Circulation Editors’ Picks

Abstract

HomeCirculationVol. 127, No. 19Circulation Editors’ Picks Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBCirculation Editors’ PicksMost Read Articles in Epidemiology and Prevention The Editors The Editors Search for more papers by this author Originally published14 May 2013https://doi.org/10.1161/CIRCULATIONAHA.113.003137Circulation. 2013;127:e597–e615Associations of Total and High-Molecular-Weight Adiponectin With All-Cause and Cardiovascular Mortality in Older Persons: The Cardiovascular Health StudySummary: Adiponectin is the most abundant protein secreted by adipocytes. This adipokine, which is suppressed in obesity, exhibits insulin-sensitizing and atheroprotective signaling properties. Clinical studies in healthy middle-aged adults document an inverse relationship between adiponectin and adverse outcomes, but in cohorts with prevalent coronary disease, heart failure, or advanced age, a direct association has been reported. We investigated these findings further by assessing the relationship of total and high-molecular-weight adiponectin with fatal events in a large cohort of older adults stratified by baseline cardiovascular disease and heart failure/atrial fibrillation. There was evidence of effect modification by baseline cardiovascular status for both adiponectin measures, such that after adjustment for potential confounders, the relationship was U-shaped among participants without prevalent cardiovascular disease, heart failure, or atrial fibrillation, null in those with prevalent cardiovascular disease only, and direct in subjects with prevalent heart failure/atrial fibrillation. Additional adjustment for putative metabolic/inflammatory intermediates abolished the inverse association with mortality at the lower range of concentrations in the first group, suggested a direct association in the second, and strengthened the association in the third. Together, these findings advance understanding of the adiponectin paradox, showing that among older adults, the associations with mortality become progressively more adverse across subgroups with increasing cardiovascular risk. Disappearance of the protective association at lower adiponectin concentrations after accounting for metabolic factors suggests that the beneficial actions of the adipokine are counterbalanced by as yet undetermined deleterious influences. Further investigation to elucidate the underlying mechanisms could lead to the identification of novel therapeutic targets in aging and related disorders.Conclusions: Adiponectin exhibits distinct associations with mortality in elders, which shift from U-shaped to flat to direct with greater baseline cardiovascular dysfunction but become more consistently adverse after accounting for metabolic/inflammatory factors presumed to be favorably regulated by the adipokine. These findings advance understanding of the adiponectin paradox as it relates to older adults.1Relationship Between Healthy Diet and Risk of Cardiovascular Disease Among Patients on Drug Therapies for Secondary Prevention: A Prospective Cohort Study of 31 546 High-Risk Individuals From 40 CountriesSummary: Although healthy diets have been shown to be associated with a lower risk of cardiovascular disease (CVD) in populations without prior CVD, much less is known about those with established CVD. We studied the association between overall diet quality and the recurrence of CVD among 31 546 individuals (age, 66.5±6.2 years) with a history of CVD enrolled in 2 randomized trials, the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET) and the Telmisartan Randomized Assessment Study in ACEI Intolerant Subjects With Cardiovascular Disease (TRANSCEND), from 40 middle- and high-income countries. A healthy diet consisted of high intake of fruits, vegetables, whole grains, nuts, and fish relative to meat and eggs. A graded association between diet quality and recurrence of CVD events across all regions and various income levels and across different categories of risk factors and comorbidities was observed. These associations were observed in people receiving proven drug therapies for secondary prevention, suggesting that the benefits of dietary modifications were in addition to those from the medications. These data suggest that at least 20% recurrence of CVD could be avoided by adhering to a healthy diet. Highlighting the importance of healthy eating by health professionals and advising high-risk individuals to improve their diet quality would substantially reduce CVD recurrence beyond drug therapy alone and save lives globally.Conclusions: A higher-quality diet was associated with a lower risk of recurrent CVD events among people ≥55 years of age with CVD or diabetes mellitus. Highlighting the importance of healthy eating by health professionals would substantially reduce CVD recurrence and save lives globally.2Prognosis of Individuals With Asymptomatic Left