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Canadian Journal of Cardiology

Cardiovascular Risk Factors and Prevention: A Perspective From Developing Countries

Open AccessPublished:February 18, 2021DOI:https://doi.org/10.1016/j.cjca.2021.02.009

      Abstract

      By the beginning of the 21st century, cardiovascular disease (CVD) had become the leading cause of premature mortality and morbidity worldwide, with 80% originating from less developed lower-income countries in line with societal and economic developments. Extensive research on causes and risk factors have been carried out since the mid-20th century and have established individual factors such as smoking, hypertension, diabetes, and dyslipidemia as CVD risk factors, followed by others. Two recent major case-control studies have summarized the role of common major CVD risk factors in determining the risk of myocardial infarction (INTERHEART study) and stroke (INTERSTROKE study). They showed that 9 and 10 common risk factors accounted for > 90% of the risk of myocardial infarction and stroke, respectively, and established the focus in prevention of these common CVDs. The efficacy of lowering blood pressure, blood glucose, and lipid-lowering therapies has been shown to reduce subsequent morbidity and mortality. Leading international health organizations have published guidelines that are updated regularly to set the standards for providing guidance for implementation and management of risk factors. Interventions can also be costly and long-term adherence, essential to be effective in reducing risks, tends to decrease drastically with time. Dietary recommendations have been incorporated into national and professional guidelines for CVD prevention since the 1960s. On the basis of new research, some existing dietary recommendation might be outdated and should be reviewed, and revised, if necessary. A perspective of CVD prevention and treatment in developing countries is highlighted.

      Résumé

      Au début du XXIe siècle, les maladies cardiovasculaires (MCV) sont devenues la principale cause de mortalité prématurée et de morbidité dans le monde, dont 80 % des cas ayant été recensés dans des pays moins développés, à revenu relativement faible, conformément à l’évolution du développement sociétal et économique. De vastes recherches menées depuis le milieu du XXe siècle sur les causes et les facteurs de risque ont permis de déterminer que les facteurs individuels comme le tabagisme, l’hypertension, le diabète et la dyslipidémie sont des facteurs de risque de MCV, suivis par d’autres. Dans deux grandes études cas-témoins menées récemment, les chercheurs ont résumé le rôle des principaux facteurs de risque courants de MCV dans la détermination du risque d’infarctus du myocarde (étude INTERHEART) et d’accident vasculaire cérébral (étude INTERSTROKE). Ils ont montré que 9 et 10 facteurs de risque courants expliquaient plus de 90 % du risque d’infarctus du myocarde et du risque d’accident vasculaire cérébral, respectivement, et ont mis l’accent sur la prévention de ces MCV courantes. L’abaissement de la pression artérielle et de la glycémie ainsi que le recours aux hypolipidémiants se sont révélés efficaces pour réduire la morbidité et la mortalité subséquentes. Des organismes sanitaires internationaux de premier plan ont publié des lignes directrices mises à jour périodiquement, visant à établir des normes destinées à guider la prise en charge des facteurs de risque. Par ailleurs, les interventions peuvent être coûteuses, et leur observance à long terme, essentielle à leur efficacité à réduire les risques, tend à diminuer considérablement au fil du temps. Depuis 1960, des recommandations alimentaires ont été intégrées dans les lignes directrices nationales et professionnelles pour la prévention des MCV. À la lumière des nouvelles recherches, certaines de ces recommandations sembleraient dépassées et devraient être examinées et, au besoin, révisées. Enfin, les auteurs abordent la prévention et le traitement des MCV dans les pays en développement.
      For the past 100 years, the trajectory of cardiovascular disease (CVD) has followed the path taken by epidemiological transition and in line with global economic development. By the mid-20th century, CVD had become the leading cause of mortality and morbidity in Western developed countries.
      GBD Collaboration
      Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015.
      Toward the end of the 20th century, CVD has transitioned to be the leading cause of premature mortality and morbidity worldwide, with 80% of CVD mortality originating from lower-income countries.
      • Murray C.J.L.
      • Vos T.
      • Lozano R.
      • et al.
      Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010.
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      • Ounpuu S.
      • Anand S.
      Global burden of cardiovascular diseases.
      • Yusuf S.
      • Reddy S.
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      • Anand S.
      Global burden of cardiovascular diseases: part II: variations in cardiovascular disease by specific ethnic groups and geographic regions and prevention strategies.
      Individuals growing up in a developing country nearly 50 years ago will recall that myocardial infarction and cardiac surgery at that time were uncommon and occurred only in a few government ministers, political leaders, and other well-to-do individuals who presumably had adopted a more “western” lifestyle.
      The rapid transition of CVD from a disease of developed countries to occurring globally, with increasing prevalence in lower-income countries is complex and reflects the extraordinary pace that society has taken. Instead of a discussion covering all perspectives of global CVD, this review reflects a perspective from populations of developing countries in the midst of economic development, evolution of CVD, and the contribution of risk factors to disease development. Current recommendations on management of risk factors are highlighted. Although it might appear that treatment and prevention of CVD should be similar in all countries, differences exist between rich developed countries and poorer countries because of differences in availability of resources and infrastructure among the countries. In this review some of the differences are highlighted, and some nutritional risk factors in light of recent evidence are discussed, which suggests that a rethinking of attitudes and beliefs on harm and benefits of some nutrients should be examined, and perhaps revised.

      Health Transitions

      Changes in health patterns have occurred in the background of major societal changes in the global population. There are several major transitions, including urban, nutrition, and activity transitions, that might greatly affect cardiovascular health (Fig. 1)
      • Zatonski W.A.
      • McMichael A.J.
      • Powles J.W.
      Ecological study of reasons for sharp decline in mortality from ischaemic heart disease in Poland since 1991.
      :
      Figure thumbnail gr1
      Figure 1Health transitions and effect on cardiovascular disease (CVD). (A) Urban transition—urbanization of population from rural areas and effects on societal setup, infrastructure, lifestyles, and health outcomes. (B) Nutrition transition—effect of urbanization on nutrition of populations. (C) Activity transition—influence of urbanization directly and indirectly on physical activities and health outcomes.

      Urban transition

      In 1970, 37% of the world’s population lived in urban areas; by 2025, this is projected to increase to 61% in developed countries but in lower proportions in developing countries. The effects of urbanization are associated with economic growth and can vary according to the country’s economic development leading to heterogeneous effects on health. In developed countries, urbanization is accompanied by economic growth, planned development of urban infrastructures, and increased spending on social services, education, and health care. In poorer countries, rapid urbanization might occur without adequate infrastructure, creating urban slums and leading to greater socioeconomic disparity.
      • Vaz M.
      • Kurpad A.
      • Pais P.
      • et al.
      Contrasting coronary heart disease risk profiles between urban and rural Indians: the PURE pilot study.
      ,
      • Reddy K.S.
      • Yusuf S.
      Emerging epidemic of cardiovascular disease in developing countries.
      Consequently urbanization could involve variable societal and health changes and adaptive or maladaptive lifestyle changes in different regions. These disparities could lead to greater prevalence of diseases including chronic noncommunicating diseases such as CVD in the disadvantaged countries and influence the prevalence of these chronic diseases to reach alarming proportions.

