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 Table of Contents  
VIEW POINT
Year : 2019  |  Volume : 8  |  Issue : 1  |  Page : 25-33

Cardiometabolic risks in India


Department of Laboratory Medicine and Pathology, Lillehei Heart Institute, University of Minnesota, Minnesota, USA; Founder CEO, South Asian Society on Atherosclerosis and Thrombosis, Division of Clinical and Preventive Cardiology, Medanta Hospitals, Gurugram, New Delhi, India

Date of Web Publication11-Feb-2019

Correspondence Address:
Gundu H R Rao
12500 Park Potomac Ave, Unit 306 N, Potomac, MD

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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JCPC.JCPC_39_18

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  Abstract 


In a recent article in this journal, we discussed diabetes and Cardiovascular disease (CVD) risks in Indians living abroad. The article was written to complement the information that was published by an elite group of the American Heart Association (AHA);-”the council members of the various subcommittees.” In the journal Circulation, AHA published a scientific statement about the CVD risk of Indians living in the USA. In the June issue of the journal PLoS Medicine, The George Institute for Global Health (GIGH), Sydney, Australia, with collaborators from; Harvard T. H. Chan School of Public Health, USA; Department of Economics, University of Gottingen, Heidelberg University, Germany; School of Public Health Johannesburg, South Africa; King's College London, UK, Indian Institute of Public Health, and Public Health Foundation of India, have published a one of a kind article on, “Geographic and sociodemographic variation of CVD disease risk in India: A cross-sectional study of 797,540 adults.” I am writing this article, as a complement to the topic reviewed by the George Institutes of Global Health and associates and other expert groups. The specific objectives of this academic exercise by the GIGH were, to determine how the CVD risk- and the factors that determine risk varies among states in India, by rural-urban location, and by individual-level sociodemographic characteristics. Rajeev Gupta and associates from Jaipur, under the aegis of South Asian Society on Atherosclerosis and Thrombosis, did a study in 2012, on “Regional variations in CVD risk in India: India heart watch.” The researchers found a wide regional variation in CVD mortality. They concluded, “that although no nationwide study of risk factors exists, there were significant state-level and rural-urban level differences in major CVD risk factors such as smoking, obesity, central adiposity, hypertension, hypercholesterolemia, and diabetes. They also stressed the need for uniform protocols, to assess the regional differences. Whereas, the report by the GIGH Collaborators group, did pooled analysis of CVD risk for 797,540 adults across India, and identified important variation in risk among individuals living in different States. According to them, CVD risk was the highest in the northern (Himachal Pradesh, Uttarakhand), northeastern (West Bengal, Nagaland, Manipur, and Mizoram), and Southern States (Kerala, Andhra Pradesh) of India. CVD risk was found to be higher in urban areas, that too among males, while mean body mass index was higher among wealthy, blood glucose, high systolic blood pressure was common in poor people of middle and older age. We have access to data from three important studies, related to the variation of CVD risk in Indians living in India, as well as abroad. It is high time, that we use these data to develop guidelines, guidance statements, novel clinical studies for validating safety and efficacy of complementary therapies for early risk factors such as oxidative stress, inflammation, and endothelial dysfunction, put together integrated noninvasive diagnostic platforms for risk assessment, risk prediction, and reduction or reversal of metabolic diseases. Having said that, I would like to emphasize the need for a national platform, to address the issues related to this very important public health problem, and to coordinate the prevention strategies.

Keywords: Arterial stiffness, atherosclerosis, endothelial dysfunction


How to cite this article:
R Rao GH. Cardiometabolic risks in India. J Clin Prev Cardiol 2019;8:25-33

How to cite this URL:
R Rao GH. Cardiometabolic risks in India. J Clin Prev Cardiol [serial online] 2019 [cited 2019 Dec 16];8:25-33. Available from: http://www.jcpconline.org/text.asp?2019/8/1/25/252012




  Introduction Top


Four major comprehensive reports have been published recently, by national and international professional organizations, American Heart Association (AHA), The Georgia Institute for Global Health (GIGH), Million Death Study Collaborators (MDSC), and Public Health Foundation of India (PHFI).[1],[2],[3],[4] In the study reported by the George Institute for Global Health (GIGH), researchers used data from two large surveys carried out between 2012 and 2014, which included a sample of 797,540 adults aged between 30 and 74 years across India. The main outcome was the predicted 10-year risk of a cardiovascular (CVD) event as calculated with the Framingham Risk Score. In addition, the Harvard-NHANES, Globorisk, and the World Health Organization (WHO)-International Society of Hypertension risk scores were also used for secondary analysis. They found that patterns of variation in CVD risk among the Indian the population were similar across all four risk scoring systems. This study was timely, as there has been no large-scale population-based study, which has examined how CVD risk varies among such a diversified Indian population. Furthermore, understanding the variability in different population groups within the country could provide useful information for targeted intervention for those who need most. Having said that, we should examine as to how this knowledge about the variability in CVD risks in different geographic and socioeconomic groups, will improve the way we screen the population for various metabolic risks, develop novel complementary therapies to manage the observed risks, and reduce the incidence of these chronic metabolic diseases. Sounds great and doable. The big question is who is going to do this? Since the severity of the CVD risks is regional, is it the responsibility of the State Government or the Central Government? Given this dilemma, way back in 2005, we published an article expressing the immediate need for a national platform to address the issues related to CVDs and development of action plans, for primary prevention and integrated treatment of heart disease in India.[5] After more than a decade, things have not changed very much. We do not have a national platform in India, to address the issues related to metabolic diseases, and we do not have any national level action plans to monitor, manage or reduce, the epidemic of these diseases. In this overview, we have just changed the title to include metabolic risks, instead of limiting to just CVD risks, and expressed our point of view on this topic.

