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Background: In this study, we explored the utility of intravenous opioid rescue analgesia in the post anesthesia care unit (PACU-OpResc) as a single marker of thoracic epidural analgesia (TEA) failure and evaluated the resource implications and quality improvement applications of this measure. Methods: We performed a retrospective analysis of all TEA placements over a three-year period at a single academic medical center in Boston, Massachusetts. The study exposure was PACU-OpResc. Primary outcome was PACU length of stay (LOS). Secondary outcomes included reasons for delayed PACU discharge and intraoperative hypotension. The analyses were adjusted for confounding variables including patient comorbidities, surgical complexity, intraoperative intravenous opioids, chronic opioid use and local anesthetic bolus through TEA catheter. Post analysis chart review was conducted to determine the positive predictive value (PPV) of PACU-OpResc for inadequate TEA. As a first Plan-Do-Study-Act cycle, we then introduced a checkbox for documentation of a sensory level check after TEA placement. Post implementation data was collected for 7 months. Results: PACU-OpResc was required by 211 (22.1%) patients who received preoperative TEA, was associated with longer PACU LOS (incidence rate ratio 1.20, 95% CI:1.07–1.34, p = 0.001) and delayed discharge due to inadequate pain control (odds ratio 5.15, 95% CI 3.51–7.57, p < 0.001). PACU-OpResc had a PPV of 76.3 and 60.4% for re-evaluation and manipulation of the TEA catheter in PACU, respectively. Following implementation of a checkbox, average monthly compliance with documented sensory level check after TEA placement was noted to be 39.7%. During this time, a reduction of 8.2% in the rate of PACU-OpResc was observed. Conclusions: This study demonstrates that PACU-OpResc can be used as a quality assurance measure or surrogate for TEA efficacy, to track performance and monitor innovation efforts aimed at improving analgesia, such as our intervention to facilitate sensory level checks and reduced PACU-OpResc. Trial registration: not applicable. [ABSTRACT FROM AUTHOR]

Inappropriate dosing of neostigmine for antagonism of neuromuscular blockade has been associated with postoperative pulmonary complications. We evaluated the effects of a quality improvement initiative tailored to optimise the use of neostigmine in antagonising neuromuscular blockade on postoperative pulmonary complications, costs and duration of hospital stay. The quality improvement initiative consisted of: a reduction in available neostigmine aliquot sizes; a cognitive aid; an educational component; and a financial incentive for the intra-operative documentation of train-of-four measurement before administration of neostigmine. We conducted a pre-specified analysis of data obtained in our quality improvement study. Additional analyses were conducted in a propensity-matched cohort. An interrupted time series design was used to discriminate between the intervention and a counterfactual scenario. We analysed 12,025 consecutive surgical cases performed in 2015. Postoperative pulmonary complications occurred in 220 (7.5%) of 2937 cases pre-intervention and 568 (6.3%) of 9088 cases post-intervention. Adjusted regression analyses showed significantly a lower risk of postoperative pulmonary complications (OR 0.73 (95%CI 0.61-0.88); p = 0.001), lower costs (incidence rate ratio 0.95 (95%CI 0.93-0.97); p < 0.001) and shorter duration of hospital stay (incidence rate ratio 0.91 (95%CI 0.87-0.94); p < 0.001) after implementation of the quality improvement initiative. Analyses in a propensity-matched sample (n = 2936 per group) and interrupted time series analysis (n = 27,202 cases) confirmed the findings. Our data show that a local, multifaceted quality improvement initiative can enhance the quality of intra-operative neuromuscular blocking agent utilisation, thereby reducing the incidence of postoperative pulmonary complications. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relation of circulating concentrations of vascular endothelial growth factor (VEGF) for the risk of developing cardiovascular disease (CVD) in a large community-based sample.Methods: We prospectively assessed the relation of circulating VEGF concentrations with the incidence of CVD among 3041 Framingham Heart Study participants (mean age 63.4±11.1 years, 59% women). Multivariable Cox proportional hazards models were estimated adjusting for standard risk factors to VEGF quartiles to incident CVD. Restricted cubic splines were used to examine the linearity of the association.Results: After a mean follow-up of 8.8 (±2.8) years, 527 individuals experienced a first CVD event. Compared with participants in the first VEGF quartile, individuals in the second VEGF quartile had a 34% increased risk for future CVD (HR 1.34, 95% CI 1.03 to 1.74; p value=0.03) and individuals in third quartile had a 59% higher risk (HR 1.59; 95% CI 1.23 to 2.05, p value=0.0003). Individuals in the highest VEGF quartile had a similar cardiovascular risk as compared with those in the lowest VEGF quartile (HR 1.18, 95% CI 0.91 to 1.53, p value=0.21). Evaluation of restricted cubic splines confirmed the nonlinear, inverted U-shaped relation of serum VEGF and CVD events (p<0.0001 for model fit, p=0.006 for non-linearity).Conclusions: Circulating VEGF concentrations exhibit a complex non-linear (inverted U-shaped) relation with the risk of developing CVD events, with the lowest risk experienced at the lower and upper end of the distribution. The underlying pathophysiological mechanisms remain to be elucidated. [ABSTRACT FROM AUTHOR]

