Identifying patients with atrial fibrillation with a single CHA2DS2-VASC risk factor who are at higher risk of stroke.

AIMS: Management of patients with a single CHA2DS2-VASc score risk factor is controversial. We attempt to identify the "truly low risk" AF patients who will not benefit from oral anticoagulation (OAC) treatment. METHODS: Retrospective cohort analysis, all incident non-valvular AF (NVAF) cases between 2004 and 2015, and age 21 and older, with up to one thromboembolic risk factor besides sex (CHA2DS2-VASc score of up to 1 for men and up to 2 for women). A "low risk" score was created for these patients using a logistic regression model on the incidence of stroke within 30-2500 days following the NVAF diagnosis. RESULTS: We identified 15,621 patients. Average age was 53.7 ± 12.3 years, 56.6% male. Mean follow-up was 5.5 years. Significant predictors of ischemic stroke were age 65-74 and diabetes (2 points each), hypertension, vascular disease, and chronic kidney disease stage 2-3 (1 point each). Stroke incidence ranged from 0.8% for score 0 and up to 3.4% for scores ≤ 2. Odds ratio for stroke among patient group with a score ≤ 2 was 4.3 (2.9-6.6) compared with score 0. Our risk score's area-under-the-curve (AUC) for prediction of stroke was 0.68 (0.65-0.71), compared with 0.60 (0.57-0.62) for the CHAD2S2-VASc score, within this low-risk group. CONCLUSION: Patients considered at low or intermediate risk using traditional risk stratification schemes, with ≥ 2 points using this proposed low-risk index (65-74 years old, diabetics or a combination of chronic renal failure and an additional risk factor), had an overall stroke risk that may justify anticoagulation therapy.

Body mass index trajectories among people with obesity and association with mortality: Evidence from a large Israeli database.

OBJECTIVE: Previous studies using longitudinal weight data to characterize obesity are based on populations of limited size and mostly include individuals of all body mass index (BMI) levels, without focusing on weight changes among people with obesity. This study aimed to identify BMI trajectories over 5 years in a large population with obesity, and to determine the trajectories' association with mortality. METHODS: For inclusion, individuals aged 30-74 years at index date (1 January 2013) with continuous membership in Clalit Health Services from 2008 to 2012 were required to have ≥1 BMI measurement per year in ≥3 calendar years during this period, of which at least one was ≥30 kg/m2. Latent class analysis was used to generate BMI trajectories over 5 years (2008-2012). Cox proportional hazards models were used to assess the association between BMI trajectories and all-cause mortality during follow-up (2013-2017). RESULTS: In total, 367,141 individuals met all inclusion criteria. Mean age was 57.2 years; 41% were men. The optimal model was a quadratic model with four classes of BMI clusters. Most individuals (90.0%) had stable high BMI over time. Individuals in this cluster had significantly lower mortality than individuals in the other trajectory clusters (p < 0.01), including clusters of people with dynamic weight trajectories. CONCLUSIONS: The results of the current study show that people with stable high weight had the lowest mortality of all four BMI trajectories identified. These findings help to expand the scientific understanding of the impact that weight trajectories have on health outcomes, while demonstrating the challenges of discerning the cumulative effects of obesity and weight change, and suggest that dynamic historical measures of BMI should be considered when assessing patients' future risk of obesity-related morbidity and mortality, and when choosing a treatment strategy.

Statin Therapy for Primary Prevention in the Elderly and Its Association with New-Onset Diabetes, Cardiovascular Events, and All-Cause Mortality.

