Association of sick sinus syndrome with incident cardiovascular disease and mortality: the Atherosclerosis Risk in Communities study and Cardiovascular Health Study

Abstract

Background: Sick sinus syndrome (SSS) is a common indication for pacemaker implantation. Limited information exists on the association of sick sinus syndrome (SSS) with mortality and cardiovascular disease (CVD) in the general population.

Methods: We studied 19,893 men and women age 45 and older in the Atherosclerosis Risk in Communities (ARIC) study and the Cardiovascular Health Study (CHS), two community-based cohorts, who were without a pacemaker or atrial fibrillation (AF) at baseline. Incident SSS cases were validated by review of medical charts. Incident CVD and mortality were ascertained using standardized protocols. Multivariable Cox models were used to estimate the association of incident SSS with selected outcomes.

Results: During a mean follow-up of 17 years, 213 incident SSS events were identified and validated (incidence, 0.6 events per 1,000 person-years). After adjustment for confounders, SSS incidence was associated with increased mortality (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.14-1.70), coronary heart disease (HR 1.72, 95%CI 1.11-2.66), heart failure (HR 2.87, 95%CI 2.17-3.80), stroke (HR 1.56, 95%CI 0.99-2.46), AF (HR 5.75, 95%CI 4.43-7.46), and pacemaker implantation (HR 53.7, 95%CI 42.9-67.2). After additional adjustment for other incident CVD during follow-up, SSS was no longer associated with increased mortality, coronary heart disease, or stroke, but remained associated with higher risk of heart failure (HR 2.00, 95%CI 1.51-2.66), AF (HR 4.25, 95%CI 3.28-5.51), and pacemaker implantation (HR 25.2, 95%CI 19.8-32.1).

Conclusion: Individuals who develop SSS are at increased risk of death and CVD. The mechanisms underlying these associations warrant further investigation.

Figure 1. Incidence rates of selected cardiovascular diseases by SSS status, overall and by race, sex and age groups, combined Atherosclerosis Risk in Communities study and Cardiovascular Health Study, 1987–2009.

Dark squares correspond to rates in SSS, light diamonds to rates in non SSS. Adj*: Standardized by age, sex and race to the combined ARIC and CHS person-time.

Figure 2. Cohort-specific and pooled hazard ratios (95% confidence intervals) of mortality and selected cardiovascular diseases comparing individuals with and without sick sinus syndrome (SSS), Atherosclerosis Risk in Communities (ARIC) study, 1987–2009, and Cardiovascular Health Study (CHS), 1989–2008.

Model 1: Cox proportional hazards model adjusted for age, sex, race, study center, education, smoking, body mass index, hypertension, total cholesterol, HDL cholesterol, diabetes, prevalent coronary heart disease, prevalent heart failure, and prevalent stroke. Model 2: Adjusted as in model 1, and for incident coronary heart disease, incident heart failure, incident stroke and incident atrial fibrillation as time-dependent covariates.