The Framingham Heart Study (FHS) has conducted seminal research defining cardiovascular disease (CVD) risk factors and fundamentally shaping public health guidelines for CVD prevention over the past five decades. The success of the Original Cohort, initiated in 1948, paved the way for further epidemiological research in preventive cardiology. Due to the keen observations suggesting the role of shared familial factors in the development of CVD, in 1971 the FHS began enroling the second generation cohort, comprising the children of the Original Cohort and the spouses of the children. In 2002, the third generation cohort, comprising the grandchildren of the Original Cohort, was initiated to additionally explore genetic contributions to CVD in greater depth. Additionally, because of the predominance of White individuals of European descent in the three generations of FHS participants noted above, the Heart Study enrolled the OMNI1 and OMNI2 cohorts in 1994 and 2003, respectively, aimed to reflect the current greater racial and ethnic diversity of the town of Framingham. All FHS cohorts have been examined approximately every 2-4 years since the initiation of the study. At these periodic Heart Study examinations, we obtain a medical history and perform a cardiovascular-focused physical examination, 12-lead electrocardiography, blood and urine samples testing and other cardiovascular imaging studies reflecting subclinical disease burden.The FHS has continually evolved along the cutting edge of cardiovascular science and epidemiological research since its inception. Participant studies now additionally include study of cardiovascular imaging, serum and urine biomarkers, genetics/genomics, proteomics, metabolomics and social networks. Numerous ancillary studies have been established, expanding the phenotypes to encompass multiple organ systems including the lungs, brain, bone and fat depots, among others. Whereas the FHS was originally conceived and designed to study the epidemiology of cardiovascular disease, it has evolved over the years with staggering expanded breadth and depth that have far greater implications in the study of the epidemiology of a wide spectrum of human diseases. The FHS welcomes research collaborations using existing or new collection of data. Detailed information regarding the procedures for research application submission and review are available at [http://www.framinghamheartstudy.org/researchers/index.php]. [ABSTRACT FROM AUTHOR]

Purpose: Shortening of telomeres, the protective structures at the ends of eukaryotic chromosomes, is associated with age-related pathologies. Telomere length is influenced by DNA integrity and DNA and histone methylation. Folate plays a role in providing precursors for nucleotides and methyl groups for methylation reactions and has the potential to influence telomere length. Method: We determined the association between leukocyte telomere length and long-term plasma folate status (mean of 4 years) in Framingham Offspring Study ( n = 1,044, females = 52.1 %, mean age 59 years) using data from samples collected before and after folic acid fortification. Leukocyte telomere length was determined by Southern analysis and fasting plasma folate concentration using microbiological assay. Results: There was no significant positive association between long-term plasma folate and leukocyte telomere length among the Framingham Offspring Study participants perhaps due to their adequate folate status. While the leukocyte telomere length in the second quintile of plasma folate was longer than that in the first quintile, the difference was not statistically significant. The leukocyte telomere length of the individuals in the fifth quintile of plasma folate was shorter than that of those in the second quintile by 180 bp ( P < 0.01). There was a linear decrease in leukocyte telomere length with higher plasma folate concentrations in the upper four quintiles of plasma folate ( P for trend = 0.001). Multivitamin use was associated with shorter telomeres in this cohort ( P = 0.015). Conclusions: High plasma folate status possibly resulting from high folic acid intake may interfere with the role of folate in maintaining telomere integrity. [ABSTRACT FROM AUTHOR]

Background: While there is widespread dissemination of patient navigation programs in an effort to reduce delays in cancer care, little is known about the impact of barriers to care on timely outcomes. Methods: We conducted a secondary analysis of the Boston Patient Navigation Research Program (PNRP) to examine the effect that the presence of barriers had on time to diagnostic resolution of abnormal breast or cervical cancer screening tests. We used multivariable Cox proportional hazards regression with time to diagnostic resolution as the outcome to examine the effect of the number of barriers, controlling for demographic covariates and clustered by patients' primary navigator. Results: There were 1481 women who received navigation; mean age was 39 years; 32% were White, 27% Black, and 31% Hispanic; 28% had private health insurance; and 38% did not speak English. Overall, half ( n=745, 50%) had documentation of one or more barriers to care. Women with barriers were more likely to be older, non-White, non-English language speakers, and on public or no health insurance compared with women without barriers. In multivariable analyses, we found less timely diagnostic resolution as the number of barriers increased (one barrier, adjusted hazard ratio [aHR] 0.81 [95% CI 0.56-1.17], p=0.26; two barriers, aHR 0.55 [95% CI 0.37-0.81], p=0.0025; three or more barriers, aHR 0.31 [95% CI 0.21-0.46], p<0.0001)]. Conclusion: Within a patient navigation program proven to reduce delays in care, we found that navigated patients with documented barriers to care experience less timely resolution of abnormal cancer screening tests. [ABSTRACT FROM AUTHOR]

