Coronary artery disease (CAD) continues to be the foremost cause of mortality globally, regardless of the progress made in medical treatments such as statins, PCSK9 inhibitors, stents, and bypass operations, alongside comprehensive lifestyle guidance aimed at prevention. Although the response to heart attacks has advanced, the fundamental causes of heart disease are still unresolved. The medical field persists in investigating different theories and therapies, yet a definitive cure for heart disease remains out of reach.
Having served as an internist and lipidologist, I dedicated years to examining lipid levels, especially high-density lipoprotein (HDL). I collaborated with pharmaceutical firms and advocated for treatments like niacin to enhance HDL levels. However, clinical trials such as AIM-HIGH and HPS2-THRIVE discredited the HDL hypothesis, demonstrating that raising HDL did not correlate with fewer cardiovascular incidents. Even CETP inhibitors, which greatly increased HDL, did not result in better patient outcomes.
Recently, attention has shifted to lipoprotein(a) [Lp(a)], another variable in combating cardiovascular disease. Pharmaceutical companies are formulating drugs aimed at Lp(a), but it has yet to be established whether decreasing Lp(a) will lead to enhanced survival rates. This trend of emphasizing drug development without solid evidence mirrors the mistakes made regarding HDL.
An underexplored field of study is the possible infectious aspect of atherosclerosis, particularly the role of the bacterium Chlamydia pneumoniae. In the 1990s, investigations conducted by researchers like Dr. J. Thomas Grayston and Dr. Allan Shor discovered C. pneumoniae within atherosclerotic plaques, indicating a potential connection between infection and cardiovascular disease. Despite strong evidence, the idea that heart disease could have an infectious component did not conform to dominant lipid-focused narratives or commercial interests.
Previous antibiotic studies utilizing short courses in older patients with severe disease showed no advantages, but those studies were deeply flawed. Anticipating a single antibiotic to rectify extensive vascular damage is impractical, similarly to how using monotherapy for advanced tuberculosis or HIV would be.
Drawing comparisons with the successful treatment of chronic inflammatory diseases like TB, leprosy, and syphilis—which were once also misunderstood as infections—suggests that we need to investigate the infectious hypothesis of atherosclerosis with greater seriousness. I propose a new clinical trial, dubbed TACTIC, aimed at younger patients with early coronary disease, identified through coronary artery calcium (CAC) scores or coronary CT angiography (CCTA). This trial would implement a combination antibiotic therapy against C. pneumoniae and assess changes in plaque burden rather than conventional outcomes such as mortality or myocardial infarction.
Securing funding for such a trial remains challenging, as there is scant financial motivation to pursue potentially curative treatments using inexpensive antibiotics instead of creating lucrative Lp(a)-lowering injectables. Despite solid scientific underpinnings and historical examples, what is lacking is the collective resolve to question current paradigms and thoroughly explore infectious causes of heart disease.
While statins continue to offer benefits, concentrating on managing risk markers instead of the underlying mechanisms may lead to many more years of ineffective intervention. It’s time to reflect on whether we have truly understood what contributes to heart disease—and perhaps have simply chosen to overlook it.