Lecture 36: Diet and Cardiovascular Disease: Epidemiological Evidence and Public Health Perspectives

Hello and welcome dear learners to the NPL course on nutritional epidemology a way towards a healthy life. In the module 4 diet, nutrients, dietary patterns and disease epidemology. For the chapter 36, we will be talking about diet and cardiovascular disease. The epidemological evidence and public health perspectives. Here in this chapter, we will be talking about cardiovascular disease as a public health challenge, diet as a modifiable risk factor, evolution of scientific evidence and from nutrients to dietary patterns, dietary fats and cardiovascular risk, current evidence and public health recommendations. So here as a cardiovascular disease is the public health challenge. You can understand that how cardiovascular disease is a leading driver for mortality and as a delies. So cardiovascular disease account for 7.9 to 19.1 million globally. So the total deaths are 56 to 58 million per year. So all the other causes are coming to 68%. So all the other causes like 38.9 million that is contributing to 68% are coming for other diseases. With respect to that the 20 million burden of whole diseases this is taken by cardiovascular disease. So Orburn's classical epidemological transition theory in 1971 displays that the demographic and epidemological transitions which comes with classical western Europe transition from century scale which is era of recent dependent. So hyper accelerated LMCI and transitions of low middle inome countries from low to high is accelerated which is like a shifting from era of infectious disease and a transition and the feminine to the era of degenerative man-made chronic diseases. what is the chronic disease that is cardiovascular disease. So the affluence policy and the paradigm ship. So now GBD data the reality is that over 75% of the global CVD deaths now occur in LMCI that is low middle- inome countries. This is the fact and there was a previous fallacy that lifestyle excess and aging and all that is an old assumption that disease was in affluence. So what is the driving factors in LMCI that is low middle- inome country is like rapid westernization of global food networks where eating of burgers, pizza, breads and sausages, beverages is increasing which is giving rise to cardiovascular diseases. A swift of urbanization which is changing the lifestyle of individuals moving from natural to unnatural situations. Also systematic gaps in early clinical screening is now which is making more the situations complex. Now moving to cardiovascular disease as a public health challenge. The granular mortality stratification and the twin engine of global cardiovascular disease mortality. Ishkemic heart disease accounts for 9.1 to 9.4 million deaths in a year. The cardiovascular pathology mortality is totally 16 million per annually. So you can understand the cardiovascular stroke is 6.6 to 6.9 million deaths per year. So the incidence of ishkeimic stroke the ishkeimic stroke is about 6.6 to 6.9 million per year. Hemoric stroke hemoric stroke accounts for hemorogic strokes which is giving 6.6 to 6.9 millions death per year. So what is a manifestation of acute mioardial infraction which is giving you acute mioardial infection in damage of infraction and chronic iskeemic heart disease failure. Chronic iskeemic failure accounts for 6.5 6.6 6 to 6.9 million deaths and the chron the chronic mioardial inffection in the chronic failure actually for accounts for chronic uh heart failure. So global mortality burden we can see over here that it highlights like the countries which are stated in blue are coming with a high burden and the high stroke which are stated into red. So you can understand the stroke driver in specific regions with subsaharan and even east Asia actually the stroke eclipse that is ishkeemic heart diseases and the critical driver uncontrolled uh systemic hypertension that is 160 to 100 where you may find the elevated blood pressure increasing the stroke risk. So here you can understand the granular mortality stratification across the globe. Now we will talk about the burden in India. South Asian cardiovascular vulnerability. The Indian subcontinent become the global epicenter of unique hyperaggressive and premature manifestation of coronary artery disease. The Indian population experiences a distinct epidemological paradox where severe multi- vessel coronary diseases occurring at much lower metabolic threshold than the observed in the western position. So it is understood that the genetic architecture that is that was uh thrifty gin and ancient survival which is rapidly towards an environmental shift is giving through urbanization and food industrialization. So what is that is coming as a trouble to Indian Asian phenotype. So there is a higher visceral abdominal ediposity that is called as high waist to hip ratio which is giving us abdominal obesity. Then it is found that profound insulin resistance that is hyperinsulinemia. Again there is a condition called as aogenic dysipidemia that is high TG low HDL and small dense LDL. So there are early onsets which can be seen that is called as atherosclerosis that the event of cardiovascular events start five to 10 years early to the main disase condition. Now we will try to understand the epidemological domination. the critical burden of cardiovascular disease in India the epidemological shift and unique risk to the union of Asian Indian phenotype. So here you can understand the non-communicable disease uh decisively overtake infectious disease in India and we have seen the transition of uh Indian disease condition specifically taking more shift