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Latin American Consensus on the management of hypertension in the patient with diabetes and the metabolic syndrome

López-Jaramillo, Patricioa; Barbosa, Eduardob; Molina, Dora I.c; Sanchez, Ramirod; Diaz, Margaritae; Camacho, Paul A.f; Lanas, Fernandog; Pasquel, Miguelh; Accini, José L.i; Ponte-Negretti, Carlos I.j; Alcocer, Luisk; Cobos, Leonardol; Wyss, Fernandom; Sebba-Barroso, Weimarn; Coca, Antonioo; Zanchetti, Albertop,* on behalf of the Latin American Society of Hypertension Consensus Expert Group

doi: 10.1097/HJH.0000000000002072
CONSENSUS DOCUMENT
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The prevalence of hypertension, type 2 diabetes mellitus (DM2) and the metabolic syndrome continues to increase in Latin America, while the rates of diagnosis, treatment and control of these disorders remain low. The frequency of the risk factors that constitute the metabolic syndrome and are associated with an increased risk of cardiovascular disease has not diminished since the publication of the previous consensus. This document discusses the socioeconomic, demographic, environmental and cultural characteristics of most associated Latin American countries and partially explains the lack of better results in improving clinical and public health actions that allow high morbidity and mortality rates caused by cardiovascular diseases and DM2 to be reduced through programs aligned with the so-called precision medicine, which should be predictive, preventive, personalized and participatory. The Consensus ratifies the diagnostic criteria expressed in the previous consensus to define hypertension and DM2 but, for the metabolic syndrome, and in the absence of evidence, the recommendation is to implement a cohort study that determines the abdominal perimeter value associated with hard outcomes, such as DM2 and CVD. Meanwhile, we recommend modifying the criterion to more than 94 cm in men and more than 84 cm in women according to WHO recommendations. We also recommend the carrying out of a study that identifies the situation of hypertension and DM2 in people of African ancestry who, in Latin America, exceed 75 million and whose epidemiology does not include solid studies. With respect to the proposed therapeutic targets, we recommended maintaining those defined in the previous consensus, but insisting that early pharmacological management of prediabetes with metformin should be introduced, as should the treatment of diabetic hypertensive patients with a combination therapy of two fixed-dose antihypertensive drugs and management with statins. To increase adherence, the use of different drugs combined in a single pill (polypill) is recommended. The simplification of the therapeutic regimen is accompanied by greater control of cardiovascular risk factors, both in primary and secondary prevention, and has been shown to be cost-effective. The consensus recommends the use of the currently available polypill combining an angiotensin-converting enzyme inhibitor, a statin and aspirin for secondary cardiovascular prevention and in patients with a high cardiovascular risk, such as hypertension patients with DM2.

aClinica de Síndrome Metabolico, Prediabetes y Diabetes, Direccion de Investigaciones FOSCAL y Facultad de Salud, Universidad de Santander (UDES), Bucaramanga, Colombia

bLiga de Combate a la Hipertensión de Porto Alegre, Brazil

cUniversidad de Caldas e IPS Médicos Internistas de Caldas, Manizales, Colombia

dHospital Universitario Fundacion Favaloro, Buenos Aires, Argentina

eClinica Platinium, Montevideo, Uruguay

fDireccion de Investigaciones FOSCAL y Facultad de Salud, Universidad Autonoma de Bucaramanga (UNAB), Bucaramanga, Colombia

gUniversidad de La Frontera, Temuco, Chile

hInstituto Médico Integral VIDA, Quito, Ecuador

iFundacion Hospital Universidad del Norte y Universidad Libre, Barranquilla, Colombia

jFundación Venezolana de Cardiología Preventiva, Caracas, Venezuela

kInstituto Mexicano de Salud Cardiovascular, Ciudad de Mexico, Mexico

lUnidad de Cardiologia, Hospital El Pino, Santiago, Chile

mServicios y Tecnologica Cardiovascular de Gautemala, S.A., Guatemala

nHypertension League, Federal University of Goias, Brazil

oHospital Clínico, Universidad de Barcelona, Spain

pIstituto Auxologico Italiano, IRCCS, and Università degli Studi of Milan, Italy

Correspondence to Professor Patricio López-Jaramillo, MD, PhD, Clinica de Síndrome Metabolico, Prediabetes y Diabetes, Direccion de Investigaciones FOSCAL y Facultad de Salud, Universidad de Santander (UDES), Bucaramanga, Colombia. Tel: + 57 7 679 7979 x6164; e-mail: jplopezj@gmail.com

Abbreviations: ACEI, angiotensin-converting enzyme inhibitor; AMI, acute myocardial infarction; ARB, angiotensin receptor blocker; BP, blood pressure; CAMDI, Central American Diabetes Initiative; CCB, calcium channel blocker; CI, confidence interval; CVD, cardiovascular disease; DIU, diuretic; DM2, type 2 diabetes mellitus; DOTA, Declaration of the Americas on Diabetes; IDF, International Diabetes Federation; LASH, Latin American Society of Hypertension; LATAM, Latin America; PAHO, Pan American Health Organization; PURE, The Prospective Urban Rural Epidemiology study; RAS, renin–angiotensin system; RCTs, randomized clinical trials; SLIM, Lifestyle Intervention on Postprandial Glucose Metabolism Study; SPC, single pill combination; UPF, ultra-processed foods; USA, United States of America

Received 10 December, 2018

Revised 22 December, 2018

Accepted 24 January, 2019

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PREVALENCE OF HYPERTENSION, DIABETES MELLITUS AND METABOLIC SYNDROME IN LATIN AMERICA

In Latin America, hypertension is responsible for 1.6 million deaths annually because of cardiovascular disease (CVD) of which 500 000 occur before 70 years of age [1]. Hypertension is the main risk factor for coronary and cerebrovascular disease, affecting between 20 and 40% of Latin American adults [2–4]. Previous LASH guidelines and consensuses [5,6] described a high prevalence of hypertension and associated risk factors, as increasingly shown by reports from many countries [6]. However, the prevalence of hypertension differs widely between studies, which may be because of different definitions of hypertension, the age of the study populations, sampling biases, which are usually very small and the methods used to measure blood pressure (BP) [4]. The Prospective Urban Rural Epidemiology (PURE) study, carried out in four Latin American countries, is a population-based project that included people of both sexes aged 35–70 years, with 7497 people from Argentina, 5557 from Brazil, 3274 from Chile and 7478 from Colombia [7]. The prevalence of hypertension was 50.8% in Argentina, 52.6% in Brazil, 46.7% in Chile and 37.5% in Colombia: 57% of hypertensive patients were aware they were hypertensive, 52.8% had received treatment and only 18.3% were controlled (SBP <140 mmHg), rising to 36.3% in treated patients. Only 12.5% of hypertensive patients were receiving combination therapy with at least two antihypertensive drugs [8].

