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1 2 REVIEW ARTICLE 3 4 5 6 7 8 Q4 Simon Barquera,a Andrea Pedroza-Tobıas,a Catalina Medina,a Lucıa Hernandez-Barrera,a 9 Kirsten Bibbins-Domingo,b Rafael Lozano,a and Andrew E. Moranc 10 a Centro de Investigacion en Nutricion y Salud, Instituto Nacional de Salud Publica, Cuernavaca, Morelos, Mexico 11 b Division of General Medicine, University of California at San Francisco, San Francisco, California, USA c 12 Division of General Medicine, Columbia University, Presbyterian Hospital, New York, New York, USA 13 Received for publication May 26, 2015; accepted June 18, 2015 (ARCMED-D-15-00387). 14 15 16 Atherosclerotic cardiovascular disease (ACD) is the leading cause of mortality world17 wide. The objective of this paper is to provide an overview of the global burden of 18 ACD and its risk factors and to discuss the main challenges and opportunities for preven19 tion. Publicly available data from the Global Burden of Disease Study were analyzed for 20 ischemic heart disease (IHD), ischemic stroke and ACD risk factors. Data from the WHO 21 Global Health Observatory were used to describe prevalence of diverse cardiometabolic 22 risk factors. World Bank Gross Domestic Product per capita (GDPc) information was 23 used to categorize countries according to income level. Cardiovascular mortality 24 decreased globally from 1990e2010 with important differences by GDPc; during 1990 there was a positive association between IHD mortality and GDPc. Higher-income coun25 tries had higher rates compared to those of lower-income countries. High levels of body 26 mass index (BMI), blood pressure, glucose and cholesterol have a differential contribu27 tion to mortality by income group over time; high-income countries have been able to 28 reduce the contribution from these risk factors in the last 20 years, whereas lower/middle 29 income countries show an increasing trend in mortality attributable to high BMI and 30 glucose. Although age-adjusted ACD mortality rate trends decreased globally, the abso31 lute number of ACD deaths is increasing in part due to the growth of the population and 32 aging, as well as to important lifestyle and food-system changes that likely attenuate 33 gains in prevention. Population and individual level preventable causes of ACD must 34 be aggressively and efficiently targeted in countries of lower economic development in 35 order to reduce the growing burden of disease due to ACD. Ó 2015 IMSS. Published by Elsevier Inc. 36 37 Key Words: Ischemic heart disease, Cerebrovascular disease, DALYs, Epidemiologic transition. 38 39 40 41 world’s first and third causes of death, respectively, causing Introduction 42 247.9 deaths/100,000 persons in 2013, representing 84.5% Atherosclerosis is an inflammatory disease of the arteries 43 of cardiovascular deaths and 28.2% of all-cause mortality associated with lipid and other metabolic alterations and 44 (1). Other less prevalent complications of atherosclerosis is the major cause of cardiovascular diseases. Atheroscle45 include atherosclerosis of the aorta and peripheral vascular rotic cardiovascular disease (ACD) includes two major con46 disease (2). ditions: ischemic heart disease (IHD) and cerebrovascular 47 The pathologic process leading to atherosclerosis is disease (mainly ischemic stroke). IHD and stroke are the 48 complex. It is commonly associated with elevated concen49 trations of low-density lipoprotein cholesterol (LDL-c) that 50 alter cellular permeability and progressively affect the arteAddress reprint requests to: Simon Barquera, Av. Universidad 655, 51 rial walls (3). This substrate promotes an inflammatory Santa Marıa Ahuacatitlan, 62100, Cuernavaca, Morelos, Mexico; Phone: 52 response in which circulating monocytes adhere to the (þ52) (777) 329-3017; FAX: ---; E-mail: [email protected]

Global Overview of the Epidemiology of Atherosclerotic Cardiovascular Disease

0188-4409/$ - see front matter. Copyright Ó 2015 IMSS. Published by Elsevier Inc. http://dx.doi.org/10.1016/j.arcmed.2015.06.006 ARCMED2029_proof ■ 29-6-2015 19-59-47

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endothelial cells which, in turn, express adhesion molecules and selectins, increasing monocytes migration to the subendothelial space. Monocytes are then converted to foamy macrophages rich in cholesterol esters and free fatty acids, which infiltrate the arterial walls and cause a pathological intimal thickening lesion inducing the conversion of the lipid pool to a necrotic core. The atherosclerotic plaque containing foamy macrophages is prone to plaque fissure or rupture that may lead to a fatal thrombosis (4). In the last several decades, an important rise in cardiovascular and other non-communicable chronic diseases (NCCDs) burden has been documented particularly in developing low- and middle-income countries (2,5e7). This epidemiological shift has been associated in part to important changes in lifestyles and diets, which have been described as the epidemiologic and nutrition transition (8e15). Recent analyses suggest the epidemiologic transition may evolve differently in the context of different countries (8,16). Energy-dense diets high in sugar, fat and sodium, together with reductions in physical activity and increasing sedentarism, are major modifiable causes of chronic diseases (17e23). Together with tobacco, these conditions represent the most important modifiable risk factors responsible for O50% of global all-cause mortality (6,12). Furthermore, there is also good evidence that specific dietary and lifestyle behaviors are associated with ACD such as excess consumption of sugar-sweetened beverages and alcohol. Downstream of these modifiable primary causes are a group of highly prevalent physiologic and metabolic alterations implicated in the increase of ACD mortality. The most notable are dyslipidemias, obesity, high glucose levels, high blood pressure and insulin resistance (5,17e22,24e29). The 2010 global cost of cardiovascular disease (CVD) has been estimated at $863 billion USD (equivalent to an average per capita cost of $125 USD) (30). In the U.S., the cost of this disease is |1e3% of the GDP with almost half of that amount related to coronary heart disease (31). These costs weigh not only on the health care system, but also on the national economic growth (12). The American Heart Association estimated that the annual cost of CVD in the U.S. in 2010 was $503.2 billion USD ($324.1 billion USD direct costs and $179.1 billion USD indirect costs) (32). According to Rayner et al. (33), the cost of CVD in Europe was |$153,194 million USD ($87,310 million USD direct costs and $65,884 million USD indirect costs). In China, the annual cost of CVD has been estimated to be more than $40 billion USD or 4% of the GDP (31). Motivated by evidence that much of ACD is a preventable health and economic burden, most countries worldwide are developing policies and initiatives to decrease cardiovascular and other NCCD burden (5,6,34,35). One major global health concern is the additional burden of these diseases for less economically developed countries.