towards non-communicable disease and it's a double burden of disease that India is facing the age standardized CBD mortality risk is also increasing in India compared to the global where the average of global is 211 India it accounts for 27 72 cardiovascular disease alone accounts for 27% to 28% of the total mortality. So what we can say is that the crisis of premature mortality in cardiovascular disease compared uh to the western population in Asia it is increasing at high. So it comes to the age starting from 40 and has a major to 55. So age scale is also being reduced compared to the western population that where it is closer to 60 65 to 70 where versus in India it is 50 55 to 60 the under 70 metric devastating structural vacuum where the CBD debt in India as a distribution here you can understand that under 70 it is like over 50% of people are getting affected among the cardiovascular disease suffering people whereas uh it is more than in the global where it is being found 25%. So the peak economic, social and parental years are being affected by cardiovascular disease. Now let us understand more in deep deconstructing the Asian Indian phenotype a unique metabolic composition. Beyond centralized BMI cut offs the normal it is like 23 and waist to hip ratio. The visceral adiposity. So normal BMI yet profound visceral fat due to evolutionary mechanism that with 350 genotype to survive the historic mas the lipoprotein triad where the ethogenic dysipidemia the triglycerides and HDLC where you may find that small dense LDL very small to large luffy that highly uh you can say easily iodizing oxidizing the bounce of accelerating the etherosclerosis. So you can understand how the risk of uh CVD is increasing in Indian population. The profound insulin resistance which is being stated that hippatic insulin resistance which is coming to state that next level the chronic hyperinsulinemia and constant free fatty and release. So the visceral fat adiposity is profound actually to see that there is an insulin resistance. So elevated baseline risk for early onset of type 2 diabetes is one which is very much related to the visceral edyposity. Now we will try to understand the socioeconomic and healthcare system consequences. What are those? The CVD financial stock in LMCI setting. So the out of pocket expenditure that OOP crisis India total health expenditure 50 to 60% is spended in the cardiovascular disease. So catastrophic health expenditure from household from shift is more towards a single episode of CVD hospitalized and you will getting the frequently exceeds one as a criteria. So the poverty trait over here is like you may have a low income families where sell agriculture assets they have all those liquidifying their savings and high interest informal death and the CBD hospitalization pushes the family to 25% of the lowincome families in absolute poverty within one year. the catastrophic health expenditure of household for non-food capacity to pay where the frequency exceeds uh the cardiovascular criteria actually to be spending with respect to a single episode of CVD which is putting more burden compared to the other disease condition. Now we'll try to understand the productive age vacuum. The population pyramid that you can see over here strikes to say that the disease strikes South Asians in prime working years compared to the higher age in other people in the global scenario. The disappearing where you can see that how it is affecting because of the lifestyle. Quantifying the loss, if you see the GDP impacts uh simulation from 2012 to 2030, India will lose billions in economic output due to premature risk of cardiovascular disease and stroke and the mortality and the disability that is being caused by the disease. India will lose billions in economic output due to premature IHD and stroke mortality and disability. What are the key drivers over here? Absentism and presentism. So absentee chronically uh we can say in UK where presentism reduce functional capacity significantly reduce labor output and here the years of life loss that is YL there you may find that young skilled people compared to unskilled worker. So the permanent detention of labor from the market long before the uh retirement age limits nation's demographic dividend. The health care system strain the chronic disease inundation. So you can understand that uh the health system mismatch is being seen that the historic public health model of infectious and maternal focus which is always there on the seasonal on seasonal shift of disease condition and most of all on MCH where you have major disease threat with infectious diseases vector bond diseases maternal and child health illnesses and vaccine campaign is something which is an episodic you can come up with the acute care which is what the public health system was known for. Now there is a critical mismatch of current disease reality which is more focusing towards the chronic uh cardiovascular diseases high blood pressure, heart failure and even a continuous multidisciplinary care which is to be offered with decades of management which is tracking from rehabilitation. But the age wise it is coming from 20 to 40 where there is a medication monitoring and complications which is being seen which is mismatch with the standard public health intervention model. What is the opportunity cost of care? The opportunity cost of care currently what we it is being demonstrated which is more for maternal health, infant nutrition and infectious disease is now being shifted towards a vital strategic conclusion where sustaining healthcare delivery requires a shifting resources needs to be more towards drug dis which are