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Thirty-two-year-old Arjun Gupta, who has had a family history of heart attacks — his father passed away at 58 and his uncles and other members of his paternal family have had some kind of cardiac episode or the other in their 40s and 50s — has been cautious. He gave up smoking, adopted healthy eating habits and took up running the day he realised that his low-density lipoprotein (LDL) or bad cholesterol levels were nearly three times higher than a normal person. “I thought these corrections were enough to manage my levels and keep them in range. But they had a tendency to rise sharply and eventually I needed medication and statins,” he says.
What Arjun has is a common genetic disorder called familial hypercholesterolemia (FH). An inherited condition, such people have increased levels of LDL cholesterol, which make them prone to not only developing heart disease at a younger age but expose them to a higher risk of mortality. Arjun not only gets himself tested regularly, the only way to keep his risk factors down, he also gets his siblings tested. This disorder is such that it allows cholesterol to build up regardless of your weight, diet, habits and exercise and the patient needs medical guidance. According to experts, anyone with just one of the 1,500 possible gene variants that cause the condition has a 50 per cent chance of passing it to their offspring.
“Family history is a risk factor for cardiovascular disease, especially if a first degree relative experienced a major cardiovascular event (heart attack/ stroke/ coronary surgery/ sudden cardiac death) below the age of 60 years. Its effect can be reduced by keeping other cardiovascular risk factors under control. Not smoking offers good protection against heart attacks, compared to smokers. This is true for both men and women, with the risk being even higher among women smokers. Please avoid exposure to second-hand smoke too,” says Dr K Srinath Reddy, cardiologist, epidemiologist and Distinguished Professor, Public Health Foundation of India (PHFI).
However, cholesterol, he says, is a different story. “Not only does the total blood cholesterol matter but the sub-fractions of cholesterol and other blood lipids too contribute to assessment of risk. Levels of LDL cholesterol and non-HDL cholesterol predict risk better than total cholesterol. Within LDL cholesterol too, the ratio of ‘small dense’ LDL fraction to the ‘big buoyant’ fraction is important (the smaller closely packed particles being more damaging to blood vessel walls). Since ‘small dense LDL’ is difficult to measure, the ratio of serum triglycerides to HDL cholesterol is a good surrogate measure. The apolipoprotein B to apolipoprotein A-I ratio, which profiles the ‘good’ to ‘bad’ cholesterol balance, is another good risk marker. It is not uncommon to find persons with ‘normal’ total cholesterol levels having heart attacks because the sub-fractions are deranged,” adds Dr Reddy.
“Familial hypercholesterolemia is an inherited condition where LDL cholesterol levels can be very high. In addition to a prudent diet and regular physical activity, specific drug therapy would be required. Statins are most often used. In statin-intolerant persons, bempedoic acid has been shown to be effective without causing myopathy. Ezetmibe too can be used in such persons and even to supplement statin therapy in others. In recent years, PCSK9 inhibitors have been shown to be especially effective in reducing LDL cholesterol and providing cardiovascular protection to patients with familial hypercholesterolemia.” says Dr Reddy.
Other risk factors matter too. “Blood pressure should be kept under control. The waist to height ratio should be less than 0.5. Blood sugar and HbA1C levels should be normal. There should be adequate sleep and regular, moderate physical activity. Keep your stress levels low. Eat plenty of fruit and vegetables, while cutting down on salt, sugar, saturated and trans-fats. Ultra-processed foods carry high risk. So, manage your Rubik’s Cube of multiple risk factors, to align the various colours well to a good cardiovascular risk profile,” he says.
What is the percentage of heart risk in those with a family history of heart disease? “Data are mostly from American studies. Sibling history has a 40 per cent higher risk. Paternal history has a 75 per cent higher risk. Maternal history has a 60 per cent higher risk. Smoking, hyperlipidemia, hypertension and diabetes carry higher risks,” says Dr Reddy.
Research has quantified the seriousness of family history in future development of heart disease. According to a study in 2021, which was published in the Journal of the American Heart Association, those with a family history of early-onset heart disease in at least one relative (parent, sibling, or child) have a 22 percent increased risk of heart disease. Another study, involving more than 55,000 participants and published in the New England Journal of Medicine, found that the risk of heart attack or stroke was 91 per cent higher in individuals with a genetic history than those who did not.
“Family history of heart disease is a non-modifiable risk. Usually, the inheritors will have a cholesterol abnormality. They have a particular kind of LDL called lipoprotein A (LPA), which is dense and carries cholesterol to the cells of the heart vessels. Not many drugs can modify LPA levels today but research is ongoing. At the moment, if you control your LDL levels very strictly, then LPA levels can be kept in check,” advises Dr Rajiv B Bhagwat, Interventional Cardiologist, Nanavati Max Super Speciality Hospital, Mumbai.
“The commonest mistake that people make is to consider the total cholesterol count. But you have to see the LDL (bad cholesterol) count, the proportion of HDL (good cholesterol) and the HDL:LDL ratio. Indians have low HDL levels anyway. They say 50mg/dL is ideal to neutralise LDL but in Indians, that level never crosses 45 mg/dL. That’s why we’ve got to work aggressively on LDL levels and keep them down. So, if you are an Indian, who is anyway prone to a higher cardiac risk than Western populations, the preferred LDL range is less than 50 mg/dL. For those with family history, this should ideally be 30mg/dL or even lesser,” he says. Then there are triglycerides. “Triglycerides are blood fats, which along with cholesterol, cause plaque build-up. Therefore, both triglycerides and LDL levels need to be significantly lower,” adds Dr Bhagwat.
He recommends that those with a family history get themselves under a monitoring regime from as young as 25. “We need to start lipid-lowering drug therapies early besides addressing modifiable risks. Medical awareness is low in India. One of my friends passed away because of a heart attack at age 50 and I got all his children screened early on. Even in my OPD, I get at least about two to three patients with a family history of heart disease a day,” says Dr Bhagwat.