Now let us briefly discuss some of the options we have, to address these issues. We have tried many a times in the past, to convince the Government of India, the importance of developing a national platform for addressing issues related to the metabolic diseases such as hypertension, excess weight, obesity, metabolic syndrome, type-2 diabetes, and vascular diseases without any success. As the founder CEO of SASAT, I have written letters to the Ex-Presidents of India, and to various Ministers of Health and Family Welfare. I had arranged an hour-long discussion with Hon. President Kalam (https://www. youtube. com/watch? v = wzKMwcoqjW0) during our SASAT conference at Hyderabad in 2002. I had written to the Ex-Health Minister Gulam Nabi Azad during his tenure, requesting his help to develop a national platform. As recently as last year, (2017). I had discussions with Union Minister Ashwini Kumar Choubey (at AIIMS, Patna), about the need for a national platform to address the issues of cardiometabolic diseases in India. I am still trying to get an audience with our Prime Minister Hon. Narendra Modi. One may ask why we need such a platform? My simple answer will be, without such a platform, it will be hard to integrate all the affordable healthcare initiatives. For instance, the limited success we have in managing HIV/AIDS in India is related to the activities of the National Aids Control Organization. On the other hand, if you look at the workings of NCD alliance in India, and read the WHO's report for 2017, it becomes evident that even the four modifiable risks that they aim (tobacco, diet, physical activity, and alcohol consumption) to control and build capacity, to reduce and treat NCDs, shows that progress around the world has been uneven and insufficient.

The sheer size and huge population of India, along with its diversity, changes in diet and lifestyles, mean that addressing issues like the management of NCDs is an enormous challenge. According to the WHO report, India is the first country in the world to develop national NCD targets aligned, to the WHO voluntary Global Targets. Having said that, I would remind the readers that Ministry of Health has suggested spending of 4.2% of the GDP, to develop National Multisectoral Plan of action, yet, the total Government expenditure for healthcare is little over 1%, which is grossly insufficient to support any effective NCD response. For instance, the ministry has supposed to have started a massive free door-to-door screening program for early detection of cancers, heart disease, and diabetes and aims to cover 200 districts by 2018. This represents less than third of the total number of districts in India. To fully redress the situation, lot more needs to be done to achieve universal health care and address the issues related to NCDs. Of course, the Government should ensure that all policies are conducive to health; all essential medicines are available at all levels; trained staff are equitably distributed; all interventions are evidence-based, effective, and safe; primary care is organized to equitable access to services, and the care services are people (patient) centric. In an article like this, it is rather difficult to cover how a Government should provide affordable health care to its subjects, readers are urged to refer to original articles, reviews, and monographs in this topic.[6],[7],[8],[9],[10]

In the meantime, all of the above mentioned metabolic diseases have gained the status of epidemics or “tsunamis.” According to the Global Burden of Disease report (2017), obesity has doubled in the last three decades and type-2 diabetes by 4-fold. Just to give readers an idea, as to what has happened in the last three decades, I will provide my own personal experience. When I visited Beijing, China, in the early 1990s, I could see bicycles everywhere, and the incidence of diabetes was at its lowest tide. In the last three decades, bicycles have totally disappeared in Beijing, and diabetes has increased by 17-fold. Framingham heart studies in the USA, have described the modifiable risk factors that promote the development of CVDs. Several clinical trials have demonstrated that management of modifiable risk factors, significantly reduce CVD-related mortality and morbidity. Indeed, just robust management of lifestyle has been shown to drastically reduce the development of acute vascular events.[11],[12] Having said that, I would like to remind the readers that in spite of these observations, CVD has remained the number one killer worldwide, for the past 100 years. What does this mean? Where did we go wrong? Are we barking up at the wrong tree, when it comes to risk factors? These are some of the important questions that need answers. Considering this awkward situation, we have developed a hypothesis which has been advocated by some of the top international scientific leaders.

In a recent article in the Journal of American College of Cardiology, Professor Valentin Fuster and associates at the Mount Sinai Hospital, New York, reported their findings of a study, which demonstrated that after age and male sex, low-density lipoprotein (LDL)-cholesterol was the main predictor for the presence of the atherosclerotic plaques, suggesting a significant correlation between LDL-cholesterol and levels of atherosclerosis.[13] Using the latest non-invasive imaging technology, they demonstrated that atherosclerotic plaques were present in 50% of the middle-aged individuals with no classical CVD risk factors. Furthermore, these individuals also had hardened arteries, suggesting the presence of altered morphology and dysfunction of the vessel walls. They concluded that, “these findings could help improve CVD risk prevention in the general population, even before the appearance of conventional risk factors, an example of primordial prevention.” In spite of the seminal findings of this important study, we find no revised guidelines recommending these procedures for early detection of vascular diseases. Studies from the University of Minnesota, under the leadership of Professor Jay N. Cohn also have demonstrated, that endothelial dysfunction (ED) and stiffening of the arteries are the earliest signs of vascular injury.[14] In fact, Professor Cohn has expressed in his views quite often, his optimism in the following way, “if there is no ED, then there are no atherosclerotic vascular diseases.”

