Correction to: Cardiovascular Disease Prevention: Training Opportunities, the Challenges, and Future Directions.

The original version of this article contains errors in Table 3. "At least 1 project/publication in the year" and "> 1 publication per year" have been switched under the titles of "Clinical Track" and "Physician-Scientist track".

Cardiovascular Disease Prevention: Training Opportunities, the Challenges, and Future Directions.

PURPOSE: Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality worldwide, necessitating major efforts in prevention. This review summarizes the currently available training opportunities in CVD prevention for fellows-in-training (FITs) and residents. We also highlight the challenges and future directions for CVD prevention as a field and propose a structure for an inclusive CVD prevention training program. RECENT FINDINGS: At present, there is a lack of centralized training resources for FITs and residents interested in pursuing a career in CVD prevention. Training in CVD prevention is not an accredited subspecialty fellowship by the American Council of Graduate Medical Education (ACGME). Although there are several independent training programs under the broad umbrella of CVD prevention focusing on different aspects of prevention, there is no unified curriculum or training. More collaborative efforts are needed to identify CVD prevention as an ACGME-accredited subspecialty fellowship. Providing more resources can encourage and produce more leaders in this essential field.

Trends in Coronary Angiography, Revascularization, and Outcomes of Cardiogenic Shock Complicating Non-ST-Elevation Myocardial Infarction.

Early revascularization is the mainstay of treatment for cardiogenic shock (CS) complicating acute myocardial infarction. However, data on the contemporary trends in management and outcomes of CS complicating non-ST-elevation myocardial infarction (NSTEMI) are limited. We used the 2006 to 2012 Nationwide Inpatient Sample databases to identify patients aged ≥ 18 years with NSTEMI with or without CS. Temporal trends and differences in coronary angiography, revascularization, and outcomes were analyzed. Of 2,191,772 patients with NSTEMI, 53,800 (2.5%) had a diagnosis of CS. From 2006 to 2012, coronary angiography rates increased from 53.6% to 60.4% in patients with NSTEMI with CS (ptrend <0.001). Among patients who underwent coronary angiography, revascularization rates were significantly higher in patients with CS versus without CS (72.5% vs 62.6%, p <0.001). Patients with NSTEMI with CS had significantly higher risk-adjusted in-hospital mortality (odds ratio 10.09, 95% confidence interval 9.88 to 10.32) as compared to those without CS. In patients with CS, an invasive strategy was associated with lower risk-adjusted in-hospital mortality (odds ratio 0.43, 95% confidence interval 0.42 to 0.45). Risk-adjusted in-hospital mortality, length of stay, and total hospital costs decreased over the study period in patients with and without CS (ptrend <0.001). In conclusion, we observed an increasing trend in coronary angiography and decreasing trend in in-hospital mortality, length of stay, and total hospital costs in patients with NSTEMI with and without CS. Despite these positive trends, overall coronary angiography and revascularization rates remain less than optimal and in-hospital mortality unacceptably high in patients with NSTEMI and CS.

Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013.

BACKGROUND: In 2010, overweight and obesity were estimated to cause 3·4 million deaths, 3·9% of years of life lost, and 3·8% of disability-adjusted life-years (DALYs) worldwide. The rise in obesity has led to widespread calls for regular monitoring of changes in overweight and obesity prevalence in all populations. Comparable, up-to-date information about levels and trends is essential to quantify population health effects and to prompt decision makers to prioritise action. We estimate the global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013. METHODS: We systematically identified surveys, reports, and published studies (n=1769) that included data for height and weight, both through physical measurements and self-reports. We used mixed effects linear regression to correct for bias in self-reports. We obtained data for prevalence of obesity and overweight by age, sex, country, and year (n=19,244) with a spatiotemporal Gaussian process regression model to estimate prevalence with 95% uncertainty intervals (UIs). FINDINGS: Worldwide, the proportion of adults with a body-mass index (BMI) of 25 kg/m(2) or greater increased between 1980 and 2013 from 28·8% (95% UI 28·4-29·3) to 36·9% (36·3-37·4) in men, and from 29·8% (29·3-30·2) to 38·0% (37·5-38·5) in women. Prevalence has increased substantially in children and adolescents in developed countries; 23·8% (22·9-24·7) of boys and 22·6% (21·7-23·6) of girls were overweight or obese in 2013. The prevalence of overweight and obesity has also increased in children and adolescents in developing countries, from 8·1% (7·7-8·6) to 12·9% (12·3-13·5) in 2013 for boys and from 8·4% (8·1-8·8) to 13·4% (13·0-13·9) in girls. In adults, estimated prevalence of obesity exceeded 50% in men in Tonga and in women in Kuwait, Kiribati, Federated States of Micronesia, Libya, Qatar, Tonga, and Samoa. Since 2006, the increase in adult obesity in developed countries has slowed down. INTERPRETATION: Because of the established health risks and substantial increases in prevalence, obesity has become a major global health challenge. Not only is obesity increasing, but no national success stories have been reported in the past 33 years. Urgent global action and leadership is needed to help countries to more effectively intervene. FUNDING: Bill & Melinda Gates Foundation.