PURPOSE: This study assessed associations of the use of statins for primary prevention with cardiovascular outcomes among adults ages ≥70 years. METHODS: In a retrospective population-based cohort study, new users of statins without cardiovascular disease or diabetes mellitus were stratified by ages ≥70 years and <70 years. Using a time-dependent approach, adherence to statins was evaluated according to the proportion of days covered: <25%, 25%-50%, 50%-75%, and ≥75%. We assessed associations of statin therapy with increased risk of new-onset diabetes mellitus and with decreased risks of major adverse cardiovascular events and all-cause mortality. RESULTS: Of 42,767 new users of statins, 5970 (14%) were ages ≥70 years. The incident rates of major adverse cardiovascular events, all-cause mortality, and new-onset diabetes mellitus in the highest to lowest proportion of days covered categories were 16.9%, 16.7%, and 9.4% and 6.3%, 1.7%, and 9.4%, respectively. For the older group, the adjusted hazard ratios of major adverse cardiovascular events and mortality were significantly decreased for the highest adherence group (proportion of days covered ≥75%): 0.71 (0.57-0.88) and 0.68 (0.54-0.84), respectively. The respective hazard ratios were less favorable for the younger group: 0.80 (0.68-0.93) and 0.74 (0.58-1.03). The risk of new-onset diabetes mellitus was increased for the younger but not the older group. CONCLUSIONS: Statin use for primary prevention was associated with cardiovascular benefit in adults ages ≥70 years without a significant risk for the development of diabetes. These data may support the use of statin therapy for primary prevention in the elderly.

Addressing bias in prediction models by improving subpopulation calibration.

OBJECTIVE: To illustrate the problem of subpopulation miscalibration, to adapt an algorithm for recalibration of the predictions, and to validate its performance. MATERIALS AND METHODS: In this retrospective cohort study, we evaluated the calibration of predictions based on the Pooled Cohort Equations (PCE) and the fracture risk assessment tool (FRAX) in the overall population and in subpopulations defined by the intersection of age, sex, ethnicity, socioeconomic status, and immigration history. We next applied the recalibration algorithm and assessed the change in calibration metrics, including calibration-in-the-large. RESULTS: 1 021 041 patients were included in the PCE population, and 1 116 324 patients were included in the FRAX population. Baseline overall model calibration of the 2 tested models was good, but calibration in a substantial portion of the subpopulations was poor. After applying the algorithm, subpopulation calibration statistics were greatly improved, with the variance of the calibration-in-the-large values across all subpopulations reduced by 98.8% and 94.3% in the PCE and FRAX models, respectively. DISCUSSION: Prediction models in medicine are increasingly common. Calibration, the agreement between predicted and observed risks, is commonly poor for subpopulations that were underrepresented in the development set of the models, resulting in bias and reduced performance for these subpopulations. In this work, we empirically evaluated an adapted version of the fairness algorithm designed by Hebert-Johnson et al. (2017) and demonstrated its use in improving subpopulation miscalibration. CONCLUSION: A postprocessing and model-independent fairness algorithm for recalibration of predictive models greatly decreases the bias of subpopulation miscalibration and thus increases fairness and equality.

All-Cause Mortality of Patients With and Without Diabetes Following Bariatric Surgery: Comparison to Non-surgical Matched Patients.

OBJECTIVE: Data are sparse regarding the survival benefit of bariatric surgery on mortality among persons with diabetes. We aimed to investigate the association of bariatric surgery, compared with usual care, on all-cause mortality in individuals who underwent surgery and matched controls, stratified by the presence of diabetes. RESEARCH DESIGN AND METHODS: This retrospective cohort study utilized population-based electronic medical record data. Individuals who underwent one of three types of bariatric surgery during 2005-2014 were included. For each surgical patient, three non-surgical individuals were matched according to age, sex, body mass index, and diabetes status. The cohort comprised 9564 individuals with diabetes and 23,976 individuals without diabetes. RESULTS: During a median follow-up of 4.2 years, adjusted hazard ratios (HRs) for mortality for non-surgery vs. surgery were 2.38 (95%CI: 1.75, 3.26) and 1.73 (95%CI: 1.26, 2.36) among individuals with diabetes and individuals without diabetes, respectively. Considered separately, HRs for mortality for laparoscopic banding, gastric bypass, and laparoscopic sleeve gastrectomy were 2.83 (95%CI: 1.73, 4.63), 2.30 (95%CI: 1.25, 4.25), and 1.89 (95%CI: 1.1, 3.32) among patients with diabetes; and 1.74 (95%CI: 1.20, 2.52), 2.66 (0.81, 8.76), and 1.16 (0.51, 2.65) among patients without diabetes. CONCLUSION: The survival advantage of bariatric surgery after a median follow-up of 4.2 years was greater among individuals with than without diabetes for the three types of surgery performed. Longer follow-up is needed to examine the effect on survival in individuals without diabetes who undergo bariatric surgery. These results suggest priority considerations for bariatric surgery candidates.

