A growing body of research appears to be altering the most common model of heart disease, one that depicts what happens to the human heart as similar to what happens in an old house. That model suggests that, like an aging bungalow, the plumbing of the heart and vasculature, over time, becomes plugged up by gunk sticking to the walls of our veins and arteries. This picture probably has been reinforced by popular discussions of cholesterol, with most people undoubtedly thinking of cholesterol as something that thickens the blood and clogs the passageways. But this picture is based on a rather faulty comparison – that thecardiovascular system is essentially equivalent to the metal or plastic plumbing of a house. But of course arteries and veins aren't inert piping but rather are made up of tissues susceptible to all the systemic changes that take place in our bodies day-to-day, minute-by-minute.
This realization is leading to a new model that sees the unhealthy build-up of materials as taking place, not inside the vessel pathways but rather inside the walls of the vessels themselves. This is the model used by researcher Peter Libby in his cover story in the May issue of Scientific American exploring the genesis of atherosclerosis. In the article, Libby focuses primarily on cellular inflammation as the cause of lesions or sores on the walls of blood vessels, with these sores then producing adjacent blood clots or resulting in materials flaking off and causing downstream clogging and infarct or embolism. This flaking may help to explain why some heart attacks are not preceded by telltale symptoms since inflammation may not always produce severe arterial clogging, Libby says. He goes on to say that this helps to explain "why therapies that focus on widening the blood passage in semi-occluded arteries ... frequently fail to prevent a future heart attack." In these cases, vessel plaques need not reduce blood flow before they rupture.
Libby's observations concerning the link between inflammation and atherosclerosis are born out by a recent study, published in the April 30 issue of Circulation, identifying elevated levels of certain proteins as a signature marker of inflammatory response in the arteries. According to research by Renu Virmani, MD, at the U.S. Armed Forces Institute of Pathology (Washington), arterial inflammation produces C-Reactive protein (CRP) when the immune system responds to infection. Virmani and her team studied the blood of 144 men and women who had suffered sudden cardiac death and found slightly elevated levels of CRP, while no such elevation of CRP was found in 158 men and women who had died of non-cardiac disease.
While there is still much work to do in this area, these observations add to increasing evidence that new diagnostic systems could be the largest area of expansion in the cardiovascular sector, and that new assays could augment the current indicators of early heart disease risk. Those indicators have tended to be measures of blood pressure, waveforms and other indirect signs of cardiovascular trouble, while newer in vivo tests could provide more direct measurements that could detect heart disease in its earliest manifestations. These more direct measurements of systemic troubles also could help lead to drug treatments that go beyond treatment of symptoms.
But cardiovascular device manufacturers probably need not fear that new drugs and diagnostics will elbow device technologies out of the cardiovascular picture. History is clear in telling us that increasing numbers of people – many of them in developing nations and a growing number of older people – will pursue risky cardiovascular behaviors that will outmuscle the power of any new diagnostics and therapeutics. And eventually these people will require the renovation of the human house that only devices – such as pacemakers, heart assist pumps and replacement hearts – will be able to provide.
New stress factors identified
Stress has frequently been related to heart disease as a general cause of hypertension and heart disease over time, but a growing number of studies suggest that clinicians need to be on the lookout for particular types of stress in particular situations as causative factors. As one instance, a study in animals seems to indicate that women who experience a period of emotional stress early in their pregnancy may pass on a higher risk of adult high blood pressure to their child. That was a key finding presented by E. Marelyn Wintour, MD, of the University of Melbourne (Melbourne, Australia) at the recent Experimental Biology 2002 annual conference. In the study, about 50 sheep were injected with cortisol, a stress hormone, over a two-day period early in their pregnancies, the researchers choosing sheep because of gestation and fetal development factors similar to humans.
The injections produced a stress load that could be compared to a stressful situation in a human mother. Other sheep received a cortisol injection at pregnancy midpoint or an injection of saline placebo. The researchers found that those ewes stressed early in pregnancy produced lambs with elevated blood pressures at about five months of age – comparable to young adulthood in humans – and their blood pressures continued to increase over most of their lifespan. In comparison, blood pressures remained relatively normal in sheep whose mothers were stressed at mid-pregnancy and in those whose mothers received placebo.