Recently, the results of a broadened sample of individuals from the PURE-LATAM study have been reported [9], including two studies with similar methodological characteristics carried out in Peru [10] and the countries of the Southern Cone of Latin America (Argentina, Chile and Uruguay) [11]. Table 1 shows the characteristics of individuals studied, in whom the global prevalence of hypertension was 44.6%, which was higher in Brazil (52.5%) and lower in Peru (19.3%): 59.6% of individuals knew they were hypertensive, which was higher in Brazil (64.8%) and lower in Colombia (51.9%), and 54.2% were receiving treatment, rising to 90.9% in persons who knew they were hypertensive, although only 37.6% were controlled (Table 1). Social inequality is one of the factors that most affects the control of hypertension, according to the PURE-Colombia study [12], which showed that the prevalence of hypertension was 37.5% in the study population, rising to 62.5% in persons with low educational levels. The study also found that the highest risk of uncontrolled hypertension occurred in overweight or obese men aged less than 50 years living in rural areas who had low educational and income levels [12]. These factors are also important in the rapidly accelerating increase in the prevalence of type 2 diabetes mellitus (DM2), which is observed globally and in Latin America.

TABLE 1

TABLE 1

The International Diabetes Federation (IDF) estimates that approximately 425 million people worldwide have DM2, of which one third are aged more than 65 years and 80% live in middle-income and low-income countries, and also estimates that the number will increase to 693 million by 2045 [13]. The prevalence of DM2 in Latin America ranges between 5.5 and 13.6% and has increased by between 3 and 12% between 2015 and 2017 in Argentina, Colombia, Costa Rica, Nicaragua and Uruguay (Fig. 1). The increase in the prevalence of DM2 also implies a significant increase in the disease burden for Latin American health systems. Thus, the risk of premature death in a patient with DM2 is higher than in those without DM2 [14] and the risk of cardiovascular death is double [15]. It is estimated that 40% of people with DM2 in Latin America are not diagnosed, making it difficult to accurately estimate the costs of managing DM2 and its complications for health systems [16,17].

FIGURE 1

FIGURE 1

As shown in Fig. 1, there are variations in the prevalence of DM2 between Latina American countries which, as happens in hypertension, may be because of the different diagnostic criteria used, the characteristics of the populations studied, the age groups evaluated and the diagnostic methods used. Migration to cities, greater access to screening and diagnostic tests, and environmental, social, cultural and economic factors that influence the demographic, epidemiological and nutritional transition, expressed as the aging of the population, changes in lifestyles (dietary habits and physical activity) and the increase in urbanization [18–20], are also influencing factors. All these factors contribute to the remarkable increase in overweight and obesity, particularly abdominal, seen in Latin America which, together with glycemic alterations, hypertension, dyslipidemia characterized by an increase in triglycerides and a decrease in HDL-cholesterol, are the components of the metabolic syndrome. The high prevalence of metabolic syndrome in Latin America described above [5] has been confirmed in a recent systematic review [21] and in new studies, such as the Central American Diabetes Initiative (CAMDI), sponsored by the Declaration of the Americas on Diabetes (DOTA) and the Pan American Health Organization (PAHO), which evaluated the prevalence of metabolic syndrome in Costa Rica (San José), Guatemala (Guatemala City), Honduras (Tegucigalpa), Nicaragua (Managua) and Belize, and reported a prevalence of metabolic syndrome of 30.3%, ranging from 23% in Honduras to 35.1% in Costa Rica. Nicaragua had the highest prevalence of hypertension (41.4%) and Guatemala the highest prevalence of hyperglycemia (28.2) [22].

Each metabolic syndrome component increases the risk of cardiovascular disease and all-cause mortality. However, the metabolic syndrome cluster increases the risk more than the sum of each independent component and is associated with a 1.5–2.5 increase in all-cause death, cardiovascular death and death because of DM2 [23,24].

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DEFINITION OF OVERWEIGHT, OBESITY AND METABOLIC SYNDROME IN LATIN AMERICA

The concept that metabolic syndrome in Latin America should consider the criterion of abdominal obesity as mandatory is based on observations from recent studies that show the incidence and prevalence of overweight and obesity have increased progressively during the last six decades and alarmingly so in the last 20 years, reaching figures of 10–20% in childhood, 30–40% in adolescence and 60–70% in adults [25,26]. Due to the fact that Mexico has Official Mexican Standards on hypertension and overweight [27,28] which are mandatory, while the guidelines of the scientific society are only suggestions on the way to approach and treat a particular problem taking into account the characteristics of the patient, in order to unify criteria for Latin America, the Consensus recommends accepting the definitions of overweight and obesity determined by law in Mexico. Consequently, we define overweight as a BMI at least 25 kg/m2 and less than 29.9 kg/m2 and in adults of short stature, at least 23 kg/m2 and less than 25 kg/m2. In persons aged less than 19 years, overweight is defined as a BMI between the 85th and 95th percentile of the WHO age and sex tables. Obesity in adults is defined as a BMI at least 30 and 25 kg/m2 in persons of short stature. In persons aged less than 19 years, obesity is defined as a BMI in the 95th percentile of the WHO BMI tables for age and sex. Low stature is defined as less than 1.50 m in adult women and less than 1.60 m in adult men [27,28].

With respect to central obesity, a mandatory criterion for the diagnosis of metabolic syndrome, the current Consensus demands that the cut-off points to be proposed must be supported by a demonstration of therapeutic benefit or association with risk. Concerning therapeutic benefits, these should come from results of randomized clinical trials (RCT) or analysis of subgroups of RCTs showing a better prognosis after treatment in Latin American patients when dealing with a certain limit of the risk factor (glycemia, BMI, definition of metabolic syndrome, abdominal perimeter). Unfortunately, this evidence was nonexistent in the Latin American population with only few cohort studies that show associations between levels of these risk factors and the incidence of cardiovascular events or the presence of another risk factor, and no studies with an estimated event risk based on a Framingham-type risk scale. The most common studies are cross-sectional or case–control, in which the risk is estimated by the presence of CVD or by risk equations. Therefore, it is difficult to make a recommendation on the cut-off points to be applied to the Latin American population, and even more so when the characteristics of the Latin American population are considered, such as differences and ethnic mixes with variable proportions of European ancestors and the native population and, in some countries, with a black or Asian population [29–37].

The measurements proposed to define central obesity are waist circumference, waist/hip ratio and waist/height ratio. In general, there is a consensus that these measurements are more closely associated with cardiovascular risk than with BMI. Indexes that correct the waist perimeter per the hip circumference (waist/hip ratio) tend to have a better correlation and predictive capacity for DM2 or CVD than the waist circumference alone, although in some reports the benefit of adding these measurements is marginal. Therefore, the Consensus recommends the use of the abdominal perimeter, with the measurement being made at the midpoint between the palpable lower margin of the last rib and the upper edge of the iliac crest, at the end of expiration, with a nonelastic tape with a tension of 100 g [38].

In the absence of Latin American studies that met the quality criteria demanded, the previous Consensus [5] followed the IDF recommendations for South and Central American ethnic groups of at least 90 cm in men and at least 80 cm in women [39]. The present consensus also considered the WHO recommendations of more than 94 cm in men and more than 80 cm in women at increased risk, and more than 102 cm in men and more than 88 cm in women at substantially increased risk [40,41]. In the absence of evidence, the recommendation of the Consensus is to carry out a cohort study to determine the value of the abdominal perimeter best associated with hard outcomes, such as DM2 and CVD. Meanwhile, we recommend modifying the criterion to more than 94 cm in men and more than 84 cm in women, according to the WHO recommendations [40,41].

