Very low LDL levels confer reduced risk for major CV events

Very low levels of LDL are associated with reduced risk for major CV events, according to the results of a new meta-analysis of statin trials.

The results may have implications for the debate over whether LDL target goals should be part of a strategy to manage CV risk factors. A 2013 guideline published by the American College of Cardiology and the American Heart Association abandoned LDL target goals in favor of initiating statin treatment based on a person’s underlying risk categories.

S. Matthijs Boekholdt, MD, PhD, and colleagues analyzed 38,153 patients assigned to statin therapy in eight trials to evaluate the association between CVD risk and very low levels of atherogenic lipoproteins achieved with statin therapy, the proportion of patients not reaching guideline-recommended lipid levels with high-dose statin therapy, and the interindividual variability in reductions of LDL, non-HDL and apolipoprotein B levels achieved with statin therapy.

The researchers observed 6,286 major CV events — defined as fatal or nonfatal MI, fatal or nonfatal stroke, hospitalization for unstable angina and other CHD — in 5,387 study participants during 155,373 person-years of follow-up.

LDL linked to CV risk

Boekholdt, of the department of cardiology at the Academic Medical Center in Amsterdam, and colleagues found that compared with patients achieving LDL >175 mg/dL, those achieving LDL 75 mg/dL to <100 mg/dL (HR=0.56; 95% CI, 0.46-0.67), LDL 50 mg/dL to <75 mg/dL (HR=0.51; 95% CI, 0.42-0.62) or LDL <50 mg/dL (HR=0.44; 95% CI, 0.35-0.55) had a lower risk for major CV events.

They found similar results for non-HDL and ApoB levels.

The researchers also found that more than 40% of those assigned high-dose statins in the trials did not achieve an LDL target <70 mg/dL, and that there was large interindividual variability in the reductions of LDL, non-HDL and ApoB levels achieved with a fixed statin dose.

The only evidence observed of safety issues in those achieving very low levels of atherogenic lipoproteins was a slightly higher risk for hemorrhagic stroke compared with those achieving moderate levels, but the number of hemorrhagic strokes observed was low and did not provide the statistical power to draw definitive conclusions, the researchers wrote.

Lower may be better

Ori Ben-Yehuda, MD, and Anthony N. DeMaria, MD, wrote in a related editorial that the finding that the major CV event rate at 1 year increases with each tier of LDL level “supports the premise that ‘lower is better’ when it comes to LDL goals.”

However, they wrote, because participants in most of the trials received a fixed statin dose and did not receive an individual goal to attain, the LDL levels achieved were “due to the complex interaction between the statin (including the dose) and the individual patient’s biology.” That, they wrote, means that it is “unclear whether it is the LDL level achieved or the patient’s ability to respond to a statin dose that is the key determinant of the better outcomes.”

Ben-Yehuda, of the Cardiovascular Research Foundation, New York, and DeMaria, of the department of medicine at the University of California, San Diego, noted that because the LDL levels are influenced by multiple factors that may affect CV risk, “the present meta-analysis does not disprove the 2013 ACC/AHA guidelines contention that there are inadequate data at the present time to indicate specific LDL targets of therapy.” Therefore, they concluded, lipid trials assessing specific LDL goals instead of specific drug doses are necessary.

For more information:

Ben-Yehuda O. J Am Coll Cardiol. 2014;64:495-497.

Boekholdt SM. J Am Coll Cardiol. 2014;64:485-494.

Disclosure: See the full study for a list of the researchers’ relevant financial disclosures. Ben-Yehuda and DeMaria report no relevant financial disclosures.