      Nutritional transition

      The poor are more likely to be obese in developed countries and less likely to be so in poorer countries.
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      • Moura E.C.
      • Conde W.L.
      • Popkin B.M.
      Socioeconomic status and obesity in adult populations of developing countries: a review.
      In most societies, the cost of energy dense foods is lower than that of less energy dense foods, such as fruits and vegetables.
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      • Darmon N.
      The economics of obesity: dietary energy density and energy cost.
      Changes in dietary patterns have been attributed to economic growth,
      • Drewnowski A.
      • Darmon N.
      The economics of obesity: dietary energy density and energy cost.
      affecting changes in food production and food policies and influencing price and availability.
      • Yusuf S.
      • Reddy S.
      • Ounpuu S.
      • Anand S.
      Global burden of cardiovascular diseases: part II: variations in cardiovascular disease by specific ethnic groups and geographic regions and prevention strategies.
      Research shows that major nutrition shifts occur with an increase in energy consumption among people living in urban areas, mainly as a result of an increase in all types of fat intakes, a decrease in whole grains and fibre, and an increase in fruits and vegetables, compared with rural areas.
      • Du S.
      • Mroz T.A.
      • Zhai F.
      • Popkin B.M.
      Rapid income growth adversely affect diet quality in China – particularly for the poor!.
      Such nutritional shifts might result in increased obesity prevalence and have strong influences on individual well-being and overall population health.

      Activity transition—mechanization and effect on physical activities

      Reduced physical activity and sedentary behaviours are associated with obesity, diabetes, and CVD. Reduced activity occurs because of changing job types, and increased mechanization at work on the same job. At home, increased sedentary behaviours in leisure time (eg, time spent using computers and watching television), and less energy expenditure in transportation (because of increased number of vehicles), and have led to markedly reduced energy expenditure during utilitarian activities.
      These nutritional and physical activity transitions, occurring more so in lower income developing countries, contribute to increasing risk of CVD in these countries. In developed countries, increased knowledge and modification of CVD risk factors, more effective implementation of prevention practices, effective therapies for risk factors and diseases, and organized health systems to identify and treat risk factors have resulted in reductions in CVD risks and outcomes. In lower income and resource poor countries, such facilities are not as well developed and worsening behavioural and lifestyle risk factors and subsequent CVD have increased rapidly with the economic transitions in these populations, resulting in the increasing prevalence of CVD.

      Risk Factors

      Knowledge and detection of risk factors that precede CVD are invaluable in identifying individuals who are more likely to develop CVD so that interventional strategies can be used to address the risk factors and modulate their effects on CVD risk. Starting with the Framingham study, initiated in the mid-20th century, numerous risk factors have been identified that are associated with subsequent CVD and has led the way to systematically manage the CVD epidemic in developed countries.
      • Hajar R.
      Framingham contribution to cardiovascular disease.
      The Framingham and other studies had identified common risk factors such as hypertension, diabetes, obesity, hyperlipidemia, tobacco smoking, sedentary lifestyle, and lack of adequate physical activities as risk factors that could be modified or prevented to reduce CVD.
      • Hajar R.
      Framingham contribution to cardiovascular disease.
      At the same time up to the mid 20th century, the rates of CVD were low in developing lower income countries, which were still dealing more with infectious diseases, malnutrition, and less so with noninfectious chronic diseases such as diabetes, CVD, or chronic lung disease. To catch up, studies similar to the Framingham and other studies were required in these countries. Unfortunately, because of rapid economic transition, high rates of death due to CVD, particularly ischemic heart and cerebral diseases, are occurring in various low- and middle-income countries by the turn of the 21st century.
      GBD 2015 DALYs and HALE Collaborators
      Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015.
      ,
      • Murray C.J.
      • Lopez A.D.
      Mortality by cause for eight regions of the world: Global Burden of Disease Study.
      CVDs have become as common in lower income countries as in developed countries, with 80% of the disease burden borne by the lower income countries.
      GBD Collaboration
      Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015.
      ,
      • Yusuf S.
      • Reddy S.
      • Ounpuu S.
      • Anand S.
      Global burden of cardiovascular diseases: part II: variations in cardiovascular disease by specific ethnic groups and geographic regions and prevention strategies.
      Prevention of CVD, particularly coronary heart disease, has been the stimulus for research over the past 100 years, with major advances made since after the Second World War. Advances in research with a focus on identifying and treating risk factors and CVD were made in Western countries, mainly in North America and Europe.
      GBD 2015 DALYs and HALE Collaborators
      Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015.
      ,
      • Murray C.J.
      • Lopez A.D.
      Mortality by cause for eight regions of the world: Global Burden of Disease Study.
      Up until recently, many people from developing countries were unsure whether extrapolation of knowledge of risk factors, and whether prevention learned from research and practice in Western countries were appropriate, because of the differences in cultures, behaviours, and lifestyles among the various countries.
      The findings from 2 recent case-control studies, the INTERHEART study
      • Yusuf S.
      • Hawken S.
      • Ounpuu S.
      • et al.
      Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.
      and INTERSTROKE study,
      • O’Donnell M.J.
      • Chin S.L.
      • Rangarajan S.
      • et al.
      Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study.
      which focused mainly on developing countries have affected the perception of CVD in these countries. Findings from these studies confirmed that people in developing countries face the same risks, and similar risk factors as in developed countries, and identified the common cardiovascular risk factors requiring targeted, systematic, sustained, and effective interventions, particularly in developing countries, to mitigate the epidemic of CVD in these regions of the world.