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Low- and middle-income countries that traditionally focused on controlling undernutrition and infectious diseases now have a growing burden from NCCDs without completely resolving pre-transition health challenges. This transformation has occurred in a very short period of time, making it difficult for countries and international health and aid organizations to respond (36e38). The objective of this paper is to provide a general overview of the global burden of ACD, its risk factors stratified by selected countries, regions and income groups, and to discuss the main challenges and opportunities for ACD prevention from the public health perspective.

Methods To describe the main epidemiological characteristics of ACD, secondary, publicly available data from the Global Burden of Disease Study 2010 (39) were obtained and analyzed for IHD and ischemic stroke. The Global Burden of Disease Study combines health loss due to deaths (years of life lost) with health loss due to non-fatal disability (years lived with disability) into a single measure of health loss, disability adjusted life years (DALYs). We obtained data series on age-standardized mortality rates and DALYs per 100,000 inhabitants (40). In addition, we obtained information on disease burden attributed to the following CVD risk factors: high body mass index (BMI) (O22 kg/ m2), high blood pressure (O113 mmHg), high glucose (O92 mg/dL), and high cholesterol (O150 mg/dL). We also included the following lifestyle risk factors: tobacco smoking, alcohol use, physical inactivity (!600 METminutes per week) and the following dietary risk factors: sodium (O1000 mg/day), transfat (O0.5% of energy), sugar-sweetened beverage (O0 sugar-sweetened beverage) and low polyunsaturated fat consumption (!12% of energy), for three points in time (1990, 2005 and 2010) with the exception of physical inactivity, for which only two points in time were available (2005 and 2010) (41). Further details on the data sources and methodology of the Global Burden of Disease Project Study are described in detail elsewhere (1,7,39e42). To describe the most recent age-standardized prevalence of diverse cardiometabolic risk factors, high BMI ($25 kg/ m2), high fasting glucose ($126 mg/dL), high blood pressure ($140/90 mmHg or medication) and high total cholesterol ($190 mg/dL), we obtained public data from the Global Health Observatory of the World Health Organization (WHO) (43). In order to summarize the data, 188 countries with available information were categorized into six population groups (super regions) as defined by the Global Burden of Disease Study: a) high-income countries, and low- and middle-income countries grouped into the following regions based on local epidemiological characteristics: b)

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160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214

215 216 217 218 219 220 221 222 223 224 225 226 227 228 229 230 231 232 233 234 235 236 237 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258 259 260 261 262 263 264 265 266 267 268 269 Table 1. Trends of age-standardized all cardiovascular disease, IHD and CVD mortality rate and DALYs by country group and selected countries (1990e2010) All cardiovascular and circulatory diseases Mortality rate 1990

