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

<div><p>Background</p><p>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.</p><p>Methods</p><p>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.</p><p>Results</p><p>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).</p><p>Conclusion</p><p>Individuals who develop SSS are at increased risk of death and CVD. The mechanisms underlying these associations warrant further investigation.</p></div

Baseline characteristics by sick sinus syndrome (SSS) diagnosis during follow-up, Atherosclerosis Risk in Communities (ARIC) study and Cardiovascular Health Study (CHS).

<p>Values correspond to means (standard deviations) or proportions. BMI: body mass index; CHD: coronary heart disease; HF: heart failure.</p><p>Baseline characteristics by sick sinus syndrome (SSS) diagnosis during follow-up, Atherosclerosis Risk in Communities (ARIC) study and Cardiovascular Health Study (CHS).</p

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.

<p>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.</p

Age, race, and sex-standardized rates (per 1000 person-years) of mortality and selected cardiovascular events in individuals with and without sick sinus syndrome (SSS), combined Atherosclerosis Risk in Communities study, 1987–2009, and Cardiovascular Health Study, 1989–2008.

<p>CI: confidence interval; IRR: incidence rate ratio.</p><p>Age, race, and sex-standardized rates (per 1000 person-years) of mortality and selected cardiovascular events in individuals with and without sick sinus syndrome (SSS), combined Atherosclerosis Risk in Communities study, 1987–2009, and Cardiovascular Health Study, 1989–2008.</p

Cohort-specific and pooled hazard ratios (95% confidence intervals) for the association of sick sinus syndrome (SSS) with atrial fibrillation and heart failure, adjusting for cardiovascular risk factors and accounting for pacemaker implantation, Atherosclerosis Risk in Communities (ARIC) study, 1987–2009, and Cardiovascular Health Study (CHS), 1989–2008.

a,b<p>Results correspond to Cox proportional hazards model adjusted for age, sex, race, center, education, smoking, BMI, hypertension, total cholesterol, HDL cholesterol, diabetes, prevalent and time-dependent CHD, prevalent and time-dependent HF (for the AF analysis only), prevalent and time-dependent stroke, time-dependent AF (for the HF analysis only). Model ^a additionally adjusted for time-dependent pacemaker implantation.</p><p>Cohort-specific and pooled hazard ratios (95% confidence intervals) for the association of sick sinus syndrome (SSS) with atrial fibrillation and heart failure, adjusting for cardiovascular risk factors and accounting for pacemaker implantation, Atherosclerosis Risk in Communities (ARIC) study, 1987–2009, and Cardiovascular Health Study (CHS), 1989–2008.</p

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.

<p>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.</p

The association of estimated salt intake with blood pressure in a Viet Nam national survey

<div><p>Objective</p><p>To evaluate the association of salt consumption with blood pressure in Viet Nam, a developing country with a high level of salt consumption.</p><p>Design and setting</p><p>Analysis of a nationally representative sample of Vietnamese adults 25–65 years of age who were surveyed using the World Health Organization STEPwise approach to Surveillance protocol. Participants who reported acute illness, pregnancy, or current use of antihypertensive medications were excluded. Daily salt consumption was estimated from fasting mid-morning spot urine samples. Associations of salt consumption with systolic blood pressure and prevalent hypertension were assessed using adjusted linear and generalized linear models. Interaction terms were tested to assess differences by age, smoking, alcohol consumption, and rural/urban status.</p><p>Results</p><p>The analysis included 2,333 participants (mean age: 37 years, 46% male, 33% urban). The average estimated salt consumption was 10g/day. No associations of salt consumption with blood pressure or prevalent hypertension were observed at a national scale in men or women. The associations did not differ in subgroups defined by age, smoking, or alcohol consumption; however, associations differed between urban and rural participants (p-value for interaction of urban/rural status with salt consumption, <i>p</i> = 0.02), suggesting that higher salt consumption may be associated with higher systolic blood pressure in urban residents but lower systolic blood pressure in rural residents.</p><p>Conclusions</p><p>Although there was no evidence of an association at a national level, associations of salt consumption with blood pressure differed between urban and rural residents in Viet Nam. The reasons for this differential association are not clear, and given the large rate of rural to urban migration experienced in Viet Nam, this topic warrants further investigation.</p></div

Age-, smoking-, alcohol-, and rural/urban-stratified adjusted^* regression models of salt intake (g/day) with systolic blood pressure and prevalent hypertension.

<p>Age-, smoking-, alcohol-, and rural/urban-stratified adjusted^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0191437#t003fn001" target="_blank">*</a>} regression models of salt intake (g/day) with systolic blood pressure and prevalent hypertension.</p

Daily salt intake.

<p>Blue = men. Red = women.</p

Characteristics of 1,083 male and 1,250 female 25–64 year old participants in the 2009 Viet Nam STEPS survey.^*

<p>Characteristics of 1,083 male and 1,250 female 25–64 year old participants in the 2009 Viet Nam STEPS survey.^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0191437#t001fn001" target="_blank">*</a>}</p