Managing your cholesterol. The right questions to ask, and when to get started on treatment?

Jan 30th, 2020
By Dr. Jinnah

Fact:

Approximately one person in the United States has a myocardial infarction every 40 seconds, and more than 1 million coronary events occur each year, of which one third are recurrent events.2 Coronary heart disease is the leading cause of death in adults in the United States, accounting for about one-third of all deaths in subjects over age 35.5

You are what you eat!

We are in the midst of a global obesity epidemic that shows no signs of abating; indeed, 40% of adult Americans are now classified as either obese or overweight. A direct result of the obesity epidemic is a surge in the prevalence of type 2 diabetes, now present in more than 28 million people in the United States. 1

The American Heart Association (AHA) estimates that adults with diabetes are two to four times more likely to experience fatal heart disease than those without diabetes. Among people aged 65 or older with the disease, the AHA reports that: around 68 percent will die from heart disease and some 16 percent will die as the result of a stroke.

Recent updated guidelines for cholesterol management suggested by the American College of Cardiology–American Heart Association (ACC–AHA) 2018/2019 have helped put things into perspective as far as primary prevention in adults without a known history of cardiovascular disease.

The imperative.

It is crucial to understand that when it comes to primary prevention, the benefits from lifestyle changes for the better are incontrovertible and of paramount importance. Even persons whose genetic profile puts them at increased risk for coronary heart disease can reduce their risk by up to 50% through changes in lifestyle. Maintenance of a normal weight, blood pressure and blood sugar level, reduction in the intake of simple sugars and refined carbohydrates, and increases in physical activity all improve lipid levels and provide other healthful benefits and should be undertaken regardless of whether pharmacotherapy is also recommended. In addition, screening for and addressing conditions that cause or worsen your cholesterol level such as hypothyroidism, or drugs like alcohol, beta-blockers, oral contraceptives and thiazides, etc is always a good idea before considering pharmacotherapy.

Dietary modifications to improve cholesterol levels include supplementing with specific nutritional components (e.g. soluble fiber, nuts, soy) and adhering to healthy dietary patterns, such as a Mediterranean diet, the Dietary Approaches to Stop Hypertension (DASH) diet, or a healthy vegetarian diet.

Partially replacing meat protein with vegetable protein (30 g/day) and dietary saturated fat intake with polyunsaturated and monounsaturated fats can reduce atherosclerotic cardiovascular disease by approximately 30%, which is of a similar magnitude to the reduction conferred by statin therapy. 3

Unfortunately, very few people can adhere to or successfully manage such lifestyle changes. The alternative and sometimes the imperative is pharmacotherapy.

Medicamento: How do statins work?

Among the various treatments available today, statins are the most commonly used, by virtue of their safety and demonstrable/proven benefit in reducing atherosclerotic cardiovascular disease via plaque stabilization, reduced inflammation, reversal of endothelial dysfunction, and decreased thrombogenicity 4. All of the mechanisms above in various degrees (pleiotropic effects of statins) serve to prevent or reduce the risk of a heart attack and stroke.

Guidelines on treatment. When and how much?

The 10-year Atherosclerotic cardiovascular disease risk or ASCVD (www.cvriskcalculator.com) is calculated by taking into account a patient's age, race, cholesterol values, sex of the individual, blood pressure reading, history of diabetes and smoking. The calculator is intended for adults 40 to 75 years of age who do not have diabetes and whose LDL cholesterol level is 70 mg per deciliter or higher but lower than 190 mg per deciliter.

After risk estimation, patients can be categorized according to their risk of disease at 10 years: low (<5%), borderline (5 to <7.5%), intermediate (≥7.5 to <20%), or high (≥20%). For most patients at low risk for disease, reinforcement of lifestyle changes alone is often sufficient. For almost everyone else statins remain the primary pharmacotherapy used to lower LDL cholesterol levels.