Mortality rate

Ischemic stroke DALYs

2010

% Change

1990

2010

% Change

1990

2010

% Change 1990

298.1 240.2 258.7 277.7 301.8 265.1

234.8 140.2 161.7 146.8 162 200.8

21.2 41.6 37.5 47.1 46.3 24.3

5688.8 4159.5 4631.8 4828.8 5436.3 5214.4

4470.9 2429 2987.4 2406.2 2800.3 3750.3

21.4 41.6 35.5 50.2 48.5 28.1

131.3 131.6 171.7 174 190.8 119.5

105.7 71.4 98.1 78.6 97.2 93.3

19.5 45.7 42.9 54.9 49 21.9

169.4 173.7 320.4 233.4

148.9 145.7 225.2 202.3

12.1 16.1 29.7 13.3

3146.3 3391.9 6457.7 5098.3

2778.4 3026 4314.7 4283.4

11.7 10.8 33.2 16

85.7 84.4 130.7 70.4

83.9 79.4 91 61.5

135.5 218.2 423.4

112.7 246.6 325.7

16.8 13 23.1

3485.9 4833.3 9010.7

2782.8 5189.6 6503.4

20.2 7.4 27.8

41.5 64.5 191

490.5 755 275.9

344.5 721.8 240.2

29.8 4.4 12.9

10211.4 6804.9 16286.2 15325.8 5350.5 4366.8

33.4 5.9 18.4

267.7 292.6 252.6 260.8 137.8 178.1 277.6 490.4

230.8 167 189.9 262.5 164.9 193.5 271.8 440.8

13.8 42.9 24.8 0.7 19.7 8.6 2.1 10.1

5114.5 6532.3 4533 5529.1 2803.7 3721.9 5882.9 8726.6

4065.1 3733.3 3246 5298.3 3313.9 3898.2 5438.3 8074.2

426.3 465.6 502.2

276.2 256 504.4

35.2 45 0.4

7173.7 8016 8988.9

4326.4 4035.9 9541

Mortality rate

DALYs

2010

% Change

1990

2010

% Change

1990

2010 % Change

2423.3 2259.8 2938.7 3130.9 3432.8 2282

1972 1218.1 1679.7 1310.4 1585.3 1729.2

18.6 46.1 42.8 58.1 53.8 24.2

59.6 42.9 31.2 45.6 50.3 46.5

42.3 22.9 19.1 24.1 24.2 33.1

29.0 46.7 38.9 47.1 51.9 28.9

795.9 533.8 406.6 533.7 646.9 685.3

597.9 301.5 296.8 276.5 315.7 462.4

33.1 77.0 37.0 93.0 105.0 48.2

2.2 5.9 30.4 12.6

1551.8 1540.3 2634.7 1540.5

1521.2 1560.3 1808.8 1311.3

2 1.3 31.3 14.9

27.8 25.7 61.3 47.3

21.2 19.3 40.9 42.5

23.9 25.0 33.2 10.2

381.1 374.6 909.8 743.0

303.8 307.8 570.5 655.8

25.4 21.7 59.5 13.3

38.2 81.6 154.6

7.9 26.5 19.1

1074.6 914.5 1456.2 1734.5 3957.9 3019.2

14.9 19.1 23.7

27.1 47.5 64.6

23.1 53.7 48.6

14.7 13.1 24.8

502.5 756.4 1807.7

406.3 840.6 765.1

23.7 10.0 136.3

309 347.6 64.1

210.9 319.5 74.4

31.8 8.1 16

6222 4051.8 7359.8 6731.1 1314.2 1362.3

34.9 8.5 3.7

34.0 114.8 53.6

25.9 117.3 46.6

23.7 2.2 13.2

597.9 438.7 2043.5 2032.1 752.7 693.8

36.3 0.6 8.5

20.5 42.8 28.4 4.2 18.2 4.7 7.6 7.5

55.7 88.4 39.5 126.3 29.6 68.2 141 264.9

70.1 47.3 38.2 133.7 56.4 78.4 144.4 257.4

25.7 46.5 3.2 5.8 90.4 15 2.4 2.8

1139.8 2257.6 826.1 2684.4 655.4 1456.8 2978.1 4688.8

1242.5 1217.8 732.7 2727.8 1223.2 1636.3 2916.9 4689.7

9 46.1 11.3 1.6 86.6 12.3 2.1 0

56.3 72.0 11.6 43.1 30.4 29.6 37.4 123.7

46.7 36.1 9.7 46.6 26.9 32.4 38.8 99.8

17.1 49.9 15.9 8.1 11.4 9.7 3.7 19.3

767.5 612.4 1305.1 806.6 226.5 191.3 688.8 730.1 451.4 375.1 450.1 469.0 571.4 556.6 1682.8 1389.5

25.3 61.8 18.4 5.7 20.4 4.0 2.7 21.1

39.7 49.7 6.1

261.7 203.9 268.5

138.7 141.2 295.2

47 30.8 9.9

4642.6 2184.1 3465.5 2172.8 4859.8 5684.6

53 37.3 17

87.7 124.8 155.1

56.7 63.5 137.7

35.3 49.1 11.2

1127.8 694.7 1597.9 760.3 2075.0 1909.1

62.3 110.2 8.7

Atherosclerotic Cardiovascular Disease Epidemiology

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Globally High income U.S. UK Finalnd Latin America and the Caribbean Mexico Guatemala Brazil Sub-Saharan Africa Senegal Ghana North Africa and Middle East Syria Afghanistan Southeast Asia, East Asia and Oceania China Samoa Vietnam South Asia Bangladesh Nepal India CentraleEastern Europe and Central Asia Croatia Czech Republic Russia

DALYs

IHD

IHD, ischemic heart disease; CVD, cardiovascular disease; DALYs, disability adjusted life years. Source: Global Burden of Disease Study 2010 (GBD 2010) Results by Cause 1990e2010eCountry Level. Seattle, WA: Institute for Health Metrics and Evaluation (IHME), 2013.

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270 271 272 273 274 275 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290 291 292 293 294 295 296 297 298 299 300 301 302 303 304 305 306 307 308 309 310 311 312 313 314 315 316 317 318 319 320 321 322 323 324

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Latin American and Caribbean, c) sub-Saharan Africa, d) North Africa and Middle East, e) Southeast Asia, East Asia, and Oceania and f) Central Europe, Eastern Europe, and Central Asia (7). In addition, we used World Bank Gross Domestic Product per capita (GDPc) information for years 1990, 2005 and 2010 to classify countries into 2013 World Bank income categories: 1) low income (GDPc !1045 USD), lower-middle income (GDPc 1046-4125 USD), upper-middle income (GDPc: 4126-12,745 USD) and high income (O12,746 USD) (44). To describe the association between the GDPc and mortality rates from IHD and CVD, we calculated a linear regression model using as dependent variable the age-standardized mortality rates and as independent variable log-transformed GDPc. Finally, we evaluated the trends of all-cause mortality attributable to metabolic and lifestyle risk factors stratifying by income category. Statistical analysis was performed using the statistical software STATA v.12 (Stata Corp, College Station, TX) (45).

