Let’s evaluate the cardiovascular risk for three hypothetical scenarios.
A 50-year-old office worker who, prior to the pandemic, was not overweight and had normal cholesterol levels. He has no family history for heart disease. During the pandemic, he worked from home, stopped exercising, did not watch his diet and gained 25 pounds.
A 50-year-old construction worker who has had high cholesterol all of his life, but has not been on medication. His father and brother both had heart attacks in their fifties. During the pandemic, he was active at work, exercised on the weekends and didn’t gain any weight.
A 65-year-old woman who did not have high cholesterol until menopause. She has no family history of heart disease, is active and eats a Mediterranean diet.
All three recently had blood work and the results are the same; cholesterol 250, HDL cholesterol 30, LDL cholesterol 135. All three are nonsmokers, do not have diabetes or high blood pressure and are not taking a statin. Entering their information into the American College of Cardiology (ACC) risk calculator yields similar results: they each have a 7.2% risk for a heart attack or stroke over the next ten years. Even though their cholesterol numbers and their risk levels are the same, is the risk for heart disease the same for all three people?
Unfortunately, the ACC risk calculator does not factor in family history of heart disease. It has been known for quite some time that having a first degree relative with heart disease at an early age is a strong risk factor for heart disease. One of the reasons for premature heart disease in families is a genetic tendency for high cholesterol, especially elevated levels at an early age (a condition known as familial hyperlipidemia). Premature heart disease is a major consequence of familial hyperlipidemia. Familial hyperlipidemia is suspected in a patient who has: 1) heart or vascular disease at a young age (for men under the age of 55, for women under 60); 2) a family history of vascular disease at a young age; 3) tendon xanthomas (cholesterol deposits on tendons - pictured above); 4) a very high LDL cholesterol (over 155 and often in the 200 to 300 range). Why do people with familial hyperlipidemia develop blockage in heart arteries earlier than those who don’t have this condition? The answer is that the plaque forming effect of LDL cholesterol is dependent on both the level of LDL and the duration of elevation. The risk for heart artery disease can be expressed in “cholesterol-years” or the average LDL level times the number of years of exposure (this is similar to a core concept in cardiology, pack years, the average number of packs of cigarettes smoked times the number of years smoked). Plaque begins to form in the heart arteries after a certain threshold of LDL exposure is reached. For example, a person can have an average LDL level of 100 mg/dl for 70 years resulting in 7 grams/dl cholesterol-years. If 7 grams/dl is the threshold for developing plaque then they will manifest heart artery disease at age 70. On the other hand, a person with familial hyperlipidemia may have an average LDL of 200 mg/dl, reach 7 grams/dl cholesterol-years and develop heart issues at 35 years old. The theoretic threshold for developing disease is lower if there is hypertension or diabetes. The threshold will be higher if a healthy lifestyle keeps LDL lower for longer.
The concept of cholesterol-years may explain why women manifest heart disease at later ages than their male counterparts. It is well know that women have low levels of heart disease (compared to men) until they hit menopause. After menopause, the rate of cardiac disease accelerates exponentially. This is because total cholesterol and LDL go up dramatically in the year after the onset of menopause. Due to the protection afforded women by their hormones before menopause, their cholesterol-years or their years of LDL exposure are less than men (especially in their teens, twenties and thirties) and therefore heart disease is shifted towards older age (when their cholesterol-years catch up to men).
With this information in mind, let’s rank the scenarios. The 50-year-old office worker has the lowest risk for heart artery disease. His cholesterol only went up over the past two years. He has a low number of cholesterol-years and a lower lifetime exposure to LDL than his counterparts. He should initiate lifestyle changes immediately. The 65-year-old woman has the next lowest risk. Her cholesterol was low until menopause, rising to high levels over the past 10 years. She has been following a good diet and exercising, so she may need to be started on a statin. The 50-year-old construction worker with familial hyperlipidemia has the highest risk. He has about 6.7 grams/dl cholesterol-years (average LDL 135 mg/dl over 50 years) and should also be started on medications immediately.
The cholesterol-years approach is a measure of exposure over time and better than relying on a single measurement of LDL. This concept also favors intervening to lower cholesterol at an earlier age, say ages 18 to 30, with lifestyle alterations or medications to protect against cardiac disease later in life.
