What is the clinical evidence from this study?

Study design: Cohort. Population: Sick sinus syndrome (n=19893). Intervention: Incident sick sinus syndrome vs. No sick sinus syndrome. Primary outcome: All-cause mortality (HR 1.39, 95% CI 1.14-1.70).

October 6, 2014Open Access

Association of Sick Sinus Syndrome with Incident Cardiovascular Disease and Mortality: The Atherosclerosis Risk in Communities Study and Cardiovascular Health Study

Key Result

Incident sick sinus syndrome was associated with increased mortality (HR 1.39) and higher risks of coronary heart disease, heart failure, stroke, and atrial fibrillation.

Study Design

Type

Cohort (n=19,893)

Multicenter

Yes

Structured PICO

Does incident sick sinus syndrome increase the risk of cardiovascular disease and mortality in adults without baseline pacemaker or atrial fibrillation?

Population

19,893 adults aged 45 and older without a pacemaker or atrial fibrillation at baseline, followed for a mean of 17 years to evaluate the association of incident sick sinus syndrome with mortality and cardiovascular disease.

Exposure

Incident sick sinus syndrome (SSS)

Comparator

Individuals without sick sinus syndrome (SSS)

Outcome

Incident coronary heart disease, stroke, heart failure, atrial fibrillation, pacemaker implantation, and all-cause mortalityhard clinical

Main Result

Hazard Ratio: 1.39 (95% CI 1.14–1.7)

Absolute Event Rate: 54.5% vs 22%

Limitations

Partial information on SSS characteristics such as severity of signs and symptoms
Unavailability of outpatient data where some SSS diagnoses might have been made
Lack of detailed data on the management of SSS patients, such as type of pacemaker implanted
Absence of systematic information on medication use at the time of SSS diagnosis and afterwards
Small number of SSS events precluded the study of race, sex, or age differences
Significant between-cohort heterogeneity for the association of SSS with mortality and some outcomes
Definition of CHD included only hard end-points, precluding assessment of angina or subclinical CHD
Potential overascertainment of heart failure events in the ARIC cohort due to reliance on ICD codes

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.

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