Objective: The association between total testosterone and metabolic syndrome has prompted speculation that low testosterone contributes to the pathophysiology of metabolic syndrome in men. We determined whether testosterone or sex hormone-binding globulin (SHBG) is independently associated with the risk of metabolic syndrome.Research Design and Methods: Cross-sectional relationships of hormone levels with metabolic syndrome were assessed in a sample of men in generation 2 of the Framingham Heart Study (FHS) who did not receive testosterone or androgen-deprivation therapy (n = 1,625) and confirmed in a validation sample of men in FHS generation 3 (n = 1,912). Hormone levels in generation 2 examination 7 were related prospectively to incident metabolic syndrome 6.6 years later at examination 8. Testosterone was measured using liquid chromatography-tandem mass spectrometry, SHBG was measured by immunofluorometric assay, and free testosterone was calculated. Metabolic syndrome was defined using the National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS Cross-sectionally, testosterone and SHBG were more strongly associated with metabolic syndrome than free testosterone in the training sample. SHBG, but not testosterone or free testosterone, was significantly associated with metabolic syndrome after adjusting for age, smoking, BMI, and insulin sensitivity (homeostasis model assessment of insulin resistance [HOMA-IR]). These findings were confirmed in a validation sample. Longitudinally, SHBG at examination 7, but not testosterone or free testosterone, was associated with incident metabolic syndrome at examination 8 after adjusting for age, smoking, BMI, and HOMA-IR. Multivariable analyses suggested that age, BMI, and insulin sensitivity independently affect SHBG and testosterone levels and the risk of metabolic syndrome and its components.Conclusions: SHBG, but not testosterone, is independently associated with the risk of metabolic syndrome. These data do not reveal an independent prospective relationship between testosterone and metabolic syndrome in men. [ABSTRACT FROM AUTHOR]

The article discusses a study which investigated the association between familial occurrence of atrial fibrillation (AF) and new-onset AF beyond established risk factors. Participants who were aged at least 30 years and free of AF were identified from the Framingham Heart Study. Symptoms and findings that suggested cardiovascular disease were ascertained based on the medical histories and physical examinations of participants. The researchers found an association between familial AF and an increased risk of AF.

Background: Studies suggest that targeting high-risk, nonhypertensive individuals for treatment may delay hypertension onset, thereby possibly mitigating vascular complications. Risk stratification may facilitate cost-effective approaches to management. Objective: To develop a simple risk score for predicting hypertension incidence by using measures readily obtained in the physician's office. Design: Longitudinal cohort study. Setting: Framingham Heart Study, Framingham, Massachusetts. Patients: 1717 nonhypertensive white individuals 20 to 69 years of age (mean age, 42 years; 54% women), without diabetes and with both parents in the original cohort of the Framingham Heart Study, contributed 5814 person-examinations. Measurements: Scores were developed for predicting the 1-, 2-, and 4-year risk for new-onset hypertension, and performance characteristics of the prediction algorithm were assessed by using calibration and discrimination measures. Parental hypertension was ascertained from examinations of the original cohort of the Framingham Heart Study. Results: During follow-up (median time over all person-examinations, 3.8 years), 796 persons (52% women) developed new-onset hypertension. In multivariable analyses, age, sex, systolic and diastolic blood pressure, body mass index, parental hypertension, and cigarette smoking were significant predictors of hypertension. According to the risk score based on these factors, the 4-year risk for incident hypertension was classified as low (<5%) in 34% of participants, medium (5% to 10%) in 19%, and high (>10%) in 47%. The c-statistic for the prediction model was 0.788, and calibration was very good. Limitations: The risk score findings may not be generalizable to persons of nonwhite race or ethnicity or to persons with diabetes. The risk score algorithm has not been validated in an independent cohort and is based on single measurements of risk factors and blood pressure. Conclusion: The hypertension risk prediction score can be used to estimate an individual's absolute risk for hypertension on short-term follow-up, and it represents a simple, office-based tool that may facilitate management of high-risk individuals with prehypertension. [ABSTRACT FROM AUTHOR]

The article presents research examining the relations between pulse pressure and the incidence of atrial fibrillation (AF), which poses a high rate of morbidity and mortality. The database of the Framingham (Massachusetts) Heart Study was mined for over 5000 adult patients initially free of AF. AF developed in 13% of patients a median of 12 years after pulse pressure assessment. The research concludes that pulse pressure is a significant risk factor for incident AF. Further research may indicate whether interventions to reduce pulse pressure will curtail the incidence of AF.

