The impact of body mass on cardiovascular outcomes in patients with acute coronary syndrome
Authors: Van Den Broek W W A , Azzahhafi J , Chan Pin Yin D R P P , Van Der Sangen N M R , Henriques J P S , Kikkert W J , Ten Berg J M 
Published: October 2024

Abstract

Background
Patients with acute coronary syndrome (ACS) and extreme body weights exhibit varying risks of bleeding and thrombotic outcomes. Furthermore, extreme body weights can influence the pharmacodynamic response to potent P2Y12 inhibitors (ticagrelor/prasugrel) and clopidogrel.

Purpose
This study aims to assess the impact of extreme body weights on cardiovascular outcomes, as well as the comparative efficacy and safety of potent P2Y12 inhibitors versus clopidogrel.

Methods
Data was extracted from the FORCE-ACS registry, a prospective, multicentre, registry, enrolling patients with ACS. Patients were stratified (in kg/m2) into the categories: underweight (body mass index [BMI] ≤20.0), normal weight (20.1–24.9), overweight (25.0–29.9), class 1 (30.0–34.9) and class 2 obesity (≥35.0). The primary thrombotic endpoint was major adverse cardiac events (MACE), a composite of cardiovascular death, myocardial infarction (MI), or stroke. The primary bleeding endpoint was defined as Bleeding Academic Research Consortium (BARC) 2, 3 or 5 bleeding. Cox proportional hazard models and Kaplan-Meier survival curves were used to estimate the risk of clinical events across the BMI categories. Restricted cubic splines were made to assess the continuous association of BMI with the risk of the primary endpoints, stratified for P2Y12-inhibitor therapy (potent vs. clopidogrel) and gender.

Results
The total included population consisted of 5,864 patients with ACS (mean age 65.2 years, 72.4% men), and were stratified into underweight (N=112 [2%]), normal weight (N=1,627 [28%]), overweight (N=2,697 [46%]), class 1 obesity (N=1,081 [18%]) and class 2 obesity (N=347 [6%]). Compared with normal weight (10.8%), the rate of primary bleeding outcome was higher in underweight (15.2%) patients, but lower in the overweight (8.9%), class 1 obesity (7.9%) and class 2 obesity (6.3%) categories. MACE occurred in 9.8% for the underweight group, 7.9% for normal weight, 7.0% for overweight, 8.0% for class, and 6.1% for class 2 obesity. After adjusting for confounding factors such as age, gender, cardiovascular risk factors, access site, and medical therapy, each unit increase in BMI was associated with a decreased bleeding risk (hazard ratio [HR] 0.97, 95% CI 0.95-0.99, p = 0.02), with no significant association found for MACE. Similar findings are demonstrated in the Kaplan Meier analysis (Figure 1A-1B). Subgroup analysis regarding bleeding risk and BMI did not show a significant interaction for potent P2Y12-inhibitor therapy versus clopidogrel and gender (P-value for interaction: 0.04 and 0.32, respectively)(Figure 2A-2D).

Conclusions
Our findings indicate a stronger correlation between BMI and bleeding risk compared to thrombotic risk, showing an increased risk for bleeding in patients with a low BMI. These results underscore the importance of careful monitoring and tailored interventions to mitigate bleeding risk in underweight patients.