August 20, 2018
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Elevated LDL, non-HDL increase CVD mortality risk

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Salim S. Virani, MD PhD, FACC, FAHA
Salim S. Virani

Patients with low 10-year atherosclerotic risk with LDL and non-HDL greater than 160 mg/dL had an increased risk for CVD mortality, according to a study published in Circulation.

“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,” Shuaib M. Abdullah, MD, MSCS, associate professor in the department of internal medicine at UT Southwestern Medical Center in Dallas, said in a press release. “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. Limiting saturated fat intake, maintaining a healthy weight, discontinuing tobacco use and increasing aerobic exercise should apply to everyone.”

Patients with low CVD risk

In the Cooper Center Longitudinal Study, researchers analyzed data from 36,375 patients (median age, 42 years; 72% men) with a 10-year atherosclerotic CVD risk less than 7.5%. Patients were excluded if they had diabetes, established CVD, plasma triglycerides greater than 450 mg/dL or died within 1 year of lipid measurement.

During the clinical visit, patients had their plasma lipids collected, as well as a complete medical evaluation that included physical examination, medical history and anthropometric measurements. Hypertension was defined as BP of at least 140/90 mm Hg or a history of hypertension.

During a median follow-up of 26.8 years, 598 CHD deaths and 1,086 CVD deaths occurred.

Compared with patients with LDL less than 100 mg/dL, the risk for CVD death was significantly higher in patients with LDL between 100 mg/dL and 129 mg/dL (HR = 1.4; 95% CI, 1.1-1.7), LDL between 130 mg/dL and 159 mg/dL (HR = 1.3; 95% CI, 1.1-1.6), LDL between 160 mg/dL and 189 mg/dL (HR = 1.9; 95% CI, 1.5-2.4) and LDL of at least 190 mg/dL (HR = 1.7; 95% CI, 1.3-2.3).

The approximate mean reduction in years free from CVD death was 1.8 years in patients with LDL between 100 mg/dL and 129 mg/dL, 1.1 years for LDL between 130 mg/dL and 159 mg/dL, 4.3 years for LDL between 160 mg/dL and 189 mg/dL and 3.9 years for those with LDL of at least 190 mg/dL.

After adjusting for atherosclerotic CVD risk factors, the HRs for patients with an LDL between 160 mg/dL and 189.9 mg/dL was still statistically significant for CVD mortality (HR = 1.7; 95% CI, 1.4-2.2). This was also seen in patients with an LDL of at least 190 mg/dL (HR = 1.5; 95% CI, 1.2-2.1).

Effects of non-HDL

Compared with patients with non-HDL below 130 mg/dL, significant links to CVD death were seen in patients with non-HDL between 160 mg/dL and 189 mg/dL (HR = 1.3; 95% CI, 1.1-1.6), between 190 mg/dL and 219 mg/dL (HR = 1.8; 95% CI, 1.4-2.2) and at least 220 mg/dL (HR = 1.5; 95% CI, 1.2-2).

The associations of LDL or non-HDL with CVD and CHD health were not affected when 10-year atherosclerotic CVD risk was decreased to less than 5%.

Christie M. Ballantyne, MD
Christie M. Ballantyne

“Further research is required to ascertain whether lipid-modifying lifestyle interventions and pharmacological therapy favorably impact CVD outcomes in low-risk individuals with elevated LDL-C and non-HDL-C,” Abdullah and colleagues wrote.

“This finding raises questions of whether 10-year or lifetime [atherosclerotic] CVD risk assessment should be performed first in individuals with LDL-C 160 to 189 mg/dL or whether they should begin lipid-lowering treatments based on long-term risk similar to individuals with LDL-C levels 190 mg/dL,” Salim S. Virani, MD, PhD, assistant professor of cardiology and cardiovascular disease fellowship program director at Baylor College of Medicine, and Christie M. Ballantyne, MD, professor of medicine and chief of the sections of cardiology and cardiovascular research at Baylor College of Medicine, wrote in a related editorial. “As noted in the current analyses, the association between LDL-C levels and CHD mortality (or CVD mortality) was not significant when analyses were truncated at 10 years.” – by Darlene Dobkowski

Disclosures: Abdullah reports no relevant financial disclosures. Virani reports he received honoraria from the American College of Cardiology and the National Lipid Association, and is on the steering committee for the patient and provider assessment of lipid management registry at the Duke Clinical Research Institute. Ballantyne reports he received grant/research support from Amgen, Esperion, Regeneron and Sanofi-Synthelabo, and is a consultant for Amgen, Esperion, Merck, Regeneron and Sanofi-Synthelabo. Please see the study for all other authors’ relevant financial disclosures.