Given these observations heralding the importance of monitoring hardening of the arteries, let us discuss some of the methodologies used for the early diagnosis of this altered vascular condition. There are various methodologies available for monitoring ED. At the University of Minnesota, clinicians and researchers use CV-Profiler, developed by the Hypertension diagnostics [Figure 1] of Minnesota. In India, researchers have used Periscope, developed by Genesis Medical Systems of Hyderabad, India. Dr. Ravi Kasliwal and associates at Medanta Hospitals, New Delhi, India, have used this system to monitor prehypertensives.[15] Dr. Albert Maarek of Miami, Florida has put together a novel noninvasive diagnostic platform, which develops information on a verity of cardiometabolic risks, including ED.[16],[17] All of these devices are useful at clinics, for monitoring flow dynamics and arterial stiffness. Yet they are not cost-effective and are not easy to use, for conducting population-based clinical studies.
Figure 1: Cardiovascular Profiler (CV-Profiler), Hypertension Diagnostics Inc., Minneapolis, Minnesota. Data on arterial stiffness (endothelial dysfunction) is obtained by measuring small artery elasticity and a large artery elasticity

Click here to view


Manufacturers of this device (CV-Profiler) claim, that the method measures noninvasively, the elasticity of large and small arteries providing an early assessment of CVD disease. Additional claims include that the method is suitable for the early detection of atherosclerotic disease, for clinically evaluating the efficacy of prescribed lifestyle modifications and medications, monitoring patients with hypertension, identifying patients with abnormal arterial function indicative of ED, and targeting those patients in need of aggressive medical intervention.

Periscope-pulse waveform monitor system developed in Hyderabad India, unlike the high-density lipoprotein Diagnostics' device, develops data from four different pulse points. As shown in [Figure 2], pulse wave velocity (PWV) is measured both at brachial pulse points and ankle pulse points.
Figure 2: Pulse wave velocity monitoring. Periscope-pulse waveform analysis methodology uses large artery elastic (C1: Capacitative compliance) and small artery elasticity (C2: Reflective compliance) to compute endothelial dysfunction. A low C2-small artery elasticity is an indication of endothelial dysfunction, vascular disease or progression in vascular disease, a predictor of cardiovascular events

Click here to view


On the other hand, LD-technologies uses a pulse oximeter and monitors pulse waveforms at the fingertips. A typical waveform, spectral analysis data, and the plethysmography analysis are presented in [Figure 3]. For additional details of this methodology, please refer our earlier publications.[16],[17]
Figure 3: TM-Oxi System: LD Technologies, Miami, Florida. (Courtesy: Dr. Albert Maarek). The figure shows analysis of pulse wave forms. The data collected on pulse waveforms are subjected to photoplethysmography analysis to measure endothelial dysfunction

Click here to view


PWV is the speed at which the blood pressure pulse travels from the heart to the peripheral artery after blood rushes out during contraction. It is mainly used to evaluate the stiffness of the artery wall. As elasticity or compliance of artery decreases, the capacity of the artery to expand (dilate) also decreases. This leads to an increase in blood flow (pulse wave) velocity. PWV increases with the stiffness of the arteries. In addition to the diagnostic systems discussed earlier in this article, there are two other Food and Drug Administration (FDA, USA) approved systems in common use, the AtCor SphygmoCor XCEL (atcormedical.com) and Complior (www.complior.com), which differ with respect to their sensor technology, and the algorithms used for calculating the pulse propagation time. The SphygmoCor device uses an arterial tonometer, for recording pressure waveforms. Propagation time is measured from the foot of the carotid waveform to that of the femoral waveform using sequential recordings, referenced to the ECG. In the Complior system, carotid and femoral waveforms are recorded simultaneously, using mechanotransducers (https://www.ncbi.nlm.nih.gov/pubmed/24509122).

As mentioned earlier, these methodologies are quite useful for monitoring arterial stiffness or ED at the clinics. What we need is a hand-held, cost-effective device, that can monitor the blood flow dynamics and relay the data to smart, analytical platforms. The fact that we could monitor pulse waveforms using the TM-Oxi system, which uses oximeter and blood pressure monitors, encourages that development of a hand-held ED-monitor is feasible. We are also exploring the idea of developing modified ultrasound apps, which can measure flow dynamics in peripheral arteries and veins. Yet another possibility we are exploring, is the use of piezoelectric flexible pressure sensors, to obtain data on PWV at various pulse points. These pressure sensors could be applied at various pulse points using wearable bands. The data generated at pulse points could be relayed to smart, analytical platforms for further processing. Successful development of such cost-effective, hand-held, diagnostic devices will facilitate screening for early changes in the vascular physiology and function at the population level.

When considering various methodologies to assess the dynamics of blood flow and alterations in the pulse wave forms, one should validate, whether all these methodologies are monitoring the same vascular function, that is ED? A recent review by US Preventive Services Task Force (USPTF) found inadequate evidence to support the hypothesis, that treatment decisions guided by ankle-brachial index (ABI), C-reactive protein (CRP), or Coronary artery calcium (CAC) score test results, when added to existing CVD risk assessment models, lead to reduced incidence of CVD events or mortality.[18] Of the three tests referred to in these studies, only ABI represents an earlier risk, the other two, hsCRP and CAC are later events in the disease progression. Yet the inclusion of these studies for risk score calculation is definitely an improvement, as it indicates a willingness to include nontraditional risk factors for risk calculations. Continuing in the same lines of thinking, we would like to suggest the inclusion of a couple of other early risk factors such as oxidative stress, and inflammation, in the development of preventive strategies. We already have discussed various methodologies for monitoring ED and let us briefly discuss the other two early markers of altered metabolism.