now being evolving. The inundation of tertiary care, the complex multi-disiplinary infrastructure which is crowded, which is on a waiting list to avail the facilities and a severe shortages in the bed which require upskilling of infrastructure in public health and even healthcare systems which may be a private or corporate. The rural deficits of facilities are putting and pushing the people into poverty. The multi- decadinal fiscal drain where you may find that weeks of cure or death was more affecting because of acute infections which was from week one to week two where you may find that the daily multi-drug resistance infections and regular diagnostic testing and frequent rehospization is pushing actually the population towards out of pocket expenditure. Now in addition from age 20 to 40 years of management or which takes the NCD as a major stroke burden from stroke and heart failure which is taking more timeline and more a drain to the out of pocket expenditure. Now we will talk about diet as a modifiable risk factor. How does diet modifiable risk factor coming into public health strategy? We will see the prevention spectrum in public health with respect to diet where you can understand the primordial prevention, primary prevention and secondary prevention where in the targets of the policy the target is more of an environment. The characteristics are you should prevent emerging factors and you should concentrate on populationwide policies where versus in the primary prevention it is like preventing the image emerging factors the control factors and you should try to target on individual care and the secondary level prevention is more going towards institution where the risk factors particularly disease condition and you should try to focus more on treating the acute events especially there needs to have more focus on high cost at the tertiary level. So the cumulative vascular damage reduced over the year from highest profile to optimal metabolic profile which is a primordial shift. Now the rise of population paradm and the strategy comparison. If you do talk about the high-risisk clinical strategy that is people who are screened and treated which is called as prescription stains and the population dietary strategies that is people making simple switches example where you have a shift and switch of salt. So why the reason is like when in the first condition the high risk clinical strategy the high cost per person where the massive moderately at a risk burden where the events prescribing status of of LDL and you may come across that if they have a screening at a proper level that can reduce that disease risk condition where in the population dietary strategy if you are trying to make a model actually you should try to make a switch off actually which is giving like a small individual who change their massive drop in populations wide clinical events. The shift from the total salt intake downwards towards protecting them modern risk in majority condition. What is now coming as economic evaluation that is health economic and policy utility. How the structural versus behavioral pattern where the downstream the behavioral strategy which is coming from clinical counseling low compliance and higher implementation cost towards a lower return. So you may understand that the behavioral int interventions which are more giving you more higher returns and where if you are not doing it it is going for a lower returns. So the upstream structural interventions are more coming from industrial brand bands and warning labels SSB tax. So minimum fiscal expenditure and massive return which is something which is called as a gain where versus when you try to upstream the interventions which are highly cost effective and often costsaving which will give more benefit and balancing the economic burden. Now we can understand the key dietary determinants of CVD. What the CVD cost us to give us more focus to understand through the lens of diet where the suboptimal diet the metabolic derangement and atherosclerosis. So the what are the harmful excesses and productive deficits. So the harmful excesses are like high sodium intake, industrial produced trans fatty acids, ultrarocessed foods, refined carbohydrates and sugar sweetened beverages. So it is being found that most of the harmful excesses are being consumed in urban population and so where we can link that excess of consumption leads to more risk of CBD in urban population versus to rural. The protective deficits we will try to understand that insufficient consumpionion of whole grains which is giving the individual the unprotectiveness towards if they are not consuming it where versus the fruits and veggies and nuts seeds and marine omega-3 fatty acids which are found to be more protective towards protecting from the athosclarosin cardiovascular disease burden. Now we'll understand the biological and metabolic pathway. the ethogenic lipoprotein remodeling the saturated fatty acids downregulated hippatic LDL receptor which is an expression which is increasing the circulating LDL and you can understand that the driver for ethogenesis is the absolute number of apo particles which are trapped into the subendothelial space undergoing oxidation and starting uh taking stricts. So okay you can get it that how a hemodynamic stress which is creating more stress and giving high rise into the blood pressure. Now we will understand the dietary exposures where you can understand the fatty fat quality the sodium the fiber and free sugars. So all these are more functionally affecting actually to increases the uh instigation or even stimulating the disease condition to go more with systemic inflammation