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DIAGNOSIS AND CLASSIFICATION OF HYPERTENSION AND BLOOD PRESSURE TARGETS TO BE ACHIEVED IN PATIENTS WITH METABOLIC SYNDROME AND DIABETES MELLITUS 2

The consensus confirms the previous concepts [5,6,42] that hypertension is diagnosed in patients with metabolic syndrome and DM2 when office BP is measured at two different times and, according to the norms that validate the measurement [5,6], is at least 140/90 mmHg. We also maintain the classification of hypertension grade 1 as BP values between 140/90 and 159/99 mmHg; grade 2 as between 160/100 and 179/109 mmHg and grade 3 as at least 180/110 mmHg. Pharmacological treatment should be initiated when BP is more than 140/90 mmHg and, despite the debate about the BP targets that should be achieved, the current Consensus recommends reaching and maintaining values of less than 140/85 mmHg, considering that the optimal goal for SBP is 130 mmHg or less, and there is no additional benefit in trying to reach levels less than 120 mmHg, and the optimal goal for DBP is 80 mmHg, recommendations that coincide with the recent guidelines of the European Society of Cardiology/European Society of Hypertension [43].

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DEFINITION OF THE DIAGNOSTIC CRITERIA FOR TYPE 2 DIABETES IN LATIN AMERICA

The diagnosis of DM2 is based on increased levels of glycemia and/or glycosylated hemoglobin (HbA1c). As these measurements are the only means to diagnose DM2, they must be adapted to each population according to genetic and epigenetic characteristics, which may vary in populations subjected to different socioeconomic conditions [44]. The WHO determined the cut-off points for glycemia and HbA1c for the diagnosis of DM2 based on the results of epidemiological studies conducted in high-income countries and which are associated with the risk of retinopathy [45,46], cut-off points that could be inadequate for medium-income and low-income countries, especially considering the association of these cut-off points with the risk of CVD [47,48]. The Consensus recommends the continued use of the WHO criteria for the diagnosis of DM2, which means meeting any of the following four criteria: criterion 1, symptoms of hyperglycemia, such as polyuria, polydipsia, polyphagia and unexplained weight loss, together with casual blood glucose at least 200 mg/dl, defining as casual the result obtained at any time of the day; criterion 2, glycemia at least 200 mg/dl 2 h after an oral glucose load. The test should be carried out as described by the WHO, using a glucose drink containing the equivalent of 75 g of glucose dissolved in water; criterion 3, fasting blood glucose at least 126 mg/dl and criterion 4, HbA1c at least 6.5%.

On the basis of the two works recently published in Latin America [49,50], the Consensus also recommends diagnosing and treating prediabetes, also known as glycemia with an increased risk of DM2, or intermediate hyperglycemia, a term proposed by the WHO referring to an intermediate metabolic state between normal glucose homeostasis and DM2 [45]. It is diagnosed by venous blood glucose levels: altered fasting blood glucose when values are between 100 and 125 mg/dl after at least 8 h of fasting, and/or glucose intolerance when glycemia values 2 h after the administration of an oral overload of 75 g of glucose are between 140 and 199 mg/dl, and/or if HbA1c values are between 5.7 and 6.4% [51]. According to the IDF, the worldwide prevalence of prediabetes varies between 6 and 14% and, for Colombia, the age-adjusted estimate (20–79 years) is 8–10% [52]. There is a large body of evidence showing that prediabetes progresses to DM2 at an annual rate of at least 10% and that, regardless of progression to DM2, it is a risk factor for cardiovascular disease [53–59]. Therefore, the Consensus recommends immediate management through changes in lifestyle and new assessments at 3 and 6 months once prediabetes is detected and diagnosed. If the patient does not respond with a weight loss of at least 5% and if HbA1C values are not normalized, pharmacological treatment with a dose of 500 mg/day of metformin should be initiated, escalating to 1500–1700 mg/day, according to tolerance.

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SOCIOECONOMIC, ETHNIC, NUTRITIONAL AND GEOGRAPHICAL CHARACTERISTICS ASSOCIATED WITH THE RISK OF HYPERTENSION, METABOLIC SYNDROME AND DIABETES MELLITUS 2

Social risk

Latin America has a series of ethnic, economic, geographic and cultural characteristics that influence the high prevalence of hypertension, metabolic syndrome and DM2 [60]. Socioeconomic inequalities, which are common in Latin America [61] and which vary according to the ethnic composition, should be considered as a conditional risk factor for CVD which, in turn, contributes to an increased social risk [62]. Inequalities in social, economic and educational conditions contribute to chronic psychosocial stress, which is a frequent risk factor in the Latin American population, and which is associated with hypertension [12,63], DM2 [44], metabolic syndrome [64,65] and CVD [66–68]. Socioeconomic inequalities and differences in access to health services between urban and rural areas in Latin America are other determinants of the differences in the prevalence of CVD risk factors and their management [68–70]. Social inequalities are so characteristic of Latin America that the Latin American hypertension guidelines were the first to include social risk as a scoring factor within the risk scale of hypertension management [71]. Figure 2 shows the components of social risk and their association with hypertension, metabolic syndrome and DM2. Factors, such as the educational level, the income level, the possession or absence of housing and whether people have permanent jobs are conditioning factors of social risk, which is directly associated with access to healthy foods and the intake of macronutrients and micronutrients. The recent results of the PURE study have shown that low-income and middle-income countries, which include the Latin American countries participating in the study, have less availability, less access to and lower consumption of fruits and vegetables [72,73], proteins and fats [74], and milk and derivatives [75] compared with high-income countries. However, the consumption of carbohydrates, especially processed and ultra-processed ones, is greater [74]. These dietary characteristics, observed throughout Latin America, and particularly in the poorer socioeconomic sectors, are a risk factor for hypertension, dyslipidemia, obesity and CVD [76,77].

FIGURE 2

FIGURE 2

Mass internal migration from the countryside to the big cities, seeking, at least in theory, greater opportunities, has led to an accelerated, disorganized process of urbanization, which is another characteristic aspect of Latin America related to poverty, with social inequities and, in some countries, situations of forced displacement because of political violence. This migration results in the formation of marginal suburbs lacking any health infrastructure, and changes in lifestyles with the adoption of unhealthy habits, such as the consumption of processed foods and sedentary lifestyles [78,79]. The Chronicles study in Peru [64] found a difference in the prevalence of obesity among rural inhabitants, migrants from rural areas to urban areas and urban dwellers. The prevalence of obesity was 3, 20 and 33%, respectively, and the prevalence of DM2 0.8, 3 and 6%, respectively.

Education and schooling are also key determinants of the risk of hypertension, DM2 and obesity [80]. The PURE-Colombia study found that, in men aged less than 50 years with lower salaries living in rural areas, the lower level of schooling was the factor that most influenced not only high BP but also the treatment and control of hypertension [12]. In Latin America, dropping out of school is common because of the economic conditions of households, which further aggravates the already-low number of individuals from lower social classes who have access to primary education and almost no possibility of accessing higher education [81]. This, in turn, is related to an increase in risk factors [80] and cardiovascular events [82], an association consistent with that found in other populations [83].