Ventricular Systolic Dysfunction in the Multi-Ethnic Study of Atherosclerosis (MESA)Summary: Individuals with congestive heart failure still endure high morbidity and mortality despite recent advances in management. Studies have shown that early identification and treatment of individuals with the asymptomatic phase of heart failure could slow the progression to the symptomatic phase and reduce subsequent morbidity and mortality. However, data on the prevalence and prognosis of individuals with asymptomatic left ventricular systolic dysfunction (ALVSD) are limited. The few available data included ALVSD individuals with known myocardial infarction, a subgroup who most likely have had contact with healthcare professionals and have been prescribed the needed therapy. The public health impact of screening for this subgroup of ALVSD is likely to be of limited value. The present study used a large multiethnic cohort, free of clinical cardiovascular disease including myocardial infarction to show that ALVSD is uncommon (prevalence of 1.7%). This low prevalence, however, translates into several hundred thousand, if not millions of community-dwelling Americans. The highest prevalence was in blacks (2.6%) and the least in Chinese Americans (0.15%). Black men with hypertension had the highest prevalence of ALVSD. The risk of developing congestive heart failure was ≈9 times higher in individuals with ALVSD in comparison with those without ALVSD after 9 years of follow-up. Individuals with ALVSD were about twice as likely to die or develop a cardiovascular event as those without ALVSD during the follow-up period. Current debate and more research should focus on how best to screen for ALVSD in individuals without clinical cardiovascular disease, because our data suggest that these individuals are at higher risk for congestive heart failure, cardiovascular disease events, and all-cause mortality.Conclusions: ALVSD is uncommon in individuals without previous clinical CVD, but it is associated with high risk for CHF, CVD, and all-cause mortality. The left ventricular mass index had good discrimination for incident CHF in Multi-Ethnic Study of Atherosclerosis (MESA) participants with ALVSD.3Cardiovascular Events as a Function of Serum Bilirubin Levels in a Large, Statin-Treated CohortSummary: Serum bilirubin has demonstrated potent antioxidant properties in vitro and in vivo, appears to be particularly effective at suppressing oxidation of lipids, and may improve endothelial function. Various studies have shown that people with low bilirubin levels have higher rates of cardiovascular disease. In support of a causal relationship, prospective studies have shown that people with genotypes causing hyperbilirubinemia have substantially lower rates of cardiovascular disease. Serum bilirubin is often measured in patients before the prescription of a statin to assess liver function. In a large population-based cohort of patients prescribed statins in the United Kingdom (n=130 052), a nonlinear L-shaped relationship between pretreatment bilirubin and cardiovascular disease was detected. After traditional risk factors were accounted for, the elevated risk was restricted to those with levels <10 to 15 μmol/L, and the relationship was similar in men and women. Bilirubin level measured before statin prescription provides information on cardiovascular disease risk in addition to traditional factors, which may reflect a combination of otherwise unmeasured genetic and environmental exposures.Conclusions: Serum bilirubin level measured before a statin prescription to assess liver function is an independent risk factor for CVD and death in both men and women.4A Nutrient-Wide Association Study on Blood PressureSummary: Raised blood pressure (BP) is a major risk factor for coronary heart disease and stroke. Risk increases in graded fashion across the BP range, with substantial risk of death and disability attributed to raised BP at normal and high-normal BPs, below current treatment thresholds. Thus, nonpharmacologic as well as pharmacological approaches are needed to deal with the population-wide BP problem. Dietary habits are known to be related to high BP, but the role of many nutrients is unclear despite intensive research efforts. We used a nutrient-wide association study design to systematically test and validate multiple associations between a wide range of nutrients and BP. We initially tested associations of 82 nutrients and 3 urine electrolytes/electrolyte ratios with BP in a 50% random sample of the population-based study, the International Collaborative Study on Macro-/Micronutrients and Blood Pressure (INTERMAP). Significant findings were validated in the remainder 50% INTERMAP population and among participants in the National Health and Nutrition Examination Survey (NHANES). We identified inverse associations between BP and intake of B vitamins (folacin, riboflavin, thiamin) previously poorly