Soluble Urokinase Plasminogen Activator Receptor Levels and Outcomes in Patients with Heart Failure.

BACKGROUND: Soluble urokinase-type plasminogen activator receptor (suPAR) is a marker of immune activation and pathogenic factor for kidney disease shown to predict cardiovascular outcomes including heart failure (HF) in various populations. We characterized suPAR levels in patients with HF and compared its ability to discriminate risk to that of B-type natriuretic peptide (BNP). METHODS AND RESULTS: We measured plasma suPAR and BNP levels in 3,437 patients undergoing coronary angiogram and followed for a median of 6.2 years. We performed survival analyses for the following outcomes: all-cause death, cardiovascular death, and hospitalization for HF. We then assessed suPAR's ability to discriminate risk for the aforementioned outcomes. We identified 1116 patients with HF (age 65±12, 67.2% male, 20.0% Black, 67% with reduced ejection fraction). The median suPAR level was higher in HF compared to those without HF (3370 [IQR 2610-4371] vs. 2880 [IQR 2270-3670] pg/mL, respectively, P<0.001). In patients with HF, suPAR levels (log-base 2) were associated with outcomes including all-cause death (adjusted hazard ratio aHR 2.30, 95%CI[1.90-2.77]), cardiovascular death (aHR 2.33 95%CI[1.81-2.99]) and HF hospitalization (aHR 1.96, 95%CI[1.06-1.25]) independently of clinical characteristics and BNP levels. The association persisted across subgroups and did not differ between patients with reduced or preserved ejection fraction, or those with ischemic or non-ischemic cardiomyopathy. Addition of suPAR to a model including BNP levels significantly improved the C-statistic for death (Δ0.027), cardiovascular death (Δ0.017) and hospitalization for HF (Δ0.017). CONCLUSIONS: SuPAR levels are higher in HF compared to non-HF, are strongly predictive of outcomes, and combined with BNP, significantly improved risk prediction.

Sleep Duration and Mortality in Patients With Coronary Artery Disease.

Extremes in sleep duration are associated with higher cardiovascular risk in the general population, but their impact in patients with documented coronary artery disease (CAD) remains unknown and potentially of clinical significance. We hypothesized that both short and long sleep duration are associated with higher mortality in CAD. We inquired about sleep durations in 2,846 patients enrolled in the Emory Cardiovascular Biobank (mean age 64 years, 38% female, 23% Black, and 82% with obstructive CAD, defined by positive coronary angiography), who were then followed for all-cause and cardiovascular mortality. Multivariate Cox proportional hazard models were calculated to examine the association of sleep duration and mortality. Sleep durations of <6.5 hours (short), ≥6.5 to <7.5 hours (normal), and ≥7.5 hours (long) were reported by 39%, 26% and 35% of the cohort, respectively. On follow-up (median 2.8 years), mortality rates were 15%, 11%, and 17%, respectively. After adjusting for demographics and risk factors, both short and long sleep duration were associated with higher all-cause mortality (hazard ratio 1.44, 95% confidence interval [1.10 to 1.89], and 1.41 [1.08 to 1.85], respectively). A similar pattern was demonstrated for cardiovascular mortality only for short (hazard ratio 1.48 [1.05 to 2.09]), but not long sleep duration. In conclusion, in patients with frank CAD, both short and long sleep duration were independently associated with higher all-cause mortality, and short sleep was independently associated with higher cardiovascular mortality. In conclusion, our study is the first to extend the observations of sleep duration and mortality from population-based studies to patients with documented cardiac disease.

Marital Status and Outcomes in Patients With Cardiovascular Disease.

BACKGROUND: Being unmarried is associated with decreased survival in the general population. Whether married, divorced, separated, widowed, or never-married status affects outcomes in patients with cardiovascular disease has not been well characterized. METHODS AND RESULTS: A prospective cohort (inception period 2003-2015) of 6051 patients (mean age 63 years, 64% male, 23% black) undergoing cardiac catheterization for suspected or confirmed coronary artery disease was followed for a median of 3.7 years (interquartile range: 1.7-6.7 years). Marital status was stratified as married (n=4088) versus unmarried (n=1963), which included those who were never married (n=451), divorced or separated (n=842), or widowed (n=670). The relationship between marital status and primary outcome of cardiovascular death and myocardial infarction was examined using Cox regression models adjusted for clinical characteristics. There were 1085 (18%) deaths from all causes, 688 (11%) cardiovascular-related deaths, and 272 (4.5%) incident myocardial infarction events. Compared with married participants, being unmarried was associated with higher risk of all-cause mortality (hazard ratio [HR]: 1.24; 95% confidence interval [CI], 1.06-1.47), cardiovascular death (HR: 1.45; 95% CI, 1.18-1.78), and cardiovascular death or myocardial infarction (HR: 1.52; 95% CI, 1.27-1.83). Compared with married participants, the increase in cardiovascular death or myocardial infarction was similar for the participants who were divorced or separated (HR: 1.41; 95% CI, 1.10-1.81), widowed (HR: 1.71; 95% CI, 1.32-2.20), or never married (HR: 1.40; 95% CI, 0.97-2.03). The findings persisted after adjustment for medications and other socioeconomic factors. CONCLUSIONS: Marital status is independently associated with cardiovascular outcomes in patients with or at high risk of cardiovascular disease, with higher mortality in the unmarried population. The mechanisms responsible for this increased risk require further study.

Draft sequencing and assembly of the genome of the world's largest fish, the whale shark: Rhincodon typus Smith 1828.

BACKGROUND: The whale shark (Rhincodon typus) has by far the largest body size of any elasmobranch (shark or ray) species. Therefore, it is also the largest extant species of the paraphyletic assemblage commonly referred to as fishes. As both a phenotypic extreme and a member of the group Chondrichthyes - the sister group to the remaining gnathostomes, which includes all tetrapods and therefore also humans - its genome is of substantial comparative interest. Whale sharks are also listed as an endangered species on the International Union for Conservation of Nature's Red List of threatened species and are of growing popularity as both a target of ecotourism and as a charismatic conservation ambassador for the pelagic ecosystem. A genome map for this species would aid in defining effective conservation units and understanding global population structure. RESULTS: We characterised the nuclear genome of the whale shark using next generation sequencing (454, Illumina) and de novo assembly and annotation methods, based on material collected from the Georgia Aquarium. The data set consisted of 878,654,233 reads, which yielded a draft assembly of 1,213,200 contigs and 997,976 scaffolds. The estimated genome size was 3.44Gb. As expected, the proteome of the whale shark was most closely related to the only other complete genome of a cartilaginous fish, the holocephalan elephant shark. The whale shark contained a novel Toll-like-receptor (TLR) protein with sequence similarity to both the TLR4 and TLR13 proteins of mammals and TLR21 of teleosts. The data are publicly available on GenBank, FigShare, and from the NCBI Short Read Archive under accession number SRP044374. CONCLUSIONS: This represents the first shotgun elasmobranch genome and will aid studies of molecular systematics, biogeography, genetic differentiation, and conservation genetics in this and other shark species, as well as providing comparative data for studies of evolutionary biology and immunology across the jawed vertebrate lineages.