Urban-rural differences in coronary heart disease mortality in the United States: 1999-2009.

OBJECTIVE: Coronary heart disease (CHD) mortality has declined in the past few decades; however, it is unclear whether the reduction in CHD deaths has been similar across urbanization levels and in specific racial groups. We describe the pattern and magnitude of urban-rural variations in CHD mortality in the U.S. METHODS: Using data from the National Center for Health Statistics, we examined trends in death rates from CHD from 1999 to 2009 among people aged 35-84 years, in each geographic region (Northeast, Midwest, West, and South) and in specific racial-urbanization groups, including black and white people in large and medium metropolitan (urban) areas and in non-metropolitan (rural) areas. We also examined deaths from early-onset CHD in females aged <65 years and males aged <55 years. RESULTS: From 1999 to 2009, there was a 40% decline in age-adjusted CHD mortality. The trend was similar in black and white people but was more pronounced in urban than in rural areas, resulting in a crossover in 2007, when rural areas began showing a higher CHD mortality than urban areas. White people in large metropolitan areas had the largest decline (43%). Throughout the study period, CHD mortality remained higher in black people than in white people, and, in the South, it remained higher in rural than in urban areas. For early-onset CHD, the mortality decline was more modest (30%), but overall trends by urbanization and region were similar. CONCLUSION: Favorable national trends in CHD mortality conceal persisting disparities for some regions and population subgroups (e.g., rural areas and black people).

Burden of arrhythmias in patients with Takotsubo cardiomyopathy (apical ballooning syndrome).

INTRODUCTION: The objective of our study was to assess the burden of arrhythmias, the gender differences in occurrence of arrhythmias and the impact of these arrhythmias on hospitalization outcomes in patients with Takotsubo Cardiomyopathy (TTC). METHODS: TTC and various arrhythmias were identified using appropriate ICD-9-CM codes from Nationwide Inpatient Sample (NIS) discharge records 2006-2010. Length of hospital stay (LOS), in-hospital mortality and total charges were used to assess the impact of the arrhythmias on TTC hospitalization. All analyses were performed using SASv9.2 (Cary Institute Inc., Cary, NC). RESULTS: A total of 16,450 patients were included in the study and 26% (n=4296) of patients had cardiac arrhythmias. Following arrhythmias were present in the descending order of frequency: atrial fibrillation (Afib) 6.9%, ventricular tachycardia (VT) 3.2%, atrial flutter (Afl) 1.9%, ventricular fibrillation and flutter 1%, paroxysmal supraventricular tachycardia (PSVT) 0.8%. Nearly two percent of the patients had sudden cardiac arrest (SCA). Males were more likely to have cardiac arrhythmias in general compared to females (OR: 1.5, 95% CI: 1.3-1.7, p-value 0.001). Occurrence of ventricular tachycardia (OR: 1.7, 95% CI: 1.3-2.2, p-value<0.001) and sudden cardiac arrest OR: 1.6, 95% CI: 1.1-2.2, p<0.001) were significantly higher in males. In contrast, Afib was significantly less in males compared to females (OR:0.8, 95% CI:0.6-0.9). Patients with arrhythmias had significantly longer length of stay, and increased cost of hospitalization and mortality. CONCLUSIONS: Arrhythmias are present in nearly one-quarter of patients with TTC and worsen the outcome. While TTC has been established as a disease mainly of females, life threatening arrhythmias like VT and SCA are more common in males.

