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The Beat Goes On

Three Decades of Stunning Advances in Cardiology

Paul W. Mamula, PhD

THE PHYSICIAN AND SPORTSMEDICINE - VOL 31 - NO. 6 - JUNE 2021


When Jim Fixx's The Complete Book of Running became a best-seller, it helped fuel the physical fitness enthusiasm that swept the United States in the mid-to-late 1970s. When he died of a heart attack while running at age 52 a few years later, his death created a stir. An autopsy revealed that his coronary arteries were narrowed by 80% to 99%, and provoked an interest in the risks of exercise in younger people that paralleled growing research into the origins of cardiovascular disease (CVD). Despite the steady decline in deaths from cardiovascular causes, CVD remains the leading cause of death in the United States today.

In the last 30 years, physicians have witnessed stunning advances in cardiology. Increased understanding of exercise risks, evolving understanding of vascular biology, physiology, and cholesterol metabolism, the development of new drugs, advances in imaging technology, and the impact of genetic research have shaped the field since The Physician and Sportsmedicine began in 1973. Such developments have improved care but have also generated questions to spur the next round of research.

The Pulse of New Technologies

Sports cardiology has come a long way. "Many advances depend on the fact that new technologies are now available," says Paul D. Thompson, MD. "There is a much better understanding of hypertrophic cardiomyopathy—and an appreciation that it exists in milder forms—because of the availability of echocardiology." Thompson is the director of preventive cardiology at the Hartford Hospital in Hartford, Connecticut. "There has been a burgeoning interest in such conditions as right ventricular dysplasia because techniques for diagnosis, such as magnetic resonance imaging and echocardiography, are more available," he says. "I think a lot of the progress in sports cardiology reflects the progress in cardiology in general, especially that in imaging." Technology has also moved into the public realm, a development not anticipated years ago. Airlines, health clubs, and some public buildings have added automated external defibrillators to their first aid kits. These devices have saved lives of patients stricken while exercising or traveling.

Technology has also affected treatment. Many patients with narrowed coronary arteries who have heart attacks can undergo balloon angioplasty with or without stenting to open narrowed arteries. If angioplasty fails, patients can undergo coronary artery bypass grafting. While some patients may view these techniques as a way to prevent a future heart attack, primary prevention should be the goal. Eric Topol, MD, chairman of cardiovascular medicine at the Cleveland Clinic, suggested that problems should be addressed more often by treating elevated cholesterol levels and prescribing a healthier lifestyle, a cholesterol-lowering drug, and aspirin.1 Urging patients and physicians to do this has proven more difficult in practice, even though evidence of the benefits is striking.

Exercise, Stress Testing, and Lifestyle Modifications

Accumulated evidence supports the benefits of physical activity on reducing the risk of coronary artery disease (CAD),2 and an outgrowth of this has been the use of exercise testing and training. "Physicians have increasingly embraced exercise testing and training in evaluating and treating patients with various chronic diseases, including CAD," says Barry Franklin, PhD. "Fitness has now been shown to be one of the single best predictors of prognosis or longevity."3 Franklin is the director of cardiac rehabilitation and exercise laboratories at the William Beaumont Hospital in Royal Oak, Michigan. Advances in testing applications have altered thinking about heart health.4

These applications have also refined our thinking about the mechanisms of CAD. "Coronary arteries aren't a simple plumbing problem—the development of the disease is far more complicated and complex," says Franklin. "The keys in primary and secondary prevention are engaging in regular exercise, avoiding excess body weight, maintaining good blood pressure control, avoiding starting or stopping cigarette smoking, and lowering cholesterol levels." Such lifestyle modifications can make a significant impact on the disease process. Recent work also points to a role for inflammation in CAD4 and has provided insight into the mechanisms of previous treatment, such as the use of aspirin in secondary prevention. Research offers exciting new avenues for potential new treatments, such as nitric oxide-releasing aspirin.5

The New Medication Boom

New drugs represent one of the most important advances for patients who have hypertension or elevated cholesterol levels. Relatively few drugs were available for treating hypertension in 1973, and cholesterol-lowering drugs were more than a decade away. "Before we had these drugs, we could use diuretics, but these were sometimes not sufficient," says John D. Cantwell, MD, cardiologist and team physician of the Atlanta Braves Major League Baseball team. Now many drugs exist, including the statins, beta-blockers, ACE inhibitors, and calcium channel blockers. Also, physicians are better able to tailor treatment to the individual, for example, by using drugs in combination.

