Marnie Bertolet

ACCF/AHA clinical practice guideline methodology summit report: A report of the American college of cardiology foundation/American heart association task force on practice guidelines

Alice K. Jacobs, MD, FACC, FAHA, Immediate Past Chair Jeffrey L. Anderson, MD, FACC, FAHA, Chair Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect Nancy M. Albert, PhD, CCNS, CCRN, FAHA Mark A. Creager, MD, FACC, FAHA David L. DeMets, PhD Steven M. Ettinger, MD, FACC Robert A. Guyton, MD,

Risk factor control for coronary artery disease secondary prevention in large randomized trials.

OBJECTIVES This study evaluated data from 3 federally funded trials that focused on optimal medical therapy to determine if formalized attempts at risk factor control within clinical trials are effective in achieving guideline-driven treatment goals for diabetic patients with coronary artery disease (CAD). BACKGROUND Despite clear evidence of benefit for CAD secondary prevention, the level of risk factor control in clinical practice has been disappointing. METHODS We obtained data from the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) diabetes subgroup, (n = 766 of 2,287), the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial (n = 2,368), and the FREEDOM (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes) trial (n = 1,900) to evaluate the proportion of patients achieving guideline-based, protocol-driven treatment targets for systolic blood pressure, low-density lipoprotein cholesterol, smoking cessation, and hemoglobin A1c. The primary outcome measure was the proportion of diabetic CAD patients meeting all 4 pre-specified targets at 1 year after enrollment. RESULTS The pooled data include 5,034 diabetic patients. The percentages of patients achieving the 1-year low-density lipoprotein cholesterol targets compared with baseline increased from 55% to 77% in COURAGE, from 59% to 75% in BARI 2D, and from 34% to 42% in FREEDOM. Although similar improved trends were seen for systolic blood pressure, glycemic control, and smoking cessation, only 18% of the COURAGE diabetes subgroup, 23% of BARI 2D patients, and 8% of FREEDOM patients met all 4 pre-specified treatment targets at 1 year of follow-up. CONCLUSIONS A significant proportion of diabetic CAD patients fail to achieve pre-specified targets for 4 major modifiable cardiovascular risk factors in clinical trials. We conclude that fundamentally new thinking is needed to explore approaches to achieve optimal secondary prevention treatment goals. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657) (Bypass Angioplasty Revascularization Investigation 2 Diabetes [BARI 2D]; NCT00006305) (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes [FREEDOM]; NCT00086450).

Comprehensive cardiovascular risk factor control improves survival: The BARI 2D trial

Background It is unclear if achieving multiple risk factor (RF) goals through protocol-guided intensive medical therapy is feasible or improves outcomes in type 2 diabetes (T2DM).

Validity of Birth Certificate-Derived Maternal Weight Data

BACKGROUND Studies using vital records-based maternal weight data have become more common, but the validity of these data is uncertain. METHODS We evaluated the accuracy of prepregnancy body mass index (BMI) and gestational weight gain (GWG) reported on birth certificates using medical record data in 1204 births at a teaching hospital in Pennsylvania from 2003 to 2010. Deliveries at this hospital were representative of births statewide with respect to BMI, GWG, race/ethnicity, and preterm birth. Forty-eight strata were created by simultaneous stratification on prepregnancy BMI (underweight, normal weight/overweight, obese class 1, obese classes 2 and 3), GWG (<20th, 20-80th, >80th percentile), race/ethnicity (non-Hispanic white, non-Hispanic black), and gestational age (term, preterm). RESULTS The agreement of birth certificate-derived prepregnancy BMI category with medical record BMI category was highest in the normal weight/overweight and obese class 2 and 3 groups. Agreement varied from 52% to 100% across racial/ethnic and gestational age strata. GWG category from the birth registry agreed with medical records for 41-83% of deliveries, and agreement tended to be the poorest for very low and very high GWG. The misclassification of GWG was driven by errors in reported prepregnancy weight rather than maternal weight at delivery, and its magnitude depended on prepregnancy BMI category and gestational age at delivery. CONCLUSIONS Maternal weight data, particularly at the extremes, are poorly reported on birth certificates. Investigators should devote resources to well-designed validation studies, the results of which can be used to adjust for measurement errors by bias analysis.