studied, and reidentified sodium-to-potassium ratio and alcohol with BP (direct), and nonheme iron, phosphorus, and magnesium intake with systolic BP (inverse). Our results highlight a complex array of nutritional correlates with BP and emphasize why traditional approaches of testing 1 association at a time may be suboptimal compared with our inclusive nutrient-wide association study paradigm. Findings for BP and B vitamins may represent potentially causative associations, which need to be probed in further observational and interventional studies.Conclusions: We identified significant inverse associations between B vitamins and BP, relationships hitherto poorly investigated. Our analyses represent a systematic unbiased approach to the evaluation and validation of nutrient-BP associations.5Trends in the Incidence of Atrial Fibrillation in Older Patients Initiating Dialysis in the United StatesSummary: Atrial fibrillation (AF) is a common condition, particularly in older individuals as well as those with chronic kidney disease, including those with end-stage renal disease requiring dialysis. Although the prevalence of AF has been defined and found to be rising rapidly in older end-stage renal disease patients, little is known about the incidence of AF in this population. This study found that at least 3 factors have contributed to the increasing AF prevalence over the past decade and a half: (1) more patients initiate dialysis with preexisting AF; (2) a modest increase of AF incidence; and (3) a considerable improvement in survival after diagnosis of AF in recent years. We also found that incidence of ischemic stroke after first diagnosis of AF has decreased in recent years. In addition, this study describes considerable racial and ethnic differences in AF incidence. Compared with non-Hispanic whites, blacks, Asian Americans, Native Americans, and Hispanics all experience considerably lower rates of diagnosed AF. Subsequent work will focus on evaluating and identifying effective clinical practices for primary and secondary AF prevention. This includes critical evaluations of interventions known to be efficacious in the non–end-stage renal disease population (but never tested in the end-stage renal disease population) as well as modifications to the delivery of dialysis that may help reduce the incidence and improve the prognosis of AF in patients with advanced chronic kidney disease undergoing chronic dialysis.Conclusions: The incidence of AF is high in older patients initiating dialysis in the United States and has been increasing over the 13 years of study. Mortality declined during that time but remained >50% during the first year after newly diagnosed AF. Because data on warfarin use were not available, we were unable to study whether trends toward better outcomes could be explained by higher rates of oral anticoagulation.6Premature Atrial Contractions in the General Population: Frequency and Risk FactorsSummary: Although premature atrial contractions (PACs) have been associated with an increased risk of death, stroke, and atrial fibrillation, they are usually considered a benign phenomenon. Accordingly, little is known about the prevalence of and risk factors for PAC occurrence in the general population. In this study of individuals aged ≥50 years, we found that only 18 (1.0%) participants did not have at least 1 PAC during Holter monitoring. The number of PACs was strongly increasing with increasing age. In multivariable regression models, PAC occurrence was significantly associated with age, height, cardiovascular disease, exercise, and plasma levels of N-terminal pro B-type natriuretic peptides and high-density lipoprotein cholesterol. The underlying mechanisms of these relationships are currently unknown. Although obesity and hypertension are 2 of the most important risk factors for the occurrence of atrial fibrillation, they were not significantly associated with PAC burden in this study. These data could suggest that obesity and hypertension are major determinants of structural left atrial remodeling but do not influence the electric activity of the atria. Given the high prevalence of PACs in the population and its negative prognostic impact, more studies are needed to better understand this phenomenon.Conclusions: To our knowledge, this is the first study to assess risk factors for PAC frequency in the general population aged ≥50 years. PACs are common, and their frequency is independently associated with age, height, history of cardiovascular disease, natriuretic peptide levels, physical activity, and high-density lipoprotein cholesterol. The underlying mechanisms of these relationships need to be addressed in future studies.7Association Between Smoke-Free Legislation and Hospitalizations for Cardiac, Cerebrovascular, and Respiratory Diseases: A Meta-AnalysisSummary: Secondhand smoke causes cardiovascular and respiratory disease, and implementation of smoke-free