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30-Year Benefits of Early vs. Delayed CVD Prevention by Lipid Lowering
Quick Takes
- The issue of early versus delayed primary prevention is very important considering that nearly 50% of ASCVD events occur prior to age 65 years and generic statins are very inexpensive.
- In support of the findings suggesting statin use at age 40 years and older with non-HDL ≥160 mg/dl, most trials of LDL lowering demonstrate that the benefit per mmol/L lowering of LDL-C is greater if initiated at an earlier age.
- While a scientifically valid conclusion, the tools used for risk estimate are not those readily accessible to the clinician.
Study Questions:
Is there evidence for an optimal time for initiation of lipid lowering in younger adults to prevent or delay onset of atherosclerotic cardiovascular disease (ASCVD) as a function of expected 30-year benefit?
Methods:
Data from 3,148 National Health and Nutrition Examination Survey (NHANES) (2009-2016) participants ages 30-59 years, not eligible for lipid-lowering treatment recommendation under the most recent US guidelines, were analyzed. The absolute and relative impact of lipid lowering was estimated as a function of age, age of initiation, and non–high-density lipoprotein (HDL) cholesterol on the expected rates of ASCVD over the succeeding 30 years. ASCVD risk (cardiovascular death, myocardial infarction, and stroke) was estimated using the additive 30-year Framingham equation. Expected risk reduction was modeled based on shorter-term effects observed in statin trials (model A) and longer-term benefits based on Mendelian randomization studies (model B).
Results:
For both models, potential reductions in predicted 30-year ASCVD were greater in older age and higher non-HDL cholesterol. Immediate initiation of lipid lowering (i.e., treatment for full 30 years) in 40-49-year-olds with non-HDL cholesterol ≥160 mg/dl would be expected to reduce their average predicted 30-year risk from 17.1% to 11.6% (model A; absolute risk reduction [ARR], 5.5%) or 6.5% (model B; ARR, 10.6%). Delaying lipid lowering by 10 years (treatment for 20 years) would result in residual 30-year risk of 12.7% (model A; ARR, 4.4) or 9.9% (model B; ARR, 7.2%) and delaying by 20 years (treatment for 10 years) would lead to expected mean residual risk of 14.6 (model A; ARR, 2.6%) or 13.9% (model B; ARR, 3.2%). The slope of the achieved absolute risk reduction as a function of delay in treatment was also higher in older age and higher non-HDL cholesterol.
Conclusions:
Substantial reduction in expected ASCVD risk in the next 30 years is achievable by intensive lipid lowering in individuals in their 40s and 50s, with non-HDL cholesterol ≥160 mg/dl. For many, the question of “when” to start lipid-lowering might be more relevant than “if.”
Perspective:
The study addressed ages 30-59 years with the relatively low threshold of non-HDL cholesterol ≥160 mg/dl in whom the mean low-density lipoprotein (LDL) cholesterol was about 150 mg/dl. There was limited value to statins in the 30-39-year-old group for which the 2018 American College of Cardiology/American Heart Association (ACC/AHA) blood cholesterol guideline provides specific recommendations. However, those with a high non-HDL from ages 20-35 years and very high from ages 35-40 years are at much higher risk and may benefit. The incremental benefit using Mendelian studies is because it is based on both lesion stabilization and prevention of new lesions, whereas in the statin trials, relative risk reduction remains constant over time.
Clinical Topics: Cardiovascular Care Team, Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Lipid Metabolism, Nonstatins, Novel Agents, Statins
Keywords: Atherosclerosis, Cholesterol, HDL, Cholesterol, LDL, Dyslipidemias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Lipids, Metabolic Syndrome, Myocardial Infarction, Primary Prevention, Risk Reduction Behavior, Stroke, Vascular Diseases
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