Trends in Mortality from Ischemic Heart Disease in the Region of the Americas, 2000–2019

Background: In latest decades, mortality rates from ischemic heart disease (IHD) had declined steadily in most of the world as a consequence of improvements in prevention and therapy. Objective: The aim of this study was to analyze trends in mortality caused by IHD in the region of the Americas from 2000 to 2019. Methods: Estimates of the age-adjusted mortality rate (AAMR) due to IHD were extracted from the Data Portal on Noncommunicable Diseases, Mental Health, and External Causes (ENLACE), Pan American Health Organization. We used Joinpoint regression to analyze significant changes in mortality trends by country, gender, geographical sub-region, and country income, according to the World Bank classification. We also calculated the average annual percent change (AAPC) mortality rate for the overall period in the Americas as a whole and by country and sub-region. Results: In the region of the Americas, the AAMR from IHD decreased from 117.80 (95% uncertainty interval (UI)) 106.64–135.90) in 2000 to 73.64 (62.65–92.66) per 100,000 in 2019. In males, from 149.08 (95% UI 138.23–168.08) to 96.02 (95% UI 83.48–117.19) and in females 92.36 (95% UI 81.35–109.42) to 54.84 (95% UI 45.28–71.76). The AAPC mortality rate in the region decreased –2.5% (95% CI: –2.7, –2.3), with joinpoints in 2007 and 2012, –2.3% (95% CI: –2.5, –2.1) in men and –2.7% (95% CI: –3.0, –2.5) in women. According to the sub-region analysis, the highest decrease was recorded in North America, AAPC –3.1% (95% CI: –3.3, –3.0) with one joinpoint in 2011, whereas there was a stagnation of the mortality rate in Central America, Mexico, and Latin Caribbean with an AAPC of 0.1 (–0.2, 0.3) with one joinpoint in 2007. Conclusions: Age-adjusted mortality rate from IHD between 2000 and 2019 has decreased in the region of the Americas. However, different trends were observed, North America had the highest reduction in AAPC, while Central America, Mexico, and Latin Caribbean Region had a stagnation. This trend was highly influenced by country income.


INTRODUCTION
Cardiovascular diseases are the leading cause of death in the region of the Americas and in the world. Ischemic heart disease (IHD) has become the first isolated cause of death [1] despite the fact that the risk factors for the majority of IHD events are known, easy to identify and potentially treatable [2]. In Latin America rheumatic heart disease and Chagas disease, once a major health problem in the region of the Americas, are now responsible for only 1% of the mortality [3].
As a consequence of the world's population growth and the increase in life expectancy, an increase in the total number of deaths from IHD has been observed worldwide [4]. In North American countries the total population increased between 2000 to 2020 from 312.8 to 369.2 million inhabitants and life expectancy changed from 76.9 to 79.2 years. In Latin America and the Caribbean countries, the population increased from 520.9 million to 652.3 million, and the life expectancy from 71.7 to 75.3 years [5]. However, the estimated death by IHD increased only slightly from 1.024,117 (18.8%) in 2000 to 1.091.311 (15.2%) in 2019 [6]. Mortality rates from IHD have declined steadily in most of the world in recent years [4] as a consequence of preventive interventions and improvements in therapy. Although, the increase in risk factors such as obesity, metabolic syndrome, and diabetes mellitus has reduced the potential benefit of these interventions. In the region of the Americas, the tendencies in mortality rates due to IHD have been variable between countries, for example, it has been reported a significant decrease in Argentina, a discrete decrease in Colombia in contrast to an increase in Mexico [7]. The aim of this study was to analyze trends in mortality caused by IHD in the region of the Americas countries from 2000 to 2019.
During the period 2000-2019, the region of the Americas showed a statistically significant decrease of -2.5% (95% CI: -2.7, -2.3) in the AAPC in mortality rates, with two joinpoints in 2007 and 2012 due to a lower AAPC after these years (Table 1, Figure 1). Mortality rates decreased significantly in twenty-four countries. Trinidad Tobago, Costa Rica, and Canada had the largest decreases (AAPC -4.3%, -4%, and -3.9%, respectively). Mortality rates increased significantly in three countries. Dominican Republic, Grenada had Mexico (AAPC 2.4%, 1.4%, and 0.6%, respectively) ( Table 2).  AAPC, average annual percent change; APC, annual percent change; CI, confidence interval. * P < 0.05 for change in trend.  Table 2 Joinpoint analysis for ischemic heart diseases mortality trends in the countries of the region of the Americas from 2000 to 2019.
AAPC, average annual percent change; APC, annual percent change; CI, confidence interval. * P < 0.05 for change in trend.
(Contd.)  Figure 1)). Throughout the sub-regions of the Americas, men showed a statistically significant decrease in mortality with an AAPC of -2.3% (95% CI: -2.5, -2.1), with two joinpoints in 2007 and 2012 (Table 3). Mortality rates between 2000 and 2020 decreased significantly in twenty countries. Canada, Trinidad and Tobago, and Costa Rica had the largest decreases, whereas we observed a significant increase in two countries: the Dominican Republic and Mexico (Table 3 and 2S).   Figure 1). Among women, we observed a steady and statistically significant decrease of -2.7% (95% CI: -3.0, -2.5) in the AAPC in the region of the Americas with two joinpoints in 2009 and 2014. Mortality rates between 2000 and 2020 decreased significantly in twenty-four countries. Costa Rica, Canada, and Chile had the largest decreases, whereas we observed a significant increase in two countries: the Dominican Republic and Grenada (Table 4 and 3S).  Figure 1).

