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

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.