The following is a summary of “Serum Cholesterol and Impact of Age on Coronary Heart Disease Death in More Than 4 Million Veterans,” published in the October 2023 issue of Cardiology by Nguyen et al.
The relationship between blood cholesterol levels and coronary heart disease (CHD) risk has been an ongoing debate, with recent studies suggesting a U-shaped association, contradicting the lipid hypothesis. The researchers aimed to investigate this U-shaped relation and evaluate the influence of age on this connection.
This prospective cohort study included 4,467,942 veterans aged over 18 years, with baseline outpatient visits recorded from 2002 to 2007 and subsequent follow-ups until December 30, 2018, within the Veterans Health Administration’s electronic health record system. After thorough adjustment for confounding factors, their analysis revealed a J-shaped correlation between total cholesterol (TC) and CHD mortality. Notably, the study group observed a plateau effect for TC levels below 180 mg/dL, while higher cholesterol levels showed an increased risk of CHD mortality. Compared to veterans with TC levels between 180 and 199 mg/dL, those with TC levels of 200 to 219, 220 to 239, 140 to 259, 260 to 279, and ≥280 mg/dL exhibited hazard ratios (HRs) for CHD death of 1.03 (95% CI, 1.02–1.04), 1.07 (95% CI, 1.06–1.09), 1.15 (95% CI, 1.13–1.18), 1.25 (95% CI, 1.22–1.28), and 1.45 (95% CI, 1.42–1.49), respectively. Similarly shaped TC-CHD mortality trends were observed among veterans with and without prior statin use at baseline.
The cholesterol paradox, indicating elevated CHD mortality risk in individuals with low cholesterol levels, predominantly stems from reverse causality, particularly in older participants. Their findings affirm the lipid hypothesis, supporting that lower blood cholesterol levels are linked to a decreased risk of CHD. Furthermore, this association remained consistent even when TC levels were low due to statin or other lipid-lowering medication use.
Source: ahajournals.org/doi/10.1161/JAHA.123.030496