      INTERHEART Study

      The INTERHEART study, a case control study of acute myocardial infarction enrolled a multiethnic cohort from 52 low-, middle-, and high-income countries in South and South East Asia, Africa, China, Japan, Europe, the Middle East, Australia/New Zealand, and North and South America.
      • Yusuf S.
      • Hawken S.
      • Ounpuu S.
      • et al.
      Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.
      There were 15,152 patients who had their first myocardial infarction and 14,820 age- and sex-matched control participants. As shown in Figure 2, 9 easily assessed and common traditional risk factors were statistically associated with increased risk of myocardial infarction. Tobacco smoking, dyslipidemia, hypertension, diabetes, abdominal obesity, and psychosocial factors were highly and significantly associated with increased risk of myocardial infarction. Daily consumption of fruits and vegetables, regular low to moderate alcohol consumption, and regular physical activities were associated with reduced risk. These associations were present in women and men, old and young, and in all regions of the world. Smoking, an adverse lipid profile, hypertension, and diabetes were particularly associated with a greater risk for myocardial infarction in younger than older individuals. People who were simultaneously exposed to all 9 risk factors had an odds ratio (OR) of 333.7 (99% confidence interval, 230.2-483.9) in developing myocardial infarction, compared with control participants without any risk factors.
      • Yusuf S.
      • Hawken S.
      • Ounpuu S.
      • et al.
      Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.
      Figure thumbnail gr2
      Figure 2Odds ratios for cardiovascular risk factors in the INTERHEART
      • Yusuf S.
      • Hawken S.
      • Ounpuu S.
      • et al.
      Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.
      and INTERSTROKE
      • O’Donnell M.J.
      • Chin S.L.
      • Rangarajan S.
      • et al.
      Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study.
      studies. INTERHEART risk factors: current smoking (vs never); diabetes mellitus (yes vs no); hypertension (self-reported history of hypertension); abdominal obesity (highest vs lowest tertile); psychosocial factors (model-dependent index combining positive exposure to depression, perceived stress at home or work [general stress], low locus of control, and major life events, all referenced against nonexposure for all 5 factors); daily fruits and vegetables (vs lack of daily consumption); exercise (regularly involved in moderate (walking, cycling, or gardening) or strenuous exercise (jogging, football, and vigorous swimming) for 4 hours or more per week); alcohol intake (consumption 3 or more times a week vs less); and ApoB/ApoA1 ratio (highest vs lowest quintile). INTERSTROKE risk factors: current smoking (vs former or never); diabetes mellitus (yes vs no); hypertension (self-reported history of hypertension or blood pressure ≥ 140/90 mm Hg); psychosocial factors (combines measures of stress [home and work], life events, and depression); diet quality (modified Alternative Healthy Eating Index [AHEI] score: highest vs lowest tertile); exercise (physically active vs other); alcohol intake (high or heavy episodic intake vs never or former drinker); and ApoB/ApoA1 ratio (highest vs lowest tertile). Odds ratios below 1 (thick horizontal line) indicate a beneficial effect. Apo, apolipoprotein.
      Another measure of public health burden, the population attributable risk (PAR), reflects the combined effect of the prevalence of the risk factor and the strength of its associated risk in the population, was estimated for each of the risk factors. As shown in Figure 3, in INTERHEART, current smoking, psychosocial factors, abdominal obesity, and dyslipidemia were associated a high PAR of 20% or more. PAR for the others were lower, either because of their low prevalence or lower risk or both. The combined PAR for all 9 risk factors was 90.4% indicating that these risk factors accounted for nearly all of the risk for myocardial infarction in the population.
      Figure thumbnail gr3
      Figure 3Population attributable risk cardiovascular risk factors in INTERHEART
      • Yusuf S.
      • Hawken S.
      • Ounpuu S.
      • et al.
      Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.
      and INTERSTROKE
      • O’Donnell M.J.
      • Chin S.L.
      • Rangarajan S.
      • et al.
      Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study.
      studies. INTERHEART risk factors: current smoking (vs never); diabetes mellitus (yes vs no); hypertension (self-reported history of hypertension); abdominal obesity (highest vs lowest tertile); psychosocial factors (a model-dependent index combining positive exposure to depression, perceived stress at home or work [general stress], low locus of control, and major life events, all referenced against nonexposure for all 5 factors); daily fruits and vegetables (vs lack of daily consumption); exercise (regularly involved in moderate [walking, cycling, or gardening] or strenuous exercise [jogging, football, and vigorous swimming] for 4 hours or more per week); alcohol intake (consumption 3 or more times a week vs less); and ApoB/ApoA1 ratio (highest vs lowest quintile). INTERSTROKE risk factors: current smoking (vs former or never); diabetes mellitus (yes vs no); hypertension (self-reported history of hypertension or blood pressure ≥ 140/90 mm Hg); psychosocial factors (combines measures of stress at home and at work, life events, and depression); diet quality (modified Alternative Healthy Eating Index [AHEI] score: highest vs lowest tertile); exercise (physically active vs other); alcohol intake (high or heavy episodic intake vs never or former drinker); and ApoB/ApoA1 ratio (highest vs lowest tertile). Apo, apolipoprotein.

      INTERSTROKE Study

      The INTERSTROKE case control study enrolled 26,919 participants, with patients having had a first stroke (10,388 participants) or intracerebral hemorrhage (3059 participants) and 13,472 matched control participants, from 32 countries in Asia, America, Europe, Australia, the Middle East, and Africa.
      • O’Donnell M.J.
      • Chin S.L.
      • Rangarajan S.
      • et al.
      Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study.
      Hypertension and cardiac causes such as atrial fibrillation and valvular heart disease were associated with the highest risks for stroke, with ORs of 3.0 or more, followed by psychosocial factors and excessive alcohol intake (Fig. 2). Hypertension and lack of exercise or physical activities were associated with a PAR of 30% or more. Poor diet quality and dyslipidemia were also associated with high PAR for stroke (Fig. 3). The study showed that 90.7% of the PAR for stroke was accounted for by 10 potentially modifiable risk factors.
      • O’Donnell M.J.
      • Chin S.L.
      • Rangarajan S.
      • et al.
      Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study.
      Although the risk factors between myocardial infarction and stroke appear similar, the extent of risk might differ (eg, hypertension was associated with greater risk in stroke whereas smoking and dyslipidemia in myocardial infarction). Differences in the prevalence of individual and community risk factors and the influence of other competing risk factors can account for the apparent differences in risk factors and their effects on the risk of developing disease in the different populations.
      • Yusuf S.
      • Hawken S.
      • Ounpuu S.
      • et al.
      Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.
      • O’Donnell M.J.
      • Chin S.L.
      • Rangarajan S.
      • et al.
      Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study.
      • Yusuf S.
      • Joseph P.
      • Rangarajan S.
      • et al.
      Modifiable risk factors, cardiovascular disease, and mortality in 155 722 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study.