In-hospital complications associated with catheter ablation of atrial fibrillation in the United States between 2000 and 2010: analysis of 93 801 procedures.

BACKGROUND: Atrial fibrillation ablation has made tremendous progress with respect to innovation, efficacy, and safety. However, limited data exist regarding the burden and trends in adverse outcomes arising from this procedure. The aim of our study was to examine the frequency of adverse events attributable to atrial fibrillation (AF) ablation and the influence of operator and hospital volume on outcomes. METHODS AND RESULTS: With the use of the Nationwide Inpatient Sample, we identified AF patients treated with catheter ablation. We investigated common complications including cardiac perforation and tamponade, pneumothorax, stroke, transient ischemic attack, vascular access complications (hemorrhage/hematoma, vascular complications requiring surgical repair, and accidental arterial puncture), and in-hospital death described with AF ablation, and we defined these complications by using validated International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. An estimated 93,801 AF ablations were performed from 2000 to 2010. The overall frequency of complications was 6.29% with combined cardiac complications (2.54%) being the most frequent. Cardiac complications were followed by vascular complications (1.53%), respiratory complications (1.3%), and neurological complications (1.02%). The in-hospital mortality was 0.46%. Annual operator (<25 procedures) and hospital volume (<50 procedures) were significantly associated with adverse outcomes. There was a small (nonsignificant) rise in overall complication rates. CONCLUSIONS: The overall complication rate was 6.29% in patients undergoing AF ablation. There was a significant association between operator and hospital volume and adverse outcomes. This suggests a need for future research into identifying the safety measures in AF ablations and instituting appropriate interventions to improve overall AF ablation outcomes.

Common values in assessing health outcomes from disease and injury: disability weights measurement study for the Global Burden of Disease Study 2010.

BACKGROUND: Measurement of the global burden of disease with disability-adjusted life-years (DALYs) requires disability weights that quantify health losses for all non-fatal consequences of disease and injury. There has been extensive debate about a range of conceptual and methodological issues concerning the definition and measurement of these weights. Our primary objective was a comprehensive re-estimation of disability weights for the Global Burden of Disease Study 2010 through a large-scale empirical investigation in which judgments about health losses associated with many causes of disease and injury were elicited from the general public in diverse communities through a new, standardised approach. METHODS: We surveyed respondents in two ways: household surveys of adults aged 18 years or older (face-to-face interviews in Bangladesh, Indonesia, Peru, and Tanzania; telephone interviews in the USA) between Oct 28, 2009, and June 23, 2010; and an open-access web-based survey between July 26, 2010, and May 16, 2011. The surveys used paired comparison questions, in which respondents considered two hypothetical individuals with different, randomly selected health states and indicated which person they regarded as healthier. The web survey added questions about population health equivalence, which compared the overall health benefits of different life-saving or disease-prevention programmes. We analysed paired comparison responses with probit regression analysis on all 220 unique states in the study. We used results from the population health equivalence responses to anchor the results from the paired comparisons on the disability weight scale from 0 (implying no loss of health) to 1 (implying a health loss equivalent to death). Additionally, we compared new disability weights with those used in WHO's most recent update of the Global Burden of Disease Study for 2004. FINDINGS: 13,902 individuals participated in household surveys and 16,328 in the web survey. Analysis of paired comparison responses indicated a high degree of consistency across surveys: correlations between individual survey results and results from analysis of the pooled dataset were 0·9 or higher in all surveys except in Bangladesh (r=0·75). Most of the 220 disability weights were located on the mild end of the severity scale, with 58 (26%) having weights below 0·05. Five (11%) states had weights below 0·01, such as mild anaemia, mild hearing or vision loss, and secondary infertility. The health states with the highest disability weights were acute schizophrenia (0·76) and severe multiple sclerosis (0·71). We identified a broad pattern of agreement between the old and new weights (r=0·70), particularly in the moderate-to-severe range. However, in the mild range below 0·2, many states had significantly lower weights in our study than previously. INTERPRETATION: This study represents the most extensive empirical effort as yet to measure disability weights. By contrast with the popular hypothesis that disability assessments vary widely across samples with different cultural environments, we have reported strong evidence of highly consistent results. FUNDING: Bill & Melinda Gates Foundation.

Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010.

BACKGROUND: Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health policy debates. In the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex. METHODS: We attempted to identify all available data on causes of death for 187 countries from 1980 to 2010 from vital registration, verbal autopsy, mortality surveillance, censuses, surveys, hospitals, police records, and mortuaries. We assessed data quality for completeness, diagnostic accuracy, missing data, stochastic variations, and probable causes of death. We applied six different modelling strategies to estimate cause-specific mortality trends depending on the strength of the data. For 133 causes and three special aggregates we used the Cause of Death Ensemble model (CODEm) approach, which uses four families of statistical models testing a large set of different models using different permutations of covariates. Model ensembles were developed from these component models. We assessed model performance with rigorous out-of-sample testing of prediction error and the validity of 95% UIs. For 13 causes with low observed numbers of deaths, we developed negative binomial models with plausible covariates. For 27 causes for which death is rare, we modelled the higher level cause in the cause hierarchy of the GBD 2010 and then allocated deaths across component causes proportionately, estimated from all available data in the database. For selected causes (African trypanosomiasis, congenital syphilis, whooping cough, measles, typhoid and parathyroid, leishmaniasis, acute hepatitis E, and HIV/AIDS), we used natural history models based on information on incidence, prevalence, and case-fatality. We separately estimated cause fractions by aetiology for diarrhoea, lower respiratory infections, and meningitis, as well as disaggregations by subcause for chronic kidney disease, maternal disorders, cirrhosis, and liver cancer. For deaths due to collective violence and natural disasters, we used mortality shock regressions. For every cause, we estimated 95% UIs that captured both parameter estimation uncertainty and uncertainty due to model specification where CODEm was used. We constrained cause-specific fractions within every age-sex group to sum to total mortality based on draws from the uncertainty distributions. FINDINGS: In 2010, there were 52·8 million deaths globally. At the most aggregate level, communicable, maternal, neonatal, and nutritional causes were 24·9% of deaths worldwide in 2010, down from 15·9 million (34·1%) of 46·5 million in 1990. This decrease was largely due to decreases in mortality from diarrhoeal disease (from 2·5 to 1·4 million), lower respiratory infections (from 3·4 to 2·8 million), neonatal disorders (from 3·1 to 2·2 million), measles (from 0·63 to 0·13 million), and tetanus (from 0·27 to 0·06 million). Deaths from HIV/AIDS increased from 0·30 million in 1990 to 1·5 million in 2010, reaching a peak of 1·7 million in 2006. Malaria mortality also rose by an estimated 19·9% since 1990 to 1·17 million deaths in 2010. Tuberculosis killed 1·2 million people in 2010. Deaths from non-communicable diseases rose by just under 8 million between 1990 and 2010, accounting for two of every three deaths (34·5 million) worldwide by 2010. 8 million people died from cancer in 2010, 38% more than two decades ago; of these, 1·5 million (19%) were from trachea, bronchus, and lung cancer. Ischaemic heart disease and stroke collectively killed 12·9 million people in 2010, or one in four deaths worldwide, compared with one in five in 1990; 1·3 million deaths were due to diabetes, twice as many as in 1990. The fraction of global deaths due to injuries (5·1 million deaths) was marginally higher in 2010 (9·6%) compared with two decades earlier (8·8%). This was driven by a 46% rise in deaths worldwide due to road traffic accidents (1·3 million in 2010) and a rise in deaths from falls. Ischaemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lower respiratory infections, lung cancer, and HIV/AIDS were the leading causes of death in 2010. Ischaemic heart disease, lower respiratory infections, stroke, diarrhoeal disease, malaria, and HIV/AIDS were the leading causes of years of life lost due to premature mortality (YLLs) in 2010, similar to what was estimated for 1990, except for HIV/AIDS and preterm birth complications. YLLs from lower respiratory infections and diarrhoea decreased by 45-54% since 1990; ischaemic heart disease and stroke YLLs increased by 17-28%. Regional variations in leading causes of death were substantial. Communicable, maternal, neonatal, and nutritional causes still accounted for 76% of premature mortality in sub-Saharan Africa in 2010. Age standardised death rates from some key disorders rose (HIV/AIDS, Alzheimer's disease, diabetes mellitus, and chronic kidney disease in particular), but for most diseases, death rates fell in the past two decades; including major vascular diseases, COPD, most forms of cancer, liver cirrhosis, and maternal disorders. For other conditions, notably malaria, prostate cancer, and injuries, little change was noted. INTERPRETATION: Population growth, increased average age of the world's population, and largely decreasing age-specific, sex-specific, and cause-specific death rates combine to drive a broad shift from communicable, maternal, neonatal, and nutritional causes towards non-communicable diseases. Nevertheless, communicable, maternal, neonatal, and nutritional causes remain the dominant causes of YLLs in sub-Saharan Africa. Overlaid on this general pattern of the epidemiological transition, marked regional variation exists in many causes, such as interpersonal violence, suicide, liver cancer, diabetes, cirrhosis, Chagas disease, African trypanosomiasis, melanoma, and others. Regional heterogeneity highlights the importance of sound epidemiological assessments of the causes of death on a regular basis. FUNDING: Bill & Melinda Gates Foundation.

