Early Heart Disease Linked To Genes, Insulin Resistance

“The study provides further evidence that genes play a large role in early-onset coronary heart disease (CHD) and that it clusters in families, regardless of environmental factors,” says Markku Laakso, M.D., chair of the department of medicine at the University of Kuopio in Finland, and senior author of the study.

The study indicates that traditional risk factors for CHD – high cholesterol, high blood pressure, smoking, obesity – only account for half of the risk for CHD. Several previous studies have demonstrated that early CHD runs in families, and genetic factors possibly explain the other 50 percent of the risk for CHD in men younger than age 55 and women younger than 65.

Researchers suspected that individuals who developed early disease might have genetic disorders that could lead to an increased risk for heart attacks.

One of the most common disorders that runs in families is insulin resistance syndrome – also known as “syndrome X” or “the metabolic syndrome” – which leads to type 2, or adult-onset diabetes. It is known to cause high levels of total cholesterol, high levels of very low-density lipoprotein (VLDL), and low levels of high-density lipoprotein (HDL, the “good” cholesterol) –all major risk factors for heart disease. Other effects of the syndrome, such as high levels of the clotting protein fibrinogen and high insulin levels, have also been linked to heart disease risk.

To determine if syndrome X clustered in this group of families, researchers determined levels of cardiovascular risk factors from siblings with and without early heart disease.

There were 101 individuals with early CHD, and 54 siblings of these individuals who were unaffected. Early CHD is defined as having a heart attack or vessel blockage of greater than 50 percent in men before age 55 and women before age 65. Oral glucose tolerance tests were performed in participants who had no previous diagnosis of diabetes. Blood glucose, insulin and serum free fatty acids were measured fasting and at one and two hours after taking 75 grams of glucose.

The researchers found that even in nondiabetic participants, individuals with CHD had higher insulin levels after the glucose tolerance test than their siblings without heart disease (475.7 vs. 331.8 picomoles per liter).

Individuals with heart disease had lower HDL levels compared to those without CHD: 1.22 millimoles per liter (mmol/L) (or 47 milligrams per deciliter, mg/dL) vs. 1.42 mmol/L (55 mg/dL). They also had higher triglyceride levels (1.91 vs. 1.68 mmol/L; or 74 vs. 65mg/dL), higher VLDL (1.25 vs. 1.06 mmol/L; or 48 vs. 41 mg/dL), and higher fibrinogen levels (3.8 vs. 3.4 g/L).

“It is not likely that lifestyle factors could explain the differences because obesity, alcohol intake, smoking and physical activity did not differ between these subjects; therefore the difference in risk between siblings is more likely due to genetic factors.

Thus the study shows that the combination of risk factors related to the insulin resistance syndrome is likely to explain the incidence of premature CHD in these families.

Further studies are needed to identify a gene predisposing to early atherosclerosis. Co-authors of the study include Anu Kareinen, M.D.; Laura Viitanen, M.D.; Pirjo Halonen M.Sc.; and Seppo Lehto, M.D.