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Ethnic and geographical factors

Another characteristic of the Latin American population is the enormous degree of mixing between ethnic groups, from Indian aborigines through the European whites and blacks of African ancestry and, more recently, large migratory groups of Asians and Syrian-Lebanese, which has contributed to the mixture of ethnicities that makes the definition and categorization of ethnic groups difficult [5,84]. However, the black skin characteristic of African ancestry, the greater risk of developing hypertension and DM2, and the large black population in Latin America, determined that the previous consensus [5] concluded that, before 2012, there was no large epidemiological study on the prevalence of hypertension and diabetes in this population, and that no study with a representative sample has investigated food intake, physical activity and body composition, factors associated with hypertension and diabetes in this group. It, therefore, recommended carrying out epidemiological, clinical and therapeutic research in persons of African ancestry living in Latin America to verify whether the results of US studies are applicable to the black population of Latin America. In addition, it was recommended that, until there was an adequate amount of data from studies in the black population of Latin America, the adoption of the guidelines of the International Society of Hypertension in Blacks, a document that highlights the high prevalence of the coexistence of hypertension with obesity and DM2, especially in women, as well as the greater frequency of cardio-renal complications associated with hypertension and DM2 [85]. In spite of the recommendation to conduct new epidemiological studies in this region, very few studies in Latin American people of African ancestry have been published between 2012 and 2018 [86,87], and those have found a higher prevalence of hypertension and lower rates of diagnosis, treatment and control of hypertension with respect to other ethnic groups. Most studies from the Caribbean islands [88–94] show that blacks in the Caribbean have a higher prevalence of hypertension than whites in the United Kingdom and that, moreover, there is higher mortality because of causes associated with hypertension than that presented by blacks in the United Kingdom, especially women. However, in the population of Cuba where there are no great differences in social risk between whites and blacks and where hypertensive patients had equal access to medications [95], it was shown that differences in BP levels were less pronounced, which underlines the fact that in addition to the proposed higher genetic sensitivity to sodium intake presented by people of African descent [96], other socioeconomic factors may be interacting to determine the higher prevalence of hypertension and DM2 observed in this specific population in Latin America [97]. The implication of clearly determining these factors is of great importance in the public health of the Latin American countries with a high percentage of blacks [84,98]. Therefore, this Consensus insists on recommending, to Latin American Science and Technology systems, the need to finance projects that clarify the causes of the greater risk in people of African ancestry of presenting a higher incidence of hypertension and DM2 (Table 2).

TABLE 2

TABLE 2

Altitude-induced hypobaric hypoxia involves adaptive changes in many physiological systems in exposed individuals and may have important effects on the regulation of BP and the glucose metabolism [99–102]. The population of Latin America living in the Andes Mountains shares similar characteristics and historical colonization patterns with people living at lower altitudes, being mostly Amerindians or mixed race. People living at high altitudes in the Andes (>3000 m above sea level) constitute a special group in whom the prevalence of hypertension and diabetes is poorly understood. However, the few existing data suggest there are no differences in the prevalence of hypertension and DM2 between them and populations living at sea level or lower altitudes, as reported in the previous consensus [5]. Recently, a higher prevalence of hypertension has been described in Colombian populations living at sea level (44.8%) than in those living at altitude (>2000 m above sea level: 36.0%) [12]. However, this study could not exclude the influence of the ethnic group because it is well known that the percentage of black people living at sea level is greater than that of those living at high altitude. In addition, altitude is related to greater exposure to cold, which increases BP levels, as has been demonstrated in other populations [103–105]. The lack of data led to the previous consensus recommending the initiation of studies to define the role of altitude and concomitant low temperatures in the risk of hypertension in Latin America. Parati et al. have initiated a series of studies in Peru, Ecuador and Colombia with the aim of defining, in the high Andean population, whether the prevalence of hypertension differs from that of people living at sea level, and of determining the mechanisms involved and their impact on the management of hypertension in these Andean high-altitude populations [106,107].

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Food characteristics

Noncommunicable chronic diseases are attributed to inadequate human behavior, especially that related to diet, physical activity, smoking and alcohol. Guidelines and consensuses on hypertension, diabetes, overweight, obesity, dyslipidemia and atherosclerotic disease agree that lifestyle modifications are the preferred first-step intervention for the prevention or treatment of these conditions, either when they occur in isolation or when they do so in various ways, as happens in metabolic syndrome . Any strategy that tries to influence these risk factors is expensive as it requires a complex approach and highly qualified professionals, making these interventions not affordable for low-income and middle-income countries, where illnesses derived from unhealthy lifestyles are the most prevalent.

In 2014, the NutriCoDE study, designed and directed by the Global Burden of Diseases Nutrition and Chronic Diseases Expert Group [108] systematically studied and analyzed 266 national adult nutrition surveys, evaluating the consumption of saturated fats, fatty acids Ω-6 and Ω-3 from fish, fatty acid Ω-3 from plants, trans fats and dietary cholesterol. The study showed that, in Latin America, there is a high level of cholesterol and trans fats in the regular daily diet. In Mexico, the consumption of cholesterol and trans fats can be as high as 4.5 g/day. Saturated fats are consumed in a similar pattern to that which occurs in other areas of the developing world comparable with Latin America, but unsaturated fatty acids are consumed in significantly smaller quantities, especially with respect to the low consumption of Ω-3 from marine fish sources. In countries, such as Bolivia, Paraguay, Argentina, Mexico and the Dominican Republic, the consumption is less than 50 g/day. This situation, which may be understood in Bolivia and Paraguay, countries without an oceanic coast, cannot be explained by this reason in the other countries mentioned, all of which have long coastlines, including the Dominican Republic, which is an island. Therefore, this imbalance in the consumption of polyunsaturated fats from fish is a consequence of cultural, economic and educational situations, which affords an opportunity to intervene in the population through education and laws that limit the consumption of trans fats, given that the largest sources of these fats are fried flours containing margarine. In addition, the high consumption of refined sugars, soft drinks with added sugar and ultra-processed foods (UPF) in ready-to-eat or drink formulations, which contain more sugar, more trans fats and more sodium, are widely consumed in Latin America, as they are accessible, practical, ubiquitous, very well publicized, tasty and highly addictive [109]. UPF consumption is associated with an increase in adult BMI at all levels of consumption, after adjustment for covariates (R2 = 0.79, P < 0.0001), to the point that the per capita sale of these products (in kg) is an independent predictor of the increase in BMI over time [110]. The Pan American Health Organization (PAHO) conducted a study to estimate UPF consumption trends using sales information from the Euromonitor International 2014 database [111], and found that, in a time series analysis using national surveys from 12 countries between 1999 and 2013, which analyzed the association between changes in annual sales per capita of UPF (in kg) and changes in the mean standardized BMI in adults, the Latin American market is the third in the world, behind Asia and Canada, with an increase of 50% in consumption between 2000 and 2013, surpassing the US market in the sale of sugary soft drinks in 2013. The five countries with the highest consumption of UPF per capita are Mexico, Argentina, Chile, Bolivia and Paraguay which, in turn, are the five countries with the highest BMI and the highest incidence of obesity.

