Cardiovascular risk after hospitalisation for unexplained syncope and orthostatic hypotension

Abstract

Objective: To investigate the relationship of hospital admissions due to unexplained syncope and orthostatic hypotension (OH) with subsequent cardiovascular events and mortality.

Methods: We analysed a population-based prospective cohort of 30 528 middle-aged individuals (age 58±8 years; males, 40%). Adjusted Cox regression models were applied to assess the impact of unexplained syncope/OH hospitalisations on cardiovascular events and mortality, excluding subjects with prevalent cardiovascular disease.

Results: After a median follow-up of 15±4 years, 524 (1.7%) and 504 (1.7%) participants were hospitalised for syncope or OH, respectively, yielding 1.2 hospital admissions per 1000 person-years for each diagnosis. Syncope hospitalisations increased with age (HR, per 1 year: 1.07, 95% CI 1.05 to 1.09), higher systolic blood pressure (HR, per 10 mm Hg: 1.06, 95% CI 1.01 to 1.12), antihypertensive treatment (HR: 1.26, 95% CI 1.00 to 1.59), use of diuretics (HR: 1.77, 95% CI 1.31 to 2.38) and prevalent cardiovascular disease (HR: 1.59, 95% CI 1.14 to 2.23), whereas OH hospitalisations increased with age (HR: 1.11, 95% CI 1.08 to 1.12) and prevalent diabetes (HR: 1.82, 95% CI 1.23 to 2.70). After exclusion of 1399 patients with prevalent cardiovascular disease, a total of 473/464 patients were hospitalised for unexplained syncope/OH before any cardiovascular event. Hospitalisation for unexplained syncope predicted coronary events (HR: 1.85, 95% CI 1.49 to 2.30), heart failure (HR: 2.24, 95% CI 1.65 to 3.04), atrial fibrillation (HR: 1.84, 95% CI 1.50 to 2.26), aortic valve stenosis (HR: 2.06, 95% CI 1.28 to 3.32), all-cause mortality (HR: 1.22, 95% CI 1.09 to 1.37) and cardiovascular death (HR: 1.72, 95% CI 1.23 to 2.42). OH-hospitalisation predicted stroke (HR: 1.66, 95% CI 1.24 to 2.23), heart failure (HR: 1.78, 95% CI 1.21 to 2.62), atrial fibrillation (HR: 1.89, 95% CI 1.48 to 2.41) and all-cause mortality (HR: 1.14, 95% CI 1.01 to 1.30).

Conclusions: Patients discharged with the diagnosis of unexplained syncope or OH show higher incidence of cardiovascular disease and mortality with only partial overlap between these two conditions.

Keywords: cardiovascular disease; hospital admission; mortality; orthostatic hypotension; unexplained syncope.

Figure 1

Flow chart summarising the selection process of study population. CV, cardiovascular; OH, orthostatic hypotension.

Figure 2

Long-term cumulative incidence of coronary events and stroke according to incident unexplained syncope- and orthostatic hypotension (OH)-related hospital admission (n=29 129). Kaplan-Meier curves with regard to coronary events (A) and stroke (B) stratified according to incident syncope-related (blue) and OH-related (red) hospital admissions: in both cases showing significantly lower event-free survival rate (Log-rank test: p<0.001) compared with patients never hospitalised for syncope or OH (green). Patients with a first-ever incident syncope-related hospital admission showed a near-significant trend (Log-rank test: p=0.061) towards higher coronary event rate compared with incident OH-related admission. OH-related hospitalisation was associated with a significantly higher risk of stroke (Log-rank test: p=0.017).

Figure 3

Risk estimation of incident cardiovascular (CV) events in Malmö Diet and Cancer Study cohort (n=29 129) associated with history of orthostatic hypotension (OH)-related or unexplained syncope-related hospitalisation during follow-up. Multivariable-adjusted (age, sex, BMI, systolic BP, antihypertensive treatment, diabetes and current smoking) Cox regression model was applied by entering incident hospitalisation for OH or syncope prior to first-ever incident CV event (ie, coronary event, stroke, atrial fibrillation, heart failure and aortic valve stenosis) as an independent variable after exclusion of prevalent CV disease. Results are presented as adjusted HRs with 95% CIs. BMI, body mass index; BP, blood pressure.

Figure 4

Long-term cumulative incidence of cardiovascular (CV) mortality rates according to incident syncope-related and OH-related hospital admission (n=29 129). Kaplan-Meier curves with regard to CV mortality stratified according to incident syncope-related (blue) and OH-related (red) hospital admission: inpatients showed a significantly lower survival rate (Log-rank test p<0.001) compared with those never hospitalised for syncope or OH (green). The black vertical line at 12 years is a landmark point indicating mean time between baseline and first-ever OH/syncope hospital admission. Thereafter, survival curves for OH/syncope-related hospital admission and non-hospitalised patients begin and continue to diverge. OH, orthostatic hypotension.