      Limitations of the INTERHEART and INTERSTROKE Studies

      Despite the apparent certainty in their findings, a causal association between risk factors and disease cannot be established from the case-control design used by these studies. Instead, the objective of these 2 studies was to quantify the effect of known risk factors on burden of disease, rather than to establish new causal relationships. Such causal relationships have been established for most of the risk factors in previous prospective cohort studies and randomized controlled trials. However, the case-control study design is efficient because there is no waiting for outcome events to occur and can also be adapted relatively easily when recruiting participants in multiple countries. Nevertheless, some features of the case control study design are not ideal. Although the case-control design allows more rapid recruitment and follow-up of study participants, compared with cohort studies or randomized trials, they might be prone to errors because of potential uncontrolled differences between the case and control participants such that chance findings can be more likely. To overcome the potential flaws, the investigators had used large sample sizes, simplicity of diagnoses, and clear definitions of case and control participants. Care in standardization of methods, from approaching potential case and control participants, ascertainment of diagnosis, and follow-up end points determination was followed in all countries. The INTERHEART study studied acute myocardial infarction alone and not the whole range of CVD and might thus be regarded by some as not truly CVD. However, this particular diagnosis is ideal for a case control design because of the ease of diagnosis. Although the diagnoses in INTERSTROKE can be more complex, using simple clinical approaches plus common imaging diagnostic approaches makes for accurate event ascertainment.

      Prevention of CVD

      Driven by the speed and scope of increasing CVD worldwide, prevention is essential.
      • Franco M.
      • Cooper R.S.
      • Bilal U.
      • Fuster V.
      Challenges and opportunities for cardiovascular disease prevention.
      There are general approaches in primary prevention of CVD that individuals should adopt irrespective of their country of origin (Fig. 4). A healthy lifestyle, screening, and appropriate therapy for conditions associated with high risk of CVD such as diabetes, hypertension, and hyperlipidemia according to local guidelines published by local professional medical authorities should be followed. Common medications such as aspirin and statins might be considered in high-risk individuals as per published guidelines.
      • Arnett D.K.
      • Blumenthal R.S.
      • Albert M.A.
      • et al.
      2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
      Individuals with previous CVD require secondary prevention and, in addition to lifestyle changes, efficacious drugs proven to prevent recurrence of future events are indicated.
      Figure thumbnail gr4
      Figure 4General approach to cardiovascular disease risk factors modification and treatment.
      • Franco M.
      • Cooper R.S.
      • Bilal U.
      • Fuster V.
      Challenges and opportunities for cardiovascular disease prevention.
      ,
      • Arnett D.K.
      • Blumenthal R.S.
      • Albert M.A.
      • et al.
      2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

      National prevention guidelines

      In prevention of CVD on a global basis, the concept of risk factors must be rendered easily understood and accepted by the populations, from different countries with different languages and varying cultures, income, and development.
      • Franco M.
      • Cooper R.S.
      • Bilal U.
      • Fuster V.
      Challenges and opportunities for cardiovascular disease prevention.
      This is a huge challenge that is usually undertaken by national and international professional bodies such as the Canadian Cardiovascular Society, the European Society of Cardiology (ESC), and the American Heart Association (AHA)/American College of Cardiology (ACC). These organizations have published guidelines that are updated regularly to set the standards for guiding management of risk factors.
      • Arnett D.K.
      • Blumenthal R.S.
      • Albert M.A.
      • et al.
      2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
      • Anderson T.J.
      • Gregoire J.
      • Pearson G.J.
      • et al.
      2016 Canadian Cardiovascular Society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult.
      • Tobe S.W.
      • Stone J.A.
      • Anderson T.
      • et al.
      Canadian Cardiovascular Harmonized National Guidelines Endeavour (C-CHANGE) guideline for the prevention and management of cardiovascular disease in primary care: 2018 update.
      • Khatib R.
      • McKee M.
      • Shannon H.
      • et al.
      Availability and affordability of cardiovascular disease medicine and their effect on use in high-income, middle-income and low income countries: an analysis of the PURE study data.
      World Health Organization
      Prevention of cardiovascular disease. Guidelines for assessment and management of cardiovascular risk.
      • Piepoli M.F.
      • Hoes A.W.
      • Agewall S.
      • et al.
      2016 European guidelines on cardiovascular disease prevention in clinical practice: the Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts). Developed with the special contribution of the European Association for Cardiovascular Prevention and rehabilitation (EACPR).
      These various documents have many similarities. One novel approach when making decisions about the choice of interventions is in dealing with the cumulative risks rather than dealing with and treating, often inadequately, each individual risk factor. This might overcome the tendency of clinicians to treat risk factors separately, avoiding inadequate management of overall risk.

      The Canadian Cardiovascular Society guidelines

      The latest Canadian guideline was an update on CVD focused on primary care that was published in 2018.
      • Anderson T.J.
      • Gregoire J.
      • Pearson G.J.
      • et al.
      2016 Canadian Cardiovascular Society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult.
      ,
      • Tobe S.W.
      • Stone J.A.
      • Anderson T.
      • et al.
      Canadian Cardiovascular Harmonized National Guidelines Endeavour (C-CHANGE) guideline for the prevention and management of cardiovascular disease in primary care: 2018 update.
      Together with parallel documents from the Canadian Hypertension Society and the Diabetes Canada, they form a comprehensive set of guidelines for CVD management. These guidelines include details for screening for and treatment of risk factors such as hypertension, diabetes, dyslipidemia, obesity, and heart failure in individuals with and without diagnosed CVD. In addition, the Canadian Guidelines Committee, recognizing the important role of dyslipidemia in CVD and the need for primary and secondary control, published guideline documents and updates on the management of this set of complex and difficult to control risk factors.
      • Anderson T.J.
      • Gregoire J.
      • Pearson G.J.
      • et al.
      2016 Canadian Cardiovascular Society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult.
      ,
      • Tobe S.W.
      • Stone J.A.
      • Anderson T.
      • et al.
      Canadian Cardiovascular Harmonized National Guidelines Endeavour (C-CHANGE) guideline for the prevention and management of cardiovascular disease in primary care: 2018 update.
      The Canadian documents could serve as a source of information, for Canadian specialists, and also for experts from other national societies.

      The AHA/ACC guidelines

      In their new revision, the AHA/ACC approached treatment on the basis of the level of 10-year CVD risk; the higher the level of risk the more intense the treatment target. Risk-based approaches are recommended for hypertension, diabetes, and hyperlipidemia, with the level of risk indicating the intensity of treatment and treatment targets. Individuals with multiple risk factors will have an opportunity to be treated appropriately for each of the risk factors.
      • Arnett D.K.
      • Blumenthal R.S.
      • Albert M.A.
      • et al.
      2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

