Should my high cholesterol be treated if I am an adult under age 40?

The American Heart Association (AHA)/American College of Cardiology (ACC) cholesterol guidelines recommend a heart-healthy diet and regular physical activity as well as lipid-lowering medications for adults with diagnosed ASCVD or those with severe hypercholesterolemia, which is defined as low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dL.¹ Diet recommendations include eating fruits, vegetables, whole grains, legumes, low-fat protein sources, and non-tropical vegetable oils along with limiting sugar and red meats. Caloric intake should be adjusted to avoid weight gain or to lose weight in individuals who are overweight. Physical activity lasting 40 minutes a day, three or four times per week is also recommended.

Atherosclerosis has been found in the blood vessels of young adults which has refocused efforts toward the prevention of atherosclerotic cardiovascular disease to even younger ages.^2,3 There are few randomized control trials (RCTs) that assess the effectiveness of lipid-lowering medication in individuals who are younger than 40 years of age toward preventing cardiovascular outcomes. The recommendation is based primarily on evidence that increased levels of LDL-C result in an increased risk of developing cardiovascular disease and that reducing LDL-C levels in other age groups has resulted in significant reductions in that risk.^4–6 Lipid-lowering treatment in children and adolescents with familial hypercholesterolemia has also been shown to lower LDL-C,^7,8 reduce carotid artery intima-media thickness,⁹ and delay cardiovascular events.¹⁰ The American Academy of Pediatrics has recommended statins for children over the age of 10 with LDL-C ≥190 mg/dL.¹¹

Although robust RCTs in the pediatric and young adult population are lacking, there is some evidence that maintaining a consistently lower LDL-C level throughout the lifespan is beneficial.¹² However, when statin treatment starts at an earlier age, safety concerns may need closer scrutiny because of the longer duration of exposure.

There are as yet no RCTs of long enough duration to evaluate the long-term safety of statins initiated in young adults.¹ Potential risks associated with longer-term use of statins include the risk of new-onset diabetes and statin-associated myopathy. The benefits of statins in young people should be weighed against known risks in older populations until more evidence is available.

Package inserts for most statins, except pravastatin, report an increased risk of elevated glucose, hemoglobin A1C, and, in some cases, new-onset diabetes compared to placebo.^13–19 Where noted, the risk is not high (4.2% for simvastatin vs 3.6% for placebo; 2.8% for rosuvastatin vs 2.3% for placebo). The effect may be particularly true for those at higher baseline risk of diabetes before statins are initiated.²⁰ According to current AHA/ACC guidelines, the modestly increased risk of new-onset diabetes is not considered a contra-indication for initiation of statin therapy because the benefits of statins outweigh this small risk.^1,21

The risk of statin-associated myopathy in young people was evaluated in a pediatric preventive cardiology practice that compared creatinine kinase (CK) levels among 474 patients followed for over 3.5 years.²² CK levels did not differ significantly between the patients taking statins and those who were not. There was a statistically significant, but clinically insignificant trend of increasing CK over time among the statin users. No muscle symptoms or rhabdomyolysis were reported among patients with elevated CK levels. Although available data on adults suggest the risk of statin-associated myopathy is small, further studies of longer duration are needed to better quantify the risk of even longer-term use of statins on muscle function.

Young adults with moderate hypercholesterolemia (≥160 mg/dL) may also benefit from lipid-lowering medications.¹ The AHA/ACC guidelines recommend that regular (every four to six years) assessment of ASCVD risk should guide medication decisions. A 30-year risk assessment tool was developed for clinical use from data in the Framingham Heart Study that followed 4,506 participants aged 20 to 59 who were free of cardiovascular disease at baseline.²³ Risk factors that influenced the onset of a first cardiovascular event included systolic blood pressure, total cholesterol, smoking, and diabetes. The pooled cohort equation used for older adults can also be used to generate clinician-patient discussion.¹ The AHA/ACC guidelines also consider statin treatment of young adults (20 to 39 years) with diabetes to be a reasonable consideration if the diabetes is of long-standing duration or associated with evidence of kidney dysfunction, retinopathy, or neuropathy.¹

^References

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