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mortality rates showed little difference in 1990; however, a reduction was observed during 2010 for high-income countries and minor changes in the lower-income ones, with higher mortality rates. For IHD, during 1990, there was a positive association between mortality and GDP per capita. Higher-income countries had higher rates compared to those countries with lower income. In 2010, a significant reduction in mortality was observed in highincome countries ( p 5 0.02) with almost no change over time for the low-income countries (Figure 1). Major Risk Factors Prevalence of cardiometabolic risk factors across countries has important variations by country and region. Overweight and obesity (BMI O25 kg/m2) had a high prevalence in developed countries such as the UK and U.S. (63.4 and 67.3%, respectively). However, developing regions also

Results Mortality and DALYs The absolute number of deaths due to ACD increased substantially since 1990. However, the age-standardized cardiovascular mortality rates per 100,000 inhabitants decreased globally from 1990e2010. High-income countries were able to reduce their CVD mortality by 42% during this time period, whereas two regions—Latin America and Caribbean, and North Africa and Middle East— reduced this outcome by 24 and 23%, respectively. Finally, three regions: sub-Saharan Africa, Southeast Asia, East Asia and Oceania, and Central Europe, Eastern Europe and Central Asia decreased their mortality rates by 13% or less in the same period and some of the countries within these regions showed no reductions in this indicator during the last 20 years. Central Europe, Eastern Europe and Central Asia were the world regions with the highest current age-standardized CVD mortality rates, which are more than twice those of Latin America and the Caribbean. Some countries have shown very promising results, for example, the Czech Republic reduced its mortality by 45% in the study period although its 2010 CVD mortality rate (256 deaths/100,000 inhabitants) is still above the world average for the same year (234 deaths/100,000 inhabitants). Russia, on the other hand, showed no improvement in the mortality rate and an important increase in the number of DALYs per 100,000 inhabitants during the period (9540/100,000 inhabitants), which is almost four times that of the UK (2406 years/100,000 inhabitants). All country regions have decreased their ischemic stroke mortality rates and DALYs/100,000 inhabitants from 1990e2010 (Table 1). From 1990e2010, the trends in mortality rates show important differences by GDPc. For ischemic stroke,

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Figure 1. Age-standardized ischemic heart disease (IHD) and ischemic stroke death per 100,000 inhabitants by Gross Domestric Product (GDP) in 1990, 2005 and 2010. p !0.05 for regression fit line for 2005 and 2010 for stroke and 1990 for IHD. Regression fit was significantly different between 1990 and 2005 for ischemic stroke and between 1990 and 2005 Q5 and between 1990 and 2010 for IHD ( p !0.05).

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Atherosclerotic Cardiovascular Disease Epidemiology

435 436 437 438 439 440 441 442 443 444 445 446 447 448 449 450 451 452 453 454 455 456 457 458 459 460 461 462 463 464 465 466 467 468 469 470 471 472 473 474 475 476 477 478 479 480 481 482 483 484 485 486 487 488 489