TRENDS OF MORTALITY BY COUNTRY INCOME
All income groups, according to the World Bank income classification, had a significant decrease in AAPC. However, the magnitude of the change decreased progressively from high to low-income categories. In high-income American region countries, the median overall AAMR decreased from 106.46 (IQR: 91.71-128.88) to 73.47 (IQR: 55.5-81.57) per 100,000. We recorded a statistically significant decrease of -2.1% (95% CI: -2.  (Table 1).  AAPC, average annual percent change; APC, annual percent change; CI, confidence interval. * P < 0.05 for change in trend. 7 Lanas and Soto Global Heart DOI: 10.5334/gh.1144

DISCUSSION
In the last 20 -year period, age-adjusted mortality rate from IHD decreased in the region of the Americas, with a large decline in the first half and a modest reduction in the second. However, the mortality tendency differs among the Americas region countries and sub-regions: it decreases in most of the countries and sub-regions and in all income categories. AAPC increased in three countries, and the improvement was limited in the Andean Area, Central America, Mexico and Latin Caribbean, and the Non-Latin Latin Caribbean. Additionally, we observed joinpoints in the adjusted rates in most of the countries. The overall reduction of -2.5% in the AAPC between 2000 and 2019 is consistent with the Global Burden of Diseases initiative estimate of a decrease in the age-standardized death rate for IHD of 11.6% in a ten years period, between 2006 and 2016 [15]. The finding that in the Americas region, age-standardized rates of death from IHD has a different trend between sub-regions mirrors what has been reported in Europe, where in Western European countries, a 30% decline in IHD deaths was registered in a 30year period, since 1980, but in Eastern Europe, the rate has only minor changes [16]. In the wealthy countries in the region of the Americas, the United States, and Canada a trend similar to Western Europe was observed. In Canada from 1986 to 2000 the AAPC declined by 3.44 percent for males and 3.42 percent for females [17]. In the United States, the age-adjusted mortality rate for IHD declined from 194.6 per 100,000 in 1999 to 109.2 per 100,000 in 2011, but the slope has flattened with a further decline of only to 90.9 per 100,000 in the next seven years [18]. This deceleration in the mortality for IHD rate, observed also in other countries of the Americas Region, reduces the possibility of a major cardiovascular disease burden control [19].
Several explanations for this diverging trend have been proposed: changes in risk factor prevalence, level of education, access to affordable and effective medication, and quality of medical care. Association of risk factor prevalence in a short term and changes in IHD mortality has been documented in Russia after the Communist decline with increased mortality associated with increased levels of smoking, alcoholism, poor diet, and low physical exercise [20]. Similarly, in East Germany, a major IHD mortality, compared with West Germany after unification was associated with higher levels of smoking, cholesterol, hypertension, obesity, and diabetes mellitus [21]. However, a recent analysis of age-standardized rates of death from IHD changes, between 2005 and 2015, in the United Kingdom, United States, Brazil, Kazakhstan, and Ukraine describes a progressive decrease in mortality, with a limited reduction of smoking and hypertension prevalence, but an increase in obesity and diabetes mellitus, suggesting that the driving force was an economic improvement [22]. Significant support for the importance of education and quality of medical as protective factors were raised in an analysis of the Population Urban Rural Epidemiology (PURE) cohort, which includes high, middle, and lowincome countries. The incidence of cardiovascular diseases was higher in individuals with low education, although the risk factors prevalence was lower in this group and was independent of the individual wealth estimates. Medical care, including management of hypertension, diabetes, and secondary prevention had an important role in cardiovascular event incidence [23]. Another analysis of the PURE cohort reports that lower availability and affordability of essential CVD medicines were associated with an increased risk of major cardiovascular outcomes [24], other evidence of the importance of medical care quality in cardiovascular prevention.
Gender differences in the prevalence of risk factors, risk factor management in primary and secondary prevention, and cardiovascular risk have been reported. Women have a lower prevalence of smoking and alcohol use, lower waist to hip ratio, and higher HDL cholesterol levels, and they have more obesity and sedentary lifestyle [25][26][27]. In the general population, women had better control of hypertension but, after a coronary event received less effective medication, and coronary artery interventions [25]. In our results, women had a lower initial and final age-standardized mortality rate, as has been reported in several communications [22,27,28], and the overall reduction AAPC in American countries was also higher in females than in males, -2.7% vs -2.3%, respectively. A similar trend was reported for stroke, with a median AAPC of -2.7% for males and females [29].
This study has several strengths. To our knowledge, this is the most recent study analyzing IHD mortality trends in the whole American Region. On the other hand, mortality data were extracted directly from an official database without calculating mortality from death count and population data. The Joinpoint regression software has been widely used to analyze mortality trends in cardio and cerebrovascular disease [30,31]. In addition, this analysis method achieves