"Live long and prosper." Maybe that Star Trek Vulcan blessing needs a rethink in the United States.
Americans are by and large prospering, but the "live long" part is in serious question: More than 70% of US adults are obese or overweight, and alarming new statistics suggest that more than 90% show early signs of developing the often-associated disorders of diabetes, heart disease or kidney disease.
The numbers are "astronomically higher than expected," said Dr. Rahul Aggarwal, a cardiology fellow at Brigham and Women's Hospital in Boston and co-author of the study.
Heart disease is now the Number One killer of Americans. It is well-established that inflammation is a major contributor to atherosclerosis and atherothrombosis (arterial plaque with a blood clot), which are major causes of cardiac morbidity and mortality. The challenges are escalating.
What could and should be done?
Despite the availability of simple ways to measure systemic and coronary artery inflammation, and new ways to reduce inflammation, routine medical practice has yet to incorporate them.
The closest thing to a "silver bullet" is colchicine, a potent anti-inflammatory agent that has been shown to reduce cardiovascular events following a stroke by almost one-third. Sold under the brand name Lodoco, colchicine has long been used to treat gout and other inflammatory conditions. It was touted as a treatment by some during the height of COVID:
....but it failed in more extensive studies:
Recent evidence suggests the drug used to treat gout might have a second career containing heart disease. A randomized clinical trial published in The Lancet involved more than 3,100 patients who had experienced a mild stroke or transient ischemic attack (TIA). They were randomly assigned to receive 0.5 mg of colchicine daily in addition to usual care versus usual care alone. The primary endpoint was a composite of possible life-threatening events, including stroke, heart attack, cardiac arrest, or hospitalization for unstable angina.
The results were promising: a significant 20% reduction in those events. And although at baseline the two groups (colchicine plus usual care versus usual care alone) showed no difference in levels of a blood marker of inflammation called hs-CRP, patients treated with colchicine had a significant reduction in hs-CRP from 28 days up to three years of treatment.
This trial expands the growing body of clinical evidence from five previous studies, which collectively indicate that colchicine administration induces a consistent reduction in heart attack, stroke, and need for coronary revascularization. Although some trials noted an increased risk of infections requiring hospitalization, this adverse effect was not statistically significant when the results of the trials were aggregated.
In June 2023, the FDA approved colchicine for reducing cardiovascular events, the first anti-inflammatory agent approved for this kind of treatment
Beyond colchicine: The CANTOS study
The saga of using anti-inflammatory treatments to treat cardiovascular disease is extensive. In 2017, the New England Journal of Medicine published the CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study) trial. It described the use of a monoclonal antibody, canakinumab, which targets and reduced the effect of a potent pro-inflammatory blood protein that is crucial for host-defense responses to infection and injury. Higher doses of the drug reduced the likely causes of heart attack, stroke, or cardiovascular death by about 15%.
Notably, the reduction in cardiovascular events occurred without any changes in the levels of fat, including cholesterol and triglycerides, which suggests that inflammation can be addressed independently of lipid lowering.
Less promising, the trial also reported a higher rate of fatal infections in the treatment group, reflecting the immune suppression caused by the drug. Despite these somewhat promising results, the higher rate of infection prompted Novartis, the drug's developer, to abandon researching it to treat heart disease.
There was another notable benefit of treatment with canakinumab: Presumably due to the multiple effects of chronic inflammation, it demonstrated in a trial the ability to reduce fatal cancers, including lung cancer.
New imaging techniques could also help in detection. In addition to blood markers like the inexpensive (less than $30) hs-CRP test, imaging techniques such as the noninvasive CT coronary angiograms (CCTA) offer direct insights into inflammation.
A recent study using CCTA found that inflammation in the coronary arteries is strongly correlated with adverse outcomes. Particularly striking, non-obstructive coronary disease, which accounted for most adverse outcomes, was often missed by traditional tests.
Intra-arterial imaging has revealed that so-called vulnerable plaques, characterized by fatty, thin-capped structures inside the arteries, predict adverse cardiovascular events. One wonders whether the addition of an anti-inflammatory drug would help.
Call to action
Despite the availability of inexpensive and effective anti-inflammatory drugs like colchicine, these therapies remain underutilized. The proprietary form and generic versions of colchicine are equally effective. The only major limiting factor was gastrointestinal side effects, particularly diarrhea.
The development of new anti-inflammatory agents with greater efficacy and fewer side effects is critical. Unfortunately, research in this area has been limited. The persistent focus on lipid-lowering and mechanical interventions (such as the insertion of stents) to relieve atherosclerotic narrowing neglects the potential benefits of addressing inflammation directly.
The medical community needs to adopt a broader approach that includes routine detection of inflammation, the use of anti-inflammatory agents, and recognition of the significant risks associated with non-obstructive arterial disease.
The future of cardiovascular care depends on integrating these insights into a more multifaceted approach to the Number One killer of Americans.
Henry I. Miller, a physician and molecular biologist, is the Glenn Swogger Distinguished Fellow at the American Council on Science and Health. He was the founding director of the FDA's Office of Biotechnology. Find Henry on X @HenryIMiller