Response to Letter Regarding Article, “Risk of Stroke in Chronic Heart Failure Patients Without Atrial Fibrillation: Analysis of the Controlled Rosuvastatin in Multinational Trial Heart Failure (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell’Insufficienza Cardiaca-Heart Failure (GISSI-HF) Trials.”

Abstract

We thank Lin and colleagues for their interest in our article.1 Their hypothesis that the seemingly paradoxical relation between lower body mass index and higher risk of stroke in patients without atrial fibrillation might be explained by leaner patients having more severe heart failure and a hemodynamic profile favoring left atrial thrombus development is plausible. However, when dichotomized into lean (<25 kg/m Patients with atrial fibrillation (n=3531) did not show a clear relationship between body mass index and risk of stroke: the hazard ratio for stroke per 5-kg/m 2 increase in body mass index (≤30) was 0.90 (95% confidence interval, 0.70-1.14; P=0.335). The unadjusted hazard ratio for risk of stroke in overweight versus lean patients was 0.76 (95% confidence interval, 0.55-1.04; P=0.085). The hazard ratio for this comparison in patients without atrial fibrillation was 0.60 (95% confidence interval, 0.46-0.79; P<0.001). The reasons for this difference, if real, are uncertain but might include any independent effect of heart failure severity on the propensity to thrombus formation being obscured by the same (and perhaps greater) effect of atrial fibrillation.

Efficacy and safety of edoxaban compared with warfarin in patients with atrial fibrillation and heart failure: insights from ENGAGE AF‐TIMI 48

“…Thus, we found HF to be a powerful independent predictor of CV death, compared with patients without HF. Furthermore, our finding of an increased incidence of stroke/SEE in HF patients is in accord with previous observational studies . However, our findings differ from those in other studies.…”

“…As the presence of HF increases the risk of thromboembolic events in patients with AF, HF has been incorporated into frequently used thromboembolic risk stratification scores, such as the CHADS 2 and the CHA 2 DS 2 ‐VASc . Even in the absence of AF, HF is an independent risk factor for thromboembolism, ranking second only to AF as the underlying cause of cardioembolic strokes …”

Heart and brain interaction in patients with heart failure: overview and proposal for a taxonomy. A position paper from the Study Group on Heart and Brain Interaction of the Heart Failure Association

“… A stepwise increase of stroke risk was observed in parallel to increasing New York Heart Association (NYHA) classes and decreasing LV ejection fractions . Patients with HF of ischaemic aetiology or with other co‐morbidities including peripheral arterial disease, hypertension, valvular heart disease, diabetes, advanced obesity, prior stroke and an estimated glomerular filtration rate < 60 mL/min/1.73 m 2 have a higher stroke risk compared to HF patients who are free from these conditions . Addressing the individual contributions of those risk factors is, however, beyond the scope of this paper.…”

The CHADS2 score predicts ischemic stroke in chronic heart failure patients without atrial fibrillation: comparison to other stroke risk scores

“…The "stroke risk score" was calculated by multiplying age (per 10 years increase) by 3.31, BMI (per 5 kg/m 2 increase up to 30) by −3.01 and then adding 4.72 in the case of NYHA III or IV, 6.26 when patients had diabetes mellitus treated with insulin and 5.91 when patients had the prior stroke [12].…”

“…(CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza cardiac-heart failure trial (GISSI-HF) [12]. This new "stroke risk score" included the following independent predictors of stroke: age, New York Heart Association (NYHA) functional class, diabetes mellitus with insulin, body mass index and prior stroke.…”