The aim of the present study was to determine whether serum urate (sUA) concentration is positively associated with subclinical atherosclerosis, independent of body mass index (BMI), among generally healthy adults.
Design and setting
The CARDIA study followed 5115 black and white individuals aged 18–30 years in 1985–1986 (year 0). Subclinical atherosclerosis comprised coronary artery calcified plaque (CAC; years 15, 20 and 25) and maximum common carotid intima–media thickness (IMT; year 20). sUA (years 0, 10, 15 and 20) was modelled as gender-specific quartiles that were pooled. Discrete-time hazard regressions and generalized linear regressions were used for analyses.
Mean sUA concentration was lower in women than in men, and increased with age. Adjusting for demographic and lifestyle factors, the highest versus lowest quartile of sUA at year 0 was associated with a 44% [95% confidence interval (CI) 20%, 73%] greater risk of CAC progression from year 15 to 25 (Ptrend < 0.001), which was attenuated by adjustment for BMI at year 0 (Ptrend = 0.45). A stronger association was found between sUA at year 15 and CAC progression at year 20 or 25 (hazard ratio 2.07, 95% CI 1.66, 2.58 for the highest versus lowest sUA quartile Ptrend < 0.001), which was attenuated but remained significant with additional adjustment for BMI at year 15 (Ptrend = 0.01). A greater increment in sUA concentration from year 0 to year 15, independent of change in BMI, was related to a higher risk of CAC progression (Ptrend < 0.001). Similar associations were found between sUA and IMT, but only in men.
sUA may be an early biomarker for subclinical atherosclerosis in young adults; starting in early middle age, sUA predicts subclinical atherosclerosis independently of BMI.
calcified plaque; intima–media thickness; subclinical atherosclerosis; urate; uric acid
Despite the benefits of regular physical activity among older adults, physical activity rates are low in this population. The Program for Active Aging and Community Engagement (PACE) is an ongoing randomized controlled trial designed to compare the effects of two interventions on physical activity at 12 months among older adults. A total of 300 men and women aged 55 years or older will be randomized into either a healthy aging (HA) control intervention (n = 150), which is largely based upon educational sessions, or a prosocial behavior physical activity (PBPA) intervention (n = 150), which incorporates structured physical activity sessions, cognitive-behavioral counseling, and opportunities to earn food for donation to a regional food bank based on weekly physical activity and volunteering. The PBPA intervention is delivered at a local YMCA, and a regional grocery store chain donates the food to the food bank. Data will be collected at baseline, 3, 6, and 12 months. The primary outcome is physical activity as assessed by the Community Healthy Activities Model Program for Seniors (CHAMPS) Questionnaire at 12 months. Secondary outcomes include physical function and health-related quality of life. If successful, the PACE study will demonstrate that prosocial behavior and volunteerism may be efficaciously incorporated into interventions and will provide evidence for a novel motivating factor for physical activity.
Randomized controlled trial; Older adults; Physical activity; Prosocial behavior; Community partnership
The purpose of this study was to identify determinants of 20 year change in left ventricular (LV) mass (LVM) and LV geometry in black and white young adults in the CARDIA Study.
Methods and Results
We studied 2426 black and white men and women (54.7% Caucasian) aged 43-55 years with cardiovascular (CV) risk factor data and echocardiograms from CARDIA year 5 and 25 examinations. In regression models, year 25 LVM or relative wall thickness was the dependent variable and with year 5 echo values, age, gender, race, body mass index (BMI), change in BMI, mean arterial blood pressure, change in mean blood pressure, heart rate (HR), change in HR, tobacco use, presence of diabetes, alcohol use, and physical activity score as independent variables. LVM and relative wall thickness increased while prevalence of normal geometry declined from 84.2% to 69.7%. Significant determinants of year 25 LVM/m2.7 were year 5 LVM, year 5 and change in BMI, year 5 and change in mean arterial pressure, year 5 and change in HR, baseline diabetes, and year 5 tobacco and/or alcohol use (overall r2 = 0.40). Significant determinants of year 25 relative LV wall thickness were year 5 value, black race, change in BMI, year 5 and change in mean arterial pressure, starting smoking, and year 5 diabetes. (overall r2 = 0.11).
Prevalence of abnormal LV hypertrophy and geometry increased from young adulthood to middle age. Both young adult CV risk traits and change in these traits predicted change in LV mass/geometry.
echocardiography; left ventricular mass; blood pressure; obesity; risk assessment
Risk markers including coronary artery calcium (CAC), carotid intima-media thickness (CIMT), ankle-brachial Index (ABI), brachial flow-mediated dilation (FMD), high sensitivity C -reactive protein (hs-CRP) and family history (FH) of coronary heart disease (CHD) have been reported to improve on the Framingham risk score (FRS) for prediction of CHD. However, there are no direct comparisons of these markers for risk prediction in a single cohort.