      The ESC guidelines

      The ESC document on prevention has placed substantial emphasis on nonpharmaceutical management. These include screening for markers of CVD or risk factors, increasing and maintaining adequate physical activity levels, appropriate dietary modifications, weight reduction as indicated, identifying smokers and advice on quitting, identifying and appropriately treating hypertension, hyperglycemia, and hyperlipidemia, and advice on optimizing risk reductions and to maintain and continue treatments to reach treatment goals.
      World Health Organization
      Prevention of cardiovascular disease. Guidelines for assessment and management of cardiovascular risk.
      ,
      • Piepoli M.F.
      • Hoes A.W.
      • Agewall S.
      • et al.
      2016 European guidelines on cardiovascular disease prevention in clinical practice: the Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts). Developed with the special contribution of the European Association for Cardiovascular Prevention and rehabilitation (EACPR).
      As in the AHA/ACC document, treatment thresholds and goals in the ESC document for initiating blood pressure-lowering medications, hypoglycemic agents, and lipid-lowering therapy are intensified in the presence of multiple risk factors. Health care personnel and caregivers are to be involved in educating and helping patients to achieve goal, even by setting healthy examples such as not smoking or using tobacco products at work.
      • Khatib R.
      • McKee M.
      • Shannon H.
      • et al.
      Availability and affordability of cardiovascular disease medicine and their effect on use in high-income, middle-income and low income countries: an analysis of the PURE study data.
      World Health Organization
      Prevention of cardiovascular disease. Guidelines for assessment and management of cardiovascular risk.
      • Piepoli M.F.
      • Hoes A.W.
      • Agewall S.
      • et al.
      2016 European guidelines on cardiovascular disease prevention in clinical practice: the Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts). Developed with the special contribution of the European Association for Cardiovascular Prevention and rehabilitation (EACPR).
      • Khatib R.
      • Schwalm J.D.
      • Yusuf S.
      • et al.
      Patient and healthcare provider barriers to hypertension awareness, treatment and follow up: a systematic review and meta-analysis of qualitative and quantitative studies.
      In many other countries in the developing world, these published guidelines might be adapted for use for their own populations. For resource-poor countries, some sections of the guidelines, particularly medications, might not be affordable. To be practical, adaptations might depend on successful modification of some guidelines within the scope of resources available in these countries and on the basis of therapies that are affordable and feasible.
      • Khatib R.
      • McKee M.
      • Shannon H.
      • et al.
      Availability and affordability of cardiovascular disease medicine and their effect on use in high-income, middle-income and low income countries: an analysis of the PURE study data.
      ,
      • Khatib R.
      • Schwalm J.D.
      • Yusuf S.
      • et al.
      Patient and healthcare provider barriers to hypertension awareness, treatment and follow up: a systematic review and meta-analysis of qualitative and quantitative studies.
      Although affordability or availability might not feature predominantly in the modern practice guidelines on CVD prevention, a study on this subject has shown that for secondary prevention, let alone primary prevention methods, such medications might be unavailable or unaffordable for a large proportion of communities and households in middle-income and low-income countries.
      • Khatib R.
      • McKee M.
      • Shannon H.
      • et al.
      Availability and affordability of cardiovascular disease medicine and their effect on use in high-income, middle-income and low income countries: an analysis of the PURE study data.
      ,
      • Khatib R.
      • Schwalm J.D.
      • Yusuf S.
      • et al.
      Patient and healthcare provider barriers to hypertension awareness, treatment and follow up: a systematic review and meta-analysis of qualitative and quantitative studies.
      This would lead to very low use of these medications. Other reasons could be inadequate knowledge about risk factors, and low acceptance of the need to continue treatment long-term in the absence of symptoms.
      • Osterberg L.
      • Blaschke T.
      Adherence to medication.

      Current Status on Risk Factors Control

      There is much less known on the extent to which risk factors have been treated and controlled. Like many chronic noncommunicable diseases, treatment of risk factors that affect the individual is expected to be lifelong. Noncommunicable chronic conditions are not episodic such as with infectious diseases, when the infection has been satisfactorily treated, treatment can cease. Although individuals might readily accept a treatment when first proposed, particularly when they are acutely sick, compliance decreases with time, on the basis of the belief that the condition (eg, hypertension) has been treated and therefore treatment can cease. It has been reported that compliance with treatment for a risk factor is initially high, but then it gradually declines over the next few years. For some populations, such as treatment with a statin, compliance might decrease by as much as 50% after 1 year.
      • Osterberg L.
      • Blaschke T.
      Adherence to medication.
      ,
      • Ho P.M.
      • Bryson C.L.
      • Rumsfeld J.S.
      Medication adherence: its importance in cardiovascular outcomes.
      This is particularly so if the individuals experience no symptoms from the risk factor or disease, such as hypertension or hyperlipidemia, but might experience or have unreasonable fear of adverse effects from the treatments. Other reasons include when the treatments themselves are expensive and unaffordable. In many other cases, the “well” individuals might dislike taking drugs long-term. Many claim that they can deal with these risk factors by themselves, by adjusting their diets or lifestyles even if they have no clear knowledge of how to do so. Unfortunately, in most cases, such lifestyle modifications are either improperly followed or abandoned and the individuals continue with the unmodified high risks.
      In the Prospective and Urban Rural Epidemiology (PURE) study from 17 countries (4 low-income, 10 middle-income, and 3 high-income countries), we were able to examine the CVD risk factor burden, treatments provided, and outcomes associated with CVD prevention in 156,424 individuals.
      • Yusuf S.
      • Rangarajan S.
      • Teo K.
      • et al.
      Cardiovascular risk and events in 17 low-, middle- and high-income countries.
      ,
      • Yusuf S.
      • Islam S.
      • Chow C.K.
      • et al.
      Use of secondary prevention drugs for cardiovascular disease in the community in high-income, middle-income and low-income countries (the PURE Study): a prospective epidemiological survey.
      Countries were categorized according to their national income status according to the classification by the World Bank at the time they were included in the study, although with time, such assigned categories might change for individual countries. The PURE study used a common standardized approach in all centres in assessing individual risk factors, community characteristics, country economic development, health care organization, and infrastructure. CVD risk was assessed using a validated score (the INTERHEART Risk Score) derived from the results of the INTERHEART study without using laboratory measurement of lipid levels, which might be inconvenient to obtain. Higher scores indicated greater risk burden. In 1 study, incident CVD and death, following common definitions of outcomes, were recorded after a mean of 4.1 years.
      • Osterberg L.
      • Blaschke T.
      Adherence to medication.
      The results showed that the high-income countries had the highest mean INTERHEART risk score at 12.9, followed by middle-income countries at 10.5, and lowest in low-income countries at 8.3 (P < 0.001). Paradoxically, low-income countries had the highest rates of major CVD events (myocardial infarction, stroke, heart failure, or death from CVD causes) at 6.43 events per 1000 person-years. The rates of CVD events were 5.38 per 1000 person years in middle-income countries and lowest in high-income countries at 3.99 per 1000 person-years (P < 0.001). Case fatality rates were also highest in low-income countries at 17.3%, intermediate in middle-income countries at 15.8%, and lowest in high-income countries at 6.5% (P < 0.01). The study also showed that high-income countries were more likely to use preventive medications and revascularization procedures than were used in middle- and low-income countries. The observation that high-income countries have the highest risk factor burden but with the lowest rates of major CVD and death compared with low-income countries might be explained by better control of risk factors and more frequent use of proven drug treatments and revascularization procedures in high- and middle-income countries.
      • Yusuf S.
      • Rangarajan S.
      • Teo K.
      • et al.
      Cardiovascular risk and events in 17 low-, middle- and high-income countries.
      ,
      • Yusuf S.
      • Islam S.
      • Chow C.K.
      • et al.
      Use of secondary prevention drugs for cardiovascular disease in the community in high-income, middle-income and low-income countries (the PURE Study): a prospective epidemiological survey.

