Richard F. Gillum

Worldwide Epidemiology of Atrial Fibrillation A Global Burden of Disease 2010 Study

Background— The global burden of atrial fibrillation (AF) is unknown. Methods and Results— We systematically reviewed population-based studies of AF published from 1980 to 2010 from the 21 Global Burden of Disease regions to estimate global/regional prevalence, incidence, and morbidity and mortality related to AF (DisModMR software). Of 377 potential studies identified, 184 met prespecified eligibility criteria. The estimated number of individuals with AF globally in 2010 was 33.5 million (20.9 million men [95% uncertainty interval (UI), 19.5–22.2 million] and 12.6 million women [95% UI, 12.0–13.7 million]). Burden associated with AF, measured as disability-adjusted life-years, increased by 18.8% (95% UI, 15.8–19.3) in men and 18.9% (95% UI, 15.8–23.5) in women from 1990 to 2010. In 1990, the estimated age-adjusted prevalence rates of AF (per 100 000 population) were 569.5 in men (95% UI, 532.8–612.7) and 359.9 in women (95% UI, 334.7–392.6); the estimated age-adjusted incidence rates were 60.7 per 100 000 person-years in men (95% UI, 49.2–78.5) and 43.8 in women (95% UI, 35.9–55.0). In 2010, the prevalence rates increased to 596.2 (95% UI, 558.4–636.7) in men and 373.1 (95% UI, 347.9–402.2) in women; the incidence rates increased to 77.5 (95% UI, 65.2–95.4) in men and 59.5 (95% UI, 49.9–74.9) in women. Mortality associated with AF was higher in women and increased by 2-fold (95% UI, 2.0–2.2) and 1.9-fold (95% UI, 1.8–2.0) in men and women, respectively, from 1990 to 2010. There was evidence of significant regional heterogeneity in AF estimations and availability of population-based data. Conclusions— These findings provide evidence of progressive increases in overall burden, incidence, prevalence, and AF-associated mortality between 1990 and 2010, with significant public health implications. Systematic, regional surveillance of AF is required to better direct prevention and treatment strategies.

Body Iron Stores and the Risk of Coronary Heart Disease

BACKGROUND Recent studies have suggested an association between higher body iron stores and the risk of coronary heart disease. To assess these findings, we examined the association between transferrin saturation and the risk of coronary heart disease, myocardial infarction, overall mortality, and mortality from cardiovascular causes in a large population. METHODS We studied a total of 4518 men and women from the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study, using a multivariate Cox proportional-hazards model. Base-line data were collected from 1971 to 1974, with follow-up through 1987. Transferrin saturation (serum iron concentration divided by total iron-binding capacity) was used as a measure of the amount of circulating iron available to tissues. RESULTS The risk of coronary heart disease was not related to transferrin-saturation levels in white men or women. Estimates of the relative risk of coronary heart disease for the fifth quintile of transferrin saturation as compared with the first quintile were 0.72 (95 percent confidence interval, 0.51 to 1.00) for men and 0.85 (95 percent confidence interval, 0.60 to 1.21) for women. The results were similar for myocardial infarction. A significant inverse association with transferrin saturation was found for overall mortality and for mortality from cardiovascular causes in white men and women. Transferrin saturation was not associated with any of the clinical outcomes in blacks, possibly owing to the small sample. CONCLUSIONS Higher transferrin-saturation levels were not associated with an increased risk of coronary heart disease or myocardial infarction. On the contrary, the results indicate that there may be an inverse association of iron stores with overall mortality and with mortality from cardiovascular causes.

Association of Cardiometabolic Multimorbidity With Mortality.

IMPORTANCE The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). MAIN OUTCOMES AND MEASURES All-cause mortality and estimated reductions in life expectancy. RESULTS In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.

Association of Cardiometabolic Multimorbidity With Mortality The Emerging Risk Factors Collaboration

IMPORTANCE The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). MAIN OUTCOMES AND MEASURES All-cause mortality and estimated reductions in life expectancy. RESULTS In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.