We compared improvement in prediction of incident CHD/cardiovascular disease (CVD) of these 6 risk markers within intermediate risk participants (5 % < FRS < 20%) in the Multi-Ethnic Study of Atherosclerosis (MESA).
Design, Setting and Participants
Of 6814 MESA participants from 6 US field centers, 1330 were intermediate risk, without diabetes mellitus, and had complete data on all 6 markers. Recruitment spanned July 2000 to September 2002; follow-up extended through May 2011. Probability- weighted Cox proportional hazard models were used to estimate hazard ratios (HR). Area under the receiver operator characteristic curve (AUC) and net reclassification improvement (NRI) were used to compare incremental contributions of each marker when added to the FRS + race/ethnicity.
Main Outcome Measures
Incident CHD defined as MI, angina followed by revascularization, resuscitated cardiac arrest or CHD death. Incident CVD additionally included stroke or CVD death.
After median follow-up of 7.6 years (IQR 7.3 – 7.8 years), 94 CHD and 123 CVD events occurred. CAC, ABI, hs-CRP and FH were independently associated with incident CHD in multivariable analyses [HR (95%CI: 2.60(1.94-3.50), 0.79(0.66-0.95), 1.28(1.00-1.64) and 2.18(1.38-3.42) respectively]. CIMT and FMD were not associated with incident CHD in multivariable analyses [HR (95%CI) 1.17(0.95- 1.45) and 0.95(0.78 −1.14) respectively]. Although the addition of the markers individually to the FRS +race/ethnicity improved the AUC, CAC afforded the highest increment (0.623 vs. 0.784) while FMD afforded the least [0.623 vs. 0.639]. For incident CHD, the NRI with CAC was 0.659, FMD 0.024, ABI 0.036, CIMT 0.102, FH 0.160 and hs-CRP 0.079. Similar results were obtained for incident CVD.
CAC, ABI, hs-CRP and FH are independent predictors of incident CHD/CVD in intermediate risk individuals. CAC provides superior discrimination and risk reclassification compared with other risk markers.
Single measures of blood pressure (BP) levels are associated with the development of atherosclerosis; however, long-term patterns in BP and their impact on CVD risk are poorly characterized.
To identify common BP trajectories throughout early adulthood and to determine their association with presence of coronary artery calcification (CAC) during middle age.
We used data from the CARDIA study from baseline in 1985-1986 through 25 years of follow-up (2010-2011).
Prospective cohort study
CARDIA participants were Black and White men and women aged 18-30 years at baseline.
We examined systolic BP, diastolic BP, and mid-BP [calculated as (SBP+DBP)/2 and an important marker of CHD risk among younger populations] at baseline and years 2, 5, 7, 10, 15, 20, and 25. Latent mixture modeling was used to identify trajectories in SBP, DBP and mid-BP over time.
Main Outcome Measure
Coronary artery calcification greater than or equal to Agatston score of 100 Agatston units at year 25.
Among 4,681 participants, we identified 5 distinct mid-BP trajectories: Low-Stable (22% [95% CI 19.9-23.7], n=987), Moderate-Stable (42% [40.3-44.3], n=2,085), Moderate-Increasing (12% [10.4-14.0], n=489), Elevated-Stable (19% [17.1-20.0], n=903) and Elevated-Increasing (5% [4.0-5.5], n=217). As compared to the Low-Stable group, trajectories with elevated BP levels had greater odds of having CAC >100. Adjusted odds ratios (95% CI) were 1.44 (0.83-2.49) for Moderate-Stable, 1.86 (0.91-3.82) for Moderate-Increasing, 2.28 (1.24-3.70) for Elevated-Stable, and 3.70 (1.66-8.20) for Elevated-Increasing groups. The adjusted prevalence of CAC ≥ 100 was 5.8% in the Low-Stable group. These ORs represent an absolute increase of 2.7%, 5%, 6.3% and 12.9% for the prevalence of CAC ≥100 for the Moderate-Stable, Moderate-Increasing, Elevated Stable and Elevated Increasing groups respectively as compared to the Low-Stable Group. Associations were not altered after adjustment for baseline and year 25 BP. Findings were similar for trajectories of isolated systolic BP trajectories, but were attenuated for diastolic BP trajectories.
Conclusions and Relevance
BP trajectories throughout young adulthood vary and higher BP trajectories were associated with an increased risk of CAC in middle age. Long-term trajectories in BP may assist in more accurate identification of individuals with subclinical atherosclerosis.
blood pressure; calcium; epidemiology; risk factors
Dyslipidemia is a known risk factor for coronary disease, but its role in heart failure (HF) development is less well-defined.
