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Do you remember the traditional lipid-lowering targets? Years ago, normal low density lipoprotein (LDL) cholesterol levels were set at 150–160 mg/dl; then came the large studies demonstrating the association between therapy for hypercholesterolemia and decreased cardiovascular morbidity, as a result of which the LDL cholesterol norm was changed to < 130 mg/dl. Later on, cardiologists were pushing down the target for people at risk for cardiovascular disease to < 100 mg/dl, and the current practice takes the target even further down, setting the LDL cholesterol target for secondary prevention and for patients with diabetes mellitus at < 70 mg/dl. It seems now that we already at the bottom of our capability to lower LDL cholesterol levels. On the one hand, we need to use very high statin doses or combination therapies to achieve this therapeutic goal, which may carry an increased incidence of severe adverse events, but, on the other hand, it gives only a small additional benefit when compared to a less aggressive treatment. I believe that people realized that we went too far in implementing specific LDL cholesterol targets that were not supported by good evidence-based data. Thus a new approach was needed, and the updated Adult Treatment Panel (ATP)-4 guidelines for prevention and treatment of hyperlipidemia put this issue into a more rational perspective [1]. The recently published document is a co-production of the NIH National Heart, Lung, and Blood Institute, and two major US cardiology societies, the American Heart Association and the American College of Cardiology. 


The new guideline makes no recommendations for specific LDL cholesterol or non-high density lipoprotein (HDL) cholesterol [i]targets[/i] for the primary and secondary prevention of atherosclerotic cardiovascular disease. Instead, the new guideline identifies four groups of primary- and secondary-prevention patients in whom physicians should focus their efforts to reduce cardiovascular disease events. In these four patient groups, the new guideline makes recommendations regarding the appropriate ‘[i]intensity[/i]’ of statin therapy in order to achieve relative reductions in LDL cholesterol. Also, a 10-year risk for atherosclerotic cardiovascular disease was set at a level of ≥ 7.5%. Four treatment groups were defined: (1) individuals with clinical atherosclerotic cardiovascular disease; (2) individuals with LDL cholesterol levels ≥ 190 mg/dl; (3) individuals with diabetes aged 40–75 years old with LDL cholesterol levels between 70 and 189 mg/dl and without evidence of atherosclerotic cardiovascular disease; (4) individuals without evidence of cardiovascular disease or diabetes but who have LDL cholesterol levels between 70 and 189 mg/dl and a 10-year risk of atherosclerotic cardiovascular disease ≥ 7.5%. For group 1, a secondary prevention scenario, a [i]high-intensity[/i] statin regimen should be used with the goal of achieving at least a 50% reduction in LDL cholesterol levels. For group 2, a primary prevention setting yet cholesterol-wise a very high-risk situation, with levels > 190 mg/dl, a [i]high-intensity[/i] statin therapy should be used with the goal of achieving at least a 50% reduction in LDL cholesterol levels. For those with diabetes aged 40–75 years of age, a [i]moderate-intensity[/i] statin treatment, defined as that lowering LDL cholesterol by 30–49%, should be used, whereas a [i]high-intensity[/i] statin treatment is a reasonable choice if the patient also has a 10-year risk of atherosclerotic cardiovascular disease exceeding 7.5%. For the individual aged 40–75 years without cardiovascular disease or diabetes but who has a 10-year risk of clinical events > 7.5% and an LDL cholesterol level anywhere from 70 to 189 mg/dl, the panel recommends treatment with a [i]moderate- or high-intensity[/i] statin regimen. To note that the strongest predictors of 10-year risk are age, sex, race, total cholesterol, HDL cholesterol, blood pressure, blood-pressure treatment status, diabetes, and current smoking status. Interestingly, the guidelines are very vague in regard to the benefit of statin therapy in patients with LDL cholesterol < 190 mg/dl, who are not diabetic and have a lower than 7.5% 10-year atherosclerotic cardiovascular risk. In these patients, the guideline says that ‘the benefit of statin therapy may be less clear’. The new risk calculator may be found in the website When one ‘plays’ with the risk calculator parameters, it shows that age > 60 for men already sets the 10-year risk at > 7.5%, even if all other risk parameters are optimal, which means that, even in the presence of LDL cholesterol level < 70 mg/dl, statins will still be indicated according to this clinical algorithm. For women, however, age 69 marks the > 7.5% risk zone.


  • Amos Pines
    Department of Medicine T, Ichilov Hospital, Tel-Aviv, Israel


  1. Stone NJ, Robinson J, Lichtenstein AH, et al. ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;129(Suppl 2):1-45
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