Background: Nutritional status has been related to clinical outcomes in patients with heart failure. We assessed the association between nutritional status, indexed by prognostic nutritional index ( PNI ), and survival in patients hospitalized for acute heart failure. Methods and Results: A total of 1673 patients (age 76±13 years, 68% men) hospitalized for acute heart failure in a tertiary medical center were analyzed. PNI was calculated as 10×serum albumin (g/dL)+0.005×total lymphocyte count (per mm ³ ). National Death Registry was linked to identify the clinical outcomes of all‐cause and cardiovascular death. With increasing tertiles of PNI , age and N‐terminal probrain natriuretic peptide decreased, and body mass index, estimated glomerular filtration rate, and hemoglobin increased. During a mean follow‐up duration of 31.5 months, a higher PNI tertile was related to better survival free from all‐cause and cardiovascular mortality in the total study population and in participants with either reduced or preserved left ventricular ejection fraction. After accounting for age, sex, estimated glomerular filtration rate, left ventricular ejection fraction, serum sodium level, and on‐admission systolic blood pressure, PNI was independently associated with cardiovascular death and total mortality (hazard ratio per 1 SD of the natural logarithm of the PNI: 0.76 [95% CI, 0.66–0.87] and 0.79 [95% CI, 0.73–0.87], respectively). In subgroup analyses stratified by age, sex, left ventricular ejection fraction, body mass index, or estimated glomerular filtration rate, PNI was consistently related to mortality. Conclusions: PNI is independently associated with long‐term survival in patients hospitalized for acute heart failure with either reduced or preserved left ventricular ejection fraction.

Background— Increased aortic stiffness is associated with numerous common diseases of aging, including heart disease, stroke, and renal disease. However, the prevalence and correlates of abnormally high aortic stiffness are incompletely understood. Methods and Results— We evaluated 2 aortic stiffness measures, carotid-femoral pulse wave velocity and forward pressure wave amplitude, in a pooled sample of the Framingham Original, Offspring, and minority Omni cohorts (mean age, 62 years; 56% women). Abnormal stiffness of each measure was defined as a value exceeding the sex-specific 90th percentile of a reference group with a low burden of conventional cardiovascular disease risk factors. Applying this criterion to the entire sample identified a 24% to 33% prevalence of abnormal stiffness measures. The prevalence of abnormal stiffness increased markedly with age, eg, for pulse wave velocity, from a few percent in both sexes aged <50 years to 64% (men) to 74% (women) in those aged ≥70 years. With adjustment for age, important correlates of abnormal aortic stiffness included higher mean arterial pressure, greater body mass index, impaired glucose metabolism, and abnormal lipids. Correlates of aortic stiffness were similar if we used age-specific rather than fixed criteria for defining abnormal stiffness. Conclusions— The prevalence of abnormal aortic stiffness increases steeply with advancing age in the community, especially in the presence of obesity or diabetes. Our data suggest that the burden of disease attributable to aortic stiffness is likely to increase considerably over the next few years as the population ages.

Aldosterone:renin ratio (ARR) is used to screen for hyperaldosteronism. Data regarding correlates of ambulatory ARR in the community and its relation to hypertension incidence are limited. We defined clinical correlates of ARR, determined its heritability, tested for association and linkage, and related ARR to blood pressure (BP) progression in nonhypertensive individuals among 3326 individuals from the Framingham Heart Study (53% women; mean age: 59 years). Ambulatory morning ARR (serum aldosterone and plasma renin concentrations) were related to clinical covariates, genetic variation across the REN locus, a 10-cM linkage map, and among nonhypertensive participants (n=1773) to progression of ≥1 Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure BP category (optimal: <120/80 mm Hg, normal: 120 to 129/80 to 84 mm Hg, high normal: 130 to 139/85 to 89 mm Hg, hypertension: ≥140/90 mm Hg), or incident hypertension (systolic BP: ≥140 mm Hg, diastolic BP: ≥90 mm Hg, or use of antihypertensive treatment). ARR was positively associated with age, female sex, untreated hypertension, total/high-density lipoprotein cholesterol ratio, hormone replacement therapy, and β-blocker use, but negatively associated with angiotensin-converting enzyme inhibitor and diuretic use. ARR was heritable (h ² =0.40), had modest linkage to chromosome 11p (logarithm of the odds: 1.89), but was not associated with 17 common variants in REN (n=1729). On follow-up (mean: 3 years), 607 nonhypertensive individuals (34.2%) developed BP progression, and 283 (16.0%) developed hypertension. Higher baseline logARR was associated with increased risk of BP progression (odds ratio per SD increment: 1.23; 95% CI: 1.11 to 1.37) and hypertension incidence (odds ratio per SD increment: 1.16; 95% CI: 1.00 to 1.33). ARR is a heritable trait influenced by clinical and genetic factors. There is a continuous gradient of increasing risk of BP progression across ARR levels in nonhypertensive individuals.

