Cardiology’s Challenge for the 2020s: Turning the Trend on Rising Mortality

The latest numbers on cardiovascular deaths put the focus on innovative ways to point the trend line down again.

Flashback to 1964. In the aftermath of the U.S. Surgeon General’s bombshell report on the hazards of smoking, deaths from heart disease have headed consistently downward (see cdc.gov/tobacco/data_statistics). There was even speculation that cancer might overtake cardiovascular disease as the single leading cause of death in the U.S.—a title the cardiology community would have happily relinquished. Some 50 years later, all bets are off. Between 2015 and 2018, the country’s cardiovascular death rate increased 2 percent, significantly so in 26 states, with only California registering a meaningful drop. The canary in the coal mine could well have been the increases in hypertension, diabetes mellitus and obesity observable between 2000 and 2016, and the disproportionate increase of these cardiovascular risk factors in young people and women (J Am Heart Assoc 2019;8:e012178). Perhaps not so coincidentally, life expectancy in the U.S. also has declined over the past three years, the longest sustained fall-off in expected life span at birth in the past century, according to the Centers for Disease Control and Prevention (CDC; cited in The Washington Post, online Nov. 29, 2018).

“These numbers should be an eye-opener for all of us,” warns Haider Warraich, MD, a cardiologist at Brigham and Women’s Hospital in Boston and author of a new book, State of the Heart: Exploring the History, Science and Future of Cardiac Disease (St. Martin’s Press, 2019). “Heart disease is still very much with us despite all the advances we’ve made in medicines over the last few decades, and this has implications for not just heart disease but for the future of society.”

There is no question that medicine and society benefited mightily from the Golden Age of Cardiology, from the 1970s onward, when age-adjusted death rates plummeted by as much as 70 percent in some western countries.  Fueling the progress were evidence-based medications targeting low-density lipoprotein (LDL) cholesterol and high blood pressure in people at risk for heart disease, by advanced new surgical and catheter-based techniques for repairing damaged arteries, and by sweeping public health and education campaigns that touched off dramatic reductions in smoking and cholesterol levels. But lurking in the wings were two malefactors—obesity and diabetes—which many health experts believe have conspired to rain on cardiovascular medicine’s longstanding parade.

On the cusp of a new decade, is there reason to believe cardiology is entering a new era where hard-won gains of the past will be reversed, where the latest uptick in cardiovascular mortality is not a statistical blip but the new normal? Knowledgeable voices in the field told CVB the verdict is anything but discouraging. While it may be hard to replicate some of the towering successes of the past, there is a palpable sense that the traditional clinical model could be changing from episodic to continuous care, a fundamental shift that would impact everything from medications to devices to how the health system delivers and patients receive their care.

“We still have a lot of work to do, but I don’t think we’re out of the Golden Age of Cardiology,” declares Richard Kovacs, MD, president of the American College of Cardiology (ACC). “We now need to move forward with new tools like personalized care, leveraging big data and artificial intelligence (AI), and caring for and monitoring patients at a distance through technologies they are wearing or carrying. The next step is to use that evidence to help them make the kind of lifestyle changes needed to prevent cardiovascular disease from occurring in the first place.”

INNOVATION ACROSS THE SPECTRUM OF CARE 

What’s clear is that the new model of the 2020s will seek to maximize gains by addressing patient needs at both extremes of the health spectrum—from identifying and treating cardiovascular disease at individuals’ cellular levels to nipping heart disease in the bud through bold preventive strategies and campaigns focused on changing risky behavior in entire populations. In other words, turning the tide on cardiovascular mortality by treating it as a lifetime, cumulative problem vs. scrambling to put out the fires once they’ve spread. 

Advanced medical devices and innovative drugs will be crucial to that effort. For example, transcatheter aortic valve replacement (TAVR) and other minimally invasive procedures like mitral valve repair and tricuspid and pulmonary valve replacement will continue to transform the treatment landscape for structural heart disease. Mitral valve repair is projected by analysts to surpass the explosive growth of TAVR by 2023, fueled by MitraClip (Abbott) which, new three-year data presented at TCT 2019 showed, can increase life expectancy and quality of life compared to standard medical therapy (Circulation, online Sept. 29, 2019). The growth of mechanical circulatory support devices such as Abiomed’s family of Impella heart pumps and the Tandem Heart (LivaNova, UK)—used during high-risk revascularization to maintain adequate perfusion and prevent irreversible end-organ damage—also are expected to significantly improve mortality by serving as a bridge to recovery or to organ transplant.