Impact of Completeness of Revascularization on Long-Term Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus Results from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D)

Background— Patients with diabetes have more extensive coronary disease than those without diabetes, resulting in more challenging percutaneous coronary intervention or surgical (coronary artery bypass graft) revascularization and more residual jeopardized myocardium. The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial provided an opportunity to examine the long-term clinical impact of completeness of revascularization in patients with diabetes. Methods and Results— This is a post hoc, nonrandomized analysis of the completeness of revascularization in 751 patients who were randomly assigned to early revascularization, of whom 264 underwent coronary artery bypass graft surgery and 487 underwent percutaneous coronary intervention. The completeness of revascularization was determined by the residual postprocedure myocardial jeopardy index (RMJI). RMJI is a ratio of the number of myocardial territories supplied by a significantly diseased epicardial coronary artery or branch that was not successfully revascularized, divided by the total number of myocardial territories. Mean follow-up for mortality was 5.3 years. Complete revascularization (RMJI=0) was achieved in 37.9% of patients, mildly incomplete revascularization (RMJI >0⩽33) in 46.6%, and moderately to severely incomplete revascularization (RMJI >33) in 15.4%. Adjusted event-free survival was higher in patients with more complete revascularization (hazard ratio, 1.14; P=0.0018). Conclusions— Patients with type 2 diabetes mellitus and less complete revascularization had more long-term cardiovascular events. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00006305.

Long chain n-3 polyunsaturated fatty acids and incidence rate of coronary artery calcification in Japanese men in Japan and white men in the USA: population based prospective cohort study

Objective To determine whether serum concentrations of long chain n-3 polyunsaturated fatty acids (LCn3PUFAs) contribute to the difference in the incidence rate of coronary artery calcification (CAC) between Japanese men in Japan and white men in the USA. Methods In a population based, prospective cohort study, 214 Japanese men and 152 white men aged 40–49 years at baseline (2002–2006) with coronary calcium score (CCS)=0 were re-examined for CAC in 2007–2010. Among these, 175 Japanese men and 113 white men participated in the follow-up exam. Incident cases were defined as participants with CCS≥10 at follow-up. A relative risk regression analysis was used to model the incidence rate ratio between the Japanese and white men. The incidence rate ratio was first adjusted for potential confounders at baseline and then further adjusted for serum LCn3PUFAs at baseline. Results Mean (SD) serum percentage of LCn3PUFA was >100% higher in Japanese men than in white men (9.08 (2.49) vs 3.84 (1.79), respectively, p<0.01). Japanese men had a significantly lower incidence rate of CAC compared to white men (0.9 vs 2.9/100 person-years, respectively, p<0.01). The incidence rate ratio of CAC taking follow-up time into account between Japanese and white men was 0.321 (95% CI 0.150 to 0.690; p<0.01). After adjusting for age, systolic blood pressure, low density lipoprotein cholesterol, diabetes, and other potential confounders, the ratio remained significant (0.262, 95% CI 0.094 to 0.731; p=0.01). After further adjusting for LCn3PUFAs, however, the ratio was attenuated and became non-significant (0.376, 95% CI 0.090 to 1.572; p=0.18). Conclusions LCn3PUFAs significantly contributed to the difference in the incidence of CAC between Japanese and white men.

Risk Factors for Incident Peripheral Arterial Disease in Type 2 Diabetes: Results From the Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D) Trial

OBJECTIVE The aim of this article was to define risk factors for incidence of peripheral arterial disease (PAD) in a large cohort of patients with type 2 diabetes mellitus (T2DM), overall and within the context of differing glycemic control strategies. RESEARCH DESIGN AND METHODS The Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D) randomized controlled trial assigned participants to insulin-sensitizing (IS) therapy versus insulin-providing (IP) therapy. A total of 1,479 participants with normal ankle-brachial index (ABI) at study entry were eligible for analysis. PAD outcomes included new ABI ≤0.9 with decrease at least 0.1 from baseline, lower extremity revascularization, or lower extremity amputation. Baseline risk factors within the overall cohort and time-varying risk factors within each assigned glycemic control arm were assessed using Cox proportional hazards models. RESULTS During an average 4.6 years of follow-up, 303 participants (20.5%) experienced an incident case of PAD. Age, sex, race, and baseline smoking status were all significantly associated with incident PAD in the BARI 2D cohort. Additional baseline risk factors included pulse pressure, HbA1c, and albumin-to-creatinine ratio (P < 0.05 for each). In stratified analyses of time-varying covariates, changes in BMI, LDL, HDL, systolic blood pressure, and pulse pressure were most predictive among IS patients, while change in HbA1c was most predictive among IP patients. CONCLUSIONS Among patients with T2DM, traditional cardiovascular risk factors were the main predictors of incident PAD cases. Stratified analyses showed different risk factors were predictive for patients treated with IS medications versus those treated with IP medications.

