Cardiovascular Disease

Cardiovascular Disease Is the Number-One Cause
of Disability and Death in the United States

Cardiovascular disease is arguably the number-one health problem in the United States. Despite remarkable progress in diagnosis and prevention, cardiovascular diseases such as heart attack, stroke, and peripheral vascular disease cause disability and death at a staggering rate.

Each year, these diseases account for 950,000 deaths in the nation—twice the number of deaths from cancer, ten times from accidents, and 25 times from AIDS. In fact, cardiovascular disease is responsible for more than half of all deaths of women in the U.S.

Stroke strikes 600,000 individuals every year. Only 10 percent of these patients fully recover, with 31 percent dying and 60 percent left with disability. Yearly costs for stroke reach a staggering $8 billion in the United States alone.

By 2015, the number of individuals over age 55 will increase from 21 to 28 percent of the American population. As our citizens age, more men and women will be at risk for cardiovascular disease. Without new treatments or preventative measures, the burden of cardiovascular disease will profoundly increase. Clearly, progress is urgently needed to discover new treatments and cures for this devastating condition.

Cardiovascular Research Today

The best opportunities for scientific progress lie in understanding the detailed mechanisms of cardiovascular disease at the molecular level and applying this understanding to develop and implement new strategies for its prevention and treatment.

As the primary cause of heart attack and stroke, atherosclerosis and the blood clots that it causes are arguable the most important problem in cardiovascular biology and disease. Atherosclerosis refers to the formation of plaques (or raised lesions) in the lining of arteries. Comprised of inflammatory cells, lipids, and connective tissue, plaques often form in the arteries that supply the heart, brain, and other vital organs. Mechanical forces and products made by the inflammatory cells themselves can cause disruption of plaque structure, exposing the plaque's contents to blood. Blood clots that form on the disrupted surface can grow in place to block blood flow or break off and move downstream to plug smaller vessels. Tissue deprived of blood supply and, hence, of oxygen becomes dysfunctional and dies if blood flow is not immediately restored.

To help ameliorate this problem, UCSF researchers are working to identify the genes that predict an individual's long-term risk for atherothrombosis and associated conditions such as hyperlipidemia, hypertension, and type-2 diabetes; to understand how these genes and conditions contribute to disease risk, to develop mechanism-based preventive measures tailored to the specific risk; and to determine whether such individualized preventive treatments are effective.

A second strategy is to identify the molecules that connect high blood cholesterol to the development of plaques, to determine how to block the formation or action of these molecules, and to ascertain whether this blockade can prevent or arrest the formation of atherosclerotic plaques or even cause them to regress. Candidate culprit molecules include oxidized components of lipoproteins (the protein-coated fat particles that carry cholesterol and other fats in the blood). These chemicals resemble molecules found on bacteria and hence trigger an inflammatory response in the vessel wall. This line of inquiry raises the possibility of developing a vaccine to prevent atherosclerosis or its progression.

A third strategy is to understand how blood clots in molecular detail and to develop methods (based on blood tests and/or imaging) to identify patients at near-term risk for heart attacks and strokes so that aggressive preventive measures can be taken. Such measures will someday include novel drugs to prevent plaque rupture and safer, more effective drugs to prevent the formation of damaging blood clots when plaques do rupture. UCSF researchers have made important progress in these areas, progress that has already led to a new class of antithrombotic drugs and promises a second. Our current plans call for a major emphasis on atherothrombosis research in the new cardiovascular research building at Mission Bay.

Congestive heart failure, caused by ineffective pumping of the heart, is a major cause of morbidity and mortality. The effects of damage caused by heart attack or by genetic abnormalities that affect the heart muscle are compounded by maladaptive signaling responses that occur when the damaged heart is constantly told by the nervous system to "pump more." Paradoxically, these maladaptive responses eventually decrease the heart muscle’s ability to contract. Ultimately, the heart remodels––changing its architecture and shape in a way that irreversibly compromises pump function. The frontier here is to understand these maladaptive signaling mechanisms in detail and to reverse them before irreversible remodeling of the heart muscle takes place.

The interface of developmental biology and cardiovascular disease research represents yet another exciting opportunity. UCSF has one of the largest communities of scientists studying cardiovascular development anywhere. The cellular processes that drive the formation of the heart and blood vessels are beginning to be understood, and many of the genes that govern these processes have been identified. It is clear that mutations in such genes are responsible for heart abnormalities in the newborn and for relatively rare forms of adult heart disease, and subtle changes in these genes may determine the risk for more common forms of adult disease. Such information is already impacting diagnosis and prevention. In addition, our improving understanding of developmental and stem cell biology may someday permit repair of damaged tissues.

CVRIHead