Combining Inpatient and Outpatient Data for Diagnosis of Non-Valvular Atrial Fibrillation Using Electronic Health Records: A Validation Study.

PURPOSE: Previous studies have demonstrated differences in atrial fibrillation (AF) detection based on data from hospital sources without data from outpatient sources. We investigated the detection of documented diagnoses of non-valvular AF in a large Israeli health-care organization using electronic health record data from multiple sources. PATIENTS AND METHODS: This was an open-chart validation study. Three distinct algorithms for identifying AF in electronic health records, differing in the source of their International Classification of Diseases, Ninth Revision code and use of the associated free text, were defined. Algorithm 1 incorporated inpatient data with outpatient data and the associated free text. Algorithm 2 incorporated inpatient and outpatient data regardless of the free text associated with AF diagnosis. Algorithm 3 used only inpatient data source. These algorithms were compared to a gold standard and their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. To establish the gold standard (documentation of arrhythmia based on electrocardiography interpretation or a cardiologist's written diagnosis), 200 patients at highest risk for having non-valvular AF were randomly selected for open-chart validation by two physicians. RESULTS: The algorithm that included hospital settings, outpatient settings, and incorporated associated free text in the outpatient records had the optimal balance between all validation measures, with a high level of sensitivity (85.4%), specificity (95.0%), PPV (81.4%), and NPV (96.2%). The alternative algorithm that combined inpatient and outpatient data without free text also performed better than the algorithm that included only hospital data (82.9%, 95.0%, 81.0%, and 95.6%, compared to 70.7%, 96.9%, 85.3%, and 92.8%, sensitivity, specificity, PPV, and NPV, respectively). CONCLUSION: In this study, involving a comprehensive data collection from inpatient and outpatient sources, incorporating outpatient data with inpatient data improved the diagnosis of non-valvular AF compared to inpatient data alone.

A comprehensive descriptive assessment of obesity related chronic morbidity and estimated annual cost burden from a population-based electronic health record database.

BACKGROUND: The growing prevalence of obesity and its complications pose a huge burden on the individual and health care systems worldwide. This study presents the frequency of multiple prevalent co-morbidities and estimated annual cost burden by body mass index (BMI) groups, age, and sex among the Israeli adult population to provide policy makers with further evidence to appropriately target interventions. METHODS: This cross-sectional study utilized population-based electronic medical records from the largest payer-provider health fund in Israel. The population included individuals ≥25 years as of 01/01/2014. A new approach assessing body system-related morbidity (BSRM) prevalence was assessed along with estimated annual cost burden for the year 2015 and presented across BMI group, age, and sex via heat maps. RESULTS: Among 1,756,791 adults, 65% had an elevated BMI (BMI > 25 kg/m2). Heat map analysis demonstrated a higher multi-BSRM prevalence and relative estimated annual cost burden among participants with obesity in all age groups. There was a notably higher multi-BSRM prevalence among men and women aged 25-29 with class III obesity (26 and 30%, respectively) compared to the corresponding BMI groups between 18·5- < 25 kg/m2 (5 and 9%, respectively). Healthcare costs were 1·72 times higher among men aged 25-29 with class III obesity and 2·75 times among women aged 25-29 with class III obesity compared to those of healthy weight. CONCLUSIONS: The detailed analysis describes the uneven distribution of burdens across BMI groups, age, and sex allowing policy makers to identify sub-populations for targeted interventions.