while developing the insulin resistance and visceral radiposity and atherosclerosis and CVD pathogenesis. So this way you can understand how a diet with respect to metabolic derangement which is being depicted over here and how it leads to atherosclerosis cardiovascular disease. Now we'll understand the evolution of scientific evidence. So here there are some dates which are stated over here. As you can see 1950s to 1970 is the one episode. The second episode is 1980 to 1990s and the third episode is from 2000 towards the present. Now what is the shift over here? The first of 1950s to 1970 is like the diet hard hypothesis where the key ecological studies evolved and the focus was more on serum cholesterol where the flaw was confounding data and here you can understand that how the shift was taking over here. Then later in 1980s to 1990 the reductionist low-fat trap was being seen where the reductionist low trap fat was more focusing on focus of total fat reduction which was to be seen as unintended sugar swap. So the result was metabolic syndrome surges actually which were giving more rise because of the shift. Now the dietary risk matrix which is the pattern currently now where we can say the whole food synergies are coming where the focus is more on the matrix over isolated macronutrients. So that is there that the evolution of dash diet and meditarian diet is now being seen as a dietary mis mix in the current days actually. Now we can understand what is the mid 20th century the diet heart hypothesis. So as you know that following the world war second the western nations experienced an unprecedented epid epidemic of premature iskeemic disease ishkeemic heart disease among the middle-aged men. So this sudden rise in mortality forced researcher to look beyond infectious pathology and explore upstream environmental occupational and dietary drivers. But the Anel Keys and the seven country studies reflects something very different. The core hypothesis uh that Dr. Anel Keys hypothesized that populationwide consumption of saturated fatty acids elevated the serum cholesterol level which in turn facilitated the development of coronary arthrogenosis. So what are the findings of this study? The seven country studies was the first large-scale study which tracked the dietary intake and cardiovascular health across structurally diverse nation. The nations included were Japan, Greece, Yugoslavia, Italy, Netherlands and US and Finland. So the findings of these seven nation studies were like they the key demonstrated issues were a strong correlation between the population with low saturated fat intake. Example, the traditional cohorts in Crit Greece and Japan had with low serum cholesterol profiles and remarkably low 10 years coronary disease mortality rates. Conversely, nations with high saturated fat intake, example Finland and US experience severe cardiovascular disease condition. So this was to be stated that how the evolution took when the specific study pointed towards the country's def differentiation towards the disease condition. Now what are the methodological limitations and ecological fallacy for both public health students? This era serves as a classical lesson in study design limitation. What we do as a wrong is it is not that how we need to correct it. The ecological fallacy comes that these early studies evaluated country level aggregate data rather than an individual level exposures. So the finding a correlation between the nation's average fat sales and its average heart disease rate does not mean every individual consuming fat will develop a heart disease. So it's like a ecological fallacy that you need to understand over here. Now what is an uncontrolled confounding? aggregate data could not statistically control for critical non-dietary cardiovascular risk factors that were changing during the post second world war. Well, you have a boom of increasing high smoking rates shifting from physical level activity to sedentary lifestyle and industrial pollution and socioeconomic disparities which were contributing actually towards this development of dietary uh related cardiovascular risk conditions. Now in the late 20s what happened the reductionist single nutrient era which was more towards a low fat trap. So how did uh it make a big change? So the policy mistransation comes like when it was in the late '7s to 80s the public health bodies and the consensus panel attempted to simplify the complex epidemological data and the data was more given to and more actionable guidelines toward the general public. The result was giving a recommendation that to reduce total dietary fat into a less than 30% of your total daily calories. But what happened is a result being depicted now over here. The unintended substitution effect made something which was very drastically and to your uh surprise the policy failed to anticipate how consumer psychology and the industrial food chemistry would respond to the generic low-fat mandate. How did the industry respond? The industry response is like to maintain product palatability when fat was removed. The food industry re-engineered commercial product by adding large amount of refined starches, high fructose corn syrup and free sugar. So you can understand how uh difficult uh it has put a burden to an individual. Then there was a carbohydrate swap. Public health messaging inadvertly encourage consumer to replace energy dense fat with a highly processed carbohydrate. So products were marked as hardy but they were fat-free completely ignoring their high sugar content and elevated glycemic load. So it was something which was a major burden actually which was coming with a different