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490 491 492 High FPG High BP High TC High BMI 493 % % % % 494 Prevalencea 1990 2010 Change Prevalenceb 1990 2010 Change Prevalencec 1990 2010 Change Prevalenced 1990 2010 Change 495 496 Global 9.8 1.3 1.5 13.7 38.4 7.1 7.0 1.1 38.9 2.1 1.7 18.1 39.0 1.7 2.2 28.0 High income 1.8 1.3 24.9 10.1 6.0 40.2 4.8 2.6 45.5 3.9 3.7 5.8 497 U.S. 8.4 2.0 1.8 9.8 29.9 9.4 5.8 38.4 53.8 5.6 2.9 47.7 67.3 5.2 5.1 0.2 498 UK 7.8 2.6 1.3 51.1 37.5 13.0 6.4 50.3 63.4 7.3 3.0 59.3 63.4 4.5 3.8 17.0 499 Finland 6.7 2.7 1.6 42.6 41.9 14.5 8.3 42.9 59.0 8.1 3.5 56.3 55.2 5.6 4.2 25.0 500 Latin American 1.5 1.6 6.8 8.5 7.3 15.0 2.5 2.0 21.7 2.3 3.2 42.1 501 and Caribbean Mexico 10.7 1.4 2.1 51.1 36.1 5.1 5.7 13.1 50.7 1.7 2.4 41.5 64.4 2.1 3.6 75.8 502 Guatemala 10.5 0.7 1.2 72.2 36.0 3.4 4.3 27.1 27.7 0.8 0.9 2.4 52.0 0.9 2.0 123.1 503 Brazil 7.8 1.7 1.9 12.7 42.3 11.2 9.4 16.2 44.2 2.9 2.5 14.6 54.1 2.7 4.0 46.0 504 Sub-Saharan 0.6 0.6 12.5 4.0 4.5 13.7 0.4 0.4 16.3 0.4 0.9 102.4 505 Africa 506 Senegal 9.1 0.5 0.7 26.9 45.1 3.2 3.7 14.0 21.4 0.4 0.3 21.1 30.2 0.4 0.9 138.9 Ghana 8.3 0.7 1.3 79.5 42.1 4.7 6.8 44.0 18.1 0.4 0.4 7.0 33.6 0.3 1.4 323.5 507 North Africa and 2.5 2.3 6.1 11.3 11.4 0.4 3.4 3.3 3.8 4.4 6.3 45.1 508 Middle East 509 Syria 13.9 4.2 4.7 11.5 41.0 15.7 15.7 0.1 40.5 6.0 5.0 16.3 58.5 7.1 9.3 30.7 510 Afghanistan 9.6 1.7 2.5 49.4 38.6 9.7 12.4 27.8 21.9 2.4 1.6 35.1 16.2 0.8 1.3 56.6 511 1.4 1.8 29.5 8.0 10.2 26.9 0.9 1.7 93.1 0.6 1.5 142.9 Southest Asia, East Asia and 512 Oceania 513 China 9.5 1.5 2.3 52.3 38.6 8.6 11.2 31.1 33.4 0.7 1.8 139.2 34.4 0.7 1.7 135.7 514 Samoa 25.2 2.6 2.9 9.9 42.7 9.4 6.9 26.8 34.6 2.1 1.2 43.1 74.3 4.7 4.3 8.8 515 Vietnam 6.5 1.1 1.1 0.0 36.8 6.6 7.9 20.6 36.1 0.5 0.8 65.3 20.6 0.0 0.4 1106.9 516 South Asia 0.9 1.7 83.5 4.3 5.8 33.0 1.2 1.2 0.0 0.3 0.7 148.3 Bangladesh 9.4 0.3 0.8 162.1 38.6 2.3 4.5 97.4 25.7 0.3 0.6 107.4 18.1 0.1 0.4 650.0 517 Nepal 9.4 0.4 1.1 158.1 38.6 3.0 5.5 87.8 23.2 0.5 0.6 23.1 18.0 0.1 0.4 300.0 518 India 9.5 1.0 1.8 76.0 35.2 4.5 5.8 27.2 27.9 1.3 1.3 2.3 22.0 0.3 0.7 142.9 519 CentraleEastern 3.2 3.4 5.9 16.1 15.9 1.0 6.5 5.4 17.9 5.8 7.3 26.0 520 Europe and 521 Central Asia Croatia 7.8 2.7 2.1 22.0 46.7 16.4 12.5 23.6 49.8 5.4 3.5 34.1 58.8 5.5 5.2 4.9 522 Czech Republic 8.1 4.5 2.7 39.2 42.7 18.7 11.9 36.5 53.9 9.4 4.1 56.8 63.4 9.1 7.2 20.4 523 Russia 9.0 3.5 4.0 13.8 43.8 16.5 17.0 3.0 50.6 7.5 6.6 12.2 58.7 6.2 8.4 35.0 524 Q3 525 CVD, cardiovascular diseases; FPG, fasting plasma glucose; BP, blood pressure; TC, total cholesterol; BMI, body mass index. a Age-standardized prevalence $126 mg/dL, 18þ years, WHO; 2014. 526 b Age-standardized prevalence $140/90 or medication, 25þ years, WHO; 2014. 527 c Age- standardized prevalence 2008 (WHO) $190 mg/dL 25þ years, WHO; 2008. 528 d Age- standardized prevalence 2014 (WHO) (BMI $25) 18þ years, WHO; 2014. 529 Source: Global Burden of Disease Study 2010 (GBD 2010) Results by Cause 1990e2010 - Country Level. Seattle, WA: Institute for Health Metrics and 530 Evaluation (IHME), 2013. Global Health Observatory Data, WHO. 531 532 (10.5%). High blood pressure was the risk factor with the had countries with a high prevalence such as Mexico in 533 highest attributable risk (AR) for CVD mortality globally Latin America (64.4%), Samoa in Southeast Asia, East 534 (AR 2010 5 7%) and by all country regions. However, Asia and Oceania region (74.3 %) and the Czech Republic 535 the high-income region has shown significant reductions in Central Europe, Eastern Europe and Central Asia region 536 (40.2%) as well as some countries such as the U.S. (63.4%). High blood pressure prevalence ranged from 537 (38.4%) and UK (50.3%) in the period from 35e46.7% except for the U.S., which had the lowest prev538 1990e2010. Two regions had substantial increases in the alence (29.3%). High-income countries had a high preva539 AR during the period: sub-Saharan Africa and Southeaste lence of hypercholesterolemia ($190 mg/dL) (U.S. 540 East Asia and Oceania (13.7 and 26.9%, respectively). 53.8%, UK 63.4 and Finland 59.0%), whereas sub541 Highly populated developing countries such as India, China Saharan African countries had a lower prevalence (Senegal 542 and Mexico also experienced significant relative increases 21.4% and Ghana 18.1%). A higher than 10% prevalence of 543 in the AR during the 20-year period (13.1, 31.1 and hyperglycemia ($126 mg/dL) was found in Samoa 544 27.2%, respectively). On the other hand, in all country (25.2%), Syria (13.4%), Mexico (10.7%) and Guatemala Table 2. Prevalence and age-standardized mortality rate of CVD attributable to metabolic risk factors by country group and selected countries (1990e2010)