There is considerable evidence, to suggest an important role for the overproduction of reactive oxygen species (ROS), in the pathogenesis of vascular diseases. These ROS can be released from nicotinamide adenine dinucleotide oxidase, xanthine oxidase, lipoxygenase, mitochondria or the uncoupling of nitric oxide synthases.[19],[20] The transcription factor nuclear factor erythroid 2–related factor 2 (Nrf2) for instance, a master regulator of detoxification, anti-oxidant, anti-inflammatory, and other cytoprotective mechanisms, is raised by health promoting factors. This transcription factor activates the transcription of over 500 genes (so-called survival genes) in the human genome, most of which have cytoprotective functions. The most healthful diets such as the Mediterranean and Okinawa are rich in Nrf2 raising nutrients. Recent studies however, have demonstrated that induction of Nrf2 and Ho-1 expression by Protandim (a mixture of five phytochemicals; Ashwagandha, Indian Bacopa, Indian Green Tea, China Milk Thistle and China Turmeric) is associated with a reduction in oxidative stress and fibrosis, preservation of the right ventricular (RV) microcirculation and RV function.[21] Studies by the pioneer scientist, professor Joe M McCord, and associates on the effect of Protandim on various pathways have shown, significant modulation by Protandim not only of pathways involving antioxidant enzymes but also those related to colon cancer, CVD disease, and Alzheimer's disease.[22],[23] We suggest that it is time that we develop similar complementary therapies using various herbal products and simple clinical studies (not clinical trials) to validate the safety and efficacy of such indigenous formulations.

Inflammatory response of the blood vessels involve complex signaling between inflammatory cells (neutrophils, lymphocytes, monocytes, and macrophages), endothelial cells, vascular smooth muscle cells, and extracellular matrix components.[24],[25],[26],[27],[28] Persistent increase in cytokines, seem to be associated with vascular dysfunction, and vascular diseases such as subclinical atherosclerosis, ED, and hypertension.[25] Furthermore, researchers at the Children's National Memorial Hospital in Washington DC, have demonstrated yet another mechanism, by which adipose tissue can induce an inflammatory response. Their studies have shown that adipocyte-derived exosomes (micro RNAs) contain mediators, capable of activating end-organ inflammatory and fibrotic signaling pathways.[28] Association between hyperglycemia and inflammation, in the initiation and promotion of vascular complications, is well established.[24] Obesity and oxidative stress, also results in chronic inflammation of the vessels, as demonstrated by elevated CRP. Studies from Minnesota, have demonstrated that in children with excess weight, just 8 weeks of moderate exercise, improved fitness, endothelial function and lowered HDL-cholesterol.[25] As we have discussed in our earlier articles on this topic, inflammation is associated with all the major metabolic risks, including in the precipitation of acute vascular events. Professor Paul Ridker, Director of the Center for CVD Disease Prevention, Brigham and Women's Hospital, Boston, Mass, has demonstrated for the first time that lowering the inflammation by using a monoclonal antibody, independent of cholesterol, reduces CVD risk.[26] In a separate study, researchers from Perelman School of Medicine, at the University of Pennsylvania, in collaboration with National Heart, Lung, and Blood Institute, have demonstrated that Ustekinumab, a monoclonal antibody used to treat skin conditions, can also improve aortic inflammation.[29] We are not trying to suggest the use of these antibodies but advocating the development of indigenous complementary therapies, aimed at reducing chronic inflammation.


  Discussions Top


In a relatively short period, we have seen the publication of four comprehensive reports on the CVD risks in Indians living in India and abroad.[1],[3],[6],[5] The seminal articles recently published by the American Heart Association (AHA) (Scientific Statement), and by the GIGH, Australia, the Public Health Foundation of India (PHFI), and the Million Death Study Collaborators (MDSC), have done a great favor for us. These are comprehensive reviews, on the excess risk of CVDs in Indians, living in India and abroad. AHA statement, which I have briefly reviewed in one of the recent issues of this journal (JCPC-2018), provides useful information about the CVD risks as well as a ten-point guidance statement, about what one should know about these risks, and how to manage these risks.[3] Whereas, the report by the GIGH collaborators, provides us with information about the CVD risk in the Indian population, living in the various States of India. The article by Prabhakaran and associates from PHFI, gives us an overview of CVD problem in India, with an Indian Perspective. Whereas the MDSC, claims that, “this is the first nationally representative study to measure CVD mortality in India, providing the complete picture of longitudinal trends to date.” What are we going to do with this information? All the four articles conclude that CVDs are great healthcare and economic burden. Yet till date, there has not been any large-scale-population-based study that examines how CVD risk varies among individuals residing in the different States of India as well as the role of sociodemographics on the risk stratification. What did GIGH collaborators discover? The average 10-year risk of a fatal or nonfatal CVD event varied widely among states in India ranging from 13% in Jharkhand to 19% in Kerala. What do these findings mean regarding developing action plans? They also found that risk scoring by four different calculators to a great extent provided similar results. We are still left with lots of unanswered questions. Major questions include what we do with this data? Who will design further studies to target this “at risk” population? Who will fund such an action plan? Even the study by the MDSC was funded by the Fogarty International Center of National Institutes of Health (USA), Dalla Lana School of Public Health, Toronto, Canada, and the Indian Council of Medical Research. In the absence of a national platform for “Cardiometabolic Diseases,” we are left just with questions and no definite answers. We urge readers to refer to the original comprehensive report for additional details of their findings.[1],[3],[6]