      Drug Use in Secondary Prevention of CVD

      In the PURE study, at a median of 4.0-5.0 years before enrollment, 5650 individuals had a self-reported ischemic heart disease event and 2292 had strokes.
      • Yusuf S.
      • Rangarajan S.
      • Teo K.
      • et al.
      Cardiovascular risk and events in 17 low-, middle- and high-income countries.
      Evidence-based cardiovascular drugs for secondary prevention were taken only in relatively low proportions by individuals who clearly had indications for treatment: antiplatelet drugs were taken by 25.3%, β-blockers by 17.4%, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers by 19.5%, and statin drugs by 14.6% of participants. High-income countries had the highest rate of use (antiplatelet drugs 62.0%, β-blockers 40.0%, ACE inhibitors 49.8%, and statin drugs 66.5%). Usage decreased with the decreasing economic status of the country, being lowest in low-income countries (antiplatelet drug use 8.8%, β-blockers 9.7%, ACE inhibitors 5.2%, and statins 3.3%).
      • Ho P.M.
      • Bryson C.L.
      • Rumsfeld J.S.
      Medication adherence: its importance in cardiovascular outcomes.
      These generally low rates of use at 4-5 years after the events could be because of issues previously discussed.

      Lifestyle Modifications in Secondary Prevention

      Individuals who have experienced a CVD event are routinely instructed to adopt healthy lifestyle behaviours. However, as reported in the PURE study, compliance had not been optimal. It was observed that among 7519 individuals with self-reported ischemic heart disease or stroke, 18.5% did not quit smoking, 35.1% adopted high levels of physical activities, 39.0% had healthy diets, with only 4.3% adopting all 3 behaviours, and 14.3% undertook none of the 3 healthy lifestyle behaviours.
      • Teo K.
      • Lear S.
      • Islam S.
      • et al.
      Prevalence of a healthy lifestyle among individuals with cardiovascular disease in high-, middle and low-income countries: the Prospective Urban Rural Epidemiology (PURE) study.
      Overall, 52.5% of individuals had quit smoking, with 74.9% in high-income countries, 56.5% in upper middle-income countries, 42.6% in the lower middle-income countries, and 38.1% in low-income countries. Physical activity levels increased with increasing income of a country but the trend was not significant. Low-income countries had the lowest prevalence of healthy diets at 28.8%, compared with 43.2% in lower middle-income, 45.1% in upper-middle, and 43.5% in high-income countries. The study reported that the prevalence estimates of healthy lifestyle behaviours were generally low and were even lower in poorer countries. Reasons for such lifestyle behaviours are unclear and could be because of economic reasons, a matter of unavailability and unaffordability of healthy foods such as fruits and vegetables, and the influence of cultures on certain behaviours.
      • Miller V.
      • Yusuf S.
      • Chow C.K.
      • et al.
      Availability, affordability, and consumption of fruits and vegetables in 18 countries across income levels: findings from the Prospective Urban Rural Epidemiology (PURE) study.

      Other Considerations

      Two additional risk factors, smoking and dietary components, are widespread and deserve separate consideration.

