Their findings, to be published in the journal Circulation online Oct. 4, should make it easier for physicians to determine which patients have early coronary heart disease and which, if any, require aggressive treatment, including dietary changes, increased exercise, stronger attempts at smoking cessation, aspirin therapy and/or cholesterol-lowering and blood pressure lowering therapies.
"Family history has for years been recognized as a risk factor in predicting a person's chance for developing coronary heart disease early on in life - separate from better-known risk factors, such as HDL and LDL cholesterol levels, blood pressure, smoking and age. But we never knew if there was a difference between sibling and parental histories of early heart disease in terms of a given individual's risk of developing early atherosclerosis," said the study's senior author, cardiologist Roger Blumenthal, M.D., an associate professor and the director of the Ciccarone Preventive Cardiology Center at The Johns Hopkins University School of Medicine. Blumenthal is also a spokesman for the American Heart Association.
"Our study shows that asymptomatic individuals with sibling history were more likely than those with just a parental history to develop early atherosclerosis, and thus closer monitoring is advised as well as earlier consideration of other therapies -- such as aspirin, blood pressure, and cholesterol-lowering therapies - to slow development of atherosclerosis."
In a cross-sectional study of nearly 8,500 adults in Ohio, one half older and the other half younger than age 52, and all having no previous signs of heart disease, the Hopkins-led team found that siblings were two and a half to three times more likely to have a higher degree of coronary atherosclerosis if a brother or sister had already been diagnosed with heart disease. Parental history was also associated with subclinical atherosclerosis, although to a lesser extent than sibling history. Gender differences among siblings or parents were not examined, so no conclusions can be made regarding specific male and female combinations.
For the study, a family history of heart disease meant that a sibling or parent experienced a fatal or non-fatal heart attack or underwent some form of coronary revascularization, including bypass surgery, by age 55.
Using electron-beam tomography, a form of CT imaging that is often used in testing for heart disease, patients were scanned for early signs of atherosclerosis, as measured by the presence and extent of coronary artery calcification. Atherosclerosis occurs when fatty deposits called plaque, and calcium, build up inside the artery walls, causing the vessels to narrow and harden. Eventually, this can lead to blockages, strain on heart muscle and/or rupturing of the vessel. Study participants were graded for atherosclerosis - on a scale from low, to moderate to high - by their levels of calcification as seen by CT scan. Study participants with a sibling history were nearly four times more likely to have advanced levels of atherosclerosis when compared to those without any family history; On the other hand, participants with just a parental history were about two times more likely to have advanced levels of coronary calcium.
Signs of calcification and plaque build-up were observed in all groups, regardless of family history, but the burden was greatest among those patients who had a parental or sibling history of early heart disease, ranging from 36 percent to 78 percent, for both men and women. Other major risk factors for early heart disease - such as smoking, high cholesterol levels, high blood pressure, diabetes and obesity - were factored into the statistical analysis.
"These data support guidelines saying that more rigorous preventive measures should be undertaken in individuals with a history of premature heart disease," said study lead author Khurram Nasir, M.D., M.P.H., a cardiology research fellow at Hopkins. "Preventive measures include cutting back on fatty foods, increasing exercise and, possibly, taking cholesterol-lowering medications. They also need to be initiated earlier if they are to have a meaningful effect. Twenty-five percent of the time, the first manifestation of coronary heart disease is sudden cardiac death. Noninvasive measures, such as electron beam tomography, to detect coronary artery calcification can be used to identify the presence of early atherosclerosis in people with a family history of premature coronary heart disease."
"Our next goals are to explore the causal mechanisms, including specific genes and environmental risk factors, that explain the strong association between the familial clustering of individuals with early forms of heart disease, especially in siblings, and increased plaque burden in the coronaries. The other overall long-term goal, of course, is to use these findings to develop faster and better means of identifying early atherosclerosis in high-risk groups and prevent its progression to full-blown heart disease."
According to the latest statistics from the American Heart Association, in 2001 atherosclerosis accounted for nearly three-fourths of all deaths from cardiovascular disease.
This study was funded by two Maryland-based foundations, the Harteveldt-Gomprecht Foundation and Maryland Athletic Club Charitable Foundations.
Other investigators in this research were Erin Donnelly Michos, M.D.; Joel Braunstein, M.D., M.B.A.; and Wendy Post, M.D., at Hopkins; John Rumberger, M.D., M.B.A., The Ohio State University, Columbus, Ohio; and Matthew Budoff, M.D., the UCLA School of Medicine, Torrance, Calif.