Background: The short- and long-term risks for developing overweight or obesity are unknown. Objectives: To estimate the short-term, long-term, and lifetime risks for developing overweight or obesity in adults in the community. Design: Prospective cohort study, 1971 to 2001. Setting: Community-based study, Framingham, Massachusetts. Participants: 4117 white participants (51.9% women) from the Framingham Heart Study. Measurements: The short-term (4 years) and long-term (10 to 30 years) risks for ever becoming overweight or more (body mass index [BMI] ≥ 25 kg/m2) or obese (BMI ≥ 30 kg/m2) for men and women at 30, 40, and 50 years of age with a normal BMI (between 18.5 kg/m2 and 25.0 kg/m2). Results: The observed 4-year rates of developing overweight varied from 14% to 19% in women and 26% to 30% in men. Four-year rates of developing obesity ranged from 5% to 7% in women and 7% to 9% in men. The long-term (30-year) risk estimates were similar for the 2 sexes generally; varied somewhat with age (in men, being lower for those 50 years of age); and, overall, exceeded 1 in 2 persons for overweight or more, 1 in 4 individuals for obesity, and 1 in 10 people for stage II obesity (BMI ≥ 35 kg/m2) across different age groups. The 30-year estimates correspond to the residual lifetime risk for overweight or more or obesity for participants 50 years of age. Limitations: These findings may not be generalizable to other races or ethnicities. Conclusions: The long-term risks for overweight or more or obesity exceeded 50% and 25%, respectively, indicating a large public health burden. These estimates suggest that the future burden of obesity-associated diseases may be substantial. [ABSTRACT FROM AUTHOR]

Examines the relation between alcohol consumption and risk for congestive heart failure (CHF) in Framingham, Massachusetts. Details on impairment in left ventricular function associated with heavy alcohol drinking; Factors causing CHF; Information on the efficacy of moderately taken alcohol in reducing CHF risk.

Background The extent to which omega-3 fatty acid status is related to risk for death from any cause and for incident cardiovascular disease (CVD) remains controversial. Objective To examine these associations in the Framingham Heart Study. Design Prospective and observational. Setting Framingham Heart Study Offspring cohort. Measurements The exposure marker was red blood cell levels of eicosapentaenoic and docosahexaenoic acids (the Omega-3 Index) measured at baseline. Outcomes included mortality (total, CVD, cancer, and other) and total CVD events in participants free of CVD at baseline. Follow-up was for a median of 7.3 years. Cox proportional hazards models were adjusted for 18 variables (demographic, clinical status, therapeutic, and CVD risk factors). Results Among the 2500 participants (mean age 66 years, 54% women), there were 350 deaths (58 from CVD, 146 from cancer, 128 from other known causes, and 18 from unknown causes). There were 245 CVD events. In multivariable-adjusted analyses, a higher Omega-3 Index was associated with significantly lower risks ( P -values for trends across quintiles) for total mortality ( P = .02), for non-CVD and non-cancer mortality ( P = .009), and for total CVD events ( P = .008). Those in the highest (>6.8%) compared to those in the lowest Omega-3 Index quintiles (<4.2%) had a 34% lower risk for death from any cause and 39% lower risk for incident CVD. These associations were generally stronger for docosahexaenoic acid than for eicosapentaenoic acid. When total cholesterol was compared with the Omega-3 Index in the same models, the latter was significantly related with these outcomes, but the former was not. Limitations Relatively short follow-up time and one-time exposure assessment. Conclusions A higher Omega-3 Index was associated with reduced risk of both CVD and all-cause mortality. [ABSTRACT FROM AUTHOR]

The article discusses the relationship between neck circumference (NC) and the development of cardiovascular disease risk factors in the Framingham Heart Study. It presents a summary of the results of the study. The article also confirms the association between NC and incident type 2 diabetes and a clinically meaningful improvement in the NRI.