Experts say drugs that build on the success of statins over the past 30 years will grow in importance in the decade ahead. Among the most promising, they say, are PCSK9 inhibitors, a biologic class of drugs that could further reshape the field of cholesterol lowering. Approved in 2015 by the FDA for familial hypercholesterolemia and atherosclerotic disease that needs additional LDL lowering, PCSK9 inhibitors are injectable, monoclonal antibodies that encode an enzyme that regulates LDL cholesterol levels. With the FOURIER and ODYSSEY OUTCOMES clinical trials having shown dramatic lowering of LDL and risk for heart attack and stroke, PCSK9 inhibitors (which are taken with statins) could be poised for major growth in the decade ahead (N Engl J Med 2017;376[18]:1713-22; N Engl J Med;2018;379[22]:2097-107).

The ability to pharmacologically affect PCSK9 has left scientists wondering if the next breakthrough could be editing or altering the mutation in the PCSK9 gene—first discovered in 2003 in three French families whose members had potentially lethal levels of LDL—thus conferring protection against heart disease for life. Given the advances in gene editing technologies like CRISPR, that scenario could well play out in the coming decade. The FDA, for example, approved in May 2018 an intravenous therapy to treat spinal muscular atrophy that delivers through a viral vector a fully functioning copy of a gene to replace the mutated version. In cardiology, people with high levels of lipoprotein(a) and cardiovascular disease also could be candidates for gene transfer therapy that targets LPA, the gene that encodes lipoprotein(a).

Another class of drug with potential disruptive impact for treating hyperlipidemia in the coming years is small interfering RNA. The novel approach embodied by these drugs targets the root cause rather than just the symptoms of the disease by blocking the production of specific cellular proteins, such as amyloid. RNA interference drugs include inclisiran, which in the ORION-11 trial—presented at the 2019 European Society of Cardiology conference—demonstrated significant and sustained reductions in LDL cholesterol compared to placebo. 

“Inclisiran is a potentially big step forward for cardiovascular prevention, and one of the biggest reasons is that it’s taken every six months through a single injection, much like a vaccine,” Warraich says. “We don’t have robust outcome data yet, but we know inclisiran is effective in improving lipid profiles. It only further shows that the pipeline here is rich.”

The notion that the next major battleground against atherosclerosis might not lie in reducing plasma levels of LDL cholesterol but rather in targeting vascular inflammation continues to intrigue scientists and cardiologists. For Joseph A. Hill, MD, PhD, professor and chief of cardiology at UT Southwestern Medical Center and editor-in-chief of Circulation, it’s one of two groundbreaking fronts (the other is metabolism) for cardiovascular medicine in the 2020s. “Increasingly, we’re learning that evidence- and molecular-driven targeting of inflammation will be important going forward,” he says. 

The CANTOS trial was a major step in demonstrating that powerful anti-inflammatory drugs that block key components of the inflammatory cascade involved in atherosclerotic heart disease can improve patient outcomes. Nevertheless, the results remain unconvincing to some in the field, reinforcing the need for additional studies to establish a clear linkage between inflammation and cardiovascular events (N Engl J Med 2017;377[12]:1119-31).

Determining which individuals could be helped most by inflammatory medicines is the role of biomarkers—a role that promises to grow exponentially in tandem with personalized medicine based on genetic signatures and biochemical parameters of individual patients. C-reactive protein (CRP) is an established inflammatory marker found in the blood that’s regarded by some physicians as an even better predictor of cardiovascular disease than LDL. Another blood-based biomarker making headway as a screening tool, often in conjunction with CRP, is myeloperoxidase, an enzyme in leukocytes that has been linked in numerous studies to inflammation and cardiovascular disease. Recent clinical evidence also shows that two blood biomarkers—elevated brain natriuretic peptide and elevated fibroblast growth factor-23—could potentially identify patients with atrial fibrillation, which often goes undiagnosed until a stroke has occurred. 

“The current approach to disease prediction uses a combination of demographic and other data like blood pressure to determine which individuals in a population will develop a clinical disease,” points out Richard Josephson, MD, professor of medicine at Case Western Reserve University and a member of the ACC’s Prevention Council. “Biomarkers measure the precursors to disease pathology, like microscopic deposits of calcium in the arteries or proteins in the bloodstream, to determine if a disease will develop. I think they will have a major impact going forward.”

MOBILE DEVICES & WEARABLES USHER IN A NEW ERA

Leading the way for potential transformative impact over the next decade is the convergence of digital health and analytics. This new schema will channel cardiovascular medicine in a preventive direction that’s practiced largely outside the hospital and clinic, and is powered by the countless daily decisions patients make regarding their physical activity, diet, medication adherence and self-monitoring of key health signals like blood pressure, heart rate and rhythm, and weight. Making all of this possible is the new generation of mobile devices and wearable sensors that could turn healthcare into a proactive vs. reactive enterprise. 

