Associations of genetic and infectious risk factors with coronary heart disease.

Coronary heart disease (CHD) is one of the most pressing health problems of our time and a major cause of preventable death. CHD results from complex interactions between genetic and environmental factors. Using multiplex serological testing for persistent or frequently recurring infections and genome-wide analysis in a prospective population study, we delineate the respective and combined influences of genetic variation, infections, and low-grade inflammation on the risk of incident CHD. Study participants are enrolled in the CoLaus|PsyCoLaus study, a longitudinal, population-based cohort with baseline assessments from 2003 through 2008 and follow-up visits every 5 years. We analyzed a subgroup of 3459 individuals with available genome-wide genotyping data and immunoglobulin G levels for 22 persistent or frequently recurring pathogens. All reported CHD events were evaluated by a panel of specialists. We identified independent associations with incident CHD using univariable and multivariable stepwise Cox proportional hazards regression analyses. Of the 3459 study participants, 210 (6.07%) had at least one CHD event during the 12 years of follow-up. Multivariable stepwise Cox regression analysis, adjusted for known cardiovascular risk factors, socioeconomic status, and statin intake, revealed that high polygenic risk (hazard ratio [HR] 1.31, 95% CI 1.10-1.56, p=2.64 × 10-3) and infection with Fusobacterium nucleatum (HR 1.63, 95% CI 1.08-2.45, p=1.99 × 10-2) were independently associated with incident CHD. In a prospective, population-based cohort, high polygenic risk and infection with F. nucleatum have a small, yet independent impact on CHD risk.

Plasma suPAR levels are associated with mortality, admission time, and Charlson Comorbidity Index in the acutely admitted medical patient: a prospective observational study.

INTRODUCTION: Soluble urokinase plasminogen activator receptor (suPAR) is the soluble form of the membrane-bound receptor (uPAR) expressed predominantly on various immune cells. Elevated plasma suPAR concentration is associated with increased mortality in various patient groups, and it is speculated that suPAR is a low-grade inflammation marker reflecting on disease severity. The aim of this prospective observational study was to determine if the plasma concentration of suPAR is associated with admission time, re-admission, disease severity/Charlson Comorbidity Index Score, and mortality. METHODS: We included 543 patients with various diseases from a Danish Acute Medical Unit during a two month period. A triage unit ensured that only medical patients were admitted to the Acute Medical Unit. SuPAR was measured on plasma samples drawn upon admission. Patients were followed-up for three months after inclusion by their unique civil registry number and using Danish registries to determine admission times, readmissions, International Classification of Diseases, 10th Edition (ICD-10) diagnoses, and mortality. Statistical analysis was used to determine suPAR's association with these endpoints. RESULTS: Increased suPAR was significantly associated with 90-day mortality (4.87 ng/ml in survivors versus 7.29 ng/ml in non-survivors, P < 0.0001), higher Charlson Score (P < 0.0001), and longer admission time (P < 0.0001), but not with readmissions. The association with mortality remained when adjusting for age, sex, C-reactive protein (CRP), and Charlson Score. Furthermore, among the various Charlson Score disease groups, suPAR was significantly higher in those with diabetes, cancer, cardiovascular disease, and liver disease compared to those without comorbidities. CONCLUSIONS: SuPAR is a marker of disease severity, admission time, and risk of mortality in a heterogeneous cohort of patients with a variety of diseases. The independent value of suPAR suggests it could be of value in prognostic algorithms.