Methods and Results
We included 5688 participants, aged 45 to 84 years, without clinical cardiovascular disease, and not receiving lipid-lowering medications at baseline, from the Multiethnic Study of Atherosclerosis. Cox-proportional hazards models were used to evaluate associations of triglyceride, total cholesterol/high-density lipoprotein–cholesterol (HDL-C) ratio, HDL-C, and non HDL-C with incident HF. We investigated for effect-modification by diabetes mellitus status and sex. During a median follow-up of 8.5 years, there were 152 incident HF cases. There were no interactions by sex. We observed significant interactions between triglyceride and diabetes mellitus (Pinteraction<0.05). We stratified our analyses by diabetes mellitus status. In participants with diabetes, the hazard ratios were 2.03 (0.97–4.27) and 1.68 (1.18–2.38) for high triglyceride and log of triglyceride, respectively, after adjusting for confounders, comorbidities, and diabetes mellitus severity/treatment. The association of high triglyceride with incident HF was attenuated by interim myocardial infarction. The hazard ratios were greatest in participants with diabetes who also had high triglyceride, low HDL-C, or high total cholesterol/HDL-C ratio (3.59 [2.03–6.33], 3.62 [2.06–6.36], and 3.54 [1.87–6.70], respectively). Lipid measures were not associated with incident HF in individuals without diabetes.
The risk of incident HF is greater in individuals with diabetes mellitus who also have high triglyceride, low HDL-C, or high total cholesterol/HDL-C ratio. The association of high triglyceride with incident HF is partly mediated by myocardial infarction.
diabetes mellitus; heart failure; lipids
Specific constellations of lipoprotein particle features, reflected as differences in mean lipoprotein particle diameters, are associated with risk of insulin resistance (IR) and cardiovascular disease (CVD). The associations of lipid profiles with disease risk differ by race/ethnicity, the reason for this is not clear. We aimed to examine whether there were additional genetic differences between racial / ethnic groups on lipoprotein profile.
Methods and results
Genotypes were assessed using the Affymetrix 6.0 array in 817 related Caucasian participants of the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). Association analysis was conducted on fasting mean particle diameters using linear models, adjusted for age, sex and study center as fixed effects, and pedigree as a random effect. Replication of associations reaching P<1.97 * 10−05 (the level at which we achieved at least 80% power to replicate SNP-phenotype associations) was conducted in the Caucasian population of the Multi-Ethnic Study of Atherosclerosis (MESA; N=2430). Variants which replicated across both Caucasian populations were subsequently tested for association in the African-American (N=1594), Chinese (N=758) and Hispanic (N=1422) populations of MESA. Variants in the APOB gene region were significantly associated with mean VLDL diameter in GOLDN, and in the Caucasian and Hispanic populations of MESA, while variation in the hepatic lipase (LIPC) gene was associated with mean HDL diameter in both Caucasians populations only.
Our findings suggest the genetic underpinnings of mean lipoprotein diameter differ by race/ethnicity. As lipoprotein diameters are modifiable, this may lead new strategies to modify lipoprotein profiles during the reduction of IR that are sensitive to race / ethnicity.
Lipoprotein size; race / ethnicity; ApoB; Hepatic Lipase; NMR
Since the Diabetes Prevention Project (DPP) demonstrated that lifestyle weight-loss interventions can reduce the incidence of diabetes by 58%, several studies have translated the DPP methods to public health–friendly contexts. Although these studies have demonstrated short-term effects, no study to date has examined the impact of a translated DPP intervention on blood glucose and adiposity beyond 12 months of follow-up.
To examine the impact of a 24-month, community-based diabetes prevention program on fasting blood glucose, insulin, insulin resistance as well as body weight, waist circumference, and BMI in the second year of follow-up.
An RCT comparing a 24-month lifestyle weight-loss program (LWL) to an enhanced usual care condition (UCC) in participants with prediabetes (fasting blood glucose=95–125 mg/dL). Data were collected in 2007–2011; analyses were conducted in 2011–2012.
301 participants with prediabetes were randomized; 261 completed the study. The intervention was held in community-based sites.
The LWL program was led by community health workers and sought to induce 7% weight loss at 6 months that would be maintained over time through decreased caloric intake and increased physical activity. The UCC received two visits with a registered dietitian and a monthly newsletter.
Main outcome measures
The main measures were fasting blood glucose, insulin, insulin resistance, body weight, waist circumference, and BMI.
Intent-to-treat analyses of between-group differences in the average of 18- and 24-month measures of outcomes (controlling for baseline values) revealed that the LWL participants experienced greater decreases in fasting glucose (−4.35 mg/dL); insulin (−3.01 μU/ml); insulin resistance (−0.97); body weight (−4.19 kg); waist circumference (−3.23 cm); and BMI (−1.40), all p-values <0.01.