Background— Serum C-reactive protein (CRP) level is a heritable complex trait that predicts incident cardiovascular disease. We investigated the clinical and genetic sources of interindividual variability in serum CRP. Methods and Results— We studied serum CRP in 3301 Framingham Heart Study (FHS) participants (mean age 61 years, 53% women). Twelve clinical covariates explained 26% of the variability in CRP level, with body mass index alone explaining 15% ( P <0.0001) of the variance. To investigate the influence of genetic variation at the CRP gene on CRP levels, we first constructed a dense linkage disequilibrium map for common single-nucleotide polymorphisms (SNPs) spanning the CRP locus (1 SNP every 850 bases, 26 kilobase [kb] genomic region). Thirteen CRP SNPs were genotyped in 1640 unrelated FHS participants with measured CRP levels. After adjustment for clinical covariates, 9 of 13 SNPs were associated with CRP level ( P <0.05). To account for correlation among SNPs, we conducted forward stepwise selection among all 13 SNPs; a triallelic SNP (rs3091244) remained associated with CRP level (stepwise P <0.0001). The triallelic SNP (C→T→A; allele frequencies 62%, 31%, and 7%), located in the promoter sequence, explained 1.4% of total serum CRP variation; haplotypes harboring the minor T and A alleles of this SNP were associated with higher CRP level (haplotype P =0.0002 and 0.004). Conclusions— In our community-based sample, clinical variables explained 26% of the interindividual variation in CRP, whereas a common triallelic CRP SNP contributed modestly. Studies of larger samples are warranted to assess the association of genetic variation in CRP and risk of cardiovascular disease.

Background— The CYP4A11 arachidonic acid monooxygenase oxidizes endogenous arachidonic acid (AA) to 20-hydroxyeicosatetraenoic acid (20-HETE), a metabolite with renovascular and tubular functions. Mice with targeted disruption of Cyp4a14 , a murine homologue of CYP4A11 , have severe hypertension. We combined molecular and biochemical approaches to identify a functional variant of the CYP4A11 20-HETE synthase and determine its association with hypertensive status in 2 independent human populations. Methods and Results— A thymidine-to-cytosine polymorphism at nucleotide 8590 resulted in a phenylalanine-to-serine substitution at amino acid 434. Expression of cDNA with serine 434 resulted in a protein with a significantly reduced AA and lauric acid metabolizing activity. In a population of 512 whites from Tennessee, the age, body mass index, and gender-adjusted OR of having hypertension attributable to the 8590C variant was 2.31 (95% CI 1.41 to 3.78) compared with the reference 8590TT genotype. In subjects from the Framingham Heart Study, the adjusted ORs of hypertension associated with the 8590C variant were 1.23 (CI 0.94 to 1.59; n=1538) in all subjects and 1.33 (CI 1.01 to 1.77; n=1331) when subjects with diabetes were excluded. No association of the variant with hypertension was detected in a population of 120 blacks. Conclusions— We identified a variant of the human CYP4A11 (T8590C) that encodes for a monooxygenase with reduced 20-HETE synthase activity. The association of the T8590C variant with hypertension supports its role as a polygenic determinant of blood pressure control in humans, and results obtained from the large population database suggest that the relevance of the variant may vary according to hypertension comorbidity.