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Dietary recommendations

Most studies have found that the gold-standard or first-line indication with respect to cardioprotective diets is the Mediterranean diet, which demonstrated effectiveness in longitudinal studies and can be recommended both in primary and secondary prevention of cardiometabolic diseases [112–115]. The Mediterranean diet is a cardio-protective diet, defined as ‘foods and beverages that were consumed in the countries that border the Mediterranean Sea in the 1960s.’ It is rich in unsaturated fats (olive oil, nuts, seeds), low in saturated fats (red meat), whole milk) and, in general, contains more fresh or natural foods (fruits, vegetables, whole grains) than processed foods. Saturated fats found in greater amounts in red meat, cheese, and whole milk increase total cholesterol and low-density lipoprotein (LDL)-cholesterol. For a long time, the intake of saturated fat, especially of animal origin, was considered the most important risk factor for cardiometabolic disease and low fat consumption was promoted at the expense of saturated fats. Recently, the PURE study established that this recommendation caused high consumption of processed carbohydrates in order to cover calorific requirements, resulting in excess consumption that increases the risk of cardiometabolic disease [74,76], whereas the adequate consumption of fats, similar to that of the Mediterranean diet, was associated with a significant reduction of 23% in total mortality risk, an 18% lower risk of stroke and a 30% lower risk of noncardiovascular mortality. Each type of fat was associated with a significant reduction in mortality risk: a reduction of 14% with saturated fats, 19% with monounsaturated fats and 20% with polyunsaturated fats. A higher intake of saturated fat was also associated with a 21% decrease in the risk of stroke (Table 3). Another important change in the dietary recommendations is the elimination of the restriction on the consumption of cholesterol of 300 mg/day as a strategy for the prevention of atherosclerotic disease. Since 2015, the warning on restricting foods with high cholesterol content, such as eggs, some meats or whole milk products, among others, has been eliminated [77].

TABLE 3

TABLE 3

This new evidence leads us to recommend a complete diet, that is, it must cover, in a balanced fashion, all dietary nutrients, be isocaloric, with 50–55% of energy ingested from carbohydrates, preferably from slowly absorbed natural carbohydrates, and must restrict the consumption of processed carbohydrates with a high glycemic index, maintain an adequate protein intake corresponding to 20–25% of the energy ingested, which the remaining 20–30% coming from fats, maintaining a 1–1–1 ratio between saturated, unsaturated and polyunsaturated fats. Currently, in the diet of most of the population of Latin America, this would entail avoiding processed foods with high calorific density, avoiding combining easily absorbed carbohydrates with fat, promoting the consumption of white meat over red meat and of foods rich in polyunsaturated fats (Ω-3) at least twice a week, such as fish and nuts, stimulating the consumption of legumes (100 g two or three times per week), including those originating in Latin America, such as quinoa and lupine (Lupino mutabilis), which are of high nutritional value and have been shown to be useful in the coadjuvant management of DM2 [77,116,117].

The consumption of natural foods offers a contribution of dietary fiber that is lost in industrial or home processed food. It is advisable to ingest the natural fruit, as the contribution of carbohydrates per gram (fructose) is lower than that of juice, which may contain more than twice that of fresh fruit. The PURE study also established that the recommendation to ingest five fruits/vegetables per day exceeds the daily carbohydrate requirements, suggesting an intake of three servings per day [73].

We emphatically and repeatedly recommend minimizing the intake of sweetened beverages, as these are very important risk factors for the Latin American population, especially children, and the intake of artificial beverages, such as soft drinks, instant tea or energy drinks. The consumption of sweeteners should be avoided, as this group of artificial additives, without calorific value, is sweeter than sugar, making it more difficult to wean patients from sweet foods. They have not shown significant benefits on health, and have recently been linked to an increase in BMI and DM2. Therefore, this Consensus does not recommend their consumption and promotes a reduction in simple sugars as the most appropriate way to reduce the calories derived from carbohydrates.

Another controversial issue in the dietary recommendations is related to salt consumption. Reports based on the results of the PURE study [118–122] confirm the positive association between sodium intake and SBP. This association is particularly evident in populations and individuals with a higher sodium intake (>5 g/day, equivalent to >12.5 g/day of salt), but not when sodium consumption is lower. Sodium intake was associated with a significant increase in stroke rates only in populations with salt intake in the upper tertile, and most were communities in China. Unexpectedly, there was an inverse association between sodium consumption and acute myocardial infarction (AMI) and mortality rates, while the increase in potassium consumption was associated with a significant decrease in all cardiovascular events. The magnitude of the association between sodium consumption and SBP (2.86 mmHg per 1 g increase in sodium consumption) was more robust than that reported in the INTERSALT (1.94 mmHg) [123] and INTERMAP (0.22 mmHg) studies [124]. However, this association only occurs in communities with a mean sodium consumption similar to that observed in China (5.58 g/day), and not in countries whose mean consumption is in the order of 4.49 g/day. These results have led some sectors to support them with data obtained in different populations [125–130], whereas others have questioned them [131,132]. The contrasting data suggest that the current recommendations for sodium intake [133,134] need to be re-evaluated [135] and that the impact of reductions in salt intake in reducing CVD should be the subject of controlled clinical studies, which are already being implemented [136]. This should allow the resolution of disputes that, as pointed out by Alberto Zanchetti, ‘are welcome, because it is through controversy that science advances’ [137]. Meanwhile, the recommendation to reduce sodium consumption as a measure preventive for hypertension and CVD should be, rather than a universal population intervention, directed and implemented in those communities and individuals in whom sodium consumption is more than 5 g/day, which will avoid the dispersion of resources in trying to introduce this measure in communities or individuals in whom the consumption of sodium is less than this amount and who will not benefit from the intervention. In addition, there is a risk that reducing sodium intake to minimum levels in populations that consume an adequate amount may increase the risk of AMI and death. On the other hand, the difficulty in ensuring good adherence to diets very restrictive in sodium is well known and, as was pointed out by Pickering [138] ‘rigid low-sodium diets are tasteless, unappetizing, monotonous, unacceptable and intolerable. To maintain them requires the asceticism of a religious fanatic.’

Lifestyle modifications should be recommended in high-risk adults, such as patients with diabetes and hypertension, as an important complement in the control of their problems and in reducing medicament use. However, major efforts should focus primarily on the creation of healthy lifestyles in the expectant mother, during childhood and throughout life, as recommended by the Lancet Commission on Hypertension [139]. Recently, the concept of the first 1000 days has been gaining acceptance [140,141]. This includes a critical period that covers 40 weeks of gestation and the first 2 years of life, as the changes generated in this stage are decisive. It is considered to be a unique window of opportunity to shape and improve health in the short-term and long-term, given that it is a stage of cell formation, multiplication and differentiation from the pluripotent stem cell. Early feeding and metabolic programming influence genetic expression by modifying, among other things, the risk of chronic noncommunicable disease. In this stage of high plasticity and accommodation to the environment, it is important that the body receives all the nutrients needed for optimal development. Deficiencies and excesses can result in metabolic changes that could predispose to the appearance of noncommunicable diseases, such as cardiovascular and metabolic diseases, among others [19,78,142]. During the first 1000 days, the most important risk factors for cardiometabolic disease in children are: obese or overweight mother, excess maternal weight gain during pregnancy, maternal smoking, rapid weight gain in the first year of life and little or no contribution of breast milk.

