Observational studies have demonstrated that total cholesterol is positively associated with ischemic heart disease and stroke rates and that this relationship is continuous as blood concentrations of cholesterol increase.1,2 There is also strong evidence that lowering cholesterol levels reduces the risk and that the greatest risk reduction occurs among those with the highest baseline levels of low-density lipoprotein cholesterol (LDL-C).3,4
The 2018 American Heart Association/American College of Cardiology (ACA/AHA) Guideline on the Management of Blood Cholesterol recommends a heart-healthy lifestyle involving dietary and exercise goals to achieve optimal cardiovascular health.5 Although there is evidence that a heart-healthy lifestyle will prevent heart attack and stroke, it is not clear the degree to which that benefit is due to a lowering of cholesterol.6 According to these current guidelines, a heart-healthy diet includes a diet that is rich in vegetables, fruits, whole grains, legumes, non-tropical vegetable oils, and healthy proteins.7,8 The dietary guidelines also recommend limiting the intake of sweets, sugar-sweetened beverages, and red meat. Caloric requirements should be determined by the need to avoid weight gain or to lose weight if you are overweight in order to minimize the risk for atherosclerotic cardiovascular disease (ASCVD).
In addition to a heart-healthy lifestyle, lipid-lowering medication, and specifically statins, are recommended to lower LDL-C for certain adults at particularly high risk for ASCVD.5,9 These include adults between the age of 20 and 75 with LDL-C levels at or above 190 mg/dL and people with diabetes. Anyone who has preexisting ASCVD can prevent future heart attacks and strokes by lowering cholesterol levels as well.5 Even people whose LDL-C cholesterol is below 190 mg/dL may benefit from statins if they have other risks for ASCVD. Calculation of 10-year ASCVD risk is used to ascertain the need for statin therapy in these individuals.10
One Cholesterol Treatment Trialists prospective meta-analysis that included 14 randomized trials of statins (total n=90,056) estimated that for each mmol/L (about 40 mg/dL) reduction in LDL-C, the risk of major vascular events (MVE) and vascular mortality was reduced by 21%.11 MVEs included myocardial infarction (MI), coronary death, need for revascularization, and fatal or non-fatal stroke. The risk of an MVE continues to be reduced by about 25% for each mmol/L reduction in LDL-C during each year after the first year that the statin continues to be taken.12
The 2018 AHA/ACC guideline uses a percentage reduction of LDL-C as the best indicator of statin efficacy.5 A given dose of statins produces a similar percentage reduction in LDL-C levels in individuals with different baseline LDL-C levels.
This guideline uses projections of future risk of ASCVD to determine the intensity of statin therapy that is recommended.5 The intensity level of a given statin regimen is defined by the typical LDL-C-lowering response that it produces. High-intensity statin doses usually lower LDL-C levels by more than 50%, moderate-intensity statin therapy by 30% to 49%, and low-intensity statin therapy by less than 30%. The magnitude of LDL-C reductions will vary from individual to individual, however, and statin therapy regimens may need to be revised based on patient response to treatment to achieve the optimal reduction of risk for ASCVD or future MVE.
- Prospective Studies Collaboration, Lewington S, Whitlock G, et al. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet. 2007;370(9602):1829-1839.
- Chen Z, Peto R, Collins R, MacMahon S, Lu J, Li W. Serum cholesterol concentration and coronary heart disease in population with low cholesterol concentrations. BMJ. 1991;303(6797):276-282.
- Silverman MG, Ference BA, Im K, et al. Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis. JAMA. 2016;316(12):1289-1297.
- Navarese EP, Robinson JG, Kowalewski M, et al. Association between baseline LDL-C level and total and cardiovascular Mortality after LDL-C lowering: a systematic review and meta-analysis. JAMA. 2018;319(15):1566-1579.
- Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139(25):e1082-e1143.
- American Heart Association Nutrition Committee, Lichtenstein AH, Appel LJ, et al. Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee. Circulation. 2006;114(1):82-96.
- Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 Suppl 2):S76-99.
- Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. J Am Coll Cardiol. 2014;63(25 Pt B):2985-3023.
- Taylor F, Huffman MD, Macedo AF, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013;(1):CD004816.
- ASCVD Risk Estimator +. http://tools.acc.org/ASCVD-Risk-Estimator-Plus/#!/calculate/estimate/. Accessed December 2, 2020.
- Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366(9493):1267-1278.
- Collins R, Reith C, Emberson J, et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. 2016;388(10059):2532-2561.