Cardiovascular disease (CVD) will become the leading cause of death worldwide. Western lifestyles do not promote healthy living, and once social inequalities are combined with economic factors and population growth, the results will be devastating. Poor nutritional habits, obesity and related conditions (e.g., diabetes, hypertension, lack of exercise, aging) are all high risk factors for CVD, and they are becoming more prevalent. As people in low- and middle-income countries also begin to adapt to Western lifestyles, their risk for CVD increases dramatically, and the rate of increase continues to accelerate with industrialization, urbanization, and globalization. In this Outlook article, I list the 10 most promising CVD treatments and interventions. Continuing to deepen our understanding of CVD will help us make the leap from treating the complex disease of CVD to enhancing global cardiovascular health in the next decade.
I. Myocardial protection in ST-segment elevation myocardial infarction
Percutaneous coronary intervention (PCI) is the primary treatment for patients with ST-segment elevation myocardial infarction (STEMI), but ischemia-reperfusion injury may occur after the procedure, which can cause myocardial infarction (MI) again. In the case of ischemic injury, the process from the onset of symptoms to reperfusion is critical (“time is myocardium”), and the risk of recurrent MI can only be reduced through collaboration between community-based medical programs and emergency medical and hospital-based lifesaving care. Reperfusion injury is the next therapeutic challenge that will be encountered, and the strategy mentioned above (PCI) alone is no longer useful; a broad-spectrum prevention of ischemia-reperfusion injury with multiple prophylactic measures targeting multiple targets is needed prior to PCI. By this approach, the symptoms of ischemia-reperfusion injury in STEMI patients will be alleviated.
II. Treatment strategies for stable complex coronary artery disease
The higher the complexity of stable complex coronary artery disease (CAD) patients, the better the prognosis for coronary artery bypass graft (CABG) revascularization compared with percutaneous coronary intervention (PCI) revascularization. As complexity decreases, PCI guided by flow reserve fraction (FFR) is a more reasonable treatment strategy, although FFR can only quantify local ischemia due to epicardial stenosis. Non-invasive methods to assess coronary flow include more advanced computed tomography (CT), magnetic resonance imaging (MRI), and positron emission computed tomography (PET) techniques, which will increasingly be used to determine the quantification of epicardial and microvascular ischemia (Figure 2). For uncomplicated CAD, the use of optimized drug therapy (OMT) alone in the initial phase is a more general strategy, especially in asymptomatic elderly patients. Not only that, but OMT is also extremely important in patients who have undergone revascularization.
Application of polypharmacy tablets to improve patient adherence
Our health care system is becoming increasingly complex and expensive, so we should focus on how to develop effective mechanisms to promote better patient adherence to medical advice. Multi-acting tablets for secondary prevention may be a good option. Clinical trials of the efficacy of multi-effect tablets have been conducted in high-, middle-, and low-income countries worldwide.
IV. Interventional Treatment of Heart Valve Disease
There are three main pitfalls of transcatheter aortic valve replacement (TAVR): (1) the high incidence of stroke and asymptomatic stroke associated with TAVR, which needs to be reduced by clinical studies of placed cerebral protection devices; (2) the increased mortality of patients with perivalvular leaks (rating ≥2+) associated with TAVR if combined with other complications; and (3) the need to strengthen clinical trials to determine whether the indications for TAVR can be further expanded, such that it should not include patients with moderate aortic stenosis (PARTNER II, SURTAVI trials), patients with degeneration after implantation of a bioprosthetic valve, and patients with selected aortic regurgitation.
Despite these issues, modified transcatheter mitral valve replacement (TMVR), which can be used as a palliative treatment strategy, has been successful in treating patients with clinically significant mitral regurgitation. In addition, the COAPT clinical trial and the RESHAPE-HF clinical trial evaluated the MitraClip system for the treatment of patients with symptomatic, functional mitral regurgitation and left ventricular insufficiency at high surgical risk.