Therefore, the introduction of mass nutritional education programs for pregnant women and children and adolescents, in addition to adults with risk factors and CVD, is a priority as are new laws and actions aimed at reducing the consumption of these products, such as an increase in taxes. These strategies are recommended by the present Consensus, which also demands from medical-scientific societies, primary and secondary educational institutions, and universities, the establishment of programs to promote, advice, endorse and organize structured campaigns to create awareness in all social sectors, and especially in children and adolescents, the risk implied by excessive consumption of these products.

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Laws on food labeling and health literacy

As mentioned above, in recent years, there has been a large increase in the sales of processed and ultra-processed foods in Latin America, including snacks and sugary drinks, a phenomenon related to the high rate of overweight and obesity. Between 1999 and 2013, sales of processed foods and sugary beverages increased hugely, mainly in countries, such as Chile and Mexico [143]. In fact, Chile is the main consumer of sugary drinks per capita in the world, followed by Mexico and the USA.

The link between processed food and obesity is well documented and begins in childhood [143]. The problem of childhood obesity requires a broad response that takes into consideration the current obesogenic environment in Latin America. In the context of the fight against obesity, a key component, which UNICEF supports in the countries of the region, is the regulation of the labeling of processed foods and beverages aimed at children and adolescents, which would contribute positively to reducing obesity levels in these age groups. [144–147].

There have been some innovative actions in Latin America, such as the taxing of soft drinks in Mexico, new food labeling in Chile and, in Brazil and Uruguay, the publication of food guidelines that adopt a food classification according to the degree of processing. Analysis of current food labeling regulations in Latin America and the Caribbean shows Chile, Ecuador and Mexico have introduced frontal labeling as a public health strategy. Food labeling is associated with several factors, such as the level of education and the type of diet (Table 4).

TABLE 4

TABLE 4

Frontal labeling is effective when displayed in a simple, consistent, eye-catching way that can be interpreted quickly. For this, it is proposed to direct the efforts of the regulation of frontal labeling at the most vulnerable groups (those with lower educational and socioeconomic levels and who live in rural areas, among others), and promote the introduction of frontal labeling of industrialized foods and beverages that is simple and striking, does not require mathematical skills, takes little time to interpret and is consistent throughout the region. The labeling must be supported by scientific evidence generated by institutions without conflicts of interest; it must include the different elements of food and beverage packaging, and must be accompanied by an educational campaign that ensures sustainability. It is important to develop these campaigns to improve understanding and use by consumers, especially parents and children. Civil society must provide information about the use and understanding of frontal labeling systems, and request and demand best practices.

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Alcohol consumption

In Latin American countries, the mean annual per capita consumption of alcohol is 2.2 l, higher than the rest of the world's regions [148]. The relationship between consumption more than 35 g/day and the risk of hypertension, metabolic syndrome, DM2 and CVD is well established [149,150]. The PURE study analyzed the data obtained in 12 of the participating countries in which alcohol consumption is allowed [150], and included 114 970 adults of whom 12 904 (11%) were from high-income countries, 24 408 (21%) from upper middle-income countries, 48 845 (43%) from low middle-income countries and 28 813 (25%) from low-income countries, with a mean follow-up of 4.3 years. Current drinking was reported by 36 030 (31%) people and was associated with a reduction in the risk of myocardial infarction [hazard ratio 0.76 (95% CI 0.63–0.93)] and an increase in types of cancer related to alcohol [hazard ratio 1.51 (95% CI 1.22–1.89)] and accidents [hazard ratio 1.29 (95% CI 1.04–1.61)]. High alcohol intake was associated with increased mortality [hazard ratio 1.31 (95% CI 1.04–1.66)]. There was a significant reduction in the hazard ratio for the composite of major CVD in high-income countries compared with people who never drank, but not in low-income and middle-income countries, which shows that alcohol consumption has different associations according to the socioeconomic status of the countries. On the basis of these data, we recommend introducing actions aimed at avoiding excess alcohol consumption in Latina American countries as a strategy to reduce the risk of hypertension and other risk factors for CVD, such as atherogenic dyslipidemia, which is extremely frequent in Latin America [151].

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Physical activity

The increase in sedentary behavior due, in large part, to technological advances in transportation and entertainment is contributing to the increase in the rates of obesity, DM2, hypertension, CVD and all-cause mortality [152,153]. Although most studies have been conducted in high-income countries, the PURE study recently evaluated the effect of physical activity on mortality and cardiovascular disease in 130 000 people without cardiovascular disease from 17 countries classified as high, medium and low income, including Latin American countries, such as Argentina, Chile, Brazil and Colombia [154]. It was shown that the greater the physical activity, the lower the prevalence of hypertension and DM2. The reduction in the relative risk between groups with high physical activity compared with groups with low physical activity was 86% for hypertension and 66% for DM2. The reduction in the relative risk for total mortality and CVD was 28 and 20%, respectively. The lowest risk was presented by people who engage in high and moderate physical activity compared with those who engaged in low physical activity. High physical activity was defined as more than 750 min per week of moderately intense physical activity, moderate physical activity as 150–750 min per week and low physical activity as less than 150 min. The benefit was independent of whether the physical activity was recreational or not, or whether individuals came from high-income, medium-income or low-income countries, which shows the association is global.

Other studies in adults have shown that aerobic physical activity reduces SBP on average by between 2 and 5 mmHg and DBP between 1 and 4 mmHg, and it is estimated that the reduction in BP can explain up to 27% of the reduction in CVD rates associated with regular physical activity [155–157]. We accept that the greatest benefit on BP is obtained from moderate-to-vigorous aerobic exercise three to four times a week, with sessions of a mean of 40 min maintained for at least 12 weeks [157,158]. Multiple prospective studies have shown that physical activity can prevent or delay the onset of DM2 [159–161] and cardiovascular events [162–169].

Currently there is special interest in the role of skeletal muscle in DM2, as this tissue is one of those most involved in the use and storage of glucose, and it is well documented that the loss of muscle mass (sarcopenia) is associated with alterations in blood glucose and BP [170–172]. It has been shown that muscle strength and muscle mass play an important role in the cardiovascular outcomes of patients with hypertension and DM2. The ORIGIN study found a 1 kg increase in prehensile strength in prediabetic and diabetic patients was associated with a reduction of between 9 and 30% in total mortality and mortality from CVD, AMI and stroke [173]. The PURE study in more than 130 000 apparently healthy people showed that a reduction of 5 kg was associated with an increase of between 7 and 17% in the risk of cardiovascular mortality, all-cause mortality and mortality because of AMI and stroke, and that, in addition, loss of prehensile strength was as predictive of CVD as increased SBP [174]. This association between lower prehensile strength and cardiovascular risk factors occurs from childhood [175]. In support of the results of these epidemiological studies, studies have shown that resistance training, the most powerful stimulus for the development of muscular strength, reduces the incidence of DM2. The SLIM study [176,177] reported a reduction of 18% in the cumulative incidence of DM2 in the intervention group, which included access to a combination aerobic and resistance training program. Currently, there are no data on this intervention in the Latin American population, although a study in young Colombian adults with excess weight observed an improvement in insulin sensitivity in the group of individuals undergoing weight training [177].