Glycated Hemoglobin Measurement and Prediction of Cardiovascular Disease

IMPORTANCE The value of measuring levels of glycated hemoglobin (HbA1c) for the prediction of first cardiovascular events is uncertain. OBJECTIVE To determine whether adding information on HbA1c values to conventional cardiovascular risk factors is associated with improvement in prediction of cardiovascular disease (CVD) risk. DESIGN, SETTING, AND PARTICIPANTS Analysis of individual-participant data available from 73 prospective studies involving 294,998 participants without a known history of diabetes mellitus or CVD at the baseline assessment. MAIN OUTCOMES AND MEASURES Measures of risk discrimination for CVD outcomes (eg, C-index) and reclassification (eg, net reclassification improvement) of participants across predicted 10-year risk categories of low (<5%), intermediate (5% to <7.5%), and high (≥ 7.5%) risk. RESULTS During a median follow-up of 9.9 (interquartile range, 7.6-13.2) years, 20,840 incident fatal and nonfatal CVD outcomes (13,237 coronary heart disease and 7603 stroke outcomes) were recorded. In analyses adjusted for several conventional cardiovascular risk factors, there was an approximately J-shaped association between HbA1c values and CVD risk. The association between HbA1c values and CVD risk changed only slightly after adjustment for total cholesterol and triglyceride concentrations or estimated glomerular filtration rate, but this association attenuated somewhat after adjustment for concentrations of high-density lipoprotein cholesterol and C-reactive protein. The C-index for a CVD risk prediction model containing conventional cardiovascular risk factors alone was 0.7434 (95% CI, 0.7350 to 0.7517). The addition of information on HbA1c was associated with a C-index change of 0.0018 (0.0003 to 0.0033) and a net reclassification improvement of 0.42 (-0.63 to 1.48) for the categories of predicted 10-year CVD risk. The improvement provided by HbA1c assessment in prediction of CVD risk was equal to or better than estimated improvements for measurement of fasting, random, or postload plasma glucose levels. CONCLUSIONS AND RELEVANCE In a study of individuals without known CVD or diabetes, additional assessment of HbA1c values in the context of CVD risk assessment provided little incremental benefit for prediction of CVD risk.

High Blood Pressure, Hypertension, and High Pulse Pressure Are Associated with Poorer Cognitive Function in Persons Aged 60 and Older: The Third National Health and Nutrition Examination Survey

OBJECTIVES: To test the hypothesis that hypertension, high blood pressure, and high pulse pressure (PP) are independently associated with lower cognitive function.

Decline in coronary heart disease mortality: Old questions and new facts

By 1979, mortality rates for coronary heart disease had declined for 14 consecutive years in the United States. Preliminary data indicate a continued decline. This review of reports published in the last five years documents the consistency of most data with the following hypotheses: (1) Reductions in population levels of hypertension and cigarette smoking have contributed to the decline in mortality from coronary heart disease. (2) Improved medical care for acute myocardial infarction has also contributed to the decline. Data are lacking to specify the contributions of changes in other risk factors, emergency medical services, medical care of chronic coronary heart disease, or other changes in the physical and social environment. Long-term, simultaneous surveillance of mortality, morbidity, medical care, and risk factors should be supported in five to 10 centers around the United States.

Geographic variation in sudden coronary death

To describe geographic variations in an indicator of sudden coronary death, data from the National Center for Health Statistics were examined for deaths occurring out of hospital or in emergency rooms in 1984 to 1986 in 42 states. In white males aged 55 to 64 years, the percent of ischemic heart disease deaths coded as occurring out of hospital or in the ER ranged from 49.6% to 70.4%. The percents tended to be higher in mountain states and around Lake Michigan. However, neighboring states sometimes had very different percents. Within regions, percents were higher in nonmetropolitan than in metropolitan areas. Standard mortality ratios for white males of all ages revealed that several states had relatively high rates of death out of hospital or in the ER. These included New York, Michigan, and Wisconsin. High rates of coronary death out of hospital or in the ER may be due to high overall coronary death rates, high percent of coronary deaths occurring out of hospital or in the ER, or both. Further studies are needed of geographic variation in sudden coronary death and cardiac arrest and factors that might explain the variation such as emergency medical services. Place of death data from death certificates may be useful in monitoring efforts to prevent sudden coronary death.

Sex differences in the relationship between work and health: The Minnesota Heart Survey

This study compares the impact ofjob experiences and related attitudes and behaviors on mens and womens risk of cardiovascular disease. Data from the Minnesota Heart Survey of approximately 2,500 employed persons are analyzed using path analysis. The job experiences examined have few powerful consequences for risk of coronary heart disease. Occupational mobility has a slightly stronger effect on mens risk than on womens, and working long hours has more detrimental consequences for health behaviors than for blood pressure or serum cholesterol level. In contrast, job experiences have considerable consequences for individual attitudes and behaviors, and these effects are generally stronger for men than women. While women report greater levels of stress than men, work hours and job deadlines contribute more substantially to stress among men.

Global burden of atrial fibrillation in developed and developing nations.

Atrial fibrillation is the most common heart rhythm disorder in the world, with major public health impact especially due to increased risk of stroke and hospitalizations. The recently published results on epidemiology of atrial fibrillation from the Global Burden of Diseases, Injuries, and Risk Factors Study confirm the existence of a significant and progressive worldwide increase in the burden of atrial fibrillation. However, there appears to be regional variation in both the burden of atrial fibrillation and availability of epidemiological data regarding this condition. In this review, the authors identify issues that are unique to the developed versus developing regions and outline a road map for possible approaches to surveillance, management, and prevention of atrial fibrillation at the global level.