Atherogenic Cholesterol Reduction

National Lipid Association published part 1 of guidelines in April 2015. Please find below key recommendations and rationales on significance of atherogenic cholesterol reduction in preventing coronary heart disease. Text has been slightly modified for easier and succinct reading.




  • Reducing elevated levels of atherogenic cholesterol will lower ASCVD risk in proportion to the extent of atherogenic cholesterol reduction. This benefit is presumed to result from atherogenic cholesterol lowering through multiple modalities, including lifestyle and drug therapies.
  • The intensity of risk-reduction therapy should generally be adjusted to the patient’s absolute risk for an ASCVD event.
  • Atherosclerosis is a process that often begins early in life and progresses for decades before resulting in a clinical ASCVD event. Therefore, both intermediate-term and long-term or lifetime risk should be considered when assessing the potential benefits and hazards of risk-reduction therapies.


Numerous clinical trials of atherogenic cholesterol–lowering therapies have demonstrated their ability to reduce the incidence of ASCVD in proportion to the amount of LDL-C and non–HDL-C reduction. Examinations of on-treatment LDL-C concentration compared with CHD events in studies of primary prevention (ie, in subjects initially free from CHD) and in studies of secondary prevention (ie, in patients with established ASCVD) also show a strong positive correlation. These effects are evident not only with atherogenic cholesterol–lowering drug therapies but also diet/lifestyle and surgical therapies. Furthermore, the relationship is present across the full spectrum of LDL-C and non–HDL-C levels. The Cholesterol Treatment Trialists’ meta-analysis of more- vs less-intensive statin regimens demonstrated that ~ 40 mg/dL change in LDL-C resulted in a 22% relative risk reduction for major ASCVD events. In addition, there was no evidence of an LDL-C threshold within the range studied. Larger LDL-C reductions, for example 2-3 mmol/L (77.4–116.1 mg/dL), could yield up to 40%-50% relative risk reduction for ASCVD.

Available therapeutic options for lowering atherogenic cholesterol and reducing risk for an ASCVD event include lifestyle and drug therapies. Lifestyle therapy is considered to be first-line intervention and is nearly universally acknowledged to be appropriate and necessary for the management of dyslipidemia among individuals ranging from lowest to highest risk for ASCVD. LDL-C (and non–HDL-C) reductions with lifestyle changes are most often in the range of 5-15%, an amount that, if maintained over a long period, may result in meaningful ASCVD risk reduction. The relationship between the degree of change in atherogenic cholesterol concentration due to lifestyle changes and the difference in CHD risk aligns with the relationship for atherogenic cholesterol– lowering drug therapies. However, in individuals at moderate to higher risk for ASCVD, a larger magnitude of atherogenic cholesterol lowering than can be achieved with lifestyle changes alone is generally warranted to substantially lower ASCVD risk. Decisions regarding the addition of atherogenic cholesterol–lowering drug therapy to lifestyle therapies for dyslipidemia management, as well as the intensity of the drug to be used, should include an investigation of the patient’s absolute risk for ASCVD, including long-term risk, tempered by clinical judgment and consideration of the interactions of cost, benefit, and safety of the drug therapies.

An early stage of atherosclerosis has been identified as fatty streaks in the coronary arteries of adolescents and young adults. Long-term follow-up in prospective studies has demonstrated that elevated serum cholesterol in early adulthood predicted an increased incidence of CHD in middle age. Thus, lowering serum cholesterol levels earlier in life is likely beneficial for altering long-term or lifetime risk for developing ASCVD. Clinical trials of statins generally indicate that each 1% decrease in LDL-C concentration is associated with about a 1% decrease in risk for CHD. However, results from epidemiologic and Mendelian randomization studies suggest a larger effect of lower LDL-C levels on CHD in groups with lower cholesterol levels throughout life. This is consistent with the hypothesis that maintaining a lower serum cholesterol concentration for periods longer than the duration of typical clinical trials (averaging roughly 5 years) has the potential to yield a greater reduction in ASCVD risk than the approximate 1% to 1% relationship and supports the benefits of approaching risk-reduction therapy from a long-term or lifetime perspective. Many of the multivariate risk calculators that have been designed for clinical use in ASCVD risk assessment and to guide decisions for initiating drug therapy were created to predict intermediate-term (eg, 10 year) risk for an ASCVD event. Short- and intermediate-term risk reduction has an important place in the management of dyslipidemia, particularly by reducing atherogenic cholesterol in patients with preexisting ASCVD to stabilize plaques and reduce the likelihood of acute coronary syndromes.

However, some individuals with a relatively low intermediate-term risk for an ASCVD event may have substantially elevated lifetime risk because of the presence of multiple or severe ASCVD risk factor disturbances. This is particularly the case for men, 40 years and women, 50 years of age with multiple or severe ASCVD risk factors, and the NLA Expert Panel concluded that consideration of long-term or lifetime risk in such patients is useful for guiding treatment decisions.

NLA Guidelines, Part 1

Journal of Clinical Lipidology

April 2015