Lipid Guidelines: Risk Factors, Lifestyle, Statins

National Lipid Association published guidelines part 1 in April 2015. Please find below key recommendations and rationales on risk factors, lifestyle and statin use in preventing coronary heart disease. Text has been slightly modified for easier and succinct reading.



  • For patients in whom lipid-lowering drug therapy is indicated, statin treatment is the primary modality for reducing ASCVD risk.
  • Non-lipid ASCVD risk factors should also be managed appropriately, particularly high blood pressure, cigarette smoking, and diabetes mellitus.
  • The measurement and monitoring of atherogenic cholesterol levels remain an important part of a comprehensive ASCVD prevention strategy.
  • Lifestyle therapy is central


Statins block hepatic cholesterol synthesis by inhibiting HMG CoA reductase and have been shown to reduce serum LDL-C levels by 18-55%, non–HDL-C by 15-50%, and triglycerides by 7-30% (in hypertriglyceridemia, the reduction is typically by 20-50%, particularly with high-potency statins) and increase HDL-C by 5-15%. A large body of RCT evidence demonstrates that statins are safe and generally well tolerated by most patients and that they decrease risk for ASCVD events in both primary and secondary prevention in amounts proportional to their atherogenic cholesterol lowering. For these reasons, they are considered to be first-line drug treatment in both primary and secondary prevention of ASCVD. Although the predominant action of statins for reducing ASCVD risk is by lowering atherogenic lipoprotein concentrations, they may also have pleiotropic effects.

Because of their favorable benefit to safety profile, moderate- and high-intensity statins are reasonable for most patients. However, in hypercholesterolemic patients who are statin intolerant, alternate atherogenic cholesterol–lowering drugs (eg, bile acid sequestrants, nicotinic acid, fibric acids, or cholesterol absorption inhibitor) or alternative statin dosing regimens may need to be considered.

Atherogenic cholesterol lowering is the focus of dyslipidemia management, and therapies to lower cholesterol will reduce ASCVD risk even in the presence of other risk factors. However, nonlipid ASCVD risk factors contribute to the acceleration of atherosclerosis and development of acute coronary syndromes. When identified, these risk factors, particularly high blood pressure, cigarette smoking, and diabetes mellitus, require management to maximize ASCVD risk reduction.

Results from RCTs of a variety of atherogenic cholesterol–lowering therapies as well as results from observational studies have generally found that lower on-treatment atherogenic cholesterol levels are associated with lower ASCVD risk. This suggests that treatment goals and periodic monitoring of atherogenic cholesterol are useful for allowing a clinician to match the aggressiveness of lipid-lowering therapy to a patient’s absolute risk for an ASCVD event and for assessing the adequacy of a patient’s response and adherence to therapy. Treatment goals and monitoring of atherogenic cholesterol are particularly valuable tools in patient–clinician communication.

A key tenet of the NLA Expert Panel recommendations is the centrality of lifestyle therapies to ASCVD prevention. Lifestyle therapies for ASCVD risk reduction generally include interventions aimed at (1) altering the composition of the diet; (2) reducing total energy intake to lower body weight and adiposity for those who are overweight or obese; (3) increasing physical activity; (4) improving risk factors associated with the metabolic syndrome (adiposity, dyslipidemia, high blood pressure, and elevated plasma glucose); and (5) ceasing tobacco use.

The application of pharmacotherapy to dyslipidemia management has been enormously successful. Many large-scale RCTs, involving, in aggregate, hundreds of thousands of participants, have shown that drug therapies (particularly statins) that lower atherogenic cholesterol levels are effective for reducing ASCVD morbidity and mortality. RCT evidence from studies examining lifestyle changes, and dietary interventions in particular, for reducing ASCVD risk is relatively less robust. Furthermore, many of these trials were conducted several decades ago when dietary habits were much different from the typical American diet of today, although results from some later RCTs also suggest benefits on ASCVD outcomes with dietary interventions.

Results from observational studies strongly suggest an influence of lifestyle habits on ASCVD outcomes that is likely to be mediated, at least in part, through effects on atherogenic cholesterol levels as well as other metabolic and hemodynamic disturbances such as obesity, hypertension, and insulin resistance. Thus, although drug therapy may be needed in those with sufficient risk, the NLA Expert Panel’s consensus view is that lifestyle therapies are an important element of risk-reduction efforts, whether or not drug therapy is also used. The beneficial impact of lower atherogenic cholesterol levels for reducing ASCVD risk is also supported by genetic studies of individuals with PCSK9 mutations and NPC1L1 protein polymorphisms, both of which result in reduced LDL-C levels throughout life, and by findings that genetic mutations resulting in modification of circulating levels of triglycerides and triglyceride-rich lipoprotein cholesterol (eg, variants associated with lipoprotein lipase, apo C3, and apo A5) are associated with altered ASCVD risk.


NLA Guidelines, Part 1

Journal of Clinical Lipidology

April 2015