A recent review by USPTF, found inadequate evidence to assess whether treatment decisions guided by -ABI, CRP, or CAC score test results, when added to existing CVD risk assessment models, lead to reduced incidence of CVD events of mortality.[18] What we have to understand, when discussing the results of such studies is, that there is a great difference between risk scores that predict timescale for the development of CVD versus those, that try to predict risk for acute vascular events. No risk score calculator can predict the precise timing for the development of acute vascular events, such as heart attacks or stroke. Just to illustrate this point, let us consider the risks that are commonly used for risk score analysis. They are common modifiable risks such as smoking, physical activity, lipid abnormalities, elevated levels of blood pressure, and blood glucose. None of the existing risk score calculators include parameters related to the functioning of the circulatory system. Whether or not there is detectable ED, or whether or not the circulating blood is prothrombotic of hemorrhagic? Ultimately, the acute vascular events are precipitated due to the narrowing of the arteries, plaque buildup, changes in the circulating blood to a prothrombotic sate, due to the activation of platelets and coagulation pathways. Given these observations, we can say with confidence that none of the risk score calculators or 100% accurate, in predicting the acute vascular events, such as heart attacks or stroke.

In countries like China and India, with huge populations, it is rather difficult to screen the entire adult population to find a target population that needs extra care or interventions. Just consider the efforts of the Ministry of Health, Government of India, which is planning to conduct door-to-door screening for the detection of metabolic diseases in 200 districts by 2018. In India, we have over 650 districts and the aim of this project is to cover one-third of the population, and the requested funding is over 4% of the GDP. India spends currently just about 1% GDP on healthcare. To cover just screening (not treatment), Government will have to spend over 10% of the GDP. As we have expressed in our earlier articles, it is easy to make statements, issue guidelines, but to implement any of these action plans, we need total commitment at the national level adequate funding. Discussing such national strategies is beyond the scope of our review. However, we wanted to bring these questions and the problems associated with such issues to the attention of the readers, to create awareness of these problems, and initiate a constructive dialogue in the scientific community. Dr. Prabhakaran of the PHFI has summarized the needs of the hour as follows: “Taking control of the CVD epidemic in India needs all the stakeholders, including the policymakers, to acknowledge and address the social determinants that are strongly linked to CVD risk factors and to the related morbidity and mortality. The rising CVD burden and the damaging consequences it has on individuals, families, and populations require urgent attention. Innovative strategies are needed to halt the progression of the CVD epidemic in resource-poor settings in India. To address the socioeconomic differentials in the burden of disease and healthcare needs of Indians, more resources need to be directed toward applying the existing knowledge base to tackle the CVD epidemic in policy, programs, capacity building, and research arenas.”[6]

By providing these comprehensive reports on a complex, chronic disease like CVD, the authors of various reviews have made our task simple. We should study these reports carefully and develop our own guidelines and guidance statements for CVD risk assessment, and management. We also should concentrate on early detection of these risks and develop appropriate interventions. I have discussed in this and other journal articles, the risk factor assessment, risk prediction, and novel management strategies.[30],[31],[32],[33],[34],[35],[36],[37],[38],[39],[40],[41],[42],[43],[44],[45],[46],[47],[48],[49] I also have discussed in my earlier publications, details about the diagnosis of early risks for metabolic diseases, integration of emerging technologies for the development of novel noninvasive risk assessment platforms. Furthermore, I have emphasized the need for the integration of healthcare, with what is good in Indian Traditional Medicine, with what is good in western medicine, for the development of affordable healthcare. Since the time we started SASAT in 1993, our collective efforts are focused on creating awareness of the incidence of metabolic diseases in India, developing novel diagnostics, complementary interventional therapies, and preventive strategies. Since my retirement from the University of Minnesota, in 2012, I have been working in India, every winter on a variety of projects associated with the exploration of novel integrated technologies for the development of affordable healthcare.

In view of the fact that all the metabolic diseases, hypertension, excess weight, obesity, metabolic syndrome, and type-2 diabetes have achieved the status of an epidemic, we the members of the SASAT, feel that there is an immediate need, to address the issues related to creating awareness, early diagnosis of the risks such as oxidative stress, inflammation, and ED, develop simple, cost-effective integrative therapies for observed risks, and integrate emerging technologies, for risk assessment, risk prediction, and risk management.[30],[32],[37],[40],[44] We have discussed earlier, some technologies useful for monitoring ED.[47] We also have discussed our own efforts to develop handheld devices or wearables that will provide information on pulse waveforms at various regional vascular beds. Now let us discuss some novel methodologies for screening complementary therapies for reduction or reversal of the ill effects of oxidative stress and inflammation.