Use of oral anticoagulation therapy in the first 3 months after the diagnosis of atrial fibrillation in Israel: A population-based study.

INTRODUCTION: Oral anticoagulation (OAC) therapy reduces the risk of ischemic stroke in patients with atrial fibrillation (AF) while increasing the risk of bleeding. Recently, non-vitamin K antagonist oral anticoagulants (NOACs) have become available with lower rates of intracranial bleeding, and some of them have presented a reduced risk of major bleeding. The purpose of this study is to evaluate the change in purchasing patterns of OACs (both warfarin and NOACs) over time in patients with AF according to stroke and bleeding risk, in the first 3 months after diagnosis. METHODS AND RESULTS: We conducted a historical cohort study using the Clalit Health Services electronic medical records database. The study population included all members aged ≥21 years, with a new diagnosis of nonvalvular AF between 2008 and 2015. A total of 58 385 cases were identified. The mean age was 73.1 (±14.1) years, and 52.3% of the patients were women. The median CHA2 DS2 -VASc score was 4 (interquartile range, 3-5). OACs were purchased by 19 705 patients (33.8%) within the first 3 months of first diagnosis of AF, with patients at higher embolic risk as stratified by the CHA2 DS2 -VASc score and having higher purchasing rates (37.1%). Between 2008 and 2010, 29% of patients purchased a vitamin K antagonist, the only available OAC at the time. OAC purchasing increased to 41.4% between 2014 and 2015, with half of the patients purchasing an NOAC. CONCLUSION: In this real-world, population-based cohort study of patients with newly diagnosed AF, we found a lower than expected rate of OAC prescription within 3 months of diagnosis but an encouraging increase in OAC purchasing over time. The use of NOACs has risen exponentially within just a few years, accounting for a greater pool of patients with being prescribed an OAC.

Risk of Stroke, Bleeding, and Death in Patients with Nonvalvular Atrial Fibrillation and Chronic Kidney Disease.

INTRODUCTION: Atrial fibrillation (AF) and chronic kidney disease (CKD) are both associated with increased risk of stroke, and CKD carries a higher bleeding risk. Oral anticoagulation (OAC) treatment is used to reduce the risk of stroke in patients with nonvalvular AF (NVAF); however, the risk versus benefit of OAC for advanced CKD is continuously debated. We aim to assess the management and outcomes of NVAF patients with impaired renal function within a population-based cohort. METHODS: We conducted a retrospective observational cohort study using ICD-9 healthcare coding. Patients with incident NVAF between 2004 and 2015 were identified stratified by CKD stage. We compared treatment strategies and estimated risks of stroke, death, or any major bleeding based on CKD stages and OAC treatment. RESULTS: We identified 85,116 patients with incident NVAF. Patients with impaired renal function were older and had more comorbidities. OAC was most common among stage 2 CKD patients (49%) and least in stages 4-5 CKD patients (27.6%). Higher CKD stages were associated with worse outcomes. Stroke rates increased from 1.04 events per 100 person-years (PY) in stage 1 CKD to 3.72 in stages 4-5 CKD. Mortality increased from 3.42 to 32.95 events/100 PY, and bleeding rates increased from 0.89 to 4.91 events/100 PY. OAC was associated with reduced stroke and intracranial bleeding risk regardless of CKD stage, and with a reduced mortality risk in stages 1-3 CKD. CONCLUSION: Among NVAF patients, advanced renal failure is associated with higher risk of stroke, death, and bleeding. OAC was associated with reduced stroke and intracranial bleeding risk, and with improved survival in stages 1-3 CKD.