Current data suggest that increases in hemoglobin may decrease nitric oxide and adversely affect vascular function. In the preclinical setting, these changes could precipitate the development of heart failure (HF). We hypothesized that higher hematocrit (HCT) would be associated with an increased incidence of new-onset HF in the community. We evaluated 3,523 participants (59% women) from the Framingham Heart Study who were 50 to 65 years old and free of HF. Participants were followed prospectively until an HF event, death, or the end of 20 years of follow up. HCT was subdivided into 4 gender-specific categories (women: HCT 36.0 to 40.0, 40.1 to 42.0, 42.1 to 45.0, >45.0; men: 39.0 to 44.0, 44.1 to 45.0, 45.1 to 49.0, >49.0). Gender-pooled multivariable Cox proportional hazards models were used to estimate the association of HCT with incident HF, adjusting for clinical risk factors. During the follow-up period (61,417 person-years), 217 participants developed HF (100 events in women). There was a linear increase in risk of HF across the 4 HCT categories (p for trend = 0.002). Hazards ratios for HF in the low–normal, normal, and high HCT categories were 1.27 (95% confidence interval 0.82 to 1.97), 1.47 (1.01 to 2.15), and 1.78 (1.15 to 2.75), respectively, compared to the lowest HCT category (p for trend <0.0001). Adjustment for interim development of other cardiovascular diseases and restriction of the sample to nonsmokers did not alter the results. In conclusion, higher levels of HCT, even within the normal range, were associated with an increased risk of developing HF in this long-term follow-up study. [ABSTRACT FROM AUTHOR]

The Framingham Heart Study is the longest-running cardiovascular epidemiological study, starting in 1948. This paper gives an overview of the various cohorts, collected data, and most important research findings to date. In brief, the Framingham Heart Study, funded by the National Institutes of Health and managed by Boston University, spans 3 generations of well phenotyped White persons and 2 cohorts comprised of racial and ethnic minority groups. These cohorts are densely phenotyped, with extensive longitudinal follow-up, and they continue to provide us with important information on human cardiovascular and noncardiovascular physiology over the lifespan, as well as to identify major risk factors for cardiovascular disease. This paper also summarizes some of the more recent progress in molecular epidemiology and discusses the future of the study. [ABSTRACT FROM AUTHOR]

Background: Whereas regular exercise is associated with lower risk of cardiovascular disease and mortality, mechanisms of exercise-mediated health benefits remain less clear. We used metabolite profiling before and after acute exercise to delineate the metabolic architecture of exercise response patterns in humans.Methods: Cardiopulmonary exercise testing and metabolite profiling was performed on Framingham Heart Study participants (age 53±8 years, 63% women) with blood drawn at rest (n=471) and at peak exercise (n=411).Results: We observed changes in circulating levels for 502 of 588 measured metabolites from rest to peak exercise (exercise duration 11.9±2.1 minutes) at a 5% false discovery rate. Changes included reductions in metabolites implicated in insulin resistance (glutamate, -29%; P=1.5×10-55; dimethylguanidino valeric acid [DMGV], -18%; P=5.8×10-18) and increases in metabolites associated with lipolysis (1-methylnicotinamide, +33%; P=6.1×10-67), nitric oxide bioavailability (arginine/ornithine + citrulline, +29%; P=2.8×10-169), and adipose browning (12,13-dihydroxy-9Z-octadecenoic acid +26%; P=7.4×10-38), among other pathways relevant to cardiometabolic risk. We assayed 177 metabolites in a separate Framingham Heart Study replication sample (n=783, age 54±8 years, 51% women) and observed concordant changes in 164 metabolites (92.6%) at 5% false discovery rate. Exercise-induced metabolite changes were variably related to the amount of exercise performed (peak workload), sex, and body mass index. There was attenuation of favorable excursions in some metabolites in individuals with higher body mass index and greater excursions in select cardioprotective metabolites in women despite less exercise performed. Distinct preexercise metabolite levels were associated with different physiologic dimensions of fitness (eg, ventilatory efficiency, exercise blood pressure, peak Vo2). We identified 4 metabolite signatures of exercise response patterns that were then analyzed in a separate cohort (Framingham Offspring Study; n=2045, age 55±10 years, 51% women), 2 of which were associated with overall mortality over median follow-up of 23.1 years (P≤0.003 for both).Conclusions: In a large sample of community-dwelling individuals, acute exercise elicits widespread changes in the circulating metabolome. Metabolic changes identify pathways central to cardiometabolic health, cardiovascular disease, and long-term outcome. These findings provide a detailed map of the metabolic response to acute exercise in humans and identify potential mechanisms responsible for the beneficial cardiometabolic effects of exercise for future study. [ABSTRACT FROM AUTHOR]