A diabetes prevention program administered through an existing community-based system and delivered by community health workers is effective at inducing significant long-term reductions in metabolic indicators and adiposity.
This study is registered at Clinicaltrials.gov NCT00631345.
Although numerous studies have translated the Diabetes Prevention Program lifestyle intervention into various settings, no study to date has reported a formal cost analysis.
To describe costs associated with the Healthy Living Partnerships to Prevent Diabetes (HELP PD) trial.
HELP PD was a 24-month RCT testing the impact of a lifestyle weight-loss intervention administered through a diabetes education program and delivered by community health workers (CHWs) on blood glucose and body weight among prediabetics.
In all, 301 participants with prediabetes were randomized in Forsyth County NC. Data reported in these analyses were collected in 2007–2011 and analyzed in 2011–2012.
The lifestyle weight-loss group had a 7% weight loss goal achieved and maintained by caloric restriction and increased physical activity. The usual care group received two visits with a registered dietitian and monthly newsletters.
Main outcome measures
Measures are direct medical costs, direct nonmedical costs and indirect costs over the 2-year study period. Research costs are excluded.
The direct medical cost (in 2010 dollars) to identify one participant was $16.85. Direct medical costs per capita for participants in the usual care group were $142 and $850 for lifestyle weight-loss participants. Per capita direct costs of care outside the study were $7454 for the usual care group and $5177 for the lifestyle weight-loss group. Per capita direct nonmedical costs were $12,881 for the usual care group and $13,836 for the lifestyle weight-loss group. The lifestyle weight-loss group in HELP PD cost $850 in direct medical costs for 2 years, compared to $2631 in direct medical costs for the first 2 years of DPP.
A community-based translation of the DPP can be delivered effectively and with reduced costs.
Prior studies demonstrating shorter length of stay (LOS) from coronary computed tomography angiography (CCTA) relative to stress testing in emergency department (ED) patients have not considered time of patient presentation. The objectives of this study were to determine whether low-risk chest pain patients receiving stress testing or CCTA have differences in ED plus observation unit (OU) LOS, and if there are disparities in testing modality use, based upon the time of patient presentation to the ED.
The authors examined a cohort of low-risk chest pain patients evaluated in an ED-based OU using prospective and retrospective OU registry data. During the study period, stress testing and CCTA were both available from 08:00 to 17:00 hrs. CCTA was not available on weekends, and therefore only subjects presenting on weekdays were included. Cox regression analysis was used to model the effect of testing modality (stress testing vs. CCTA) on OU LOS. Separate models were fit based on time of patient presentation to the ED using four hour blocks beginning at midnight. The primary independent variable was testing modality: stress testing or CCTA. Age, sex, and race were included as covariates. Logistic regression was used to model testing modality choice by time period adjusted for age, sex, and race.
Over the study period, 841 subjects presented Monday through Friday. Median LOS was 18.0 hours (IQR 11.7 to 22.9 hours). Objective cardiac testing was completed in 788 of 841 (94%) patients, with 496 (63%) receiving stress testing and 292 (37%) receiving CCTA. After adjusting for age, race, and sex, patients presenting between 08:00 and 11:59 hrs not only had a shorter LOS associated with CCTA (p < 0.0001), but also had a greater likelihood of being tested by CCTA (p = 0.001). None of the other time periods had significant differences in LOS or testing modality choice for CCTA relative to stress testing.
In an OU setting with weekday and standard business hours CCTA availability, CCTA testing was associated with shorter LOS among low-risk chest pain patients only in patients presenting to the ED between 08:00 and 11:59 hrs. That time period was also associated with a greater likelihood of being tested by CCTA, suggesting that ED providers may have intuited the inability of CCTA to shorten LOS during other times.
To evaluate the strength of association of body mass index (BMI) and waist circumference (WC) with incident heart failure (HF), exploring our associations by ethnicity and age.
Design and Methods
We included 6,809 participants, aged 45–84 years, without clinical cardiovascular disease (2000–2002), from the Multi-Ethnic Study of Atherosclerosis. Cox-Proportional hazards models were used to examine associations of BMI and WC with incident HF. The predictive abilities of BMI and WC were compared using receiver operating characteristic curves.
Over a median follow-up of 7.6 years, there were 176 cases. BMI and WC were associated with incident HF in men [1.33 (1.10–1.61) and 1.38 (1.18–1.62) respectively] and women [1.70 (1.33–2.17) and 1.64 (1.29–2.08) respectively]. These associations became non-significant after adjusting for obesity-related conditions (hypertension, dysglycemia, hypercholesterolemia, left ventricular hypertrophy, kidney disease and inflammation). The associations of BMI and WC did not vary significantly by ethnicity or age-group, but were inverse in Hispanic men. The area under the curve for BMI and WC was 0.749 and 0.750, respectively, in men and 0.782 and 0.777, respectively, in women.
