Most of these new devices are supported by early and encouraging evidence from early phase trials for both safety and efficacy. However, the data from the Medtronic phase 3 study on renal denervation failed to show a significant reduction in the interventional group as compared with control. Importantly, it is not clear if or which of the effects of interventional therapies are sustained over time. Thus, it is clear that rigorous clinical trial data will be essential before any of the technologies can be adopted as a standard of care.
With regard to novel biopharmaceutical entities for hypertension treatment, as discussed earlier, pharmaceutical companies have not focused substantial attention to the development of new hypertension drugs. According to Pharmaceutical Research and Manufacturers of America, in , biopharmaceutical research companies were developing medicines for cardiovascular disease—14 of which were for hypertension; in comparison, 42 were for heart failure.
Finally, many successful drugs and devices are likely to be directed toward a relatively small minority of the hypertensive population because of costs. With the promise of precision medicine, there remains the potential of developing safer and more effective drugs for specific populations. Furthermore, biotechnology is advancing at rapid speed and novel approaches are being discovered that can change the approach to treatment from traditional drugs and devices. Indeed, new technologies hold promise for the development of breakthrough hypertension treatments.
Some of these technologies may exert long-lasting effects, which may make treatment simpler and efficient. RNAi is a naturally occurring regulatory mechanism to silence gene expression.
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Already, RNAi has been used successfully for cardiovascular research and is being evaluated for human therapy. PCSK9, an enzyme expressed and secreted into the bloodstream predominantly by the liver, plays an important role in cholesterol metabolism and also seems to modulate hypertension.
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In phase 2 clinical trial, RNAi has been shown to significantly reduce levels of PCSK9 and low-density lipoprotein cholesterol in humans for 6 months of follow-up. As for hypertension, example of an important therapeutic target is angiotensinogen, the sole substrate of the renin-angiotensin system. Studies have demonstrated a relationship between angiotensinogen and hypertension, suggesting that decreased production of angiotensinogen may be a useful target for novel hypertension drugs. Indeed, researchers have already shown that siRNA can be used to reduce angiotensinogen production in the liver of rats, which resulted in decreased plasma angiotensinogen and decreased blood pressure in both hypertensive and normotensive rats.
These results were sustained suggesting that this treatment would not need to be administered daily. Another promising strategy is the use of genome editing to target genes for human hypertension therapy. Wang et al 45 showed that single infusions in nonhuman primates of adeno-associated virus vector expressing an engineered meganuclease targeting PCSK9 results in dose-dependent disruption of PCSK9 in liver, as well as a stable reduction in circulating PCSK9 and serum cholesterol.
These results suggest that PCSK9-targeting genome-editing therapies could be effective in humans. However, further research will be needed to prevent off-target effects, unwanted immune effects, and validate the efficacy of the technology in clinical trials.
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In the future, genome editing using CRISPR-Cas9 holds promise for curing genetic hypertension, and in targeting angiotensinogen and other targets, resulting in possible long-term control of essential hypertension. Hypertension is associated with complications such as thrombotic and hemorrhagic stroke, retinopathy, acute myocardial infarction and heart failure, proteinuria and renal failure, and atherosclerotic vascular disease including stenoses and aneurysms.
The heart and brain have limited capacity for regeneration after damage. New regenerative medicine strategies including stem cell therapy, cellular reprogramming, and tissue engineering hold promise for tissue regeneration and restoration of function after myocardial infarction and stroke. One approach is stem cell therapy, which aims to reduce cardiac degeneration by regenerating cardiomyocytes. Stem cells are undifferentiated cells theoretically capable of renewing themselves indefinitely under appropriate conditions through mitotic cell division, and can maintain, generate, or replace damaged tissue by differentiating into specialized cell types.
Researchers are studying different types of stem cells to repair damaged heart muscle, including embryonic stem cells, adult stem cells, and induced pluripotent stem cells. Different strategies have been developed to enhance cardiac regeneration. First is the use of cell therapy involving the injection of adult progenitor cells from bone marrow, adipose tissue, and myocardium into ischemic hearts in human clinical trials.
The studies have yielded unimpressive results. Investigators have also attempted the use of mesenchymal stem cells or cardiospheres, but the results too have been disappointing. Studies have demonstrated that the injected cells engraft poorly and exhibit poor viability after transplantation. The use of induced pluripotent stem cell holds promise but are still in the experimental stage. Given the challenges of cell therapy approaches, scientists have recently recognized the potential to turn almost any somatic cell into any other cell type using direct reprogramming approach.
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We and others have directed the efforts reprogramming directly fibroblasts to cardiomyocytes without passing through a stem cell state. Already, direct reprogramming has allowed investigators to turn cardiac fibroblasts into cardiac myocytes. Another molecular approach is to induce existing cardiomyocytes to enter cell cycle and proliferate.
Recent studies suggest that stimulation of cardiomyocyte cell cycle regulators such as CDK1 [cyclin-dependent kinase 1], CDK4, cyclin B1, and cyclin D1 hold promise for transforming the postmitotic cell into an actively dividing cell. Another approach to cardiac regeneration is the tissue engineering by engrafting tissue patches by seeding cardiac progenitors or stem cells into polymer or extracellular matrix scaffolds and gels; such tissues are then affixed and integrated into the damaged heart.