Preparedness measures for the anticipated surge of coronavirus disease 2019 (COVID-19) cases within eastern Massachusetts included the establishment of alternate care sites (field hospitals). Boston Hope hospital was set up within the Boston Convention and Exhibition Center to provide low-acuity care for COVID-19 patients and to support local healthcare systems. However, early recognition of the need to provide higher levels of care, or critical care for the potential deterioration of patients recovering from COVID-19, prompted the development of a hybrid acute care-intensive care unit. We describe our experience of implementing rapid response capabilities of this innovative ad hoc unit. Combining quality improvement tools for hazards detection and testing through in situ simulation successfully identified several operational hurdles. Through rapid continuous analysis and iterative change, we implemented appropriate mitigation strategies and established rapid response and rescue capabilities. This study provides a framework for future planning of high-acuity services within a unique field hospital setting. [ABSTRACT FROM AUTHOR]

Background: Longitudinal studies of mitral valve prolapse (MVP) progression among unselected individuals in the community, including those with nondiagnostic MVP morphologies (NDMs), are lacking.Methods and Results: We measured longitudinal changes in annular diameter, leaflet displacement, thickness, anterior/posterior leaflet projections onto the annulus, coaptation height, and mitral regurgitation jet height in 261 Framingham Offspring participants at examination 5 who had available follow-up imaging 3 to 16 years later. Study participants included MVP (n=63); NDMs, minimal systolic displacement (n=50) and the abnormal anterior coaptation phenotype (n=10, with coaptation height >40% of the annulus similar to posterior MVP); plus 138 healthy referents without MVP or NDMs. At follow-up, individuals with MVP (52% women, 57±11 years) had greater increases of leaflet displacement, thickness, and jet height than referents (all P<0.05). Eleven participants with MVP (17%) had moderate or more severe mitral regurgitation (jet height ≥5 mm) and 5 others (8%) underwent mitral valve repair. Of the individuals with NDM, 8 (80%) participants with abnormal anterior coaptation progressed to posterior MVP; 17 (34%) subjects with minimal systolic displacement were reclassified as either posterior MVP (12) or abnormal anterior coaptation (5). In comparison with the 33 participants with minimal systolic displacement who did not progress, the 17 who progressed had greater leaflet displacement, thickness, coaptation height, and mitral regurgitation jet height (all P<0.05).Conclusions: NDM may evolve into MVP, highlighting the clinical significance of mild MVP expression. MVP progresses to significant mitral regurgitation over a period of 3 to 16 years in one-fourth of individuals in the community. Changes in mitral leaflet morphology are associated with both NDM and MVP progression. [ABSTRACT FROM AUTHOR]

The article discusses a study which used the community-based sample of the Framingham Heart Study to test whether a genetic risk score (GRS) associated with coronary artery disease (CAD) was also associated with heart failure with reduced ejection fraction (HFREF) compared to heart failure with preserved ejection fraction (HFPEF) risk. The study also looked at the prognostic importance of a CAD-related GRS in survival after HFPEF and HFREF.

Abstract: Background: We assessed GGT fractions correlates and their reference values in the Offspring Cohort of the Framingham Heart Study. Methods: Correlates of GGT fractions were assessed by multivariable regression analysis in 3203 individuals [47% men, mean age (SD): 59 (10) years]. GGT fractions reference values were established by empirical quantile analysis in a reference group of 432 healthy subjects [45% men, 57 (10) years]. Results: Fractional GGT levels were higher in men than in women (P <0.0001). In both sexes, fractions were associated with: triglycerides were associated with b-GGT, alcohol consumption with m-, s- and f-GGT. C-reactive protein with m- and s-GGT, while plasminogen activator inhibitor-1 with b- and f-GGT. Body mass index, blood pressure, glucose and triglycerides correlated with b- and f-GGT. In comparison with the reference group [b-GGT/s-GGT median (Q1–Q3): 0.51 (0.35–0.79)U/L], subjects affected by cardiovascular disease or diabetes showed no change of b/s ratio [0.52 (0.34–0.79)U/L, 0.57 (0.40–0.83)U/L, respectively]. The b/s ratio was higher in presence of metabolic syndrome [0.61 (0.42–0.87)U/L, P <0.0001], while lower in heavy alcohol consumers [0.41 (0.28–0.64)U/L, P <0.0001]. Conclusions: Metabolic and cardiovascular risk markers are important correlates of GGT fractions, in particular of b-GGT. [Copyright &y& Elsevier]