In addition, it has been shown that in children, the greatest muscle strength is associated with lower BP levels [171], and in individuals with hypertension it has been shown that both aerobic training and strength training are well tolerated and effective in reducing BP, with mean reductions of 11/5 mmHg (systolic/diastolic) after moderate-to-high intensity training, and with minor but significant effects using dynamic strength training, whereas isometric activity results in a reduction in BP similar to or greater than that observed with aerobic training [178–181].

In low-income and middle-income countries where, because of fetal programming and nutritional deficiencies during the early stages of life, the PURE study showed a higher prevalence of lower muscle mass and strength, with clear regional and country differences that made it necessary to establish differentiated reference ranges [182]. Therefore, avoiding sarcopenia is essential, and we recommend an increase in strength training and protein intake, which can significantly reduce the loss of muscle mass during the negative energy balance. In addition, after high protein diets, a decrease in HbA1c has been reported as has a trend to BP reduction in people with DM2, without adverse effects on blood lipids [183].

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Environmental pollution

More than 90% of the world's population is exposed to pollution levels that exceed the WHO air quality guidelines, which recommend a level of good quality air environments of less than 10 μg/m3 of particulate pollutants [184–186]. The Lancet Commission on Pollution and Health [187] and the Global Burden of Disease [188,189] estimate that diseases caused by all forms of pollution were responsible for 9 million deaths in 2015, more than those attributed to obesity, alcoholism, traffic accidents, child or maternal malnutrition, and of the combination of AIDS, tuberculosis and malaria, and being surpassed only by hypertension and the combination of all nutritional factors.

The most worrisome environmental pollutants are volatile organic compounds and nanoparticles less than 2.5 μm in diameter (PM2.5). Recent calculations estimate that 3.15 million deaths per year are attributable to PM2.5, which places environmental pollution among the top 10 risk factors for global mortality [187–189]. More than half the health burden of these particles is related to cardiovascular disease, and it has been shown that exposure to PM2.5 increases the risk of AMI, hospitalizations and deaths because of heart failure, stroke and arrhythmias [190–194].

Inhalation of PM2.5 can trigger acute elevations in BP over the subsequent hours or days, and long-term exposure can lead to an increase of 13% in the risk of new cases of hypertension [195–199]. PM2.5 and other environmental pollutants can worsen insulin resistance and promote DM2 [200–202]. Although most studies have been conducted in high-income countries, there is evidence that the situation in Latin America is similar [202–208]. This information shows that, in addition to changes in diet and physical activity to prevent hypertension, DM2 and CVD, it is the responsibility of Latin American governments to take measures to reduce environmental pollution through environmental protection agencies.

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Smoking

Smoking continues to be one of the main avoidable causes of morbidity and mortality, with almost six million deaths each year worldwide because of diseases associated with smoking [189]. The recent meeting of the Working Group of the European-Latin American Respiratory Diseases Society held in Madrid showed that Latin America is making progress in smoking control [209], but that it is still necessary to increase the strictness of antismoking laws, increase taxes on cigarettes and develop alternative packaging plans. In Latin America, the results of smoking control programs have been reported in recent years [210–226], with excellent results obtained in Uruguay, Brazil, Chile and Panama through actions, such as the prohibition of smoking in public places, the imposition of high taxes and the inclusion of large warnings on cigarette packages, all agreed with the active participation of the leaders of governments, including, in Uruguay, the direct participation of the President of the Republic. Unfortunately, the same does not occur in other countries of the region, such as Argentina, Peru, Guatemala, Honduras and Nicaragua. The PURE study analyzed this situation in 12 953 adults from countries that ratified the international reference framework for smoking control, and found that the implementation of control policies is weak, especially in the lower income countries, and that the possibilities of quitting smoking are greater when antismoking measure are effective, social acceptance of smoking is lower and knowledge of the health damage is greater [227]. The implementation of these actions throughout Latin America is crucial to combat the increase not only in the incidence of cancer and CVD, whose association with smoking is well described, but also of DM2, as demonstrated by a recent meta-analysis of 88 prospective studies that involved almost six million participants and 295 446 new cases of DM2. This study showed that, compared with those who never smoked, the increaser in relative risk was 37% in active smokers, 14% in ex-smokers and 22% in nonsmokers with passive exposure. In addition, it was shown that the relationship is dose-dependent and it is estimated that 11.7% of cases of DM2 in men and 2.4% in women were attributable to smoking, equivalent to 27.8 million cases of diabetes worldwide. There is no doubt that efforts to reduce smoking will have a significant effect on the global burden of DM2 [228], and that the weight gain associated with smoking cessation does not affect the benefits of reducing cardiovascular and all-cause mortality [229].

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PHARMACOLOGICAL TREATMENT IN HYPERTENSIVE PATIENTS WITH METABOLIC SYNDROME AND TYPE 2 DIABETES

Metabolic syndrome alone does not justify pharmacological treatment, as it is not considered a disease, but an agglomeration of different risk factors. Therefore, it is necessary to treat each of its constituents separately but at the same time [230]. As already discussed in the previous points, weight reduction, increased regular physical activity, reduced alcohol intake, smoking cessation, moderation of sodium intake, increased potassium consumption through greater fruit and vegetable intake and an adequate balance in the consumption of macronutrients are some of the important lifestyle changes recommended. By modifying these factors, the response to pharmacological treatment is improved and overall cardiovascular risk is reduced. In patients with diabetes mellitus and metabolic syndrome , the initiation of early antihypertensive treatment and BP control improve the survival and prognosis of cardiometabolic diseases [231,232], reducing the residual risk. The benefit is even greater than that attributable to the benefit of reaching glycemic and metabolic goals [233]. Therefore, treatment should be started as soon as BP is greater than 140/90 mmHg [234] and the goals are to reach less than 140/90 mmHg, and as far as possible to achieve less than 130/80 mmHg [235,236], which is associated with a decrease in the risk of coronary heart disease, left ventricular hypertrophy, heart failure, cerebrovascular accidents and deterioration of renal function [237–243] (Table 5).

TABLE 5

TABLE 5

On the basis of various clinical studies, the Consensus recommends starting with combination treatment in a single pill (SPC), with the drugs of choice in patients with diabetes or metabolic syndrome being renin–angiotensin system (RAS) blockers, either and angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB), combined with a calcium channel blocker (CCB) or a thiazide-like diuretic, such as indapamide at low doses (DIU). If this dual treatment fails, triple (RAS and CCB combined with DIU) or quadruple treatment should be used (Fig. 3). Numerous studies show that combined therapy with two pharmacological groups is required in 50–70% of patients to achieve the goals [244,245]. One aspect to be considered is the antihypertensive effect of some hypoglycemic drug groups, particularly sodium-glucose co-transporter inhibitors [246], and therefore, BP should be carefully monitored in patients already receiving antihypertensive therapy, who should eventually be prescribed these antihypertensive drugs to avoid the sum of the effects and severe symptomatic hypotension.

