Higher LDL Cholesterol Increases Risk Even in Otherwise Healthy People

Robert Eckel, MD

A study of over 36,000 patients with low 10-year heart disease risk found significant associations of elevated LDL cholesterol levels with cardiovascular disease and coronary heart disease mortality.

Participants with low-density lipoprotein cholesterol (LDL-C) levels of 100-159 mg/dL had a 30% to 40% higher risk of cardiovascular disease death compared to those with levels below 100 mg/dL. Those with LDL-C of 160 mg/dL or higher had a 70% to 90% increased risk of cardiovascular death compared to those below 100 mg/dL.

"Our study demonstrates that having a low 10-year estimated cardiovascular disease risk does not eliminate the risk posed by elevated LDL over the course of a lifetime," said lead study author Shuaib Abdullah, MD, at University of Texas Southwestern Medical Center and Veteran's Affairs North Texas Healthcare System in Dallas, Texas, in a statement.

The study included participants from the Cooper Center Longitudinal Study who did not have a history of cardiovascular disease or diabetes mellitus. These participants were defined as low-risk (<7.5%) for 10-year atherosclerotic cardiovascular disease events.

Of the 36,375 participants, 72% were men and the median age was 42 years. They were followed for a median of 26.8 years over the course of the study, during which time 1086 cardiovascular disease and 598 coronary heart disease deaths occurred.

Compared with LDL-C <100 mg/dL, LDL-C categories 100 to 129 mg/dL, 130 to 159 mg/dL, 160 to 189.9 mg/dL, and ≥190 mg/dL were associated with a significantly higher risk of cardiovascular disease death, with hazard ratios of 1.4 (95% CI, 1.1—1.7), 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. Those groups experienced mean reductions in years free of cardiovascular disease death of 1.8, 1.1, 4.3, and 3.9, respectively.

The study additionally found that non-high-density lipoprotein cholesterol (HDL-C) levels were also associated with cardiovascular disease death (CVD). Compared to non—HDL-C <130 mg/dL, non–HDL-C levels 160 to 189 mg/dL, 190 to 219 mg/dL, and ≥220 mg/dL were significantly associated with CVD death, with hazard ratios 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.

"High cholesterol at younger ages means there will be a greater burden of cardiovascular disease as these individuals age. This research highlights the need to educate Americans of any age on the risks of elevated cholesterol, and ways to keep cholesterol at a healthy level throughout life," said Robert Eckel, MD, past president of the American Heart Association and Director of the Lipid Clinic at University of Colorado Hospital in Aurora.

Even when restricting participants to those with a 10-year risk of <5%, the associations of LDL cholesterol and non-HDL cholesterol with cardiovascular disease death remained.

"Those with low risk should pursue lifestyle interventions, such as diet and exercise, to achieve LDLs levels as low as possible, preferably under 100 mg/dL,” recommended Abdullah. “Limiting saturated fat intake, maintaining a healthy weight, discontinuing tobacco use, and increasing aerobic exercise should apply to everyone."

The authors noted the limitations of the study, including that lipid-modifying treatments were not documented at baseline and there was not information about participants who may have begun such treatment over the course of the study. Additionally, the Cooper Center Longitudinal Study is not a population-based study, and participants are of higher socioeconomic groups and have lower 10-year cardiovascular risk compared with the overall US population.

The study, “Long-Term Association of Low-Density Lipoprotein Cholesterol With Cardiovascular Mortality in Individuals at Low 10-Year Risk of Atherosclerotic Cardiovascular Disease,” was published in Circulation, a journal of the American Heart Association.