legislation is followed by drops in hospitalizations and deaths from these diseases. This meta-analysis of 45 studies of 33 smoke-free laws found that smoke-free legislation was associated with significantly lower rates of hospital admissions (or deaths) for coronary events, other heart disease, cerebrovascular accidents, and respiratory disease. There was a dose-response relationship between the strength of the law; more comprehensive laws (including workplaces, restaurants, and bars) had the largest health benefits. This study provides strong evidence not only of the health benefits of smoke-free laws, but also of the need to enact comprehensive laws without exceptions.Conclusions: Smoke-free legislation was associated with a lower risk of smoking-related cardiac, cerebrovascular, and respiratory diseases, with more comprehensive laws associated with greater changes in risk.8Sex-Related Trends in Mortality in Hospitalized Men and Women After Myocardial Infarction Between 1985 and 2008: Equal Benefit for Women and MenSummary: During the past decades, medical management and outcomes of acute myocardial infarction have improved substantially. It has been suggested that women with myocardial infarction have benefitted less from these improvements in treatment and outcomes compared with men because they were underrepresented in clinical trials. With the present study, however, we are the first to test this suggestion over a 24-year study period. We demonstrate that adjusted short- and long-term mortality rates were similar and declined markedly and equally in women and men during the 24 years studied. Furthermore, we also present long-term mortality data, up to 20 years after the myocardial infarction, which are sparse. This study is important because it helps to direct both further research and further management, in which women deserve to be treated with the same evidence-based care. In addition, the observed temporal trends are encouraging and suggest that both men and women will benefit from further improvements in care for acute myocardial infarction.Conclusions: The fact that adjusted mortality rates for men and women treated for myocardial infarction in an intensive coronary care unit were similar and declined markedly over a 24-year period suggests that both sexes benefit from the evidence-based therapies that have been developed and implemented during this time period.9Association of Mild to Moderate Chronic Kidney Disease With Venous Thromboembolism: Pooled Analysis of Five Prospective General Population CohortsSummary: Chronic kidney disease (CKD) is a major health problem that affects 10% to 16% of the general adult population. Whereas associations of CKD with arterial thromboembolism and mortality are well known, the association of CKD with venous thromboembolism (VTE) is uncertain. In the present study, we assessed the association of CKD with venous thrombosis in 5 general population cohorts. The key CKD measures (ie, decreased estimated glomerular filtration rate and elevated albumin-to-creatinine ratio) were both associated with an increased risk of VTE, even for values in the normal ranges. Subjects with CKD (ie, estimated glomerular filtration rate <60 mL/min per 1.73 m2 or albumin-to-creatinine ratio ≥30 mg/g) had a 54% higher risk of VTE in comparison with subjects without CKD. The associations were similar for unprovoked and provoked VTE, and for pulmonary embolism and deep-vein thrombosis, as well. CKD measures showed largely similar associations with VTE across subgroups of traditional cardiovascular risk factors, such as hypertension, diabetes, age, and sex. Given the effect size of the association, individual-level implications may be limited. Nevertheless, because of the high prevalence of CKD, population-level VTE burden owing to CKD is estimated to be high, especially in populations with high CKD prevalence such as those with diabetes mellitus and hypertension. Future studies are warranted to assess whether CKD is also associated with recurrent VTE. If confirmed, these findings may have implications for the duration of anticoagulant treatment for first VTE.Conclusions: Both estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) are independently associated with increased risk of VTE in the general population, even across the normal eGFR and ACR ranges.10Long-Term Cardiovascular Risk of Nonsteroidal Anti-Inflammatory Drug Use According to Time Passed After First-Time Myocardial Infarction: A Nationwide Cohort StudySummary: Recently, there has been much focus on the cardiovascular risk of commonly used nonsteroidal anti-inflammatory drugs (NSAIDs), and the American Heart Association in 2007 published a focused update discouraging the use of NSAIDs in patients with established cardiovascular disease. Despite this, many patients with cardiovascular disease receive NSAIDs. Given the burden posed by NSAIDs after myocardial infarction (MI), it is important