BODY WEIGHT, LIPOPROTEIN (A), AND INCIDENT CARDIOVASCULAR DISEASE IN THE UK BIOBANK

Abstract

Therapeutic Area: ASCVD/CVD Risk Factors Background: Elevated lipoprotein (a) (Lp[a]) is a recognized risk factor for atherosclerotic cardiovascular disease (ASCVD). However, there is a scarcity of research investigating its impact on ASCVD risk across different body weight categories. Methods: The UK Biobank is a large prospective observational study across the United Kingdom. The analysis included individuals without prior cardiovascular disease (CVD) during the baseline period (2006-2010). Those with a baseline body mass index (BMI) below 18.5 kg/m² were excluded. Data were retrieved and analyzed between November-December 2023. ASCVD was defined as a composite of peripheral arterial disease, coronary artery disease, myocardial infarction, ischemic stroke, and cardiovascular mortality based on the International Classification of Diseases (ICD) 9 and ICD 10 codes. Normal weight was defined as BMI 18.5-24.9, overweight as BMI 25.0-29.9, and obese as BMI ≥30. The study cohort was stratified into six (6) groups as follows: Group 1: Normal weight with Lp(a) <50mg/dL, Group 2: Normal weight with Lp(a) ≥ 50mg/dL, Group 3: Overweight with Lp(a) <50mg/dL, Group 4: Overweight with Lp(a) ≥ 50mg/dL, Group 5: Obese with Lp(a) <50mg/dL, and Obese with Lp(a) ≥ 50mg/dL. Using the multivariable Fine-Gray sub distribution hazards regression with the competing risk of all non-CVD death, we estimated the hazard ratios (HR) for incident ASCVD in the six groups. Results: Of the 358,762 individuals included in the study, 55.1% were women; mean (SD) age was 56.3 (±8.1) years. During a median follow-up period of 13.7 years, 29,295 (8.2%) ASCVD events occurred. Compared to the reference group (normal weight, Lp(a) <50mg/dL), Lp(a) ≥ 50mg/dL was associated with increased adjusted hazard ratios (95% CI) for incident ASCVD of 1.14 (1.08–1.20), 1.07 (1.02–1.11), and 1.09 (1.04–1.15) among those with normal weight, overweight, and obese, respectively. However, in the absence of Lp(a) ≥ 50mg/dL, higher BMI categories were associated with a reduced risk of ASCVD (Table). Conclusions: These findings show that elevated Lp(a) is associated with an increased risk of ASCVD across all body weight categories, emphasizing the potent and independent role of Lp(a) as a cardiovascular risk factor.