Should statin (HMG-CoA reductase inhibitor) therapy be initiated for hypercholesterolemia despite a favorable cholesterol ratio and elevated high-density lipoprotein (HDL) levels?

From the Guidelines

Treating high cholesterol with a statin is recommended even if the ratio is good and HDL is high, especially if the patient has other risk factors or significantly elevated LDL cholesterol levels. The decision to treat high cholesterol with a statin should be based on the overall cardiovascular risk, not just the cholesterol ratio or HDL levels, as stated in the 2018 cholesterol clinical practice guidelines 1. According to these guidelines, patients with clinical ASCVD should receive high-intensity or maximally tolerated statin therapy to reduce LDL-C levels, regardless of their HDL levels.

Key considerations for statin therapy include:

• The presence of other risk factors such as diabetes, hypertension, smoking history, or family history of premature heart disease
• The level of LDL cholesterol, with significantly elevated levels (typically above 190 mg/dL) being a strong indication for statin therapy
• The use of risk assessment tools, such as the ASCVD risk calculator, to estimate the 10-year risk of heart attack or stroke
• The intensity of statin therapy, which should match the patient's risk level, with higher-risk individuals requiring more potent statins at higher doses, as recommended in the guidelines 1.

Common statins and their dosages include:

• Atorvastatin (10-80 mg daily)
• Rosuvastatin (5-40 mg daily)
• Simvastatin (10-40 mg daily)

It is essential to note that while HDL is protective, its levels alone do not determine treatment decisions, and the focus has shifted toward addressing overall risk rather than optimizing specific lipid fractions, as emphasized in the guidelines 1. By prioritizing overall cardiovascular risk and using statin therapy as recommended, patients can effectively reduce their risk of heart attack and stroke.

From the Research

Statin Therapy for High Cholesterol

• The decision to treat high cholesterol with a statin, even if the ratio is good and HDL is high, depends on various factors, including the individual's overall cardiovascular risk profile 2, 3.
• Research suggests that a disturbed lipid metabolism, including low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C), contributes to the formation of plaques and the development of atherosclerotic cardiovascular disease (ASCVD) 2.
• The LDL-C/HDL-C ratio has been proposed as a valuable tool to evaluate coronary heart disease risk, and it may be more efficacious to continue using this ratio as a standard tool to evaluate cardiovascular disease (CVD) risk in all populations 3.

Residual Risk for CVD

• Even when LDL-C is well regulated, mainly with statin therapy, a residual risk for CVD still occurs, and it is attributable to the disturbances of other lipid components, namely TG and HDL-C 2.
• The TG/HDL-C ratio has been proposed as a novel biomarker for predicting the risk of metabolic syndrome (MetS) and CVD, including CAD, PAD, and CCVD 2.
• Switching from statin monotherapy to statin/ezetimibe combination therapy has been shown to result in additional LDL-C level reductions and improve the likelihood of achieving LDL-C targets 4.

Discordance between Lipid Parameters

• The total cholesterol (TC)/HDL-cholesterol ratio may carry additional information not available in more commonly used single cholesterol measures, and discordance between lipid parameters might help assess the impact of such additional information on the risk of atherosclerotic cardiovascular disease 5.
• Individuals with LDL-cholesterol and non-HDL-cholesterol less than the median, but with discordant TC/HDL-cholesterol at or above the median, had a greater risk of incident atherosclerotic cardiovascular disease compared to those with TC/HDL-cholesterol less than the median 5.