      Tobacco smoking

      Smoking is 1 of the 2 most important risk factors for CVD, but data on tobacco are largely from developed Western countries.
      • Pechacek T.
      • Asma S.
      • Blair N.
      • Eriksen M.
      Tobacco: global and community solutions.
      • Teo K.K.
      • Ounpuu S.
      • Hawken S.
      • et al.
      Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case-control study.
      • Pirie K.
      • Peto R.
      • Reeves G.K.
      • Green J.
      • Beral V.
      The 21st century hazards of smoking and benefits of stopping: a prospective study of one million women in the UK.
      • Jha P.
      • Ramasundarahettige C.
      • Landsman V.
      • et al.
      The 21st century hazards of smoking and benefits of cessation in the United States.
      • Hackshaw A.
      • Morris J.K.
      • Boniface S.
      • Tang J.L.
      • Milenkovic D.
      Low cigarette consumption and risk of coronary heart disease and stroke: meta-analysis of 141 cohort studies in 55 study reports.
      The INTERHEART and other studies have extended these findings to developing countries and showed that various forms of tobacco use (cigarettes, pipes, beedies, and chewing) were harmful, and accounted for a PAR of 44.0% in men and 16.0% in women (36% overall).
      • Teo K.K.
      • Ounpuu S.
      • Hawken S.
      • et al.
      Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case-control study.
      Global consumption of cigarettes has steadily risen in the 20th century. Currently, consumption is leveling off and even decreasing in some high-income countries, but increasing in low-income and middle-income countries.
      • Teo K.K.
      • Ounpuu S.
      • Hawken S.
      • et al.
      Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case-control study.
      The harmful effects of tobacco use on CVD, cancers, and total mortality were mainly observed from cigarette smoking in Western countries.
      • Pirie K.
      • Peto R.
      • Reeves G.K.
      • Green J.
      • Beral V.
      The 21st century hazards of smoking and benefits of stopping: a prospective study of one million women in the UK.
      • Jha P.
      • Ramasundarahettige C.
      • Landsman V.
      • et al.
      The 21st century hazards of smoking and benefits of cessation in the United States.
      Other major studies have reported on the prevalence of tobacco use in India, China, the Asia-Pacific region, Mexico, Cuba, and Russia.
      • Kim A.S.
      • Ko H.J.
      • Kwon J.H.
      • Lee J.M.
      Exposure to secondhand smoke and risk of cancer in never smokers: a meta-analysis of epidemiologic studies.
      • Lv J.
      • Chen W.
      • Sun D.
      • et al.
      Gender-specific association between tobacco smoking and central obesity among 0.5 million Chinese people: the China Kadorie Biobank study.
      • Thomson B.
      • Rojas N.A.
      • Lacey B.
      • et al.
      Association of childhood smoking and adult mortality: prospective study of 120 000 Cuban adults.
      • Renteria E.
      • Jha P.
      • Forman D.
      • Soerjomataram I.
      The impact of cigarette smoking on life expectancy between 1980 and 2010: a global perspective.
      • Kuri-Morales P.
      • Emberson J.
      • Alegre-Diaz J.
      • et al.
      The prevalence of chronic diseases and major disease risk factors at different ages among 150,000 men and women living Mexico City: cross-sectional analyses of a prospective study.
      • Barzi F.
      • Huxley R.
      • Jamrozik K.
      • et al.
      Association of smoking and smoking cessation with major causes of mortality in the Asia Pacific Region: the Asia Pacific Cohort Studies Collaboration.
      • Zaridze D.
      • Maximavith D.
      • Zemlyanaya G.
      • Aitakov Z.N.
      • Boffetta P.
      Exposure to environmental tobacco smoke and risk of lung cancer in non-smoking women from Moscow, Russia.
      Tobacco provides no physiological or pharmacological benefit to users. It has been estimated that there are approximately 1.3 billion smokers worldwide, 82% of whom are from middle- and low-income countries.
      • Teo K.K.
      • Ounpuu S.
      • Hawken S.
      • et al.
      Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case-control study.
      Deaths due to tobacco use are correspondingly high with 100 million deaths worldwide from tobacco-related diseases in the 20th century and, with current trends, could increase to 1 billion deaths in the 21st century. The INTERHEART and INTERSTROKE studies reported that participants who were current smokers at the time of enrollment had a greater risk of myocardial infarction (OR, 2.95) and acute stroke (OR, 1.67). These risks were reported in all regions worldwide.
      • Yusuf S.
      • Hawken S.
      • Ounpuu S.
      • et al.
      Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.
      ,
      • O’Donnell M.J.
      • Chin S.L.
      • Rangarajan S.
      • et al.
      Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study.
      The prevalence of current smoking is lower in high-income countries (< 20%) and higher in lower-income countries (40% or more in male individuals).
      • Teo K.K.
      • Ounpuu S.
      • Hawken S.
      • et al.
      Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case-control study.
      Current smokers in lower-income countries will accumulate risk the longer they continue smoking. Former smokers were much more prevalent in high-income countries, where the a large percentage of individuals who had ever smoked had quit, whereas in lower-income countries, much fewer current smokers had quit. Although current smoking in women was somewhat lower than in men in high-income countries, smoking in women was consistently much less prevalent in lower-income countries. In the Middle East, Africa, South Asia, China, and Latin America, only 10% or fewer women currently smoked. Men and women with similar exposures were more likely to experience similar risks. In the INTERHEART study, women who smoked 1-19 cigarettes per day had an OR of 2.11 for acute myocardial infarction and those who smoked 20 or more cigarettes had an OR of 5.11. Corresponding ORs for men were 2.06 and 4.48, respectively. Former smokers were at moderately higher risk than never smokers and the risk decreased with an increase in the duration of quitting.
      • Teo K.K.
      • Ounpuu S.
      • Hawken S.
      • et al.
      Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case-control study.
      Two major studies, the Global Burden of Disease (GBD) study on tobacco
      GBD 2015 Tobacco Collaborators
      Smoking prevalence and attributable disease burden in 195 countries and territories, 1990-2015: a systematic analysis from the Global Burden of Disease Study 2015.
      and the Global Adult Tobacco Survey (GATS)
      • Palipudi K.M.
      • Gupta P.C.
      • Sinha D.N.
      • et al.
      Social determinants of health and tobacco use in thirteen low and middle income countries: evidence from Global Adult Tobacco Survey.
      have summarized the available data by pooling the available individual studies representing mostly middle- and lower-income countries. Using different methodologies and with different objectives, the research studies reported the prevalence of smoking that differed from each other. The GBD study synthesized data, using a methodology they had validated, from 2818 data sources and databases from 195 countries and reported gradual declines in cigarette smoking in most countries over a period of 10-20 years. The GATS pooled data were analyzed using standard pooling methods from 14 individual middle- and low-income countries and reported high prevalence of smoking in the lower-income countries.
      • Palipudi K.M.
      • Gupta P.C.
      • Sinha D.N.
      • et al.
      Social determinants of health and tobacco use in thirteen low and middle income countries: evidence from Global Adult Tobacco Survey.
      The future risks from smoking would depend on the predictive accuracy of these 2 projections and on strategies designed worldwide to reduce tobacco use and the effectiveness in enforcing these international strategies. Faced against these are the pushbacks taken by the tobacco industry. Whether the future predicted risk of 1 billion deaths from tobacco-related disease in the 21st century would come true depends on the effectiveness of strategies aimed at reducing and eliminating tobacco use in populations.

      Dietary considerations

      A number of dietary recommendations have been incorporated into national and professional guidelines as means of lowering risk factors and reducing risk of CVD. Dietary recommendations were formulated in the 1970s on the basis of the scientific evidence at that time and have remained mostly unchanged in the subsequent years. However, recent research into these areas suggest reconsiderations of some of these recommendations might be warranted.

