Key result
The highest quartile of small dense LDL-C was associated with an increased risk of incident coronary heart disease compared to the lowest quartile (HR 1.51; 95% CI 1.21-1.88).
Why the study?
To investigate the relationship between plasma levels of small dense low-density lipoprotein-cholesterol and risk for incident coronary heart disease.
Do higher plasma levels of small dense low-density lipoprotein-cholesterol (sdLDL-C) predict risk for incident coronary heart disease in men and women?
Cohort (n=11,419)
Yes
Do higher plasma levels of small dense low-density lipoprotein-cholesterol (sdLDL-C) predict risk for incident coronary heart disease in men and women?
Hazard Ratio: 1.51 (95% CI 1.21–1.88)
Higher plasma sdLDL-C levels independently predict incident coronary heart disease, even in individuals considered to be at low cardiovascular risk based on their LDL-C levels.
May refine CHD risk stratification; hypothesis-generating for targeted therapies, requires prospective trials before practice change.
OBJECTIVE: To investigate the relationship between plasma levels of small dense low-density lipoprotein-cholesterol (sdLDL-C) and risk for incident coronary heart disease (CHD) in a prospective study among Atherosclerosis Risk in Communities (ARIC) study participants. APPROACH AND RESULTS: Plasma sdLDL-C was measured in 11 419 men and women of the biracial ARIC study using a newly developed homogeneous assay. A proportional hazards model was used to examine the relationship among sdLDL-C, vascular risk factors, and risk for CHD events (n=1158) for a period of ≈11 years. Plasma sdLDL-C levels were strongly correlated with an atherogenic lipid profile and were higher in patients with diabetes mellitus than non-diabetes mellitus (49.6 versus 42.3 mg/dL; P<0.0001). In a model that included established risk factors, sdLDL-C was associated with incident CHD with a hazard ratio of 1.51 (95% confidence interval, 1.21-1.88) for the highest versus the lowest quartile, respectively. Even in individuals considered to be at low cardiovascular risk based on their LDL-C levels, sdLDL-C predicted risk for incident CHD (hazard ratio, 1.61; 95% confidence interval, 1.04-2.49). Genome-wide association analyses identified genetic variants in 8 loci associated with sdLDL-C levels. These loci were in or close to genes previously associated with risk for CHD. We discovered 1 novel locus, PCSK7, for which genetic variation was significantly associated with sdLDL-C and other lipid factors. CONCLUSIONS: sdLDL-C was associated with incident CHD in ARIC study participants. The novel association of genetic variants in PCSK7 with sdLDL-C and other lipid traits may provide new insights into the role of this gene in lipid metabolism.
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Dodge et al. (2020) conducted a cohort in incident coronary heart disease (CHD) (n=11,419). Small dense low-density lipoprotein-cholesterol (sdLDL-C) vs. Lowest quartile of sdLDL-C was evaluated on Incident CHD events (HR 1.51, 95% CI 1.21-1.88). The highest quartile of small dense LDL-C was associated with an increased risk of incident coronary heart disease compared to the lowest quartile (HR 1.51; 95% CI 1.21-1.88).
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