Behavior and knowledge trajectories among adult offspring of patients with an acute cardiac event: A call for a turning point in cardiac prevention.

INTRODUCTION: Early detection is critical in the prevention of cardiovascular disease (CVD). An at-risk population for cardiac disease-and conveniently approachable in terms of timing-is cardiac patients' offspring, at the moment when the parent is hospitalized for his or her own cardiac event. Based on the theoretical underpinning of life turning points, defined as perceived life course-changing events, we suggest that adult children would view the parent's cardiac event as a significant life turning point and that this understanding would motivate them to learn about CVD and to change their lifestyles accordingly. The current study's main goal was therefore to assess the baseline level and change over time in the adult offspring's knowledge of cardiac risk factors and cardiac health-promoting behaviors. METHOD: In a prospective design, 69 Israeli adult offspring of individuals newly diagnosed with an acute coronary event were approached and interviewed at 3 time points (on average 17 days, 55 days, and 125 days after the parent's hospitalization). RESULTS: Contrary to our assumption, no significant change over time was detected among the adult children with regard to body mass index, physical activity, eating behaviors, or smoking. In fact, over time, they seemed to know less about CVD risk factors than they did originally. CONCLUSION: Adult children of cardiac patients seem to be reluctant to spontaneously engage in health-promoting behaviors. The option of approaching them, in a primary preventive act, as early as during a parent's hospitalization should be further investigated. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Translating clinical trial results into personalized recommendations by considering multiple outcomes and subjective views.

Currently, clinicians rely mostly on population-level treatment effects from RCTs, usually considering the treatment's benefits. This study proposes a process, focused on practical usability, for translating RCT data into personalized treatment recommendations that weighs benefits against harms and integrates subjective perceptions of relative severity. Intensive blood pressure treatment (IBPT) was selected as the test case to demonstrate the suggested process, which was divided into three phases: (1) Prediction models were developed using the Systolic Blood-Pressure Intervention Trial (SPRINT) data for benefits and adverse events of IBPT. The models were externally validated using retrospective Clalit Health Services (CHS) data; (2) Predicted risk reductions and increases from these models were used to create a yes/no IBPT recommendation by calculating a severity-weighted benefit-to-harm ratio; (3) Analysis outputs were summarized in a decision support tool. Based on the individual benefit-to-harm ratios, 62 and 84% of the SPRINT and CHS populations, respectively, would theoretically be recommended IBPT. The original SPRINT trial results of significant decrease in cardiovascular outcomes following IBPT persisted only in the group that received a "yes-treatment" recommendation by the suggested process, while the rate of serious adverse events was slightly higher in the "no-treatment" recommendation group. This process can be used to translate RCT data into individualized recommendations by identifying patients for whom the treatment's benefits outweigh the harms, while considering subjective views of perceived severity of the different outcomes. The proposed approach emphasizes clinical practicality by mimicking physicians' clinical decision-making process and integrating all recommendation outputs into a usable decision support tool.

All-Cause Mortality Following Bariatric Surgery in Smokers and Non-smokers.

INTRODUCTION: Bariatric surgery is associated with lower all-cause mortality, but many studies exclude smokers. We sought to determine if the association of mortality and bariatric surgery differs between smokers and non-smokers. MATERIALS AND METHODS: We conducted a retrospective cohort study in a large Israeli integrated payer/provider health care organization. A total of 7747 adult patients who underwent bariatric surgery between January 1, 2005, and December 31, 2014, were selected and compared with non-surgical patients (and were matched on age, sex, diabetes, and BMI using a sequential/simultaneous stratification matching). A total of 30,742 patients with a median follow-up of 4.3 years were included in this study with less than 1% lost to follow-up. The type of bariatric surgery (gastric banding, Roux-en-Y gastric bypass, or sleeve gastrectomy) and smoking status were determined from electronic health records. The rate of all-cause mortality in matched surgical and non-surgical patients was compared in smoking and non-smoking subgroups, adjusted for key potential confounders. RESULTS: There was a statistically significantly higher mortality associated with not having bariatric surgery in both smoking (HR, 1.99; 95% CI, 1.54-2.56) and non-smoking (HR, 1.93; 95% CI, 1.12-3.34) subgroups. Although smokers had higher rates of mortality overall (2.6% in smokers compared with 1.7% in non-smokers), the mortality hazard ratio (comparing matched non-surgical patients to surgical patients) did not differ significantly between smokers and non-smokers (p for interaction = .67). CONCLUSIONS: Bariatric surgery was associated with significantly lower mortality in both smokers and non-smokers.

