Impact of BMI on the Outcomes of Intensive LDL-C Lowering Therapy

Patients receiving intensive low-density lipoprotein-cholesterol- (LDL-C) lowering therapy may have better clinical outcomes when their body mass index (BMI) is normal vs high, according to a study published in The American Journal of Cardiology.

In this meta-analysis, researchers searched PubMed, Embase, and CENTRAL databases, as well as Clinicaltrials.gov through April 2019. Inclusion criteria were randomized controlled trials (RCTs) in which the efficacy of therapies aiming to reduce LDL-C levels by upregulating the LDL receptors was examined in patients recommended for intensive LDL-C lowering. Studies were included if they had a sample size ≥1000 patients with reported baseline BMI, and if the follow-up was ≥48 weeks (n=266,148 patients). The study’s primary outcome was cardiovascular mortality. The secondary endpoints were all-cause mortality, myocardial infarction (MI), revascularization (coronary artery bypass grafting, coronary or other arterial percutaneous interventions), cerebrovascular events, and major adverse cardiac events (MACE).

For every 1 kg/m² increase in BMI, treatment with a more vs less intensive LDL-C therapy was associated with the following hazard ratios (HRs): cardiovascular mortality (HR, 1.07; 95% CI, 1.02-1.13), all-cause mortality (HR, 1.03; 95% CI, 0.99-1.06), MACE (HR, 1.04; 95% CI, 1.01-1.07), MI (HR, 1.06; 95% CI, 1.02-1.09), revascularization (HR, 1.08; 95% CI, 1.03-1.12), and cerebrovascular events (HR, 0.99; 95% CI, 0.94-1.03). Patients with a BMI <25 kg/m² had the highest risk reduction in cardiovascular mortality (HR, 0.57; 95% CI, 0.37-0.86) followed by participants with a BMI ranging from 25 to 29.9 kg/m² (HR, 0.86; 95% CI, 0.80 to 0.92) and patients with a BMI ≥30 kg/m² (HR, 0.96; 95% CI, 0.68-1.33; interaction, P =.05).

Study limitations include the lack of patient-level data, and the use of BMI to assess obesity.

“These results could be due to the higher mortality rate of obese patients that may artificially lower the efficacy of therapy, or due to a true limitation of therapeutic efficacy in these patients,” noted the researchers. “Although weight reduction is encouraged to improve the cardiovascular risk profile, professional guidelines focus on concrete LDL-C targets in patients with established [atherosclerotic cardiovascular disease]. With the increasing rate of obesity and its hazardous impact on cardiovascular health, data such as the ones presented in this study should provide an enhanced rationale for public health initiatives focused on the importance of keeping a healthy body weight throughout life.”

Disclosure: One study author declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of author’s disclosures.

Reference

Khan SU, Khan MU, Rias H, et al. Meta-analysis of the relation of body mass index to cardiovascular outcomes in patients receiving intensive low-density lipoprotein cholesterol lowering therapy [published online December 10, 2019]. Am J Cardiol. doi: 10.1016/j.amjcard.2019.12.006