The association between obesity and incident HF is largely mediated by obesity-related conditions. BMI and WC have similar predictive abilities for incident HF.
Obesity; heart failure; body mass index and waist circumference
Recent obesity prevention initiatives focus on healthy neighborhood design, but most research examines neighborhood food retail and physical activity (PA) environments in isolation. We estimated joint, interactive, and cumulative impacts of neighborhood food retail and PA environment characteristics on body mass index (BMI) throughout early adulthood.
Methods and Findings
We used cohort data from the Coronary Artery Risk Development in Young Adults (CARDIA) Study [n=4,092; Year 7 (24-42 years, 1992-1993) followed over 5 exams through Year 25 (2010-2011); 12,921 person-exam observations], with linked time-varying geographic information system-derived neighborhood environment measures. Using regression with fixed effects for individuals, we modeled time-lagged BMI as a function of food and PA resource density (counts per population) and neighborhood development intensity (a composite density score). We controlled for neighborhood poverty, individual-level sociodemographics, and BMI in the prior exam; and included significant interactions between neighborhood measures and by sex. Using model coefficients, we simulated BMI reductions in response to single and combined neighborhood improvements. Simulated increase in supermarket density (from 25th to 75th percentile) predicted inter-exam reduction in BMI of 0.09 kg/m2 [estimate (95% CI): -0.09 (-0.16, -0.02)]. Increasing commercial PA facility density predicted BMI reductions up to 0.22 kg/m2 in men, with variation across other neighborhood features [estimate (95% CI) range: -0.14 (-0.29, 0.01) to -0.22 (-0.37, -0.08)]. Simultaneous increases in supermarket and commercial PA facility density predicted inter-exam BMI reductions up to 0.31 kg/m2 in men [estimate (95% CI) range: -0.23 (-0.39, -0.06) to -0.31 (-0.47, -0.15)] but not women. Reduced fast food restaurant and convenience store density and increased public PA facility density and neighborhood development intensity did not predict reductions in BMI.
Findings suggest that improvements in neighborhood food retail or PA environments may accumulate to reduce BMI, but some neighborhood changes may be less beneficial to women.
Numerous studies have translated the Diabetes Prevention Program (DPP) for community-based settings, and the results are encouraging. This commentary discusses one community-based DPP translational study, Healthy Living Partnerships to Prevent Diabetes, in detail, as well as the implications of DPP translational studies for public policy.
Health care access is associated with improved control of multiple chronic diseases, but the association between health care access and weight change is unclear. This study aims to test the association between health care access and weight change.
The Coronary Artery Risk Development in Young Adults (CARDIA) study is a multi-center population-based prospective study. Weight change was calculated at 3 and 13 years after CARDIA year 7 (1992–1993). Health care access was defined as no barriers or one or more barriers to access (health insurance gap, no usual source of care, not seeking care due to expense). Intermediary variables evaluated included history of dieting, and use of diet pills, meal replacements, or weight control programs.
Four cities in the United States.
Participants were aged 18–30 years at baseline (1985–1986). Analyses include 3922 black and white men and women with relevant data from CARDIA years 7, 10, and 20 (1992–1993, 1995–1996, and 2005–2006, respectively).
Mean weight change was +4.9 pounds by 3 years and +18.7 pounds by 13 years, with no differences by health care access. Being on a weight-reducing diet was not consistently associated with health care access across examinations. Use of diet pills, meal replacements or organized weight control programs was low, and did not vary by health care access.
Weight gain was high irrespective of health care access. Public health and clinical approaches are needed to address weight gain.
health care accessibility; body weight change
Physical inactivity contributes to metabolic syndrome (MetS) in overweight/obesity. However, little is known about this relationship in prediabetes.
The study purpose is to examine relationships between physical activity (PA) and MetS in prediabetes. The Healthy Living Partnerships to Prevent Diabetes tested a community translation of the Diabetes Prevention Program (DPP). Three hundred one overweight/obese prediabetics provided walking minutes/week (WM) and total activity minutes/week (AM) via the International Physical Activity Questionnaire. MetS was at least 3 of waist (men ≥ 102 cm, women ≥ 88 cm), triglycerides (≥150 mg·dl), blood pressure (≥130·85 mm Hg), glucose (≥100mg·dl), and HDL (men < 40mg·dl, women < 50mg·dl).
The sample was 57.5% female, 26.7% nonwhite/Hispanic, 57.9 ± 9.5 years and had a body mass index (BMI) 32.7 ± 4 kg·m2. Sixty percent had MetS. Eighteen percent with MetS reported at least 150 AM compared with 29.8% of those without MetS. The odds of MetS was lower with greater AM (Ptrend = .041) and WM (Ptrend = .024). Odds of MetS with 0 WM were 2.08 (P = .046) and with no AM were 2.78 (P = .009) times those meeting goal. One hour additional WM led to 15 times lower MetS odds.