For those at high risk, the use of a high-intensity statin (example 40-80 mg of atorvastatin or 20 mg of rosuvastatin) to reduce the LDL cholesterol level by 50% or more is recommended in combination with adoption of a healthy lifestyle. For those at intermediate risk, the initiation of a moderate-intensity (example 10-20 mg of atorvastatin or 5-10 of rosuvastatin) statin to reduce the LDL cholesterol level by 30% or more is recommended along with the adoption of a healthy lifestyle.

The 2018 and 2019 ACC–AHA guidelines recognize that the benefits of lipid pharmacotherapy remain uncertain in persons whose risk of atherosclerotic cardiovascular disease at 10 years is 5 to <20%.  Among patients at intermediate risk and selected patients with borderline risk for disease, it may be reasonable to measure the atherosclerosis burden by assessing the coronary-artery calcium score with computed tomography (without administration of contrast material) to further refine risk estimation either upward or downward.  Statins are generally recommended for persons who have a coronary-artery calcium score that is 100 or higher or who are in the 75th percentile or higher for their age, sex, and race. Statins should also be considered in persons with scores of 1 to 99, particularly if they are 55 years of age or older.On the other hand, a coronary-artery calcium score of 0 identifies persons among whom event rates are expected to be well below 7.5% over a 10-year period. For such persons, treatment with statins may be withheld or deferred (with the exception of cigarette smokers and persons with familial hypercholesterolemia)

For persons with severe primary hypercholesterolemia (an LDL cholesterol level ≥190 mg per deciliter), the likelihood of familial hypercholesterolemia (inherited condition associated with premature coronary artery disease and death) is increased and there is no need to calculate the 10-year risk of atherosclerotic cardiovascular disease; treatment is recommended to mitigate the substantial lifetime risk of disease. A high-intensity statin (or the maximum tolerated dose) is recommended.

In patients with diabetes who are between 40 and 75 years of age and have an LDL cholesterol level of 70 mg per deciliter or higher, there is also no need to calculate 10-year risk. A moderate-intensity statin should be recommended. The reason for this is that hyperlipidemia in a patient with diabetes at any level of cholesterol is associated with a greater risk of coronary artery disease, than in a non-diabetic patient.3

Why statins.. Where is the evidence of benefit and safety?

First discovered in 1976 by a Japanese biochemist Akira Endo, statins have been around for commercial use for more than 3 decades and are the established standard of care for both primary and secondary prevention of atherosclerotic cardiovascular disease.

Data from controlled trials have shown, that for every reduction of 39 mg per deciliter in LDL cholesterol level, statins reduce the risk of coronary events and death by 22% and 10%, respectively.

For the vast majority of patients in whom statins are indicated, the benefits outweigh the risks. The risk of serious muscle injury associated with statins is very low (<0.1%) and the risk of serious liver injury is even lower (approximately 0.001%). There is a modest increase in the risk of diabetes mellitus of 0.2% per year (depending on the person’s baseline risk for diabetes), but the benefits of statins generally also outweigh risks for patients with diabetes.

There is controversy regarding the extent of muscle pain that is related to statins. It remains uncertain how frequently the symptoms reported are truly attributable to statins or to “nocebo” effects, in which patients may perceive the side effects of medications that are actually caused by the anticipation of negative effects.

Once initiated, statins should generally be continued long-term. The benefits are greater in the second, third, and fourth years than in the first year. In long-term follow-up of the West of Scotland Coronary Prevention Study, 5 years of statin treatment were reported to confer a 20-year legacy of continued benefit.3

In conclusion

We die because of a fault in our plumbing. Taking a statin if indicated, keeps our pipes open for longer than would be the case otherwise!

  1. Heavier but Healthier — Diabetes and Smoking Cessation. NEJM Editorial August 16th, 2018
  2. Ticagrelor or Prasugrel in Acute Coronary Syndromes — The Winner Takes It All?. NEJM Editorial October 17th 2019
  3. Lipid Management for the Prevention of Atherosclerotic Cardiovascular Disease. Review article. NEJM October 17, 2019
  4. Mechanisms of benefit of lipid-lowering drugs in patients with coronary heart disease. Up to date
  5. Epidemiology of coronary artery disease. Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association
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