Elevated Remnant Cholesterol & Lp-PLA2 Linked to Increased Cardiovascular Risk, Especially in Younger Men
A new study published in Diabetes, Obesity and Metabolism reveals a significant association between elevated levels of remnant cholesterol (RC) and lipoprotein-associated phospholipase A2 (Lp-PLA2) and an increased risk of adverse cardiovascular events, including stroke, heart attack, and major adverse cardiovascular events (MACE). The findings, based on a 12-year prospective study, highlight the importance of these biomarkers, particularly in younger male populations.
The research underscores a growing understanding of the role of RC and Lp-PLA2 in the development of cardiovascular disease (CVD) and other health complications. RC has emerged as a key risk factor not only for CVD but also for type 2 diabetes, chronic kidney disease, and all-cause mortality. Lp-PLA2, a biomarker of vascular inflammation, has been identified as an indicator of plaque susceptibility and a potential early detection marker for CVD.
Investigators evaluated the impact of RC and Lp-PLA2 levels using a composite endpoint of adverse events within a community of individuals with asymptomatic multivascular abnormalities. This approach, they noted, provides a more comprehensive assessment of vascular burden than focusing on isolated outcomes. “Our findings suggest that the combined assessment of RC and Lp-PLA2 may be an important indicator for vascular risk management and a potential therapeutic target for CVD,” the study authors concluded.
12-Year Study Reveals Significant Risk Increase
The study followed 1,864 participants from Kailuan General Hospital over a 12-year period, collecting clinical and biochemical data through routine medical examinations every two years. Participants were categorized into high and low groups based on the median expression levels of RC and Lp-PLA2.
Over the course of the study, 500 composite adverse events were recorded, including 169 strokes (9.2%), 51 myocardial infarctions (MIs) – or heart attacks – (2.8%), 210 MACEs (11.5%), and 342 all-cause deaths (18.7%). Notably, patients with high levels of both RC and Lp-PLA2 experienced a disproportionately higher rate of these events: 58 strokes (12.1%), 13 MIs (2.7%), 70 MACEs (14.6%), 127 all-cause deaths (26.6%), and a total of 175 composite endpoints. A Kaplan-Meier analysis confirmed a significantly increased cumulative risk of cardiovascular events in the high-RC/Lp-PLA2 group compared to those with low levels of both biomarkers.
Combined Elevation Significantly Boosts Risk
Analyzing the direct associations between biomarker levels and outcomes, researchers found an adjusted hazard ratio (aHR) of 1.43 (95% CI, 1.07–1.91; P = .030) for incident composite adverse events among participants with high RC and Lp-PLA2 levels, compared to the reference group with low levels.
Further analysis revealed that elevated RC alone was associated with a 73% increased risk of all-cause death (aHR: 1.73 [95% CI, 1.13–2.62]), while elevated Lp-PLA2 alone carried a 150% increased risk (aHR: 2.50 [95% CI, 1.71–3.64]). The combination of elevated RC and Lp-PLA2 demonstrated a 61% increased risk of all-cause death (aHR: 1.61 [95% CI, 1.10–2.38]).
Age and Sex Play a Critical Role
Interestingly, the study revealed that the association between elevated RC and Lp-PLA2 levels and increased risk was most pronounced in participants aged 60 years or less and in male participants. This suggests that targeted CVD management and prevention strategies may be particularly beneficial for these groups. The investigators believe the destabilizing and proinflammatory effects of these factors contribute to the heightened risk of cardiovascular events.
These findings reinforce the importance of comprehensive lipid management and highlight the potential for RC and Lp-PLA2 to serve as valuable markers for identifying individuals at increased risk of CVD. Further research in larger and more diverse populations is needed to validate these findings and refine risk assessment strategies.