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regions, high BMI increased AR for CVD mortality (global relative increase 1990e2010 5 28%); however, trends in the last 20 years reflect the transition stage of the different country regions. For example, high-income countries are experiencing a relative reduction (5.8%), with some individual countries having greater reductions (i.e., Finland 25%). In contrast, Latin America has experienced a relative increase in AR for CVD mortality (42.1%), and Southeast-East Asia and Oceania was the country region

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with the highest relative increase (142.9%). CentraleEastern Europe and Central Asia was the country region where high fasting glucose (3.4%), high blood pressure (15.9%), high cholesterol (5.4%) and high BMI (7.3%) had the highest ARs for CVD mortality in 2010 (Table 2). As illustrated in Figure 2, high levels of body mass index, blood pressure, glucose and cholesterol have a differential contribution to all-cause mortality by income group over time. High-income countries have been able to reduce

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Figure 2. Age-standardized all-cause mortality rate attributable to metabolic risk factors in 1990, 2005 and 2010 by World Bank income classification. aLow income GDPc !1045 USD; low middle income GDPc 1046-4125 USD; upper middle income; GDPc 4,126-12,746 USD; high income: GDP O12,746 USD. b Significantly different between years ( p !0.05).

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600 601 602 603 604 605 606 607 608 609 610 611 612 613 614 615 616 617 618 619 620 621 622 623 624 625 626 627 628 629 630 631 632 633 634 635 636 637 638 639 640 641 642 643 644 645 646 647 648 649 650 651 652 653 654

Atherosclerotic Cardiovascular Disease Epidemiology

655 656 657 658 659 660 661 662 663 664 665 666 667 668 669 670 671 672 673 674 675 676 677 678 679 680 681 682 683 684 685 686 687 688 689 690 691 692 693 694 695 696 697 698 699 700 701 702 703 704 705 706 707 708 709

their contribution from these four risk factors in the last 20 years and were the only country group showing this trend for BMI and glucose. On the other hand, lower/middleincome countries show an increasing trend in agestandardized mortality rates for high BMI and glucose. AR from dietary factors, tobacco smoking and alcohol use for cardiovascular disease mortality and their relative change from 1990e2010 are presented in Table 3. The high-income region has been able to decrease the risk from most of these factors in the 20-year period. For example, this region reduced by 26% the relative contribution of high sodium diets, whereas Latin American countries decreased the AR of these risk factors by only 9%. China, India, Russia and Mexico—all highly populated developing countries—have experienced an increased contribution of high sodium to CVD mortality. Other important factors such as trans-fat consumption, sugar-sweetened beverages, tobacco smoking and alcohol use show increasing trends in lowerand middle-income developing regions. There were no physical inactivity data from 1990 to analyze country trends over time; however, CentraleEastern Europe and Central Asia and North Africa and the Middle East had the highest AR in 2010. High-income countries were the only group to show AR reductions from 2005e2010 (25%); UK and Finland have been able to decrease the physical inactivity AR O30% in only 5 years. High-income and Latin American regions had similar ARs in 2010; however, the trend is increasing in this region. As observed with cardiometabolic risk factors, when we analyze trends over time of high sodium intake, sugarsweetened beverages, high trans-fat, tobacco consumption and alcohol consumption contribution to all-cause mortality by country-income group, high-income countries show decreasing trends over time (with the exception of sugarsweetened beverages), whereas lower income countries show an increasing trend in sugar-sweetened beverages, high trans-fat and alcohol consumption and modest reductions in sodium and tobacco (supplementary Figure 1).

Discussion ACD is the leading cause of mortality worldwide. It is a major public health epidemic that places an enormous burden on the population. In future years, ACD burden will increase at a higher rate in developing countries including many with O100 million inhabitants (7,36). More and improved quality epidemiologic data are necessary in order to better understand the burden of these diseases worldwide (7,46e50). There is a consensus that the most preventable drivers for this epidemic are modifiable factors associated with environment and lifestyle (8,49). Thus, prevention and control are possible and immediate action is needed. However, current results demonstrate that efforts to close the gap between knowledge and action are still far from

7

satisfactory, in particular for countries with lower resources where polarization of the transition is often common and pre-transitional diseases are as yet unresolved (37,38,51e55). Although the standardized ACD mortality rate trends reflect a relative reduction in all country regions, the absolute number is increasing globally in part due to growth and aging of the population as well as to important lifestyle and food- system changes in low- and middle-income countries in transition from infectious diseases to NCCDs. Trends toward differences in mortality and DALYs among countries according to GDPc suggest that economic development is associated to a certain degree with ACD, although ACD mortality varied considerably within income categories. This may imply that there are different patterns of disease characteristic of different epidemiologic and nutrition transition stages that generally, but not universally, track with country income. Lower income countries have a relatively low prevalence of cardiometabolic (i.e., high levels of blood pressure, sugar, lipids) and lifestyle (i.e., low physical inactivity, low consumption of unhealthy products, sugar-sweetened beverages, tobacco or alcohol) risk factors. Lower- and upper middle-income countries have the most important increasing trends of these risk factors and are rapidly shifting to a stage of transition where NCCDs are major public health problems, catching up with the prevalence of developed nations of these conditions or even surpassing them. On the other hand, high-income countries remain with elevated prevalence of risk factors, but their trends are stable or show only modest reductions. In other words, they have apparently reached the apex and are stabilizing or starting to show decreasing trends that may, in part, be explained by a) a saturation equilibrium effect (stabilization in the obesity of NCCD prevalence at an unacceptably high level, suggesting that the unhealthy obesogenic environment maintains its pressure) (56,57); b) positive impact of major public health policies to promote health education, NCCD screening, early detection and control of risk factors and decreasing consumption of unhealthy products such as soda and sugar-sweetened beverages, fat, salt, alcohol and tobacco through taxes and regulations) (58e64); c) diverse therapeutic advances such as development of statins (65,66); and d) environmental and lifestyle changes such as increasing physical activity, active transportation, and healthier diets (27,28,67e70). Of course, these influences may all contribute to the decline in ACD mortality, although to different degrees. One major global challenge is to identify to what extent some preventable causes of ACD could be most efficiently transformed in countries of lower economic development translating and implementing programs in order to achieve healthier environments and lifestyles (67). For example, given that high-blood pressure is the factor with the highest AR in all country/regions and its known association with sodium intake has been demonstrated, population