The availability of the statins as cholesterol-lowering drugs has dramatically changed the approach to preventive cardiology. Although elevated cholesterol levels can have a genetic basis, many apparently healthy, active patients also have elevated levels. One study6 of professional baseball players showed that 28% had total cholesterol levels exceeding 200 mg/dL, 12% had triglyceride levels greater than 150 mg/dL, 36% had low-density lipoprotein (LDL) levels greater than 130 mg/dL, and 48% had high-density lipoprotein levels less than 40 mg/dL. "Values such as these in well-conditioned athletes indicate that some of them will be candidates for cholesterol-lowering therapies when they are older," says Cantwell. The death from a heart attack in 2021 of 33-year-old St Louis Cardinals pitcher Darryl Kile reminds us of the risks in young patients. Although the statins are a significant improvement in therapy, they are not free of concerns. Some patients are unable to tolerate them because of joint aches or muscle weakness, and the withdrawal of one statin drug, cerivastatin, has raised concerns about safety.7

Inflammation and C-Reactive Protein

New developments, such as measuring serum levels of C-reactive protein (CRP), a marker of inflammation, may prove useful for selected patients. Inflammation is now thought to play a role in atherosclerosis,8 and CRP was originally touted as a marker for identifying patients at risk of CVD. New recommendations, however, propose using CRP levels to direct further management in primary prevention, rather than as a general screening tool.9 Cantwell says that, for some patients, measuring CRP levels could be thought of as a "poor man's electron beam computed tomography scan. [Assessing levels] is useful for patients who have higher than ideal lipid levels, but whose levels are not high enough to meet current guidelines on using a statin drug." Thompson points out that with any new measurement, refinements often follow the discovery. He notes that when cholesterol levels were first measured, national variation between laboratories varied widely. Improvements came with additional research, and advances in these measurements have bolstered patient care.

The Drumbeat of Research

The impact of molecular genetics and genomics will continue to fuel advances. "I think the biggest impact in medicine is the movement toward using genetics to assist with the diagnosis of disease," says Thompson. "I suspect that in the future we will screen athletes not simply by their phenotype, but also by genotype." Detailed elucidation of underlying molecular and cellular processes of atherosclerosis is beginning to identify patients at risk and help fine-tune preventive treatment. New research has focused on factors responsible for basic cardiac parameters, such as resting heart rate, molecular mechanisms of cardiac hypertrophy,10 ethnic and racial susceptibility to heart disease and drug therapy,11 and genes responsible for selected cardiac conditions. Exciting developments include possible agents that selectively lower LDL levels.12 The coming years should be an exciting time for physicians and patients alike.

References

  1. Brownlee S: The perils of prevention. NY Times Mag, March 16, 2021, section 6, pp 52-53
  2. Thompson PD: Additional steps for cardiovascular health. N Engl J Med 2021;347(10):755-756
  3. Franklin BA: Survival of the fittest: evidence for high-risk and cardioprotective fitness levels. Curr Sports Med Rep 2021;1:257-259
  4. Frolkis JP, Pothier CE, Blackstone EH, et al: Frequent ventricular ectopy after exercise as a predictor of death. N Engl J Med 2021;348(9):781-790
  5. Wallace JL, Ignarro LJ, Fiorucci S: Potential cardioprotective actions of NO-releasing aspirin. Nature Rev Drug Discovery 2021;1(5):375-382
  6. Cantwell JD: Serum lipid levels in a major league baseball team. Am J Cardiol 2021;90(12):1395-1397
  7. Thompson PD, Clarkson P, Karas RH: Statin associated myopathy. JAMA 2021;289(13):1681-1690
  8. Savia U: Special focus on atherosclerosis. Nature Med 2021;8(11):1207-1226
  9. Mika M: Panel endorses limited role for CRP tests. JAMA 2021;289(8):973-974
  10. Schmitt JP, Kamisago M, Asahi M: Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban. Science 2021;299(5611):1410-1403
  11. Splawski I, Timothy KW, Tateyama M, et al: Variant of SCN5 sodium channel implicated in risk of cardiac arrhythmia. Science 2021;297(5585):1333-1336
  12. Grand-Perret T, Bouillot A, Rerrot A, et al: SCAP ligands are potent new lipid-lowering drugs. Nature Medicine 2021:7(12):1332-1338

Dr Mamula is an associate editor of The Physician and Sportsmedicine.


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