.“Our patients are asking for care where they are, when they want it, and that’s going to move us out of the hospital, and probably even out of our outpatient offices, to provide not just preventive care but ongoing management of chronic conditions,” says ACC President Kovacs, who is also a professor of cardiology at Indiana University School of Medicine. 

As mobile devices connected to smart phones become ever more sophisticated and dependable in monitoring and predicting atrial fibrillation, ischemia, heart failure and much more, it seems only a matter of time before hospital admissions and readmissions are reduced and, just as importantly, patients become highly engaged, well-informed self-managers of their health.

Digital patient portals will help nourish that movement, according to Steven Bailey, MD, chair of the Department of Medicine at LSU Health in Shreveport, La., and editor-in-chief of Catheterization & Cardiovascular Interventions. “Digital portals that integrate with EMR [electronic medical records] and allow patients and doctors to communicate on a regular basis will be crucial to improving care,” he says, adding that his own health system, part of Ochsner Health, uses an online patient portal with a multidisciplinary team to provide realtime, proactive coaching and therapy adjustments. “As physicians, we need to be able to understand what’s happening to patients in the home rather than just in our office, and to embrace technology to provide care to populations rather than just individual patients.”

The government, for its part, is expected to soon finalize rules that will enable patients to have their medical record information sent directly to third-party apps like Apple Health Records, a giant step it hopes will help people better manage their illnesses and understand their treatment choices.

Much of modern medicine has already migrated outside the hospital, points out Circulation Editor-in-Chief Hill, adding that the movement will intensify as devices that can detect fluid in the lungs of heart failure patients, for example, enter the mainstream. In perhaps a hint of what’s to come, researchers at Sensible Medical based in Israel have developed a vest that patients wear over their clothes that uses radar technology to scan inside the body and monitor fluid accumulation in the lungs. The information is then transmitted wirelessly to their physician. Also on the near horizon are devices strapped to the arm or forehead that can collect entire metabolic panels noninvasively, and microradar sensors that will detect heart and lung activity without the need for electrodes.

Preventing physicians from being inundated by the avalanche of patient data flowing from mobile devices and wearable sensors will be the twin buffers of artificial intelligence (AI) and machine learning. These algorithmic tools will enable cardiologists to identify with more precision patients at high risk for catastrophic cardiac events and potentially change their course by initiating preventive therapy. “It is likely that AI will become essential to the practice of clinical medicine,” asserts a Journal of the American College of Cardiology report. “… AI will drive improved patient care because physicians will be able to interpret more data in greater depth than ever before” (2018;71:2668-79). 

PREVENTIVE MEDICINE & POPULATION HEALTH AS THE NEXT FRONTIERS

A real challenge for cardiology in the coming decade will be to use AI, analytics and other emerging technologies in ways that push the profession beyond its traditional roles, into areas like preventive medicine and population health, which promise to multiply the number of people whom physicians can impact through the targeted messages they bring.

“It’s not enough to just have information—the question is how do make that information compelling enough so that people want to change their behavior,” emphasizes Warraich. “If your prevention efforts are just focused in the clinic, then you’ve missed the opportunity to reduce the amount of salt intake by people, for example, or the calorie-rich foods they consume, or countless other daily activities that seem purposefully designed to increase their risk of heart disease. If we’re going to make real progress in our field, then we need to deliver therapies on a population-wide scale.”

Warraich’s prescription for achieving this goal? For one thing, change the healthcare system to incentivize and reward physicians for heart attacks they’ve helped to avert. Also, talk to patients in a way that sensitizes them to the risks of heart disease before serious problems develop. And enlist cardiologists to become vocal advocates within communities for the fight against cardiovascular disease—much like the robust national effort around breast cancer, which significantly raises both disease awareness and millions of dollars for cancer research. 

Kovacs, too, offers his personal view that cardiology “needs to go into population health areas we’ve been less comfortable with in the past, like particulate air pollution and healthy/walkable cities. They’re not high tech,” he says, “but they could have major impact on the health of our patients.” He touts the ACC-backed national antismoking campaign that resulted in raising the minimum age for purchasing cigarettes as “the kind of thing we should be doing again to bend the [mortality] curve.

“Cardiology as a specialty has been very influential in changing treatment paradigms and using best science,” he says. “I have no doubt we can play a leading role in finding solutions to public health challenges like the obesity epidemic and access to healthy foods. What we set our minds to we accomplish.” 

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