FIGURE 3

FIGURE 3

Very low awareness, treatment and control of hypertension in the population in general, and particularly, in patients with metabolic syndrome and DM2 [247,248] is a serious problem, as 95% do not have controlled BP even though the number of antihypertensive drugs used is higher in patients with DM2 and metabolic syndrome . The benefit of antihypertensive treatment in risk reduction is only achieved when it starts as soon as possible, and goals are reached quickly and are maintained lifelong, in order to avoid accelerating vascular damage [249]. In a critical reassessment of controlled and randomized studies of the effect of BP reduction in hypertensive patients, Zanchetti et al. showed the divergence between international medical societies in establishing a BP value that justify interventions and setting the goals that must be achieved to obtain a greater reduction in major cardiovascular outcomes [250]. However, it is clear that the earlier pharmacological intervention is implemented and the management of all risk factors is addressed, the easier it is to prevent or halt the pathogenic process leading to cardiovascular diseases [251]. In addition, and considering that one in four hypertensive patients has DM2 [252,253] and that the administration of statins to these patients increases the prevention of cardiovascular events by almost double, as shown by the HOPE-3 study [254–256], the recommendation of this Consensus is to use two antihypertensive medications, a statin and metformin as initial treatment. However, although antihypertensive and hypoglycemic drugs are listed as essential medicines by the WHO [257], availability and access to them are limited in medium-income and low-income countries, as shown by the PURE study [258–261]. Although at least one antihypertensive drug was available in 90% of the pharmacies surveyed, the availability of two or more drugs was lower in medium-income and low-income countries and, given the economic conditions, access was also low because of the high costs relative to the low ability to pay of most households in these countries. As with hypertension, many people with DM2 remain unidentified, untreated or inadequately treated, especially in the lowest income countries, despite the existence of easy screening tests and effective medications [262]. The availability of and access to essential medicines to treat DM2 was very low in poor countries, both in terms of availability in pharmacies and the unattainable costs for the large majority. Thus, metformin was available in 100% and insulin in 94% of pharmacies in high-income countries, but only in 65 and 10%, respectively, of pharmacies in low-income countries. Although only 0.7% of households with diabetic patients in high-income countries cannot afford to buy metformin, this rises to 26.9% in poor countries. Access is even worse for insulin, with 63% of households in poor countries unable to buy it.

Therefore, in order to improve the control of hypertension and DM2, it is essential that Latin American health systems guarantee availability and access to a core group of basic medicines, and that standardized treatment algorithms should be introduced, as previously proposed by LASH [244,245] and the WHO/PAHO [263–267]. This strategy is currently being piloted within the HEARTS program in Barbados, Cuba, Colombia and Chile [268], based on the positive experience obtained in other programs [269,270].

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THE POLYPILL: A STRATEGY TO IMPROVE THE ADHERENCE AND CONTROL OF HYPERTENSION AND CARDIOVASCULAR EVENTS

Adherence to long-term treatment is defined as the degree of adherence to pharmacological treatment, and following a diet and/or the adoption of lifestyle changes that correspond to the recommendations agreed with the physician or other health professionals. Many reasons why patients abandon treatment have been evaluated. Table 6 shows the main causes of nonadherence to prescribed treatments [271].

TABLE 6

TABLE 6

The use of polypharmacy and the dosing frequency is one of the factors that most influence treatment abandonment, and it has been shown that patients are more adherent to treatment if they take a single tablet instead of several a day [272]. Among the different strategies proposed to increase adherence, combination of different basic drugs in a single pill (polypill) to treat different risk cardiovascular factors (hypertension and dyslipidemia) makes the patient much more adherent to medical treatment than when they must take several a day. The simplification of the therapeutic regimen is accompanied by better results in terms of therapeutic adherence and, as a consequence, a greater control of cardiovascular risk factors, both in primary prevention [273,274] and in secondary prevention [275], and has been shown to be cost effective [276]. The only available polypill in Latin America providing careful in-vitro and in-vivo studies which have shown the safety, tolerability and bioequivalence of all its components with the drugs given separately combine ramipril, atorvastatin and aspirine [277]. This polypill was obtained by research conducted in Spain from the Centro Nacional de Investigationes Cardiovasculares (CNIC) in collaboration with Ferrer International, and approved in 2014 by the European Medical Agency for use in secondary prevention of cardiovascular events in adult patients. Considering all these reasons, the Consensus recommends the use of the currently available polypill containing ramipril, atorvastatin and aspirin for patients in secondary cardiovascular prevention and in high-risk cardiovascular patients with indication of aspirin in the therapeutic regimen, such as patients with hypertension and DM2 (Table 7).

TABLE 7

TABLE 7

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ACKNOWLEDGEMENTS

Latin American Society of Hypertension (LASH) Consensus Expert Group

Chairs: Patricio Lopez-Jaramillo (Colombia), Eduardo Barbosa (Brazil)

Coordinators: Dora Ines Molina (Colombia), Ramiro Sanchez (Argentina)

Advisors: Alberto Zanchetti (Italy), Antonio Coca (Spain), Carlos Morillo (Canada), Gianfranco Parati (Italia), Vicente Lahera (Spain)

WORKING GROUP 1: EPIDEMIOLOGY OF HTA, DM2 AND MS IN LATIN AMERICA

Chair: Margarita Diaz (Uruguay)

Coordinator: Paul Antony Camacho (Colombia)

Members: Jose Ortellado (Paraguay)

Carlos Calderon (Colombia)

Segundo Seclen (Peru)

WORKING GROUP 2: DIAGNOSIS OF HTA, DM2, MS, OBESITY

Chair: Fernando Lanas (Chile)

Coordinator: Miguel Pasquel (Ecuador)

Members: Ana Isabel Barrientos (Honduras)

Carlos Meza Galo (Honduras)

WORKING GROUP 3: GENETIC AND ENVIRONMENTAL FACTORS

Chair: José Luis Accini (Colombia)

Coordinator: Carlos Ponte (Venezuela)

Members: Isaac Sinay (Argentina)

Alfonso Bryce (Perú)

Gustavo Aroca (Colombia)

Miguel Urina (Colombia)

WORKING GROUP 4: DIETARY RISK FACTORS

Chair: Luis Alcocer (Mexico)

Coordinator: Leonardo Cobos (Chile)

Members: Joffre Lara (Ecuador)

Livia Machado (Venezuela)

Raul Villar (Chile)

WORKING GROUP 5: PHARMACOLOGICAL TREATMENT

Chairman: Fernando Wyss (Guatemala)

Coordinator: Weimar Sebba-Barroso (Brazil)

Members: Vladimir Ulluari (Ecuador)

Gregorio Sanchez (Colombia)

Osiris Valdez (Dominican Republic)

Enrique Gomez-Alvarez (Mexico)

Daniel Mantilla-Garcia (Colombia)

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Conflicts of interest

There are no conflicts of interest.

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* Professor Zanchetti passed away in March 2018 before the Consensus document was finalized. His contribution was invaluable in setting priorities, interpreting the available evidence and establishing final recommendations. His advice will remain in our memories.

Keywords:

hypertension; metabolic syndrome; type 2 diabetes mellitus

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