Wintour cited a variety of other studies, both animal and human, leading to the same conclusion concerning stress in the early gestation period. As one example, heightened blood pressures have been seen in people whose mothers were pregnant with them during the last years of World War II. In the current study, the researchers reported the cortical dose adversely impacting the early development of brains and kidneys in the fetal lambs.
In another recent study on the impact of stress on cardiovascular health, researchers recently have found that immune globulin intravenous (IGIV) products may cause clotting.
There may be a connection between IGIV and serious blood clot problems, according to warnings issued by Baxter Healthcare (Deerfield, Illinois) and the American Red Cross (Washington), in a posting on the FDA's web site. IGIV consists of antibodies derived from pooled human plasma, which are stabilized with sugars or proteins, such as glucose, sucrose or albumin. The product helps fight infection in those with weakened immune systems, and is used in patients with HIV infection, bone marrow transplant and certain types of leukemia. But caution is needed in administering IGIV to patients with cardiovascular disease or previous clot-related problems, and those cautions have been added to the labeling of products made by Baxter and the Red Cross. Baxter's product is Gammagard S/D, while the Red Cross distributes Polygam S/D.
Pharmacists, nurses and other health care workers involved in the administration of immune globulin intravenous are urged to read and follow the package insert. Patients with risk factors such as coronary artery disease, hypertension (high blood pressure), cerebrovascular disease and diabetes should be carefully evaluated, the Red Cross noted.
Cholesterol lowered with calcium
A new study published in the April issue of the American Journal of Medicine reported that calcium citrate supplements can lower the cholesterol levels of post-menopausal women. The study, "Effects of Calcium Supplementation on Serum Lipid Concentrations in Normal Older Women: A Randomized Controlled Trial," was led by Ian Reid, professor in the department of medicine at the University of Auckland (Aukland, New Zealand). The study was conducted as part of a larger trial to assess the effects of calcium on fracture incidence.
"This study showed that 1 gram of calcium (as the citrate) taken daily lowers the damaging component of blood cholesterol (LDL or low-density lipoprotein) and increases the protective cholesterol (HDL or high-density lipoprotein). As a result, calcium citrate may reduce the incidence of heart attacks and angina in postmenopausal women," said Reid.
According to Reid, this study was designed to determine the effect of calcium supplementation with calcium citrate (1 gram daily as Citracal Ultradense) on circulating lipid concentrations in normal older women. Subjects were restricted to postmenopausal women who were not receiving therapy for hyperlipidemia or osteoporosis. A total of 223 women (mean age, 72) received calcium citrate, or placebo for one year. Fasting serum lipid concentrations were obtained at baseline, and at two, six and 12 months.
The use of calcium citrate had a beneficial effect on cholesterol levels, and the results of this study support findings from earlier studies that demonstrated calcium supplementation has a positive effect on cholesterol levels. Other studies have also shown that calcium intake is inversely associated with cardiovascular disease. "Based on our data, one could predict that calcium citrate supplements may help otherwise healthy postmenopausal women reduce cholesterol, improve heart health and possibly even reduce the rate of cardiovascular related events by 20% to 30%," Reid noted. "These data provide reason to encourage the more widespread use of calcium supplementation in postmenopausal women," he added.
"This is exciting news for women," said Miriam Nelson, PhD, author of the "Strong Women" series of books and director of the Center for Physical Fitness and associate professor of nutrition at the USDA Human Nutrition Research Center on Aging located at Tufts University (Medford, Massachusetts). "We all know calcium is essential for strong bones. However, this study also showed calcium citrate may play a role in reducing heart attacks and cardiovascular related deaths in postmenopausal women. This indicates a renewed need for sufficient calcium intake. I recommend taking a daily calcium citrate supplement and vitamin D to help women maintain strong bones and a healthy heart."
Future clinical trials should explore the effect of calcium supplementation on lipids in other populations, including men, and larger studies should be undertaken to assess the effects of calcium supplementation on the risk of cardiovascular events, according to Reid. "Our results indicate that the benefits of calcium supplementation go beyond osteoporosis."