Oxidative stress is by and large considered, as an imbalance between the production of ROS, and their elimination by protective mechanisms. Oxidative stress can induce chronic inflammation and also activate a variety of transcription factors, which modulate the expression of a variety of proinflammatory genes. We already have discussed earlier the use of Protandim to alleviate the ill effects of oxidative stress. Polyphenols from a variety of natural sources have been proposed to be useful as adjuvant therapy for their anti-inflammatory effect. It is well known that many of the major phytochemicals, such as terpenoids, anthocyanins, flavonoids, and polyphenols, possess significant anti-inflammatory properties. Given the bio-diversity that exist in India, we suggest developing simple in vitro as well as in vivo screening methodologies, to test the phytochemicals for their safety and efficacy against proinflammatory pathways. A study from the UK indeed screened 64 medicinal plant products form 61 species using multitarget, cell-based approach; they found three phytochemicals, which were effective in inhibiting NF-kappa B in cells. In these studies, these phytochemicals were also tested against cytokines such as Interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha.[46] By using such simple multi-targeted cell-based assays, we should be able to develop some very potent anti-inflammatory phytochemicals.[48]


  Conclusions Top


Four major comprehensive reports have been published recently, by national and international professional organizations (AHA, GIGH, MDSC, and PHFI), in reputed scientific journals, about the incidence of CVDs in India, about the excess incidence of CVD and other related diseases in Indian living aboard and the geographic and sociodemographic variation in CVD risk in India.[1],[3],[6] In an earlier article in this journal, we have discussed the incidence of diabetes and CVD in Indians living in India and abroad.[45] We also have supported a study, “India Heart Watch” which focused on lifestyle and its influence in CVDs in different regions across India.[4] This study conducted under the leadership of Prof Rajeev Gupta of Jaipur came to the similar conclusions as that of GIGH studies. The studies by the researchers of PHFI concluded: “Taking control of the CVD epidemic in India needs all the stakeholders, including the policymakers, to acknowledge and address the social determinants that are strongly linked to CVD risk factors and the related morbidity and mortality.” We and others interested in this topic believe strongly that publishing epidemiological data or comprehensive studies like the ones we have reviewed, will not solve the immediate problems associated with these diseases, which have reached epidemic status. We need to establish a consortium of Industrial and Academia experts, which is inclusive in a sense, which will involve all the stakeholders associated with solving these lifestyle diseases. We also recommend the establishment of a “National Institute” to address the issues related to Cardiometabolic diseases. In the meantime, we urge the readers, experts, and the like-minded individuals, to use our SASAT platform headquartered in Medanta hospitals, New Delhi, as a national platform, to discuss an issue related to the effective management of metabolic diseases.

Regarding early diagnosis of the risks and effective management of the observed risks, we have discussed in several of earlier articles that in Asian countries like India and China the earliest risk is not at the level of ED but at the level of conception.[36],[46] In Asian countries millions of children or born with low birth weight. Seminal work from the CSI Holdsworth Memorial Mission Hospital, Mysore, India, has demonstrated that this cohort is at “high risk” for developing metabolic diseases.[36] Studies from Harvard scientists have demonstrated that these issues related to maternal and neonatal malnutrition could be alleviated by providing micronutrient supplements.[49] When discussing the early diagnosis of metabolic risks, excess weight and obesity in children should be a top priority.[50],[51],[52],[53],[54] It has been estimated that worldwide over 22 million children under the age of five or obese and one in 10 or overweight. The proportion of school-going children affected has doubled in the last two decades. Given the fact that there are no established annual visits for health checkups, the majority of the prediabetes and prehypertensives are left out in the preventive programs. According to experts, “for the tracking of obesity and the associated risk factors, childhood is an important period for prevention. Till date, evidence would support preventative interventions that encourage physical activity and a healthy diet, restrict sedentary activities and offer behavioral support. However, these interventions should involve not only the child but the whole family, school, and community. If the current global obesity epidemic is to be halted, further large-scale, well-designed prevention studies are required.”[53] In spite of the concerns and the recommendations of various experts, according to the American Association of Pediatrics (AAP), there's little sign of improvement. Obesity has been doubled in children and quadrupled in adults in the last three decades. New guidelines by the AAP emphasize prevention, rather than just the treatment of this condition.

In this mini-review, which expresses our point of view, we have discussed some of our (SASAT) collective efforts in improving the development of complementary diagnostic and therapeutic approaches.[45] Given the fact that clinical studies are time-consuming, expensive and at times not conclusive, we have suggested simple ways of developing clinical studies, to validate and develop evidence-based knowledge about the safety and efficacy of indigenous complementary therapies. Since we consider diagnosis and management of early risks, may reduce, reverse or prevent metabolic diseases, in this overview, we have discussed the role of three early risks; oxidative stress, inflammation, and ED. We are collaborating with various groups in India, in promoting these ideas, and those interested in working with us, either in the area of validating complementary therapies, or development of noninvasive biomedical devices, should contact us. We are looking for novel integrated approaches for the development of affordable healthcare, and we welcome constructive comments and collaborations.

Acknowledgment

Author wishes to express his thanks to Professor Ravi R Kasliwal, the president SASAT, and Dr. Manish Bansal, the secretary SASAT, Medanta Hospitals, New Delhi, India, for their continuing support of his (SASAT) educational activities in India, and for facilitating the publication of this article in the Journal of Clinical and Preventive Cardiology.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest



 
  References Top

1.
Volgman AS, Palaniappan LS, Aggarwal NT, Gupta M, Khandelwal A, Krishnan AV, et al. Atherosclerotic cardiovascular disease in South Asians in the United States: Epidemiology, risk factors, and treatments: A scientific statement from the American Heart Association. Circulation 2018;138:e1-e34.  Back to cited text no. 1
    
2.
Palaniappan LP, Araneta MR, Assimes TL, Barrett-Connor EL, Carnethon MR, Criqui MH, et al. Call to action: Cardiovascular disease in Asian Americans: A science advisory from the American Heart Association. Circulation 2010;122:1242-52.  Back to cited text no. 2
    
