Global Burden of Cardiovascular Diseases and Risk Factors, 1990 – 2019 Update From the GBD 2019 Study

Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased signi ﬁ cantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases of disease burden in burden continues its decades-long rise for all and pressure-lowering drugs; GHE is the social enterprise arm of TGI (Dr. Rodgers does not have a direct ﬁ nancial interest in these patent applications or investments). Dr. Sundström holds ownership in companies providing services to Itrim, Amgen, Janssen, Nordisk, Eli Lilly, Boehringer Ingelheim, Bayer, P ﬁ zer, and AstraZeneca, outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

C ardiovascular disease (CVD) remains a major cause of premature mortality and rising health care costs (1,2). Cardiometabolic, behavioral, environmental, and social risk factors are major drivers of CVD. Consistent, comparable, and systematic analysis of long-term trends and patterns in global CVD are essential to guide public policy and provide benchmarks for decision makers.
Beginning with ischemic heart disease (IHD) and stroke, this article provides information on the burden of CVD, including 13 underlying causes of cardiovascular death and 9 related risk factors at the global, regional, and national levels (Supplemental Manuscript received October 29, 2020; revised manuscript received November 6, 2020, accepted November 6, 2020. To improve accessibility across a wide range of audiences, we have structured the review such that each section can be read independently for those most interested in a subset of causes or risks. Discussion pertinent to each topic is included within every section. This article is a collaborative effort involving the Journal of the American College of Cardiology, the National Heart, Lung, and Blood Institute, and the Institute for Health Metrics and Evaluation at the University of Washington designed to provide crucial population-level information that can guide action for CVD and risk factor prevention, treatment, and control (2).

GLOBAL BURDEN OF DISEASE STUDY METHODS
GBD 2019 is a multinational collaborative research study that estimates disease burden for every country in the world (1,4). The study is an ongoing effort, updated annually, and is designed to allow for consistent comparison over time from 1990 to 2019, by age and sex, and across locations. The study produces standard epidemiological measures such as incidence, prevalence, and death rates as well as summary measures of health, such as DALYs. DALYs represent the sum of years of life lost prematurely and years lived with disability; can be estimated from life tables, estimates of prevalence, and disability weights; and may be expressed as counts or rates.
Annual updates to the study include new diseases, new data sources, and updates to methods. All results are available via the GBD Compare website (5), and all input data is identified via the Global Health Data Exchange website (6). The study is performed in compliance with Guidelines for Accurate and Trans- Atrial fibrillation (AF) and atrial flutter (AFL) were defined by electrocardiogram. Hypertensive heart disease (HHD) was defined as symptomatic heart failure due to the direct and long-term effects of hypertension. Cardiomyopathy was defined as symptomatic heart failure due to primary myocardial disease or toxin exposure to the myocardium, such as alcohol. Acute myocarditis was defined as an acute and time-limited condition due to myocardial inflammation using health system administrative data. Endocarditis and rheumatic heart disease (RHD) were defined by their clinical diagnosis. Estimates of RHD include cases identified by clinical history and physical examination, including auscultation or standard echocardiographic criteria for definite disease.
Mortality was estimated by using vital registration data coded to the International Classification of Disease (ICD) system or household mortality surveys known as verbal autopsy. Statistical methods were used to increase the comparability of mortality data sources, including the reclassification of codes that are nonspecific or unspecified, noise reduction algorithms, and Bayesian geospatial regression software

HIGHLIGHTS
The burden of CVD, in number of DALYs and deaths, continues to increase globally.
CVD burden attributable to modifiable risk factors continues to increase globally.
Countries should invest in existing costeffective public health programs and clinical interventions to target modifiable risks, promote healthy aging across the lifespan, and reduce disability and premature death due to CVD.  suggest that population growth and aging are major drivers of the increase in total CVD ( Figure 1B).
In 2019, total CVD DALYs were higher in men than women before age 80 to 84 years (Supplemental   Figure 4). These regional and national differences in total CVD burden and mortality reflect differences in prevalence of CVD risk factors as well as access to health care (8). Differences in access to effective primary and secondary prevention strategies may also play a role in differences in total CVD burden, especially in low-and middle-income countries (LMICs) (9).