name. Now we can understand the epidemological counter effect. This single nutrient approach did not slow the cardiovascular disease epidemic. Instead it altered the population metabolism. How it is we will try to understand it. The metabolic inversion where the diet high in refined carbohided decreased protective HDL cholesterol increase small dense uh ethogenic LDL particles and raised circulatory triglycerides. The obesity surge instead of preventing chronic diseases the lower fat era coincided with global surge in obesity insulin resistance and type 2 diabetes malitis. This outcome proved a key public health issue. The issue was the quality and the matrix of macronutrients matter far more than the total aggregate percentage which was more to be seen as a lesson. Now we'll try to understand the modern paradigm shift. The whole dietary pattern in the food matrix. Now there is a shifting away from the reductionism to the modern food matrix. Now when the modern nutritional epidemology recognizes that humans eat complex meals not isolated nutrients single nutrient evaluations are flooded. Previously there was a reductionist view now there is a modern matrix view. Now what it is being seen as deconstructing the food matrix and the nutrients health effect is mediated by physical and chemical structure where you will find this coming as a food matrix. The dairy matrix example is like processed red meat as a saturated fat where a fermented dairy products where unsweetened yogurt and aged cheese which is coming as a neutral or inverse CVD association and the dairy components alter fat metabolism. Now the clinical and population proof is of dash and predeemed the dash trial which is giving a dietary pattern rich in fruits, vegetable, whole grains and low fatty dairy. the significant increase in potassium, magnesium and fiber. The DASH trial where it is being seen as systemic BP lowered as effectively as pharmaceutical monotherapy where the DASH diet is being more targeted towards sodium restriction. the pre-mid study that the prevalence of diet meditarian which is evaluated to show that a high cardiovascular risk individuals on a traditional Mediterranean diet where unrestricted total fat but rich in extra virgin olive oil, nuts, fish and legumes which is like 30% relative risk in reductionist. The Mediterranean diet is cons is a composition of low-fat control diet versus there is a 30% relative risk in reduction. So definitive proof of whole food quality drives long-term vascular health. Now from nutrients to dietary pattern limitations of reductionist approach in nutritional epidemology from the decades that we have unded that nutritional science relied on reductionist model. A paradigm borrowed from infectious disease and def deficiency epidemology. This model assumes that a single isolated dietary component correlates directly and linearly with the specific health outcome. While highly effective for identifying micronutrient deficiencies for example vitamin C and scurvy reductionist fails when applied to multiffactorial chronic non-communicable disease such as cardiovascular disease. The example is being practically demonstrated and can be seen over here in the figure. Now what is the breakdown of reductionism methodological limitations in diet CBD epidemology? The colon problem the problem of back substitution varying chemical structures and overlooking lowd do synergies. So in the figure one the colonary problem shows a central figure overwhelmed by interwoven data stream. The tight correlation of saturated fat with sodium and its inverse relationship with fiber and potassium means that the signal converge be before entering the statistical model which is shown in the funnel model. This statistical overlap results in a fuzzy output signal and a large question mark illustrating the impossibility of isolating a single factor. Now what is figure two giving? Figure two is giving the back substitution or treat totter balance that is energy balance. It shows that reducing the specific macronutrient that is the fat low creates an immediate void that must be filled. The graphic visualizes the global low-fat trap where the calories are substituted with the larger block of refined carbohids that is sugar. And the figure three varying chemical structures a microscope and a chemical diagrams are used to emphasize that not all saturated fats are equal. It contracts two specific compounds that is great that is a short chain which supports gut health against the pleinate that is long chain which downregulates the LDL receptors. grouping them under a single broad metric is shown to mask the essential biological differences where versus the figure four that is a low dose synergies the timeline of 10 years to 40 years visualizes the cumulative protective effect of multiple nutrient that is fiber potassium magnesium omega3 in increasing artery health. The complexity contrast with the single large single major cause icon that is crossed out illustrating why a reductionist search for one major culprit will fail when study chronic decaying long pathology. Now here you can see the nutrient interactions and the holistic food matrix which is now being explored where you can understand from high isolated nutrients to natural food matrix and the code transport mechanism a comparison where you can understand a paradigm shift in nutritional impedemology is now being exemplary uh stated and the specification scenario which are being experimented. A real world eating behavior. A paradigm shift in public health research where the core concept of food not isolated nutrient which is like we need not to uh consider actually how the food is to be taken