Abstract: Objectives: Red blood cell (RBC) levels of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA, the omega-3 index, expressed as a percent of total fatty acids) are inversely related to risk for cardiovascular disease (CVD). Although several mechanisms underlying this relationship have been proposed, understanding the associations between the omega-3 index and markers of CVD in the community can shed additional light on this question. The objectives of this study were to define the relations between the omega-3 index and clinical factors and to determine the heritability of the omega-3 index. Methods: RBC samples (n = 3196) drawn between 2005 and 2008 from participants in the Framingham Study [Examination 8 of the Offspring cohort plus Examination 3 of the Omni (minorities) cohort] were analyzed for fatty acid composition by gas chromatography. Results: The mean (SD) omega-3 index was 5.6% (1.7%). In multivariable regression models, the factors significantly and directly associated with the omega-3 index were age, female sex, higher education, fish oil supplementation, dietary intake of EPA + DHA, aspirin use, lipid pharmacotherapy, and LDL-cholesterol. Factors inversely associated were Offspring cohort, heart rate, waist girth, triglycerides and smoking. The total explained variability in the omega-3 index for the fully adjusted model was 73%, which included major components due to heritability (24%), EPA + DHA intake (25%), and fish oil supplementation (15%). Conclusion: The variability in the omega-3 index is determined primarily by dietary and genetic factors. An increased omega-3 index is associated with a generally cardioprotective risk factor milieu. [Copyright &y& Elsevier]

Abstract: Objective: Several bone marrow-derived cell populations have been identified that may possess angiogenic activity and contribute to vascular homeostasis in experimental studies. We examined the extent to which lower quantities of these circulating angiogenic cell phenotypes may be related to impaired vascular function and greater arterial stiffness. Methods: We studied 1948 Framingham Heart Study participants (mean age, 66±9 years; 54% women) who were phenotyped for circulating angiogenic cells: CD34+, CD34+/KDR+, and early outgrowth colony forming units (CFU). Participants underwent non-invasive assessments of vascular function including peripheral arterial tone (PAT), arterial tonometry, and brachial reactivity testing. Results: In unadjusted analyses, higher CD34+ and CD34+/KDR+ concentrations were modestly associated with lower PAT ratio (β =−0.052±0.011, P <0.001 and β =−0.030±0.011, P =0.008, respectively) and with higher carotid-brachial pulse wave velocity (β =0.144±0.043, P =0.001 and β =0.112±0.043, P =0.009), but not with flow-mediated dilation; higher CD34+ was also associated with lower carotid-femoral pulse wave velocity (β =−0.229±0.094, P =0.015). However, only the association of lower CD34+ concentration with higher PAT ratio persisted in multivariable analyses that adjusted for standard cardiovascular risk factors. In all analyses, CFU was not associated with measures of vascular function or arterial stiffness. Conclusions: In our large, community-based sample of men and women, circulating angiogenic cell phenotypes largely were not associated with measures of vascular function or arterial stiffness in analyses adjusting for traditional risk factors. [Copyright &y& Elsevier]

Background--Heart failure (HF) is a clinical syndrome characterized by signs and symptoms involving multiple organ systems. Longitudinal data demonstrating that asymptomatic cardiac dysfunction precedes overt HF are scarce, and the contribution of noncardiac dysfunction to HF progression is unclear. We hypothesized that subclinical cardiac and noncardiac organ dysfunction would accelerate the manifestation of HF. Methods and Results--We studied 1038 participants of the Framingham Heart Study original cohort (mean age, 76±5 years; 39% men) with routine assessment of left ventricular systolic and diastolic function. Major noncardiac organ systems were assessed with the use of serum creatinine (renal), serum albumin (hepatic), ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1:FVC ratio; pulmonary), hemoglobin concentration (hematologic/ oxygen-carrying capacity), and white blood cell count (systemic inflammation). On follow-up (mean, 11 years), there were 248 incident HF events (146 in women). After adjustment for established HF risk factors, antecedent left ventricular systolic dysfunction (hazard ratio, 2.33; 95% confidence interval, 1.43 to 3.78) and diastolic dysfunction (hazard ratio, 1.32; 95% confidence interval, 1.01 to 1.71) were associated with increased HF risk. After adjustment for cardiac dysfunction, higher serum creatinine, lower FEV1 :FVC ratios, and lower hemoglobin concentrations were associated with increased HF risk (all P<0.05); serum albumin and white blood cell count were not. Subclinical dysfunction in each noncardiac organ system was associated with a 30% increased risk of HF (P = 0.013). Conclusions--Antecedent cardiac dysfunction and noncardiac organ dysfunction are associated with increased incidence of HF, supporting the notion that HF is a progressive syndrome and underscoring the importance of noncardiac factors in its occurrence. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To conduct an investigation of clinical and genetic correlates of lipoprotein-associated phospholipase (Lp-PLA2) activity and mass in a large community-based cohort. Higher circulating Lp-PLA2 predicts cardiovascular disease risk, but sources of inter-individual variability are incompletely understood. Methods: We conducted stepwise regression of clinical correlates of Lp-PLA2 in four Framingham Heart Study cohorts (n =8185; mean age 50±14 years, 53.8% women, 9.8% ethnic/racial minority cohort). We also conducted heritability and linkage analyses in Offspring and Generation 3 cohorts (n =6945). In Offspring cohort participants we performed association analyses (n =1535 unrelated) with 1943 common tagging SNPs in 233 inflammatory candidate genes. Results: Sixteen clinical variables explained 57% of the variability in Lp-PLA2 activity; covariates associated with Lp-PLA2 mass were similar but only explained 27% of the variability. Multivariable-adjusted heritability estimates for Lp-PLA2 activity and mass were 41% and 25%, respectively. A linkage peak was observed for Lp-PLA2 activity (chromosome 6, LOD score 2.4). None of the SNPs achieved experiment-wide statistical significance, though 12 had q values <0.50, and hence we expect at least 50% of these associations to be true positives. The strongest multivariable-association with Lp-PLA2 activity was found for MEF2A (rs2033547; nominal p =3.20×10−4); SNP rs1051931 in PLA2G7 was nominally associated (p =1.26×10−3). The most significant association to Lp-PLA2 mass was in VEGFC (rs10520358, p =9.14×10−4). Conclusions: Cardiovascular risk factors and genetic variation contribute to variability in Lp-PLA2 activity and mass. Our genetic association analyses need replication, which will be facilitated by web posting of our genetic association results. [Copyright &y& Elsevier]