Meeting PA goals reduced MetS odds in this sample, which supported PA for prediabetes to prevent MetS.
obesity; walking; physical activity
“Physicians-recruiting-physicians” is the preferred recruitment approach for practice-based research. However, yields are variable; and the approach can be costly and lead to biased, unrepresentative samples. We sought to explore the potential efficiency of alternative methods.
We conducted a retrospective analysis of the yield and cost of 10 recruitment strategies used to recruit primary care practices to a randomized trial to improve cardiovascular disease risk factor management. We measured response and recruitment yields and the resources used to estimate the value of each strategy. Providers at recruited practices were surveyed about motivation for participation.
Response to 6 opt-in marketing strategies was 0.40% (53/13290), ranging from 0% to 2.86% by strategy; 33.96% (18/53) of responders were recruited to the study. Of those recruited from opt-out strategies, 8.68% joined the study, ranging from 5.35% to 41.67% per strategy. A strategy that combined both opt-in and opt-out approaches resulted in a 51.14% (90/176) response and a 10.80% (19/90) recruitment rate. Cost of recruitment was $613 per recruited practice. Recruitment approaches based on in-person meetings (41.67%), previous relationships (33.33%), and borrowing an Area Health Education Center’s established networks (10.80%), yielded the most recruited practices per effort and were most cost efficient. Individual providers who chose to participate were motivated by interest in improving their clinical practice (80.5%); contributing to CVD primary prevention (54.4%); and invigorating their practice with new ideas (42.1%).
This analysis provides suggestions for future recruitment efforts and research. Translational studies with limited funds could consider multi-modal recruitment approaches including in-person presentations to practice groups and exploitation of previous relationships, which require the providers to opt-out, and interactive opt-in approaches which rely on borrowed networks. These approaches can be supplemented with non-relationship-based opt-out strategies such as cold calls strategically targeted to underrepresented provider groups.
Comparative effectiveness research (CER) aims to provide decision-makers the evidence needed to evaluate the benefits and harms of alternative clinical management strategies. CER has become a national priority, with considerable new research funding allocated. Cardiovascular disease is a priority area for CER. This workshop report provides an overview of CER methods, with an emphasis on practical clinical trials and observational treatment comparisons. The report also details recommendations to the National Heart Lung and Blood Institute for a new framework for evidence development to foster cardiovascular CER, and specific studies to address eight clinical issues identified by the Institute of Medicine as high priorities for cardiovascular CER.
comparative effectiveness; research methods; clinical trials
Population distribution estimates by age and race/ethnicity from the U.S. Census Bureau for the years 2010 and 2050 were combined with estimates of stroke incidence from population-based surveillance studies to forecast the distribution of incident stroke cases for the years 2010 and 2050. Over these 40 years, the number of incident strokes will more than double, with the majority of the increase among the elderly (age 75+) and minority groups (particularly Hispanics). These increases are likely to present major logistical, scientific, and ethnical issues in the near future.
stroke; incidence; aging; race; projections
High salt intake may affect left ventricular mass (LVM). We hypothesized that urinary sodium (UNa) and sodium / potassium ratio (UNa/K) are associated with LVM in a predominantly normotensive cohort young adults. The Coronary Artery Risk Development in Young Adults (CARDIA) study is a multicenter cohort of black and white men and women aged 30 ± 3.6 years at the time of baseline echocardiographic examination (1990–1991). Two-dimensionally guided M-mode LVM indexed to body size (gm/m2.7) was calculated and urinary sodium (UNa) and potassium (UK) excretion assessed (average of three 24-hour urinary samples, n=1,042). Linear and logistic regression analysis was used. Participants were 57% women, and 55% black. Only 4% were hypertensive. Mean±SD UNa, UK, and UNa/K ratio were 175.6±131.0 mmol/24hour, 56.4±46.3 mmol/24hour and 3.4±1.4, respectively. Participants in the highest vs. lowest UNa excretion quartile had the greatest LVM (37.5 vs. 34.0 g/m2.7, p<0.001). Adjusted for age, sex, education and race, LVM averaged 0.945gm/m2.7 higher per SD of UNa/K (p=0.001). The relationship between UNa/K and LVM persisted among 399 participants with repeat echocardiographic measures five years later. In logistic regression analysis adjusted for age, sex, education and race, each SD higher baseline UNa/K was associated with 23% and 38% greater chance of being in the highest quartile of LVM at baseline (OR 1.23; p=0.005) and five years later (OR 1.38; p=0.02). A higher sodium to potassium excretion ratio is significantly related to cardiac structure even among healthy young adults.
urinary sodium; urinary potassium; sodium / potassium ratio; left ventricular mass
The amount of cholesterol per LDL particle is variable and related in part to particle size, with smaller particles carrying less cholesterol. This variability causes concentrations of LDL cholesterol (LDL-C) and LDL particles (LDL-P) to be discordant in many individuals.