in isolated nutrient but as a whole as a whole meal actually which is a rapid absorption and food matrix. The whole food and the meals actually which we can be seen in the food matrix. The culture of combinations and dietary habits in regional, cultural and soio economic factors which we have been seen both benefiting towards taking a limit to a particular food in isolation. The limits of dietary recall and the path forwards which are broadening the patterns actually as improving the data reliability and giving more from the transitional single nutrient recall to a tracking of the border patterns of taking more meditarian versus ultrarocessed food. Now the dietary patterns as a modern framework where the a prior methods of hypothesis driving indexing and now a posterior methods of datadriven exploratory pattern which are giving us that the global public health application shifting to patterns capturing the high complex compounding effects on the modern and providing a stronger scientific foundation for cardiovascular prevention strategies. Here you can understand like how the patterns are being shifted towards understanding the scientific evidence which are more uh in specific for foods for health counties and in the statistical modeling to identify the existing eating eater eats with a population's data. Now the dietary fats and cardiovascular the dietary fats acids are classified by the chemical structure which directly dictates the physiological impacts in the trans fatty acids which are more towards chemical nature which are produced by the partial hydrogenation of vegetable oils converting liquid oils into solid fats to extend the shelf life and cardiovascular impact is that the trans fat are more hazardous dietary lipids per calorie consumed. The rise of LDLC and lower highdensity lipoprotein cholesterol increases the triglycerides and promote systemic inflammation and induce uh endothelial dysfunction. What is the public health consensus that the total elimination of industrial trans fats from the global supply food supply is the primary public health priority. Now we'll talk about the saturated fatty acids. The chemical nature of hydrocarbon change with no doubt bonds. Major sources include red meat, butter, lad, palm oil and coconut oil. The nuanced reality is that SFA generally increase circulating LDLC by down reggulating LDL receptors. However, the impact varies heavily based on the chain line and food matrix. Here you can understand how it is with laurens, mistric and palistic acids and ceric acid. The substitution rule is that the cardiovascular effect of reducing saturated fat depends entirely what is being replaced. Where you are replacing SFAs with refined carbohidates and sugar which yields no reduction in the CVD and replacing SFA with monossaturated or polyaturated fat significantly reduces the CVD risk. The dietary fatty acids and cardiovascular classification can be seen over here where the trans fatty acids and saturated fatty acids which comes with public health consensus and the cardiovascular impact where the saturated fasciated chemical nature chemical acid res sources and the nuance reality which is being seen is pointed. Now the unsaturated fatty acids uh graphs has been seen where how it gives you more detail understanding as which are the sources where versus what are the major sources the mechanism and even containing more and double bond the mechanism and importance which is highlighting towards this association and the associated disease effect. What is the current evidence and public health recommendation? It is more pointing towards having areas of concern to be highlighted particularly for industrial trans fat elimination. Total exclusion from all commercial and food preparation. Emphasis on high quality plant mattresses. Restriction of refined cardiovascular and SSBs and prioritization of unsaturated fats and sodium reduction which is being stating to reduce salt intake to lower populationwide blood pressure levels and stroke incidence. Essential guideline comparison saturated fat, sodium and dietary pattern which is given by WHO, American Health Association and European Society of Cardiovascular Cardiology which is more pointing towards dietary key dietary pattern focuses which are more being stated from saturated fat target to sodium salt targets. areas of ongoing scientific debate in nutrition which we can see that the complex dairy matrix is being more into discussion versus a sodium threshold and the pure coconut oil debate which is to being highlighted over here. What is the key takeways of this topic that the whole pattern of over single nutrients where the cardiovascular health is driven by overall dietary pattern and complex food matrix not isolate nutrients. So the macronutrient quality is very crucial which is being stated over here and a strategic substitution reducing saturated fats only lowers the cardiovascular risk if it is replaced with monossaturated or polyaturated fats. Replacing it with the refined starches or added sugar offers no clinical benefit. The double benefit of plants increasing the whole plant foods protects the cardiovascular disease in two ways by reducing exposure to harmful components and increasing protective factors. A primary prevention priority should be implementing populationwide dietary changes in one of the most effective and financially sustainable public health tools available to reduce the global burden of cardiovascular disease. So with this we come an end to this chapter and you can take this references for the help to understand this chapter in more detail. So with this thank you thank you very much. [music] >> [music] [music]