to understand the long-term trends in this condition; whether use of NSAID is of greatest risk the first year after the patient’s first-time MI and declines as the years pass, or whether use of NSAID changes the declining incidence of cardiovascular risk the years after the MI. In this case, recommendations for long-time caution with these agents may be needed after MI. The current study addresses the risk of all NSAIDs in a selected population of post-MI patients. We present a comprehensive analysis on the effect of time passed following first-time MI NSAID treatment on risk of death or coronary death/recurrent MI in a nationwide cohort of MI survivors. We found that, that the risk of death and coronary death/recurrent MI remains elevated in NSAID users for up to 5 years after the first MI. Our results indicate that use of NSAIDs is associated with persistently increased coronary risk regardless of time elapsed after MI. Thus, long-term caution with use of NSAIDs is advised in all patients after MI. We believe that these strong messages must be distributed as widely as possible to clinicians taking care of patients with cardiovascular disease.Conclusions: The use of NSAIDs is associated with persistently increased coronary risk regardless of time elapsed after first-time MI. We advise long-term caution in the use of NSAIDs for patients after MI.11Television Watching, Leisure Time Physical Activity, and the Genetic Predisposition in Relation to Body Mass Index in Women and MenSummary: Sedentary behavior and physical inactivity have independent effects on obesity and related cardiometabolic diseases. Previous studies on gene-lifestyle interaction and obesity have focused mostly on the FTO gene and physical activity, whereas little attention has been paid to sedentary behavior as indicated by television (TV) watching. In 2 prospective cohorts with 7740 women and 4564 men, we calculated a genetic risk score based on 32 established body mass index–associated variants to capture the overall genetic susceptibility and to examine its interactions with leisure time TV watching and physical activity in relation to adiposity. Our results indicate that prolonged TV watching might accentuate the genetic predisposition to elevated adiposity, whereas greater leisure time physical activity might attenuate the genetic association. These findings suggest that deleterious effects of genetic factors could be modified by lifestyle factors and challenge the common lay perception of deterministic genetic predisposition to obesity. Our data provide new information in understanding the interplay between genes and environment and emphasize the important role of both increases in exercise levels and reductions in sedentary behaviors in public health efforts to prevent obesity and related cardiometabolic diseases, particularly in individuals who are more genetically predisposed to obesity.Conclusions: A sedentary lifestyle, indicated by prolonged TV watching, may accentuate the predisposition to elevated adiposity, whereas greater leisure time physical activity may attenuate the genetic association.12Right Ventricular Structure Is Associated With the Risk of Heart Failure and Cardiovascular Death: The Multi-Ethnic Study of Atherosclerosis (MESA)-Right Ventricle StudySummary: The roles of right ventricular (RV) structure and function in health and disease have not been well studied. Although historical animal studies suggested that the RV did not contribute importantly to cardiac function, more recent studies of patients with diseases such as pulmonary arterial hypertension and congestive heart failure have shown that RV size and ejection fraction are independent predictors of survival. Whether the RV has an important role in community-based adults is unknown. This study showed that the presence of RV hypertrophy (measured by MRI) in adults without clinical cardiovascular disease at baseline was associated with an increased risk of heart failure or cardiovascular death. This association held after accounting for left ventricular mass but was stronger in participants with lower left ventricular mass. There are several explanations for this finding. Patients with left ventricular hypertrophy may have an increased risk of events directly attributable to the left ventricular pathology, explaining why the effect of RV hypertrophy is stronger in its absence. RV hypertrophy could indicate a higher risk of heart failure by serving as a sensitive barometer of left ventricular function. Increased RV afterload may also be seen in conditions such as sleep-disordered breathing and/or subclinical pulmonary vascular disease, which could cause both RV hypertrophy and an increased risk of events. Alternatively, RV hypertrophy could directly contribute to the onset of heart failure. Clinical cardiovascular disease–free adults with RV hypertrophy are at higher overall risk of heart failure and death, warranting