3.
Geldsetzer P, Manne-Goehler J, Theilmann M, Davies JI, Awasthi A, Danaei G, et al. Geographic and sociodemographic variation of cardiovascular disease risk in India: A cross-sectional study of 797,540 adults. PLoS Med 2018;15:e1002581.  Back to cited text no. 3
    
4.
Gupta R, Guptha S, Sharma KK, Gupta A, Deedwania P. Regional variations in cardiovascular risk factors in India: India heart watch. World J Cardiol 2012;4:112-20.  Back to cited text no. 4
    
5.
Rao GH. Need for a national platform and action plans for primary prevention and integrated treatment of heart disease in India. South Asian J Prevent Cardiol 2005;9:133-41.  Back to cited text no. 5
    
6.
Prabhakaran D, Jeemon P, Roy A. Cardiovascular diseases in India: Current epidemiology and future directions. Circulation 2016;133:1605-20.  Back to cited text no. 6
    
7.
NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: A pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. Lancet 2017;390:2627-42.  Back to cited text no. 7
    
8.
NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in diabetes since 1980: A pooled analysis of 751 population-based studies with 4.4 million participants. Lancet 2016;387:1513-30.  Back to cited text no. 8
    
9.
WHO. Global Status Report on Non-communicable Disease 2014. WHO; 2014. p. 298.  Back to cited text no. 9
    
10.
WHO. Global Action Plan for the Prevention and Control of NCDs 2103-2020. WHO; 2013. p. 55.  Back to cited text no. 10
    
11.
Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): Case-control study. Lancet 2004;364:937-52.  Back to cited text no. 11
    
12.
Khera AV, Emdin CA, Drake I, Natarajan P, Bick AG, Cook NR, et al. Genetic risk, adherence to a healthy lifestyle, and coronary disease. N Engl J Med 2016;375:2349-58.  Back to cited text no. 12
    
13.
Fernández-Friera L, Fuster V, López-Melgar B, Oliva B, García-Ruiz JM, Mendiguren J, et al. Normal LDL-cholesterol levels are associated with subclinical atherosclerosis in the absence of risk factors. J Am Coll Cardiol 2017;70:2979-91.  Back to cited text no. 13
    
14.
Cohn JN, Duprez DA, Grandits GA. Arterial elasticity as part of a comprehensive assessment of cardiovascular risk and drug treatment. Hypertension 2005;46:217-20.  Back to cited text no. 14
    
15.
Kasliwal RR, Bansal M, Mehrotra R, Trehan N. Relationship of arterial stiffness with hypertension and its management in a North-India population free of cardiovascular disease. J Clin Prevent Cardiol 2012;1:1-8.  Back to cited text no. 15
    
16.
Maarek AA, Gandhi PG, Rao GH. Identifying autonomic neuropathy and endothelial dysfunction in type 11 diabetic patients. EC Neuropathy 2015;2:63-78.  Back to cited text no. 16
    
17.
Gandhi PG, Rao GH. The spectral analysis of photoplethysmography to evaluate an independent cardiovascular risk factor. Int J Gen Med 2014;7:539-47.  Back to cited text no. 17
    
18.
US Preventive Services Task Force, Curry SJ, Krist AH, Owens DK, Barry MJ, Caughey AB, et al. Risk assessment for cardiovascular disease with nontraditional risk factors: US preventive services task force recommendation statement. JAMA 2018;320:272-80.  Back to cited text no. 18
    
19.
Csányi G, Miller FJ Jr. Oxidative stress in cardiovascular disease. Int J Mol Sci 2014;15:6002-8.  Back to cited text no. 19
    
20.
Madamanchi NR, Vendrov A, Runge MS. Oxidative stress and vascular disease. Arterioscler Thromb Vasc Biol 2005;25:29-38.  Back to cited text no. 20
    
21.
Bogaard HJ, Natarajan R, Henderson SC, Long CS, Kraskauskas D, Smithson L, et al. Chronic pulmonary artery pressure elevation is insufficient to explain right heart failure. Circulation 2009;120:1951-60.  Back to cited text no. 21
    
22.
Hybertson BM, Gao B, Bose SK, McCord JM. Oxidative stress in health and disease: The therapeutic potential of Nrf2 activation. Mol Aspects Med 2011;32:234-46.  Back to cited text no. 22
    
23.
McCord JM, Fridovich I. The biology and pathology of oxygen radicals. Ann Intern Med 1978;89:122-7.  Back to cited text no. 23
    
24.
Donath MY. Targeting inflammation in the treatment of type-2 diabetes: Time to start. Nature Rev Drug Dis 2041;3:465-76.  Back to cited text no. 24
    
25.
Kelly AS, Wetzsteon RJ, Kaiser DR, Steinberger J, Bank AJ, Dengel DR, et al. Inflammation, insulin, and endothelial function in overweight children and adolescents: The role of exercise. J Pediatr 2004;145:731-6.  Back to cited text no. 25
    
26.
Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 2017;377:1119-31.  Back to cited text no. 26
    
27.
Sprague AH, Khalil RA. Inflammatory cytokines in vascular dysfunction and vascular disease. Biochem Pharmacol 2009;78:539-52.  Back to cited text no. 27
    
28.
Ferrante SC, Nadler EP, Pillai DK, Hubal MJ, Wang Z, Wang JM, et al. Adipocyte-derived exosomal miRNAs: A novel mechanism for obesity-related disease. Pediatr Res 2015;77:447-54.  Back to cited text no. 28
    
