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Treatment of high LDL saves lives of those with diabetes or cardiovascular disease

J Fam Pract. 2004 February;53(2):93-105
By
Joseph William Lemaster, MD, MPH
James J. Stevermer, MD, MSPH
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  • BACKGROUND: It is recommended that patients with diabetes mellitus but without symptomatic cardiovascular disease should receive lipid-lowering therapy to keep LDL levels no more than 100 mg/dL. The authors of this analysis compared life expectancy (years of life saved) by achieving ideal changes in LDL and high-density lipopro-tein (HDL) cholesterol among those with diabetes mellitus (but who were free of cardiovascular disease) vs those with previous cardiovascular disease but not diabetes.
  • POPULATION STUDIED: The researchers used their previously validated “Cardiovascular Disease Life Expectancy Model,” a Markov-type model, which accurately predicted the cardiovascular mortality observed due to lipid lowering in the Scandinavian Simvastatin Survival Study (4S), among others. In this study, they calculated life expectancy in a theoretical population of patients, aged 30 to 74 years, with either diabetes or cardiovascular disease, based on national prevalence data from the Third National Health and Nutrition Examination Survey (NHANES III).
  • STUDY DESIGN AND VALIDITY: This model identified risk factors for cardiovascular death (gender, smoking, mean blood pressure, prior cardiovascular disease, age, glucose intolerance, and the natural log of the LDL/HDL ratio) to predict cardiovascular deaths using a survival simulation model. The researchers used NHANES III data to estimate risk factors and cholesterol levels for patients with coronary artery disease or diabetes, and to allow extrapolation to the entire adult US population. They estimated that statins would cause a 35% reduction in LDL and an 8% increase in HDL (as found in the 4S trial). They performed sensitivity analysis including treatment of patients with LDL between 100 and 130, and ending the benefit of statin therapy at age 75.
  • OUTCOMES MEASURED: The researchers predicted years of life saved due to prevention of cardiovascular mortality from use of statins.
  • RESULTS: The projected benefit of treating dyslipidemia would be similar for US adults aged 30 to 74 with either diabetes alone or cardiovascular disease alone. Men with LDL at least 130 mg/dL and diabetes could expect to gain 3.4 years of life with this therapy, while men with cardiovascular disease could expect to gain 2.7 years. Women with diabetes would gain 2.4 years of life with therapy, while women with cardiovascular disease would gain 2.1 years. The researchers attributed most of the difference in years gained between diabetics and patients with cardiovascular disease to a higher prevalence of smoking in the NHANES III cohort with cardiovascular disease. If lipid therapy were supplied to subjects with LDL between 100 and 130, or if the benefit of therapy stops at age 75, the lifetime benefit would still be slightly better for those with diabetes. Overall in the US 25.4 million life-years would be saved by giving lipid therapy to those with diabetes, while 16 million years would be saved by giving it to those with cardiovascular disease.

 

RACTICE RECOMMENDATIONS

Hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin) therapy that effectively reduces low-density lipoprotein (LDL) cholesterol increases life expectancy at least as much among those with diabetes mellitus without cardiovascular disease as among those with established cardiovascular disease alone.

While this result is only based on a validated theoretical model, it was extrapolated to the entire American population, and is consistent with randomized clinical trials. Public health programs and health care providers should give as much emphasis to treating elevated LDL among those with diabetes who are still free of cardiovascular disease as among those with already established cardiovascular disease.

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