This approach may help overcome current challenges in cell-based treatment—the presence of prosurvival factors in engineered tissue patches can potentially improve cell retention and engraftment. Other advances in biotechnology and sciences may play future roles in hypertension research and therapy.
These include optogenetics, 3-dimensional printing, synthetic biology to name a few. For example, optogenetics, a technique that can be used to control the activity of neurons genetically engineered to express a light-sensitive opsin channel-rodopsin with light, which allows scientists to turn neurons on or off using light, could be used to better understand the neural circuit of BP control.
As noted earlier, blood pressure regulation is complex, shaped by the interaction of multiple physiological systems, as well as the environment and genes. Other breakthroughs and emerging areas of science hold promise for advancing our understanding of the factors shaping hypertension and thereby transforming hypertension treatment; these advances include epigenetics, nutrigenomics, and better understanding of the microbiome.
Advances in epigenetics could shed new insights into the environmental factors affecting hypertension. Likewise, the emerging field of nutrigenomics will study the genomic basis of dietary responses and research on the microbiome could further our understanding of the role of nutrition and the gut microbiota in hypertension.
edutoursport.com/libraries/2020-11-20/2664.php Studies have shown that alterations in gut microbiota composition are associated with the chronic, multifactorial conditions such as obesity, diabetes mellitus, and cardiovascular disease. Recent studies in rats and humans have also suggested a link between alterations in gut microbiota and essential hypertension.
Achieving better hypertension control would require the effective development of implementation science: better access to diagnosis and effective treatment combined with improvement in treatment quality and outcomes—standardization of treatment protocols, a better understanding of what works and what does not, and dissemination of best practices across a range of healthcare settings.
Recently, there has been a major push to transform healthcare delivery with a focus on achieving better integrated, coordinated, high-value care. It is recognized that care delivery is fragmented, the components are not aligned, and the information is siloed.
At the same time, the growing burden of chronic disease elevates the need for better healthcare coordination and integration across different care setting and providers. For hypertension in particular, high-quality care requires patient awareness of preventive care, regular blood pressure screening, effective communication between healthcare providers and patients, involvement of other clinical specialties, and active self-management by patients. Importantly, studies indicate that team-based, coordinated care and shared decision-making are associated with improved outcomes and reduced costs for the treatment of hypertension.
At the global level, achieving real transformation will require a concerted global effort. The GSHT draws on lessons learned from the successful, mass scale-up of HIV and tuberculosis treatment in low- and middle-income countries. The GSHT Project is based on the following 4 principles: 1 agreement on standardized treatment approaches, 2 recognition that all members of the healthcare team—primary care workers, community volunteers, pharmacists, nurses, and others—are critical to controlling blood pressure, 3 elimination of cost barriers to treatment and simplification of treatment regimens, 4 ensure accountability.
Results of the GSHT Project were promising, resulting in increases in blood pressure control rates, development of registries for improved care, and improved prescribing practices. Finally, achieving global BP control will require a population health strategy that centers on a multisectoral, convergent approach. Population health has been defined as the health outcomes of a group of individuals, including the distribution of such outcomes within the group.
A number of different factors work in concert to influence individual and population health outcomes—from genetics to health care to social, behavioral, and environmental factors. Improving population health cannot be achieved without attention to these myriad factors. As a result, success in advancing population health will depend on a cross-sector effort and partnerships between health providers, communities, policy makers, business, and more. Progress in population health cannot depend on a single sector. Instead, it requires convergence of health sciences and across all policies—educational, social services, economic development, environmental, nutrition and food marketing, urban design, and health policies.
Importantly, effective strategy will include incorporating cultural, social, and behavioral considerations. Population health requires the development of population science, incorporating the new sciences such as data science, precision public health, health equity, and the convergence of these fields. Data sharing as well as a systems approach that measures and identifies accountability for population health outcomes will be critical. An important step is to identify the most cost-effective way to detect and treat as many as possible. Hypertension is one of the most significant public health challenges and the biggest contributor to the global burden of disease.
Improving health outcomes worldwide will require concerted global action to address the burden of hypertension. The field of hypertension needs transformation Figure. Its future will depend on the successful convergence of digital data and biotechnological and biomedical sciences coupled with their implementation in healthcare delivery with new models of delivery and the effective strategy for population health. Hypertension: need for transformation.
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To control or eliminate hypertension, there is a need for system-wide transformation in research and clinical care as well as the convergence of disciplines. This figure highlights the 5 key areas where progress is needed to advance hypertension control and treatment. Achieving maximum benefit will require convergence of these areas.
Dzau reports having served as a director for Medtronic Inc until July and as a director for Alnylam Pharmaceuticals July In addition, Dr. Home Hypertension Vol. View PDF. Tools Add to favorites Download citations Track citations Permissions. Jump to. Future of Hypertension The Need for Transformation. Victor J. Dzau Victor J.
Dzau Correspondence to Victor J. Celynne A. Balatbat Celynne A.
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