29.
University of Pennsylvania School of Medicine. Drug that treats psoriasis also reduces aortic vascular inflammation: Randomized trial shows 19 percent improvement over placebo group. ScienceDaily; 2018. Available from: https://www.sciencedaily.com/releases/2018/02/180216110541.htm. [Last accessed on 2018 Aug 21].  Back to cited text no. 29
    
30.
Rao GH. Risk assessment, risk prediction, and effective management of risk factors for cardiovascular diseases. Editorial J Clin Prevent Cardiol 2012;1:9-10.  Back to cited text no. 30
    
31.
Rao GH. Prevention of vascular disease and development of affordable health care for all: Thinking out of box. View point. J Clin Prevent Cardiol 2012;1:31-4.  Back to cited text no. 31
    
32.
Rao GH, Gandhi PG. Need for a non-invasive diagnostic platform for early detection and management of cardio-metabolic disorders. J Clin Prevent Cardiol 2014;3:93-8.  Back to cited text no. 32
    
33.
Rao GH. Prevention or reversal of cardiometabolic diseases. J Clin Prevent Cardiol 2018;7:22-8.  Back to cited text no. 33
    
34.
Rao GH. Flow velocity, fluid dynamics and vascular pathology. Sci Pages Heart 2016;1:001.  Back to cited text no. 34
    
35.
Rao GH. Management of diabetes epidemic: Global perspective. EC Endocrinol Metab Res 2018;3:63-72.  Back to cited text no. 35
    
36.
Rao GH, Bharathi M. Mother and child:First step for prevention of cardiometabolic diseases. J Cardiol (Photon J) 2016;109:179-86.  Back to cited text no. 36
    
37.
Rao GH. Integrative approach to the management of cardiometabolic diseases. J Cardiol Cardiovasc Sci 2018;2:37-42.  Back to cited text no. 37
    
38.
Rao GH. Vascular disease risks: Known and the unknown? J Cardiol 2018;2:000127.  Back to cited text no. 38
    
39.
Rao GH. Non-traditional approaches to the diagnosis and management of type-2 diabetes mellitus: Point of view. J Diabetes Metab 2015;6:489. [doi: 10.4172/2155-6156.1000489].  Back to cited text no. 39
    
40.
Rao GH. Integration of novel technologies for the management of type-2 diabetes. Arch DiabetesObes 2018;1:ADO.MSID.000102.  Back to cited text no. 40
    
41.
Rao GH. Management of excess weight, and obesity: A global perspective. Interv Obes Diabetes 2018;1:IOD000523.  Back to cited text no. 41
    
42.
Rao GHR: Integrative approach to the management of cardiometabolic diseases. J Cardiol and Cardiovasc Sci 2018; 2:21-42.  Back to cited text no. 42
    
43.
Diagnosis of early risks, management of risks and reduction of vascular diseases. J Clin Cardiol Diagn 2018;1:1-11.  Back to cited text no. 43
    
44.
Risk prediction, assessment, and management of type-2 diabetes. Review. EC Endocrinol And Met Res 2018;3:30-41.  Back to cited text no. 44
    
45.
Rao GH. Cellular and molecular approaches to therapy. Clin Med Pathol 2018;1:DCMP. 000511.  Back to cited text no. 45
    
46.
Rao GH. Diabetes and cardiovascular disease in South Asians: A global perspective. J Clin Prev Cardiol 2018;7:161-7.  Back to cited text no. 46
    
47.
Rao GH. Diagnosis of early risks, management of risks, and reduction of vascular disease. J Clin Cardiol Diagn 2018;1:1-11.  Back to cited text no. 47
    
48.
Bremner P, Rivera D, Calzado MA, Obón C, Inocencio C, Beckwith C, et al. Assessing medicinal plants from South-Eastern Spain for potential anti-inflammatory effects targeting nuclear factor-kappa B and other pro-inflammatory mediators. J Ethnopharmacol 2009;124:295-305.  Back to cited text no. 48
    
49.
Kawai K, Spiegelman D, Shankar AH, Fawzi WW. Maternal multiple micronutrient supplementation and pregnancy outcomes in developing countries: Meta-analysis and meta-regression. Bull World Health Organ 2011;89:402-11B.  Back to cited text no. 49
    
50.
Ranjani H, Mehreen TS, Pradeepa R, Anjana RM, Garg R, Anand K, et al. Epidemiology of childhood overweight & obesity in India: A systematic review. Indian J Med Res 2016;143:160-74.  Back to cited text no. 50
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51.
Kar SS, Kar SS. Prevention of childhood obesity in India: Way forward. J Nat Sci Biol Med 2015;6:12-7.  Back to cited text no. 51
    
52.
Misra A, Bhardwaj S. Prevention and impact of childhood obesity in India. J Clin Prev Cardiol 2014;3:5-11.  Back to cited text no. 52
    
53.
Ke C, Gupta R, Xavier D, Prabhakaran D, Mathur P, Kalkonde YV, et al. Divergent trends in ischaemic heart disease and stroke mortality in India from 2000 to 2015: A nationally representative mortality study. Lancet Glob Health 2018;6:e914-23.  Back to cited text no. 53
    
54.
Ells LJ, Campbell K, Lidstone J, Kelly S, Lang R, Summerbell C, et al. Prevention of childhood obesity. Best Pract Res Clin Endocrinol Metab 2005;19:441-54.  Back to cited text no. 54
    


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