Key result
Very high ApoA1 levels (highest decile) were associated with increased cardiovascular mortality compared to the lowest risk eighth decile (HR 1.21; 95% CI 1.07-1.37; P<0.0022).
Why the study?
While low HDL-C associates with greater cardiovascular risk, studies also report heightened mortality at very high HDL-C levels; the sex-specific association between elevated ApoA1 levels and adverse outcomes was investigated.
Do very high serum ApoA1 levels increase the risk of cardiovascular and all-cause mortality in individuals without coronary artery disease?
Cohort (n=402,783)
Do very high serum ApoA1 levels increase the risk of cardiovascular and all-cause mortality in individuals without coronary artery disease?
Hazard Ratio: 1.21 (95% CI 1.07–1.37)
p-value: p=< 0.0022
Very high levels of ApoA1 are associated with increased cardiovascular and all-cause mortality, demonstrating a U-shaped risk relationship similar to that seen with HDL cholesterol.
Very high ApoA1 warrants caution in primary-prevention risk assessment; leaves open causal role and requires prospective confirmation.
BACKGROUND: Apolipoprotein A1 (ApoA1) is the principal protein component of high-density lipoprotein (HDL). Although low HDL cholesterol (HDL-C) levels are known to be associated with greater cardiovascular risk, recent studies have also shown heightened mortality risk at very high HDL-C levels. AIMS: To investigate the sex-specific association between elevated ApoA1 levels and adverse outcomes, and their genetic basis. METHODS: A prospective cohort study of United Kingdom Biobank participants without coronary artery disease at enrollment was performed. The primary exposure was serum ApoA1 levels. The primary and secondary outcome measures were cardiovascular and all-cause death, respectively. RESULTS: In 402 783 participants followed for a median of 12.1 years, there was a U-shaped relationship between ApoA1 levels and both cardiovascular as well as all-cause mortality, after adjustment for traditional cardiovascular risk factors. Individuals in the highest decile of ApoA1 levels (1.91-2.50 g/L) demonstrated higher cardiovascular (HR 1.21, 95% CI 1.07-1.37, P < 0.0022) and all-cause mortality (HR 1.14, 95% CI 1.07-1.21, P < 0.0001) compared with those within the lowest risk eighth decile (1.67-1.75 g/L). The U-shaped relationship was present in both sexes, though more pronounced in men. Sensitivity analyses showed that cardiovascular mortality rates were higher in those with greater alcohol intake (P < 0.004). Adjustment for polygenic variation associated with higher ApoA1 levels did not attenuate the effect of very high ApoA1 levels on mortality. In the sub-group with very elevated HDL-C levels (> 80 mg/dL in men, > 100 mg/dL in women), there was no association between ApoA1 levels and mortality. CONCLUSION: Both very low and very elevated ApoA1 levels are associated with higher cardiovascular and all-cause mortality.
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Faaborg‐Andersen et al. (2022) conducted a cohort in without coronary artery disease (n=402,783). Serum ApoA1 levels vs. Lowest risk eighth decile (1.67-1.75 g/L) was evaluated on Cardiovascular death (HR 1.21, 95% CI 1.07-1.37, p=< 0.0022). Very high ApoA1 levels (highest decile) were associated with increased cardiovascular mortality compared to the lowest risk eighth decile (HR 1.21; 95% CI 1.07-1.37; P<0.0022).
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