further studies of mechanisms and potential treatment interventions.Conclusions: RV hypertrophy was associated with the risk of heart failure or death in a multiethnic population free of clinical cardiovascular disease at baseline.13Prospective Study of Restless Legs Syndrome and Coronary Heart Disease Among WomenSummary: Restless legs syndrome (RLS), also known as Willis Ekbom disease, is a common, bothersome sensorimotor disorder characterized by an almost irresistible urge to move the legs, accompanied by unpleasant sensation in the legs and a worsening of the symptoms in the evening or during the night. Cross-sectional epidemiological studies have suggested a positive association between RLS and coronary heart disease (CHD), but this association was not confirmed by 2 subsequent prospective studies. In this article, the association was prospectively examined, taking into account the duration of RLS symptoms based on the Nurses’ Health Study, a well-characterized prospective cohort comprising 70977 women. We found that women with physician-diagnosed RLS, especially those with longer disease duration, tend to have a higher risk of developing CHD. In this analysis, RLS preceded the development of CHD, which suggests but cannot prove a causal role for RLS in CHD. The results suggest that the long-term impact of RLS or RLS-associated conditions may contribute to cardiovascular disease. If the association between RLS and CHD is confirmed in future studies, we suggest that clinicians should screen for RLS because it may be helpful in judging a patient’s cardiovascular risk combined with other known risk factors for CHD.Conclusions: We observed that women with RLS for at least 3 years had an elevated risk of CHD. These results suggest that RLS or RLS-associated conditions may contribute to the origin of cardiovascular disease.14Predictors of Early and Late Enrollment in Cardiac Rehabilitation, Among Those Referred, After Acute Myocardial InfarctionSummary: Cardiac rehabilitation (CR) is a key component of the comprehensive care of acute myocardial infarction (AMI) patients and is a Class I recommendation after AMI. While improving the use of CR has been a longstanding goal for quality improvement, there remains a gap between referral to CR and subsequent participation. In our study, despite a high CR referral rate of 66% post-AMI, only 29% referred patients participated in CR at 1-month and less than half participated at 6-months after AMI, making it an important quality improvement target. Several patient-oriented and medical factors affect early and late CR enrollment even after receiving CR referral after AMI. Women, the uninsured, and patients with hypertension, peripheral arterial disease, lower physical function, and prior percutaneous coronary intervention are less likely to participate at 1-month while non-Caucasians, older individuals, smokers and individuals with economic burden were less likely to participate at 6-months after AMI. These individuals represent populations at significantly increased cardiovascular risk who may benefit from the more intense secondary prevention services provided in CR. Since CR is associated with beneficial changes in cardiovascular risk factors and better outcomes, more aggressive efforts to increase CR participation after AMI are needed. There are still substantial gender and socio-economic disparities in CR use that will require additional interventions to overcome. While creating a performance measurement for referral is an important first step, creating a second measure to examine actual participation might be a successful adjunct to insure participation if proper denominator specifications can be created.Conclusions: Among patients referred for CR post-AMI, participation remains low both at 1 and 6 months after AMI. Because CR is associated with beneficial changes in cardiovascular risk factors and better outcomes after AMI, more aggressive efforts are needed to increase CR participation after referral.15Prognostic Utility of Novel Biomarkers of Cardiovascular Stress: The Framingham Heart StudySummary: Biomarkers for predicting cardiovascular events in community-based populations have not consistently added information to standard risk factors. A limitation of many previously studied biomarkers is their lack of cardiovascular specificity. We examined 3 novel biomarkers induced by cardiovascular stress (soluble ST2, growth differentiation factor-15, and high-sensitivity troponin I) in 3428 participants in the Framingham Heart Study followed up for a mean of 11.3 years. After adjustment for traditional risk factors, the 3 new biomarkers were associated with each end point (P<0.001) except coronary events. Individuals with multimarker scores in the highest quartile had a 3-fold risk of death (P<0.001), 6-fold risk of heart failure (P<0.001), and 2-fold risk of cardiovascular events (P=0.001). Addition of the multimarker score to clini