Genomic Risk Stratification Predicts All-Cause Mortality After Cardiac Catheterization.

BACKGROUND: Coronary artery disease (CAD) is influenced by genetic variation and traditional risk factors. Polygenic risk scores (PRS), which can be ascertained before the development of traditional risk factors, have been shown to identify individuals at elevated risk of CAD. Here, we demonstrate that a genome-wide PRS for CAD predicts all-cause mortality after accounting for not only traditional cardiovascular risk factors but also angiographic CAD itself. METHODS: Individuals who underwent coronary angiography and were enrolled in an institutional biobank were included; those with prior myocardial infarction or heart transplant were excluded. Using a pruning-and-thresholding approach, a genome-wide PRS comprised of 139 239 variants was calculated for 1503 participants who underwent coronary angiography and genotyping. Individuals were categorized into high PRS (hiPRS) and low-PRS control groups using the maximally selected rank statistic. Stratified analysis based on angiographic findings was also performed. The primary outcome was all-cause mortality following the index coronary angiogram. RESULTS: Individuals with hiPRS were younger than controls (66 years versus 69 years; P=2.1×10-5) but did not differ by sex, body mass index, or traditional risk-factor profiles. Individuals with hiPRS were at significantly increased risk of all-cause mortality after cardiac catheterization, adjusting for traditional risk factors and angiographic extent of CAD (hazard ratio, 1.6; 95% CI, 1.2-2.2; P=0.004). The strongest increase in risk of all-cause mortality conferred by hiPRS was seen among individuals without angiographic CAD (hazard ratio, 2.4; 95% CI, 1.1-5.5; P=0.04). In the overall cohort, adding hiPRS to traditional risk assessment improved prediction of 5-year all-cause mortality (area under the receiver-operating curve 0.70; 95% CI, 0.66-0.75 versus 0.66; 95% CI, 0.61-0.70; P=0.001). CONCLUSIONS: A genome-wide PRS improves risk stratification when added to traditional risk factors and coronary angiography. Individuals without angiographic CAD but with hiPRS remain at significantly elevated risk of mortality.

Symptoms characteristic of heart failure among CKD patients without diagnosed heart failure.

BACKGROUND: Epidemiological studies typically diagnose heart failure (HF) at the time of hospitalization, and have not evaluated the prevalence of HF symptoms in CKD patients without a prior HF diagnosis. METHODS AND RESULTS: We modified the Kansas City Cardiomyopathy Questionnaire (KCCQ) to detect and quantify symptoms characteristic of HF (dyspnea, edema, and fatigue) among 2883 chronic kidney disease (CKD) patients without diagnosed heart failure in the Chronic Renal Insufficiency Cohort (CRIC). The KCCQ is a 23-item instrument that quantifies the impact of dyspnea, fatigue, and edema on physical, social, and emotional functions (scored 0 to 100). The median KCCQ score was 92, and 25% had KCCQ scores <75. Compared with cystatin C­based estimated glomerular filtration rate >50 mL·min·1.73 m(2) (reference), estimated glomerular filtration rate 40 to 50, 30 to 40, and <30 were independently associated with lower KCCQ scores (<75); adjusted odds ratios and (95% CI): 1.38 (1.06-1.78), 1.39 (1.09-1.82), and 2.15 (1.54-3.00), respectively. Lower hemoglobin (Hb) levels also had independent associations with KCCQ <75: Hb >14 g/dL (reference), Hb 13 to 14 g/dL (1.03; 0.76-1.40), Hb 12 to 13 g/dL (1.41; 1.04-1.91), Hb 11 to 12 g/dL (1.56; 1.12-2.16); and Hb <1 g/dL (1.65; 1.15-2.37). CONCLUSION: CKD patients without diagnosed HF have a substantial burden of symptoms characteristic of HF, particularly among those with lower estimated glomerular filtration rate and hemoglobin levels.