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710 711 712 713 714 715 716 717 718 719 720 721 722 723 724 725 726 727 728 729 730 731 732 733 734 735 736 737 738 739 740 741 742 743 744 745 746 747 748 749 750 751 752 753 754 755 756 757 758 759 760 761 762 763 764

8

Table 3. Age-standardized mortality rate of CVD attributable to life style risk factors by country group and selected countries (1990e2010)

High sodium diet

1990

Low polyunsaturated fatty acids diet

1990

2010

% Change

1990

2010

% Change

Sugar-sweetened beverages

Tobacco smoking

Physical inactivitya

Alcohol use

% % % 1990 2010 Change 1990 2010 Change 1990 2010 Change

2005

2010

% Change

0.4 1.2 2.5 1.4 0.5 0.8

0.5 0.8 1.7 0.6 0.2 0.8

16.7 32.5 32.5 53.3 50.0 2.7

0.4 1.2 1.3 1.7 2.2 0.4

0.5 0.8 0.8 0.9 1.4 0.5

17.5 29.9 33.6 48.0 37.6 16.3

0.2 0.1 0.2 0.1 0.1 0.2

0.2 0.1 0.2 0.1 0.1 0.1

20.0 30.8 19.0 46.0 43.0 17.6

3.0 4.8 5.1 7.0 4.8 3.6

2.9 2.8 2.9 2.9 2.8 2.7

2.7 42.1 44.4 59.0 42.7 26.3

0.5 0.4

0.1 0.3

88.5 14.3

1.9 3.3 3.7 3.8 4.3 1.9

2.0 2.5 2.9 2.6 3.0 2.2

9.1 25.5 21.7 30.9 31.2 13.1

1.0 0.8 3.1 0.9

1.3 1.0 3.0 1.0

22.1 27.5 5.8 7.6

1.2 0.1 1.0 0.1

1.7 0.2 0.9 0.1

43.0 110.0 12.2 2.7

0.4 0.2 0.5 0.1

0.7 0.3 0.6 0.1

97.1 73.3 7.8 30.0

0.1 0.2 0.1 0.1

0.2 0.2 0.1 0.1

21.4 0.0 21.3 0.0

2.6 1.7 4.5 1.0

2.6 1.3 3.2 0.9

3.5 22.2 28.9 7.2

0.3 0.2 0.5 0.3

0.3 0.2 0.5 0.3

10.3 23.5 5.9 3.6

1.7 0.6 2.3 0.3

2.2 1.1 2.6 0.8

29.9 80.0 10.7 164.5

1.0 1.1 3.4

1.2 1.5 3.6

13.7 35.5 8.3

0.1 0.1 1.3

0.1 0.1 1.2

56.7 76.5 7.8

0.1 0.2 0.6

0.1 0.3 0.8

17.3 100.0 41.4

0.1 0.2 0.1

0.1 0.1 0.1

34.5 63.0 13.3

0.7 0.6 4.1

0.6 1.0 3.9

3.1 60.0 5.4

0.1 0.2 0.3

0.1 0.3 0.3

37.4 56.3 7.1

0.3 0.6 3.0

0.8 1.2 4.1

200.0 106.9 35.2

4.7 2.7 3.1

5.2 3.4 3.9

10.9 26.6 24.1

1.3 0.6 0.1

1.8 0.9 0.3

38.5 41.7 78.6

1.3 0.4 0.3

1.4 0.6 0.5

11.8 42.5 60.0

0.2 0.4 0.2

0.2 0.6 0.2

13.3 54.1 28.6

8.3 2.8 3.6

7.7 3.2 4.3

7.0 15.1 19.6

0.4 0.3 0.5

0.6 0.5 0.6

55.3 72.4 7.4

4.5 1.5 1.9

6.4 4.3 2.2

41.4 177.9 10.8

3.4 1.4 2.8 2.7 0.8 1.1 1.6 4.2

4.5 0.8 3.1 3.1 1.4 1.8 2.0 4.9

31.5 38.5 9.5 15.7 74.4 71.0 29.9 16.3

14.0 0.2 0.1 0.2 0.1 0.3 0.2 0.6

0.3 0.1 0.1 0.3 0.6 0.8 0.4 0.7

98.0 33.3 102.9 106.7 321.4 171.0 85.7 23.3

0.2 0.7 0.2 0.2 0.0 0.1 0.2 1.3

0.4 0.6 0.4 0.4 0.1 0.2 0.4 1.2

50.0 21.6 72.7 105.6 488.2 183.0 100.0 7.0

0.2 0.1 0.0 0.2 0.0 0.1 0.3 0.1

0.1 0.1 0.3 0.2 0.3 0.3 0.5 0.1

61.4 34.5 831.0 4.3 553.1 269.0 96.0 30.1

4.0 6.1 2.5 3.0 1.1 1.8 2.4 5.6

4.8 3.6 3.2 3.8 2.5 3.5 3.1 6.3

22.3 41.7 26.0 25.8 126.1 88.5 30.1 12.0

0.7 0.4 0.1 0.2 0.0 0.0 0.3 3.5

0.7 0.3 0.6 0.3 0.0 0.6 0.3 4.6

3.0 15.4 517.0 31.8 81.5 1584.2 25.9 31.9

2.2 1.6 0.7 1.4 0.6 0.7 1.5 6.1

2.3 1.9 0.9 2.0 1.0 1.3 2.1 4.9

5.5 15.2 24.7 45.6 69.5 81.1 39.2 19.2

3.4 4.5 4.1

3.1 3.3 5.1

6.3 26.8 23.8

0.9 1.6 0.6

0.6 0.9 0.8

26.4 45.5 39.7

0.8 1.4 1.5

0.6 0.8 1.3

17.9 44.9 9.5

0.1 0.1 0.1

0.1 0.0 0.1

28.7 40.0 48.1

5.3 6.7 5.7

3.6 4.0 7.5

31.9 39.8 31.2

1.3 5.9

0.6 7.8

50.8 31.6

4.5 5.1 6.9

3.3 3.8 5.7

27.0 25.0 17.9

CVD, cardiovascular diseases. a Physical inactivity information for trends is presented for a 5-year period (2005e2010). Source: Global Burden of Disease Study 2010 (GBD 2010) Results by Cause 1990e2010 - Country Level. Seattle, United States: Institute for Health Metrics and Evaluation (IHME), 2013.

-

6.8 26.2 21.8 38.2 34.1 9.0

(2015)

2.4 2.1 2.1 1.8 2.3 2.0

-

2.2 2.8 2.7 3.0 3.6 2.2

Barquera et al./ Archives of Medical Research