Abstract: Background: Public health recommendations advocate breastfeeding in infancy as a means to reduce obesity in later life. Several prior studies relating breastfeeding to cardiovascular risk factors have been limited by lack of adjustment for maternal and participant confounding factors. Methods: We ascertained breastfeeding history via questionnaire from mothers enrolled in the Framingham Offspring Study. In their young to middle-aged adult children enrolled in the Framingham Third Generation, we examined the relations between maternal breastfeeding history (yes, no) and cardiovascular risk factors, including body mass index (BMI), high-density lipoprotein (HDL) cholesterol, total cholesterol, triglycerides, fasting blood glucose, and systolic and diastolic blood pressure levels. We applied generalized estimating equations to account for sibling correlations and adjusted for maternal and participant lifestyle, education, and cardiovascular risk factors. Results: In Third Generation participants (n = 962, mean age = 41 years, 54% were women), 26% of their mothers reported breastfeeding. Compared with non-breastfed individuals, breastfed adult participants had lower multivariable-adjusted BMI (26.1 kg/m2 vs 26.9 kg/m2, P = .04) and higher HDL cholesterol levels (HDL 56.6 mg/dL vs 53.7 mg/dL, P = .01). On additional adjustment for BMI, the association between breastfeeding and HDL cholesterol was attenuated (P = .09). Breastfeeding was not associated with total cholesterol, triglycerides, fasting blood glucose, systolic blood pressure, or diastolic blood pressure. Conclusion: Breastfeeding in infancy is inversely associated with adult BMI and positively associated with HDL cholesterol. Associations between breastfeeding and BMI may mediate the association between breastfeeding and HDL cholesterol. [Copyright &y& Elsevier]

Background: Inequity in cancer outcomes for minorities and vulnerable populations has been linked to delays in cancer care that arise from barriers to accessing care. Social service barriers represent those obstacles related to meeting life's most basic needs, like housing and income, which are often supported by public policy, regulation and services., Objective: To examine the association between social service barriers and timely diagnostic resolution after a cancer screening abnormality., Design: Secondary analysis of the intervention arm of Boston Patient Navigation Research Program (2007-2008) conducted across six urban community health centers. Subjects with no barriers, other barriers, and social service barriers were compared on their time to diagnostic resolution., Subjects: Women ≥ 18 years of age with a breast or cervical cancer screening abnormality., Main Measures: Social service barriers included: income supports, housing and utilities, education and employment, and personal/family stability and safety. Time to event analyses compared across five groups: those with no barriers, one barrier (other), one barrier (social service), two or more barriers (all other), and two or more barriers (at least one social service)., Key Results: 1,481 navigated women; 31 % Hispanic, 27 % Black, 32 % White; 37 % non-English speakers and 28 % had private health insurance. Eighty-eight women (6 %) had social service barriers. Compared to those without social service barriers, those with were more likely to be Hispanic, younger, have public/no health insurance, and have multiple barriers. Those with two or more barriers (at least one social service barrier), had the longest time to resolution compared to the other four groups (aHR resolution < 60 days = 0.27, ≥ 60 days = 0.37)., Conclusion: Vulnerable women with multiple barriers, when at least one is a social service barrier, have delays in care despite navigation. The impact of patient navigation may never be fully realized if social service barriers persist without being identified or addressed.