High LDL Levels Can Increase Cardiovascular Mortality Even in Low Risk Population Results From the Cooper Center Longitudinal Study

Sudarshana Datta, M.D.
By Sudarshana Datta, M.D. on

A recent study published in Circulation found that higher levels of low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDLC) increased the relative risk of long-term cardiovascular disease (CVD) mortality by 50% to 80%, in healthy participants that were considered to be at a low 10-year risk prior to the beginning of the study.

Existing literature has not been conclusive in determining the long-term effects of LDL-C on CVD and coronary heart disease (CHD) mortality in a low-risk cohort, despite the fact that this represents a majority of the population. A recent study was conducted in 36,375 adults who were at a relatively low risk (<7.5%) of atherosclerotic CVD (ASCVD) were followed up for an average period of 26.8 years to observe the effects of LDL-C and non-HDL-C on CVD and CHD mortality.

The study observations imply further that appropriate LDL-C and non-HDLC thresholds need to be considered when evaluating lipid-lowering medication in individuals that were previously considered low-risk. Participants were grouped into four categories with LDL-C levels measuring 100-129 mg/dL, 130-159 mg/dL, 160-189.9 mg/dL, and ≥ 190 mg/dL. When compared with participant data who were at an LDL-C level <100 mg/dL, the hazard ratios (HR) for CVD death were observed to be 1.4 (95% CI, 1.1-1.17), 1.3 (95% CI, 1.1-1.6), 1.9 (95% CI, 1.5-2.4), and 1.7 (95% CI, 1.3-2.3) respectively. The years free of CVD death was reduced by 1.8, 1.1, 4.3, 3.9 years respectively. Further analyses led to the observation of independent association the 160-189.9 mg/dL and ≥ 190 mg/dL groups with CVD death HRs of 1.7 (95% CI, 1.4-2.2) and 1.5 (95% CI, 1.2-2.1). For non-HDLC comparisons, participants with <130 mg/dL were used as reference and compared to participants with 160 to 189 mg/dL, 190 to 219 mg/dL, and ≥220 mg/dL. Participants with higher levels were associated with significantly higher CVD death, with HRs of 1.3 (95% CI, 1.1-1.6), 1.8 (95% CI, 1.4-2.2), and 1.5 (95% CI, 1.2-2.0) respectively.

Lower non-HDL-C thresholds were associated with increased CHD mortality rate than their corresponding LDL-C levels, which was recommended as a secondary target for treatment in the 2013 AHA/ACC guidelines for adult treatment. To sum it up, ≥ 100 mg/dL of cholesterol was at a ≥30% and participants with ≥130 mg/dL was at a ≥50% of relative risk associated with CHD deaths, and non-HDLC ≥160 mg/dL was associated with CVD and ≥130 mg/dL was associated with CHD mortality.

Additionally, participants with documented lipid panel measurements between the periods of 1978 and 1998 were included in the study to minimize the effect of lipid-lowering medication which became more prevalent in the early 2000s. The study estimated that the results were more pronounced in participants with a lower risk of 10-year ASCVD (<5%) at the beginning of the study.

While the study draws scientific evidence to the undesirable effects of increased concentrations of LDL-C and/or non-HDL-C on risk of CVD in the short-term, the observations did not document factors like lipid-modifying statin therapy intake at baseline (although not very common in low-risk populations, rampant use in recent years),  participant transition from low to high risk, low to no records of other endpoints due to the participants being low-risk, and race data etc. was not taken into consideration since this is not a population-based study.

In conclusion, the present study establishes the connection between LDL-C and non-HDL-C with CVD and CHD mortality rates. This forms the basis for further research to discover novel outcomes for future cardiovascular studies when evaluating the effects of lipid-modifying lifestyle and treatment in CVD therapy.

Source: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.034273

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