Global Burden of Cardiovascular Diseases
America and the Caribbean, and Eastern and Southeastern Asia, where the share of older persons is projected to double between 2019 and 2050 (11,12).
Increased attention to promoting ideal cardiovascular health and healthy aging across the lifespan is necessary (13). Equally importantly, the time has come to implement feasible and affordable strategies for the prevention and control of CVD and to monitor results (14).  Figure 2B). Increasing absolute numbers of incident and prevalent IHD cases in most countries mean that national health systems will need to address increasing demand for IHD-related preventive and therapeutic services as these trends continue.
At the global level, substantially more total DALYs due to IHD were experienced by men than women.
IHD DALYs rose rapidly for men beginning at age 30 years (Supplemental Figure 5 Age-standardized rates of DALYs and deaths due to stroke were substantially greater in men compared to women, but prevalence was greater in women, suggesting the possibility of greater risk of death and disability in men but better stroke survival in women.
Similar patterns were observed in men and women with IS, intracerebral hemorrhage, and subarachnoid hemorrhage.
Roth et al. to 2019. Shaded regions represent 95% uncertainty intervals. Abbreviations as in Figure 1.

Global Burden of Cardiovascular Diseases
There is tremendous regional disparity in the burden of stroke. Age-standardized rates of deaths and   Figure 14B). The trends for the absolute and age-standardized estimates closely resemble those for high blood pressure. Taken together, the increasing global prevalence and rates of HHD can be explained by population growth and  Figure 16). The significance of this is uncertain because no such peaks are noted for high blood pressure or other contributing factors, and it can represent regional differences in disease coding, including that of peripartum cardiomyopathy. Inequalities in access to both primary and secondary prevention are a potential cause of these regional and sex differences.
The global prevalence of HHD and absolute rates of adverse outcomes are expected to continue to rise due to population growth and aging. The age-   Most of the prevalence increase occurred outside of high-income countries (HICs) and was due to improvements in survival and population growth.
Health systems will be increasingly burdened with adolescents and adults needing care for their congenital heart conditions. Age-standardized rates for RHD prevalence have closely tracked with all-age rates, but age-standardized mortality has exceeded all-age mortality until the past few years, highlighting the differential mortality years, a pattern that is also seen in the rise of deaths from 238,000 (95% UI: 212,000 to 257,000) to 340,000 (95% UI: 285,000 to 371,000) (Supplemental Figure 19A). However, over the same period, the age-standardized rate of death has decreased from 8.0 per 100,000 (95% UI: 6.4 to 8.6 per 100,000) to 5.6   (20).
Although the morbidity and mortality rates from cardiomyopathies and myocarditis collectively present a substantial global disease burden in 2019, the regional differences in the burden (Figure 7) suggest that public health interventions should be tailored to the specific etiologies of cardiomyopathy to lower these rates in the future.  Figure 21B). This indicates that the global increase in AC prevalence is related, in part, to population growth and aging.
Several countries in East Asia and the Caribbean regions showed opposite trends, with increasing age-standardized values for almost all indicators.
Factors that might explain these regional differences remain incompletely understood.
At the global level, substantially more total DALYs due to AC were experienced by men than women.
DALYs from AC rose rapidly among men beginning from age 25 years, being significantly higher in men than women across all ages (Supplemental Figure 22). Women are generally considered more susceptible to alcohol-induced damages than men, which may reflect sex-specific differences in alcohol consumption, type, blood level, distribution, or metabolism. However, the higher level of alcohol     However, because the risk factors for this disease   Figure 27B). In 2019, the age-standardized  Population-based studies of the prevalence of nonrheumatic valvular heart disease remain rare, and further research is needed to understand if sex differences in prevalence are due to differences in disease burden, health-seeking behavior, or rates of diagnosis.
There is substantial heterogeneity among countries in age-standardized prevalence and DALYs due to CAVD (Figure 11). Prevalence is low (<20 per 100,000) in several regions of the world, notably,  At the global level, substantially more total DALYs due to MV disease were experienced by women than men. For almost all age groups, MV disease DALYs were higher in women than men ( Figure 12). Globally, women and men had similar DALYs in the 40-to 44-year age groups, but the levels diverged after age 65 years, when women had more than one-third more DALYs due to MV disease than men, peaking at age 75 to 79 years. Prior studies have found that women with severe regurgitation have higher mortality and lower surgery rates than men, which may account for some of the increased DALYs in older women (32).
Age-standardized DALYs due to MV disease were highest for both men and women in Central Europe; specifically, high rates were seen in Serbia, Bosnia   Figure 31). Women ages 75 years and older had more DALYs due to endocarditis than men in the same age group.
There is wide variation in the regional agestandardized DALY rate due to endocarditis (Supplemental Figures 32 and 33   and 2019 (Supplemental Figure 34B). The trends in age-standardized rates of deaths and YLLs were flat from 1990 to 2019, and prevalence, YLDs, and DALYs declined slightly. Overall, the PAD prevalence increase reflects population growth rather than a major change in age-specific incidence. In both 1990 and 2019, cross-sectional analyses show that the numbers of prevalent cases increased with age in both men and women up to 70 years of age and prevalence rates increased throughout the whole age spectrum.
Numbers and rates of cases were higher in women than men at all ages. Deaths and DALYs showed increases with age comparable to prevalence except that deaths and DALYs were higher in men than women up to very old age.
The numbers of prevalent cases increased in both men and women at all ages by up to 2-fold since 1990, but age-standardized prevalence rates were slightly lower in 2019 than in 1990. Numbers of deaths and DALYs were higher in 2019 compared to 1990 in both men and women at all ages, but over the same period, age-standardized death rates remained much the same, and DALY rates fell slightly.
Age-standardized DALY rates varied by world re- Lowest DALY rates were found in Asia, Andean   Figure 36B). These data indicate that the increases in total number of disease events can be attributed to population growth and aging. However, in some regions-for example, Oceania-the agestandardized rates of DALYs, deaths, YLDs, and YLLs increased between 1990 and 2019.
Globally, DALYs due to high SBP in 2019 were higher among men compared with women from ages 15 to 19 through 70 to 74 years, but higher among women compared to men in those 80 to 84 years or older ( Figure 15). Age-standardized DALYs were higher among men compared with women in all regions of the world (Supplemental Figure 37).
In 2019, there was an approximately 8-fold variation across regions in age-standardized DALYs attributed to high SBP (Supplemental Figure 38).

