Epidemiology of stroke in chronic heart failure patients with normal sinus rhythm: Findings from the DIG stroke sub-study

Abstract

Background-Little is known about the epidemiology of stroke in chronic systolic and diastolic heart failure (HF) patients in normal sinus rhythm (NSR) receiving angiotensin-converting enzyme (ACE) inhibitors. Because all HF patients in the Digitalis Investigation Group (DIG) trial (N=7788) were in NSR and nearly all were receiving ACE inhibitors, a survey-based stroke substudy was conducted but its findings have never been published.Methods-DIG investigators confirmed a total 222 cases of stroke of which 144 had neurological deficit ≥24 hours. We used logistic regression models to determine predictors of incident stroke among all 7788 patients and predictors of neurological deficit ≥24 hours and allcause mortality among 222 stroke patients.Results-Age ≥65 years (adjusted odds ratio {AOR}, 1.36; 95% confidence interval {CI}, 1.02-1.80; P=0.035), nonwhite race (AOR, 0.65; 95% CI, 0.42-0.99; P=0.047), hypertension (AOR, 1.46; 95% CI, 1.11-1.94; P=0.008), diabetes mellitus (AOR, 1.37; 95% CI, 1.03-1.82; P=0.030), and cardiomegaly (AOR, 1.39; 95% CI, 1.03-1.86; P=0.030) were independent predictors of stroke. However, among those with stroke, nonwhites had higher odds of neurological deficits ≥24 hours (AOR, 2.86; 95% CI, 1.01-8.07; P=0.047) and death (AOR, 3.28; 95% CI,; P=0.012).Conclusion-Older age, hypertension, diabetes and cardiomegaly were associated with increased incidence of stroke among HF patients with NSR receiving ACE inhibitors. The association of race and stroke, however, was complex. While nonwhite race was associated with decreased risk of stroke, among those with stroke, nonwhite race was associated with increased stroke severity and mortality.

Heart Failure and Stroke

“…The studies support consideration of the CHA 2 DS 2 -VASc score for prediction of the risk of stroke in HF irrespective of AF presence. Indeed, several studies examined the components of the CHA 2 DS 2 -VASc score and demonstrated their individual association with stroke in HF: congestive HF represented by a decreased ejection fraction (hazard ratio [HR] 0.98–2.15) [ 15 •, 34 , 62 , 63 ], hypertension (HR 1.18) [ 15 •, 62 , 64 , 65 ], age (HR 1.34–1.35) [ 14 , 15 •, 62 – 64 ], diabetes mellitus (HR 1.114–1.87) [ 14 , 15 •, 16 ••, 62 , 63 , 65 ], prior stroke/TIA (HR 1.81–2.68) [ 14 , 15 •, 39 , 63 , 64 ], vascular disease (HR 1.34) [ 66 ], and gender (HR 0.569) [ 15 •, 62 , 63 ]. In WARCEF sub-study with patients with sinus rhythm, the ejection fraction was associated with stroke only if its baseline values were less than 15% [ 62 , 63 ].…”

Blood Pressure and Stroke in Heart Failure in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study

“…Hypertension was not a risk factor for stroke in a study of patients with left ventricular systolic dysfunction,9 and in Studies of Left Ventricular Dysfunction, hypertension imparted a small relative risk of stroke only in men (RR 1.32 95%CI: 1.04-1.69; p=0.02) but no significant risk in women 10. Two recent sub-studies of the Digitalis Investigation Group trial11, 12 however, showed a history of hypertension to be an independent predictor of stroke (adjusted odds ratio 1.46; 95% CI:1.11-1.94)12 and a risk factor for hospitalization for stroke (hazard ratio 1.52; 95%CI:1.11-2.08) among patients with HF.…”

Antithrombotic therapy for heart failure in sinus rhythm

“…Similarly, one community based study reported a 17.4 fold increase risk of ischemic stroke within the first month after heart failure diagnosis [7]. However, the Digitalis Investigation Group stroke substudy found an annual stroke risk of only 1% [8].…”