V. Pathogenesis and management of atrial fibrillation
The classical pharmacological approach to the treatment of atrial fibrillation is to control the heart rate or rhythm and to surgically slow the transition from the coagulation state to the subsequent pathological process, such as catheter radiofrequency ablation and percutaneous left auricular occlusion, which are used early in atrial fibrillation.
The search for the mechanisms that cause atrial fibrillation or stroke is an immediate challenge – a process that will involve using cutting-edge “anatomical” techniques and imaging to identify the causative genes, molecular mechanisms, protein structures, and dynamic processes of disease. In my opinion, increased investment in this area of research will advance the improvement of prevention and treatment of atrial fibrillation.
VI. Aggressive hypertension treatment
Hypertension is the most significant risk factor for cardiovascular disease in today’s society, so we need to address hypertension in a comprehensive manner, including comprehensive data registries, sharing of functional evaluation indicators, routine blood pressure measurement, and universal access to the benefits of combination medications against hypertension. While eligibility criteria and guidelines for antihypertension will continue to be debated, it is incumbent upon governments and food industry producers to take on the burden of reducing salt intake in food for all.
In my opinion, three questions deserve particular attention in the coming years: (1) What exactly is the ideal blood pressure for people with specific diseases or for a particular ethnic group? By what socially driven strategy can this ideal blood pressure be maintained for the entire population? (2) What exactly is the role of salt in hypertension? How urgent is the need for salt reduction programs? (3) 10% of patients diagnosed with hypertension are refractory to hypertension, and the challenge is to identify those patients who respond to renal sympathetic ablation therapy.
VII. Cholesterol and diabetes
Statins are the first-line agents for lowering low-density lipoprotein cholesterol (LDL-C) levels, but there are still a large number of patients who are unable to tolerate statins. In my opinion, receiving subcutaneous injections of PCSK9 inhibitors every two weeks or once a month may be a boon for three groups of patients: those who cannot tolerate statins, those who experience severe side effects while taking statins, or those who cannot achieve LDL-C target levels with statin therapy. For patients with hereditary hypercholesterolemia, PCSK9 can be a “magic bullet”.
Ongoing research suggests that surgical procedures for the treatment of obesity are effective in curbing the prevalence of obesity and diabetes and can help reduce the probability of clinical events in patients with obesity and diabetes.
VIII. Heart-brain interactions
Given the strong relationship between increasingly prominent cardiovascular risk factors, cardiovascular disease, dementia and aging, finding effective strategies to promote the health of older adults, preserve their ability to work and be able to screen for future risk factors for developing dementia will be one of the most important challenges facing public health. In the field of Alzheimer’s disease screening, blood tests, eye exams or odor tests are technologies that are currently being developed and have great potential to intervene in the natural regression of the disease. Nevertheless, improving survival and quality of life in older adults can only be achieved by changing those adverse environmental and behavioral factors from a young age, preferably from childhood onwards.
IX. Promoting cardiovascular health
Successfully reducing the societal burden of CVD will require a sustained, multi-year concerted effort by many parties, including key stakeholders in CVD, related chronic diseases, other global health domains, global, national, and local organizations, and more. Actions by major funding agencies, such as the Gates Foundation, have been working to limit the spread of infectious diseases and provide financial support to support global anti-smoking programs. In my view, support from these institutions will continue to grow over the next decade.
X. Cell and Gene Therapy
Although the technologies associated with cell and gene therapies have not yet reached the human trial stage, in my view, the “third generation” cell therapies that have emerged – those involving the delivery of targeted biological agents to specific sites in the body to stimulate the growth of endogenous cardiovascular in situ stem cells or progenitor cell growth, rather than by direct injection or use of cells for treatment (Figure 8). Another approach is to harness the potential of human pluripotent stem cells and induce their differentiation into functional cardiomyocytes, thus providing a platform for regenerative medicine, disease models, tissue engineering and drug development, screening and toxicity studies. In conclusion, the progress made so far has not been as rapid or smooth as initially envisioned, but we should remain cautiously optimistic about the development of the field of cardiovascular gene and cell therapy.