Original paper

Normal LDL-cholesterol levels are associated with subclinical atherosclerosis in the absence of risk factors

  • Individuals without cardiovascular (CV) risk factors are normally considered low risk for atherosclerosis and cardiovascular disease (CVD) and yet they still have CV events.
  • Subclinical atherosclerosis may be found in approximately half of middle aged individuals without major conventional CV risk factors and in around a third of those who have optimal risk factor profiles.
  • Low density lipoprotein cholesterol (LDL-C) even at levels currently considered normal can predict subclinical atherosclerosis in individuals free of CV risk factors.
  • This finding supports more effective LDL-C lowering strategies to prevent early development or progression of atherosclerosis.

To gain greater understanding of predictors of subclinical atherosclerosis (e.g. plaque or coronary artery calcification) in individuals free of cardiovascular (CV) risk factors, participants from the PESA (Progression of Early Subclinical Atherosclerosis) study, without conventional CV risk factors, were evaluated. Out of a total 4184 participants in the PESA study 1779 were assessed as being CV risk factor free. The 4184 PESA participants were middle-aged men and women between 40 to 54 years.

Cardiovascular (CV) risk factor free was defined as:

  • No current smoking
  • Untreated blood pressure less than 140/90 mmHg
  • Fasting glucose less than 126 mg/dl
  • Total cholesterol (TC) less than 240 mg/dl
  • Low-density lipoprotein cholesterol (LDL-C) less than 160 mg/dl
  • High density lipoprotein cholesterol (HDL-C) greater than or equal to 40 mg/dl

A sub group of 740 people with optimal CV risk factors was also identified based on blood pressure levels less than 120/80 mmHg, fasting glucose less than 100 mg/dl, glycosylated haemoglobin (HbA1c) of less than 5.7% and TC less than 200 mg/dl.

Ultrasound detected plaques; coronary artery calcification; serum biomarkers and lifestyle adjusted odds ratios were measured. Subclinical atherosclerosis (plaque or coronary artery calcification) was found in nearly half of the participants free of CV risk factors (49.7%).  In the group with optimal CV risk factors, 37.8% had atherosclerosis.

Along with unmodifiable risk factors such as age and male sex the modifiable risk factor serum LDL-C was found to be independently associated with the presence and extent of atherosclerotic changes in both the CV risk factor free and optimal CV risk factor groups. Increased LDL-C levels demonstrated a linear and significant rise in the prevalence of atherosclerosis from an 11% increase in the 60-70 mg/dl LDL-C category to a 64% in the 150 to 160 mg/dl LDL-C group.

This study supports a more aggressive strategy to lower LDL-C. It gives further strength to the argument for “the lower the better” and “the earlier the better” when it comes to LDL-C levels. The LDL-C levels in the sub populations analysed were well within the range that is considered normal which reinforces the concept that in fact healthy LDL-C concentrations are probably much lower than those that are currently recommend. This study provides evidence of a unique and independent role for LDL-C in the early development of atherogenesis and has important implications for cardiovascular disease prevention. A healthy diet and lifestyle including the LDL-C lowering benefit of plant sterols/stanols as part of dietary options can help in maintaining LDL-C levels at low levels through the lifetime.