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Global High income U.S. UK Finalnd Latin America and Caribbean Mexico Guatemala Brazil Sub-Saharan Africa Senegal Ghana North Africa and Middle East Syria Afghanistan Southest Asia, East Asia and Oceania China Samoa Vietnam South Asia Bangladesh Nepal India Central Europe, Eastern Europe and Central Asia Croatia Czech Republic Russia

% 2010 Change

High trans-fat diet

Atherosclerotic Cardiovascular Disease Epidemiology

interventions that reduce dietary sodium though promotion, education, incentives and regulation have been considered ‘‘best-buy’’ low-cost alternatives accessible to lower income countries (42,67,71e77). Important progress in primary and secondary prevention is already contributing to better results, mostly in developed countries where access and resources for health care are better. However, behavior modification interventions to improve diet, physical activity and other healthy lifestyles have shown very modest effects (78e80). Although there is an important amount of ongoing research and developments to promote individual changes for healthier lifestyles, it is clear that focusing on individuals without attempting to modify the environment will not assure the much needed results. A careful evaluation of the national and subnational context and drivers must precede an adequate development of comprehensive prevention policies. Diverse authors have already identified critical primary causes that must be controlled to improve chances of healthier lifestyles (8,36,49,67,81e85). Among them, some of the most important are as follows: a) place special attention on vulnerable groups such as children who must have adequate access to healthy diets and be protected from any form of marketing of foods and beverages, b) assure access to free potable water and promote it as the first alternative for hydration and as a disincentive to the alarming consumption of sugar-sweetened and other caloric beverages that currently represent |20% of the daily energy intake, c) enforce an adequate front-of-pack labeling system to help consumers make healthier choices at point-ofpurchase, d) promote physical activity and reduction of daily sedentary activities, making community, school and work environment more user-friendly for active transportation and sports activities and protecting efforts from marketing of unhealthy foods and beverages. At the national level, regulations and taxes could be a disincentive for consumption of unhealthy products such as those high in sugar, salt or fat. Several countries have implemented national taxes on unhealthy ingredients to discourage consumption. In Mexico, a 10% sugarsweetened beverage and 8% sweet snack excise tax was implemented during January 2014 with positive preliminary results that could contribute to reduce added sugar consumption. Other low- and middle-income countries are developing similar promising obesity prevention strategy initiatives that could be critical at the population level (86). These efforts are necessary to provide an adequate environment where healthy behaviors are more likely to be adopted and maintained and must be supported by all sectors of society to achieve a healthier future population.

Acknowledgments This work was carried out with support from the International Development Research Centre (INFORMAS project no. 107-

9

731-001) and the Public Health Agency of Canada. Additional Q1 funding was provided by NIH-Fogarty RO3 TW009061.

Supplementary data Supplementary data related to this article can be found online at http://dx.doi.org/10.1016/j.arcmed.2015.06.006.

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