LDL-P measured by nuclear magnetic resonance (NMR) spectroscopy, calculated LDL-C, and carotid intima-media thickness (IMT) were assessed at baseline in the Multi-Ethnic Study of Atherosclerosis (MESA), a community-based cohort of 6814 persons free of clinical CVD at entry and followed for CVD events (n=319 during 5.5-year follow-up). Discordance, defined as values of LDL-P and LDL-C differing by ≥ 12 percentile units to give equal-sized concordant and discordant subgroups, was related to CVD events and to carotid IMT in models predicting outcomes for a 1 SD difference in LDL-C or LDL-P, adjusted for age, sex and race.
LDL-C and LDL-P were associated with incident CVD overall: hazard ratios (HR [95% CI]) 1.20 [1.08, 1.34] and 1.32 [1.19, 1.47], respectively, but for those with discordant levels, only LDL-P was associated with incident CVD (HR: 1.45 [1.19, 1.78]) (LDL-C HR: 1.07 [0.88, 1.30])). IMT also tracked with LDL-P rather than LDL-C, i.e., adjusted mean IMT of 958, 932, and 917 μm in the LDL-P > LDL-C discordant, concordant, and LDL-P < LDL-C discordant subgroups, respectively, with the difference persisting after adjustment for LDL-C (p=0.002) but not LDL-P (p=0.60).
For individuals with discordant LDL-C and LDL-P levels, the LDL-attributable atherosclerotic risk is better indicated by LDL-P.
LDL particle number; LDL cholesterol; cardiovascular disease risk; NMR; lipoproteins
Reduced heart rate variability (HRV) in older patients with heart failure (HF) is common and indicates poor prognosis. Exercise training (ET) has been shown to improve HRV in younger patients with HF. However the effect of ET on HRV in older patients with HF is not known.
Methods and Results
Sixty-six participants (36% males), age 69±5 years, with HF and both preserved ejection fraction (HFPEF) and reduced ejection fraction (HFREF), were randomly assigned to 16 weeks of supervised ET (ET group) versus attention-control (AC group). Two HRV parameters (the standard deviation of all normal RR intervals (SDNN) and the root mean square of successive differences in normal RR intervals (RMSSD)) were measured at baseline and after completion of the study. When compared with the AC group, the ET group had a significantly greater increase in both SDNN (15.46 ± 5.02 ms in ET versus 2.37 ± 2.13 ms in AC, P = 0.016), and RMSSD (17.53 ± 7.83 ms in ET versus 1.69 ± 2.63 ms in AC, P = 0.003). This increase was seen in both genders and HF categories.
ET improves HRV in older patients with both HFREF and HFPEF.
International guidelines recommend that the decision threshold for troponin should be the 99th percentile of a normal population, or, if the laboratory assay is not sufficiently precise at this low level, the level at which the assay achieves a 10% or better coefficient of variation (CV). Our objectives were to examine US hospital laboratory troponin reports to determine whether either the 99th percentile or the 10% CV level were clearly indicated, and whether nonconcordance with these guidelines was a potential barrier to detecting clinically important microscopic or ‘microsize’ myocardial infarctions (MIs). To confirm past reports of the clinical importance of microsize MIs, we also contrasted in-hospital, 28-day and 1-year mortality among those with microsize and nonmicrosize MI.
In the REasons for Geographic And Racial Differences in Stroke national prospective cohort study (n=30,239), 1029 participants were hospitalized for acute coronary syndrome (ACS) between 2003–2009. For each case, we recorded all thresholds of abnormal troponin on the laboratory report and whether the 99th percentile or 10% CV value were clearly identified. All cases were expert adjudicated for presence of MI. Peak troponin values were used to classify MIs as microsize MI (< five times the lowest listed upper limit of normal) and nonmicrosize MI.
Participants were hospitalized at 649 acute care US hospitals, only 2% of whose lab reports clearly identified the 99th percentile or the 10% CV level; 52% of reports indicated an indeterminate range, a practice that is no longer recommended. There were 183 microsize MIs and 353 nonmicrosize MIs. In-hospital mortality tended to be lower in the microsize than in the nonmicrosize MI group (1.1 vs. 3.6%, p = 0.09), but 28-day and 1-year mortality were similar (2.5% vs. 2.7% [p = 0.93] and 5.2% vs. 4.3% [p = 0.64], respectively).
Current practices in many US hospitals created barriers to the clinical recognition of microsize MI, which was common and clinically important in our study. Improved hospital troponin reporting is warranted.
