life socioeconomic position (SEP) on incident heart failure in blacks and whites is unknown. The authors examined the relation between early-life SEP and incident, hospitalized heart failure among middle-aged US participants (2,503 black and 8,519 white) in the Atherosclerosis Risk in Communities (ARIC) Study. Early-life SEP indicators assessed included parental education, occupation, and home ownership. From 1987 to 2004, 221 and 537 incident heart failure events were identified in blacks and whites, respectively. In Cox proportional hazards regression, early-life SEP was inversely related to incident heart failure after adjustment for age, gender, and study center (for blacks, hazard ratio (HR) = 1.39, 95% confidence interval (CI): 1.00, 1.95; for whites, HR = 1.32, 95% CI: 1.06, 1.64). Additional adjustment for young and mid-to-older adulthood SEP and established heart failure risk factors attenuated this association towards the null in both blacks and whites. Of the SEP measures, mid-to-older adulthood SEP showed the strongest association with incident heart failure in both blacks (HR = 1.32, 95% CI: 0.90, 1.96) and whites (HR = 1.39, 95% CI: 1.11, 1.75). SEP over the life course is related to the risk of incident heart failure, with SEP later in adulthood having a more prominent role than earlier SEP.