      Dietary sodium

      Much has been published on the association of high sodium consumption and CVD. Many reports have indicated the potential harm from excess dietary sodium intake and recommended that sodium intake should be reduced to less than 2.0 g per day.
      EFSA Panel on Nutrition
      Novel Foods and Food Allergens (NDA), Turck D, Castenmiller J, et al. Dietary reference values for sodium.
      ,
      Diet, Nutrition, and the Prevention of Chronic Diseases.
      This recommendation appeared to have been reached on the basis of moderate-sized short-term randomized clinical trials suggesting that reducing sodium intake could be associated with lower blood pressure levels and population-based observational studies reporting that sodium intake of 2.0 g per day or less in some populations could be associated with lower blood pressure levels.
      • Sacks F.M.
      • Svetkey L.P.
      • Vollmer W.M.
      • et al.
      Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) Diet.
      The conclusion was then made that lowering sodium intake could keep the blood pressure low and in turn reduce the risk for CVD. This position has been endorsed by the major cardiovascular organizations such as the World Health Organization, and the European and American professional organizations. However, because sodium is an essential element in physiological processes and metabolism, it raises an important question: at what level is sodium intake considered excessive and potentially detrimental?
      The PURE study group and other investigators examined the association between the amount of dietary sodium intake and risk of major morbidity and mortality in the PURE population itself and in studies of other high-risk populations.
      • Mente A.
      • O’Donnell M.
      • Rangarajan S.
      • et al.
      Urinary sodium excretion, blood pressure, cardiovascular disease, and mortality: a community-level prospective epidemiological cohort study.
      • O’Donnell M.
      • Mente A.
      • Rangarajan S.
      • et al.
      Urinary sodium and potassium excretion, mortality and cardiovascular events.
      • Mente A.
      • O’Donnell M.
      • Rangarajan S.
      • et al.
      Association of urinary sodium excretion with cardiovascular events in individuals with and without hypertension: a pooled analysis of data from four studies.
      • Stolarz-Skrzypek K.
      • Kuznetsova T.
      • Thijs L.
      • et al.
      Fatal and nonfatal outcome, incidence of hypertension, and blood pressure changes in relation to urinary sodium excretion.
      • O’Donnell M.J.
      • Yusuf S.
      • Mente A.
      • et al.
      Urinary sodium and potassium excretion and risk of cardiovascular events.
      • Pfister P.
      • Michels G.
      • Sharp S.J.
      • et al.
      Estimated urinary sodium excretion and risk of heart failure in men and women in the EPIC-Norfolk study.
      • Mente A.
      • O’Donnell M.J.
      • Rangarajan S.
      • et al.
      Association of urinary sodium and potassium excretion with blood pressure.
      In the PURE study, the population attributable fraction for high sodium consumption (> 6 g per day) for CVD (3.2%) and death (3.9%), were relatively small in the overall cohort. This was consistent with other studies in which a modest association was observed when the direct association of urinary sodium excretion (as an indirect measure of sodium intake) was examined. However, the observation that individuals who consumed less than 4.0 g sodium per day had higher risk of CVD and deaths compared with those who consumed 4-6 g per day has produced a U-shaped relationship, leading to uncertainty about the implications of current recommendations. Other prospective cohort studies, individually and in meta-analyses have also consistently reported a U-shaped association between sodium intake and CVD events in healthy and high-risk populations. These studies indicated that higher sodium intake is associated with increased blood pressure and an increased CVD risk. These studies also suggest a limit below which sodium intake would be unsafe. Studies showed that the relationship between sodium intake and hypertension is not linear; analyses of the data from PURE study showed increments of 2.11 mm Hg in systolic blood pressure (SBP) and 0.78 mm Hg in diastolic blood pressure for each 1 g increment in estimated sodium excretion. However, the slope of this association was steeper in individuals with higher sodium intake and also steeper for persons with hypertension and with increased age. The amount of potassium intake was inversely associated with SBP, with a steeper slope of association in individuals with hypertension than for those without and a steeper slope with increased age.
      In a number of studies, the findings indicate that the association of high sodium intake and CVD risk is confined to those with baseline blood pressure higher than 140/90 mm Hg. Only approximately 10% of the population in the PURE study had hypertension and high sodium consumption of 6 g/d or more, and 22% of the world population consume 6 g/d of sodium. In 1 recent trial it was reported that reducing SBP by 6 mm Hg in those with initial SBP > 143 mm Hg was associated with a 25% reduction in CVD risk. This reduction in CVD risk was not observed in those with lower initial blood pressure, despite similar reductions in blood pressure. Other studies report that a small proportion of the population, approximately 5%, consume 3 g or less of sodium a day, and were at increased harm.
      Examination of average sodium intake estimates in Canada and other Western countries have shown remarkable consistency in sodium intake. It has been observed that approximately 95% of the world’s population consumes more than 3 g/d of sodium and only 22% consume 6 g/d or more. As an essential element, sodium helps to maintain physiological wellness. It is an essential cation crucial to the action potential of all cells in the body and sodium homeostasis is under tight physiological regulation. Sodium intake is governed by neural mechanisms that regulate sodium intake and related homeostatic mechanisms, and has been postulated to have inflammatory responses to infections and might be part of an essential defense mechanism to external infections. Steps taken to reduce sodium intake to levels below these safe levels could lead to adverse outcomes. Advising and enforcing an intake of 3 g/d or less in all individuals to decrease risk would be a huge challenge, which should only be addressed by sound scientific justification, which is lacking at present. The basis for sodium restriction has been made on modelling processes using limited data. The data might suggest a case can be made to reduce sodium intake in individuals with hypertension and high sodium intake, however it remains unclear whether the remaining more than 90% of the population will benefit from dietary sodium reduction. Although the rationale might appear logical, there is limited information in completing the link from surrogate measures on sodium intake to conclusive clinical outcomes. With the availability of new data from recent studies by numerous investigators, it is suggested that the hypothesis on sodium intake should be re-examined.

      Association between micronutrients and CVD and mortality

      Ecological and observational studies in the 1970s that had examined the effect of micronutrients in the diet were carried out mostly in European and North American countries where the CVD mortality was high. Findings from these studies had led to a series of dietary recommendations on the basis of observations and assumption of a linear association between saturated fatty acid intake and low-density lipoprotein cholesterol, and then the association between low-density lipoprotein cholesterol and CVD events. The current guidelines therefore recommend a low-fat diet (< 30% energy) and limiting saturated fatty acids to < 10% of energy intake by replacing them with unsaturated fatty acids. The assumptions for these recommendations did not consider the effects of saturated fatty acids on other lipoproteins such as high-density lipoprotein cholesterol, ratio of total cholesterol and apolipoproteins, and blood pressure, which could affect the risk of CVD. By reducing the saturated fatty acid and low fat in the diet, the proportions of carbohydrates, fats, and proteins would have to be adjusted upward and the effects of such adjustments could influence CVD risk. The unintended consequences of such adjustments must be included in the consideration of dietary changes. In the PURE study, death and major CVD events were analyzed on data from 135,335 participants aged 35-70 years.
      • Dehghan M.
      • Mente A.
      • Zhang X.
      • et al.
      Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): a prospective cohort study.
      Dietary intake was recorded using validated food frequency questionnaires. The results from these studies showed that higher carbohydrate intake was associated with increased risk of total mortality but not with the risk of CVD or CVD mortality. Intake of total fat and each type of fat (saturated fat, monounsaturated fat, and polyunsaturated fat) was associated with lower risk of total mortality. Higher saturated fat intake was associated with lower risk of stroke. Total fat and saturated and unsaturated fats were not significantly associated with myocardial infarction or CVD mortality.
      • Dehghan M.
      • Mente A.
      • Zhang X.
      • et al.
      Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): a prospective cohort study.
      These recent findings are in contrast to current dietary practice, on the basis of widespread guidelines. It is important to reconsider the current recommendations, keeping in mind totality of the data, including what has been reported recently along with previous evidence as well as current beliefs and practices over the past few decades.

      Conclusion

      The trajectory of CVD worldwide has changed over the past 100 years, spreading mainly in developed countries in the initial stages to globally in recent years, with 80% originating from lower-income countries. Advances have been made in the understanding of CVD, identifying and avoidance of risk factors, treatment of the CVD, and changes in lifestyle modifications. Such advances do not occur evenly in all countries. Advances in therapy, identification of risk factors, and treatments occur unevenly and will need to be adapted to suit the particular populations to obtain the optimal outcomes. Recent evidence suggests that some of the existing dietary recommendations might be outdated and should be reviewed and if necessary, revised.

      Funding Sources

      The authors report no funding sources.

      Disclosures

      The authors have no conflicts of interest to disclose.

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