Acute coronary syndrome; Troponin; Quality control
The association between metabolic syndrome and electrocardiographic (ECG) abnormalities is not well established.
ECG tracings of 6,765 men and women aged 45–84 years, free of clinical cardiovascular disease, from the Multi-Ethnic Study of Atherosclerosis were obtained (2000–2002) and classified as normal or having major or minor abnormalities. We evaluated the associations of metabolic syndrome and its components with ECG abnormalities, adjusting for age, ethnicity, and gender and testing for effect modification by ethnicity and gender.
The associations of metabolic syndrome, hypertension, and high triglycerides with ECG abnormalities varied significantly by gender. In males, metabolic syndrome and hypertension were significantly associated with major ECG abnormality [1.69 (1.33–2.13), and 2.22 (1.72–2.86), respectively] after adjusting for ethnicity and gender. Hypertension was also associated significantly with minor ECG abnormality in males after adjusting for age and ethnicity. In females, metabolic syndrome and hypertension were significantly associated with major [1.84 (1.44–2.37), and 1.68 (1.27–2.22), respectively] and minor [1.38 (1.19–1.59), and 1.53 (1.32–1.79), respectively] ECG abnormalities after adjusting for age and ethnicity. High triglycerides were only significantly associated with major ECG abnormality in females after adjusting for age and ethnicity. After adjusting for age, ethnicity, and gender, central obesity and high fasting blood glucose were significantly associated with major and minor ECG abnormalities, whereas low high-density lipoprotein cholesterol was significantly associated with major ECG abnormality only.
Metabolic syndrome and its components are associated with major and/or minor ECG abnormalities. The relationship of metabolic syndrome, hypertension, and high triglycerides with ECG abnormalities varied according to gender.
The aim of this study was to examine the relationship between frequent and unrecognized hypoglycemia and mortality in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study cohort.
RESEARCH DESIGN AND METHODS
A total of 10,096 ACCORD study participants with follow-up for both hypoglycemia and mortality were included. Hazard ratios (95% CIs) relating the risk of death to the updated annualized number of hypoglycemic episodes and the updated annualized number of intervals with unrecognized hypoglycemia were obtained using Cox proportional hazards regression models, allowing for these hypoglycemia variables as time-dependent covariates and controlling for the baseline covariates.
Participants in the intensive group reported a mean of 1.06 hypoglycemic episodes (self-monitored blood glucose <70 mg/dL or <3.9 mmol/L) in the 7 days preceding their regular 4-month visit, whereas participants in the standard group reported an average of 0.29 episodes. Unrecognized hypoglycemia was reported, on average, at 5.8% of the intensive group 4-month visits and 2.6% of the standard group visits. Hazard ratios for mortality in models including frequency of hypoglycemic episodes were 0.93 (95% CI 0.9–0.97; P < 0.001) for participants in the intensive group and 0.98 (0.91–1.06; P = 0.615) for participants in the standard group. The hazard ratios for mortality in models, including unrecognized hypoglycemia, were not statistically significant for either group.
Recognized and unrecognized hypoglycemia was more common in the intensive group than in the standard group. In the intensive group of the ACCORD study, a small but statistically significant inverse relationship of uncertain clinical importance was identified between the number of hypoglycemic episodes and the risk of death among participants.
Poor prognosis in heart failure (HF) patients with diabetes is often attributed to increased co‐morbidity and advanced disease. Further, this effect may be worse in women.
To determine whether the effect of diabetes on outcomes and the sex‐related variation persisted in a propensity score‐matched HF population, and whether the sex‐related variation was a function of age.
Of the 7788 HF patients in the Digitalis Investigation Group trial, 2218 had a history of diabetes. Propensity score for diabetes was calculated for each patient using a non‐parsimonious logistic regression model incorporating all measured baseline covariates, and was used to match 2056 (93%) diabetic patients with 2056 non‐diabetic patients.
All‐cause mortality occurred in 135 (25%) and 216 (39%) women without and with diabetes (adjusted HR = 1.67; 95% CI = 1.34 to 2.08; p<0.001). Among men, 535 (36%) and 609 (41%) patients without and with diabetes died from all causes (adjusted HR = 1.21; 95% CI = 1.07 to 1.36; p = 0.002). Sex–diabetes interaction (overall adjusted p<0.001) was only significant in patients ⩾65 years (15% absolute risk increase in women; multivariable p for interaction = 0.005), but not in younger patients (2% increase in women; p for interaction = 0.173). Risk‐adjusted HR (95% CI) for all‐cause hospitalisation for women and men were 1.49 (1.28 to 1.72) and 1.21 (1.11 to 1.32), respectively, also with significant sex–diabetes interaction (p = 0.011).
Diabetes‐associated increases in morbidity and mortality in chronic HF were more pronounced in women, and theses sex‐related differences in outcomes were primarily observed in elderly patients.