Rates of DALYs were lowest for both women and men
in the high-income Asia Pacific region and highest in  Figure 16A). The agestandardized mortality rate due to high fasting   Figure 39).
DALYs due to high fasting plasma glucose increased with age, peaked at 70 years, and then declined.
Age-standardized DALYs due to high fasting plasma glucose were higher in Oceania, followed by Central Asia (Supplemental Figure 40). There were large variations between countries in high fasting plasma glucose DALY burden, with notably high rates in Uzbekistan, Afghanistan, Papua New Guinea, Egypt, and Oman (Supplemental Figure 41)  Over the study period, the global all-age rates for DALYs, deaths, and YLLs remained relatively static and increased for YLDs (Supplemental Figure 42B).   Great efforts are needed to promote the prevention of obesity and its progression to more severe forms (36). A multifactorial approach is required to promote improving dietary quality, especially reductions in simple sugars, complex carbohydrates, and total calories. Community prevention programs, like the Diabetes Prevention Program, duplicated in many programs (37), are needed (36). Optimizing efforts to promote physical activity and exercise training are needed, as well as reductions in sedentary behavior   higher than in 1990 (Supplemental Figure 52), which represents an epidemic of CKD of unknown origin that appears to be common in coastal lowlands, with repeated heat stress, pesticide, and heavy metal exposure implicated as potential causes (39).  Figure 54A). Trends for both all-age and age-standardized DALYs and death rates attributable to HAP have also declined sharply, indicating the impact of exposure reduction (Supplemental Figure  54B). However, agestandardized rates of DALYs attributable to HAP remain high throughout much of sub-Saharan Africa, which has yet to experience the benefits of improved access to clean household energy sources seen in India, China, and much of Southeast Asia (Supplemental Figure 55). The highest rates of DALYs for HAP were in Oceania; Eastern, Western and Central sub-Saharan Africa; and South Asia, driven by differences in exposure.
DALYs attributable to PM 2.5 and HAP were higher in men, driven by sex differences in rates of the diseases affected by air pollution (Supplemental Figures 56 and 57). These sex differences were less pronounced for HAP given that women tend to be more highly exposed. DALYs attributable to HAP had the largest impacts in infancy and early childhood, whereas for PM 2.5 , it was between ages 30 and 90 years.
Increased attention to air pollution as a CVD risk factor is warranted and will require concerted action and collaboration between government health    Abbreviations as in Figure 1.
Roth et al.    Abbreviations as in Figure 1.
Roth et al. Over time, the all-ages rate of DALYs, deaths, and YLLs due to LPA has increased, and the agestandardized rate has decreased (Supplemental Figure 63B). This pattern reflects increased burden due to growth and aging of the population, an effect that is removed by age standardization.
Total global DALYs due to LPA were similar for men and women until the 65-to 69-year age group, with men consistently higher (Supplemental Figure 64). Age-standardized DALYs due to LPA were highly