A Legacy of Research & Discovery

Heart Disease

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Reducing risks. Improving odds.

Data from the 2008 JUPITER Trial suggest a 54 percent heart attack risk reduction and a 48 percent stroke risk reduction in people at risk for heart disease who use statins as preventive medicine. 

After 30 years in use, statins remain the “gold standard” for high cholesterol treatment. 

Statins:

  • Lovastatin/Mevacor
  • Simvastatin/Zocor
  • Pravastatin/Pravacol
  • Atorvastatin/Lipitor
  • Rosuvastatin/Crestor

Two of UT Southwestern’s Nobel Laureates are at the heart of that success. After years of research, Drs. Michael Brown and Joseph Goldstein shared the 1985 Nobel Prize for their revolutionary discovery of the underlying mechanisms of cholesterol metabolism. 

By studying an inherited disease called familial hypercholesterolemia that leads to extremely high levels of cholesterol, Drs. Brown and Goldstein found that cells have receptors on their surfaces that regulate how much cholesterol-containing particles called low-density lipoprotein (LDL) end up circulating in the blood stream. A combination of hereditary factors and food intake causes a reduction in the number of LDL receptors, thereby increasing the levels of LDL in the blood. Increased levels of cholesterol in the blood can accumulate in the walls of arteries causing atherosclerosis and eventually a heart attack or a stroke.

6 Nobel Prizes

That understanding allowed the development of statin drugs, which block enzymes the liver uses to produce cholesterol. Today, millions of people take statins, making them one of the most widely prescribed medications in the world. New federal cholesterol guidelines could triple the number of Americans taking statins to lower their cholesterol, reducing the risk of heart disease and stroke for countless people.

Photos: Dr. Michael Brown (left) and Dr. Joseph Goldstein

Today, millions of people take statins, making them one of the most widely prescribed medications in the world.

Anti-PCSK9 Antibodies:

  • Alirocumab/Praluent
  • Evolocumab/Repatha

Helen Hobbs

When statins aren’t enough, there’s a new class of drugs called PCSK9 inhibitors that dramatically lower LDL cholesterol levels. The story of this class of drugs also stems from research success at UT Southwestern.

In 2000, UT Southwestern physician-scientist Dr. Helen Hobbs, a protégé of Drs. Brown and Goldstein, launched the Dallas Heart Study. Researchers collected extensive health information and genetic profiles from several thousand individuals of different ethnic backgrounds in Dallas County to study cardiovascular disease.

The database has proven invaluable in cardiovascular research and allowed Dr. Hobbs and her UT Southwestern colleague Dr. Jonathan Cohen to identify individuals with mutations in a gene that produces PCSK9 proteins. They were further able to show that individuals who had one mutation in the PCSK9 gene had low cholesterol levels. Drs. Hobbs and Cohen eventually identified a woman who had two PCSK9 mutations and extremely low cholesterol levels, but was otherwise healthy. Their findings helped spur further research leading to the production of PCSK9 inhibitors, two of which were approved in 2015 by the FDA. In clinical studies, one of the inhibitors, alirocumab, reduced LDL cholesterol in individuals taking statins an additional 44 to 58 percent on average.

Photo: Dr. Helen Hobbs