Supply and Utilization of Pediatric Subspecialists in the United States

OBJECTIVE: The wide geographic variation in pediatric subspecialty supply in the United States has been a source of concern. Whether children in areas with decreased supply receive less subspecialty care or have worse outcomes has not been adequately evaluated. Among children with special health care needs, we examined the association between pediatric subspecialty supply and subspecialty utilization, need, child disease burden, and family disease burden. METHODS: We measured pediatric subspecialist supply as pediatric subspecialists per capita in each residential county. By using the 2009–2010 National Survey of Children With Special Health Care Needs and controlling for many potential confounders, we examined the association between quintile of pediatric subspecialty supply and parent-reported subspecialty utilization, perceived subspecialty need, and child and family disease burden. RESULTS: County-level pediatric subspecialty supply ranged from a median of 0 (lowest quintile) to 59 (highest quintile) per 100 000 children. In adjusted results, compared with children in the highest quintile, children in the lowest quintile of supply were 4.8% less likely to report ambulatory subspecialty visits (P < .001), 5.3% less likely to perceive subspecialty care needs (P < .001), and 2.3% more likely to report emergency department visits (P = .018). There were no meaningful differences between pediatric subspecialty supply quintiles for other measures of child or family disease burden. CONCLUSIONS: Children living in counties with the lowest supply of pediatric subspecialists had both decreased perceived need for subspecialty care and decreased utilization of subspecialists. However, the differences in supply were not associated with meaningful differences in child or family disease burden.

Pulmonary symptoms and diagnoses are associated with HIV in the MACS and WIHS cohorts

BackgroundSeveral lung diseases are increasingly recognized as comorbidities with HIV; however, few data exist related to the spectrum of respiratory symptoms, diagnostic testing, and diagnoses in the current HIV era. The objective of the study is to determine the impact of HIV on prevalence and incidence of respiratory disease in the current era of effective antiretroviral treatment.MethodsA pulmonary-specific questionnaire was administered yearly for three years to participants in the Multicenter AIDS Cohort Study (MACS) and Women’s Interagency HIV Study (WIHS). Adjusted prevalence ratios for respiratory symptoms, testing, or diagnoses and adjusted incidence rate ratios for diagnoses in HIV-infected compared to HIV-uninfected participants were determined. Risk factors for outcomes in HIV-infected individuals were modeled.ResultsBaseline pulmonary questionnaires were completed by 907 HIV-infected and 989 HIV-uninfected participants in the MACS cohort and by 1405 HIV-infected and 571 HIV-uninfected participants in the WIHS cohort. In MACS, dyspnea, cough, wheezing, sleep apnea, and incident chronic obstructive pulmonary disease (COPD) were more common in HIV-infected participants. In WIHS, wheezing and sleep apnea were more common in HIV-infected participants. Smoking (MACS and WIHS) and greater body mass index (WIHS) were associated with more respiratory symptoms and diagnoses. While sputum studies, bronchoscopies, and chest computed tomography scans were more likely to be performed in HIV-infected participants, pulmonary function tests were no more common in HIV-infected individuals. Respiratory symptoms in HIV-infected individuals were associated with history of pneumonia, cardiovascular disease, or use of HAART. A diagnosis of asthma or COPD was associated with previous pneumonia.ConclusionsIn these two cohorts, HIV is an independent risk factor for several respiratory symptoms and pulmonary diseases including COPD and sleep apnea. Despite a higher prevalence of chronic respiratory symptoms, testing for non-infectious respiratory diseases may be underutilized in the HIV-infected population.

Relationships of pulmonary function, inflammation, and T-cell activation and senescence in an HIV-infected cohort.

Objective:To determine associations between circulating markers of immune activation, immune cell senescence, and inflammation with HIV-associated abnormalities of pulmonary function. Design:HIV infection is an independent risk factor for abnormal pulmonary function. Immune activation, immune senescence, and chronic inflammation are characteristics of chronic HIV infection that have been associated with other HIV-associated comorbidities and may be related to pulmonary disease in this population. Methods:Participants from an HIV-infected cohort (n = 147) completed pulmonary function testing (PFT). Markers of T-cell activation and senescence were determined by flow cytometry, and plasma levels of interleukin-6, interleukin-8, and C-reactive protein (CRP) were measured, as was telomere length of peripheral blood mononuclear cells (PBMC). Regression models adjusting for clinical risk factors were constructed to examine relationships between biomarkers and PFT outcomes. Results:Activated CD25+ T cells and activated/senescent CD69+/CD57+/CD28null CD4+ T cells, interleukin-6, and CRP were associated with PFT abnormalities. Shortening of PBMC telomere length correlated with airflow obstruction and diffusing impairment. Paradoxically, circulating senescent CD57+/CD28null CD8+ T cells were associated with better PFT outcomes. Conclusion:Circulating T cells expressing markers of activation and inflammatory cytokine levels are independently correlated with PFT abnormalities in HIV-infected persons. Overall telomere shortening was also associated with pulmonary dysfunction. The paradoxical association of senescent CD8+ T cells and better PFT outcomes could suggest an unrecognized beneficial compensatory function of such cells or a redistribution of these cells from the circulation to local compartments. Further studies are needed to differentiate and characterize functional subsets of local pulmonary and circulating T-cell populations in HIV-associated pulmonary dysfunction.