Sex differences in physical activity trajectories and risks for adverse outcomes in patients with implantable cardioverter defibrillators

Background Physical activity (PA) is recommended for most patients with implantable cardioverter defibrillators (ICDs), but women are typically less active than men and have increased risk of adverse outcomes. Activity patterns can vary over time and may differ by sex. It is unclear if these differences contribute to increased sex-specific cardiovascular health risks. Purpose This study was designed to examine the association between PA (mean and slope) and the risks of all-cause mortality and hospitalization for heart failure (HF) among patients with ICDs, and to assess if this association is modified by sex. Methods This retrospective study included a nationwide sample of real-world patients with Medtronic ICDs (with and without cardiac resynchronization therapy or CRT-D) implanted 1/01/2010-1/23/2021. Daily PA (minutes per day) were obtained from accelerometers built into the ICDs and linked with clinical data from electronic health records. Outcomes were all-cause mortality and a composite of all-cause mortality and HF hospitalization. Patients were followed from 60 days post-implantation until an event, loss to follow-up (last recorded encounter), or follow-up end. Mean PA and the slope of PA over time were analyzed continuously and by tertiles. Multivariable Cox models estimated the relations of PA and PA change with outcomes, with non-linear relationships assessed using restricted cubic splines. Final estimates were pooled from 13 multiple-imputed datasets. All analyses were stratified by sex. Results In 13,369 ICD/CRT-D patients (67.3 [9.6] years; 5.1% women), mean PA was 143 min/day for men and 129 min/day for women. Over a mean follow-up of 3.3 years, PA declined by 0.32 min/day in men and 0.26 min/day in women. Optimal PA was about 240 min/day for men and 180 min/day for women. Relative to men with low PA (< 92 min/day), the mortality HR was 0.48 for moderate PA (91-172 mins; 95%CI 0.42-0.55) and 0.30 for high PA (≥172 mins; 95%CI 0.26-0.34). For the composite event, HRs were 0.62 for moderate PA (95%CI 0.57-0.68) and 0.46 for high PA (95%CI 0.41-0.52). Relative to women with low PA (≤ 120 min) those with high PA (>120 min/day) showed a lower risk of death (HR 0.39; 95%CI 0.16-0.97) and of the composite (HR 0.74; 95%CI 0.49-1.11). The lowest risks of death and HF hospitalization were observed with a 0.15 min/day decrease in men and a 0.18 min/day decrease in women. A 0.5 min/day PA decline was associated with 177% greater risk of death in men (HR 2.77; 95%CI 2.61-2.94) and 166% in women (HR 2.67; 95%CI 2.51-2.83). Rapid PA increases were also associated with risk. A 0.1 min/day PA increase was associated with a 62% risk of death in men (HR 1.62; 95%CI 1.47-1.77), and 56% risk in women (1.56; 95%CI 1.42-1.72). Conclusions Men had higher optimal PA than women, but all patients with high PA had lower risks of death or hospitalization. Rapidly increasing PA also appears to be associated with adverse outcomes.