Oxidative stress is associated with impaired arterial elasticity.

AIMS: Arterial stiffening may lead to hypertension, greater left ventricular after-load and adverse clinical outcomes. The underlying mechanisms influencing arterial elasticity may involve oxidative injury to the vessel wall. We sought to examine the relationship between novel markers of oxidative stress and arterial elastic properties in healthy humans. METHODS AND RESULTS: We studied 169 subjects (mean age 42.6 ± 14 years, 51.6% male) free of traditional cardiovascular risk factors. Indices of arterial stiffness and wave reflections measured included carotid-femoral Pulse Wave Velocity (PWV), Augmentation Index (Aix) and Pulse Pressure Amplification (PPA). Non-free radical oxidative stress was assessed as plasma oxidized and reduced amino-thiol levels (cysteine/cystine, glutathione/GSSG) and their ratios (redox potentials), and free radical oxidative stress as derivatives of reactive oxygen metabolites (dROMs). Inflammation was assessed as hsCRP and interleukin-6 levels. The non-free radical marker of oxidative stress, cystine was significantly correlated with all arterial indices; PWV (r=0.38, p<0.001), Aix (r=0.35, p<0.001) and PPA (r=-0.30, p<0.001). Its redox potential, was also associated with PWV (r=0.22, p=0.01), while the free radical marker of oxidative stress dROMS was associated with Aix (r=0.25, p<0.01). After multivariate adjustment for age, gender, arterial pressure, height, weight, heart rate and CRP, of these oxidative stress markers, only cystine remained independently associated with PWV (p=0.03), Aix (p=0.01) and PPA (p=0.05). CONCLUSIONS: In healthy subjects without confounding risk factors or significant systemic inflammation, a high cystine level, reflecting extracellular oxidant burden, is associated with increased arterial stiffness and wave reflections. This has implications for understanding the role of oxidant burden in pre-clinical vascular dysfunction.

Prospects for a cardiovascular disease prevention polypill.

Cardiovascular diseases (CVD) account for one-third of annual global mortality. The aggregated benefits of concurrently controlling common CVD risk factors, such as dyslipidemia and hypertension, in people at overall risk for CVD is postulated to be more efficient than treating each individual risk factor to target. Administration of a polypill consisting of cholesterol-lowering (statins), antihypertensive, and antiplatelet agents together would simultaneously lower multiple risk factors, and applying such a population risk-reduction strategy would drastically reduce CVD incidence. This idea has generated much controversy and debate over the past decade. A few studies have emerged providing early evidence about the safety and efficacy of such a pill, and the results of ongoing and planned studies of outcome are eagerly anticipated. In this article, we review and interpret the existing evidence as well as explore the potential of a polypill for primary and secondary prevention of CVD.