Comparison of Stroke Risk Stratification Scores for Atrial Fibrillation.

Several stroke risk stratification scores have been developed to guide clinical decision-making in patients with nonvalvular atrial fibrillation (AF). The aim of this study was to compare the performance of the CHADS2, CHA2DS2-VASc and R2CHADS2 risk scores to predict stroke. This retrospective cohort study was based on electronic medical records from Clalit Health Services (CHS), the largest payer provider healthcare organization in Israel. Data of CHS members with AF diagnosis between 2004 and 2015 were extracted. Demographic and co-morbidity data were used to calculate the 3 risk scores, and the performance of the scores to predict stroke were compared using area under the curve and net reclassification index. Of the 89,213 CHS members with AF, 52.3% were women and median age was 76 years. The proportions of patients at high risk were 66.2%, 86.7%, and 71.1% in the CHADS2, CHA2DS2-VASc, and R2CHADS2, respectively, with stroke incidence rates of 2.91, 2.35, and 2.80 per 100 person-years, respectively. Area under the curves for stroke prediction were 0.61 for both CHADS2 and CHA2DS2-VASc and 0.59 for R2CHADS2. Net reclassification index analysis demonstrated a net improvement of 0.089 in the index when CHA2DS2-VASc was compared with CHADS2 and a net reduction of 0.083 when R2CHADS2 was compared with CHADS2. In conclusion, current stroke stratification scores have comparable but limited ability to predict stroke in patients with AF. Stroke prevention strategies may vary depending on the applied stratification. There is a need for a better stroke risk stratification score for patients with AF.

Net clinical benefit of anticoagulant treatments in elderly patients with nonvalvular atrial fibrillation: Experience from the real world.

BACKGROUND: Oral anticoagulation (OAC) is effective in stroke prevention in elderly patients with nonvalvular atrial fibrillation (AF), but older patients are also at higher risk of bleeding. OBJECTIVE: We aimed to examine whether OAC has net clinical benefit (NCB) in elderly patients with AF. METHODS: This is a retrospective cohort study of patients with AF, aged 75 years and older, who were diagnosed from January 1, 2013, through December 31, 2015. Incidences of stroke and intracranial hemorrhage (ICH) were estimated as the number of events per 100 person-years. The NCBs were estimated with respect to time in therapeutic range (TTR) (<60% or ≥60%) and treatment type (warfarin and low or high dose of direct oral anticoagulants [DOACs]). RESULTS: We included 11,760 patients, of whom 4982 (42.4%) were treated with OACs: 2042 (17.4%) with warfarin and 2940 (25.0%) with DOACs. Among patients treated with warfarin, those who achieved TTR ≥ 60% had a lower incidence of stroke (2.54 per 100 person-years vs 5.21 per 100 person-years; P = .01) but without a statistically significant lower incidence of ICH (0.68 per 100 person-years vs 1.10 per 100 person-years; P = .45) and a higher NCB (9.78 vs 6.52) than did those with TTR < 60%. Among patients treated with DOACs, patients treated with the high dose had a statistically significant similar incidence of stroke (8.40 per 100 person-years vs 9.81 per 100 person-years; P = .67), a statistically significant lower incidence of ICH (0.33 per 100 person-years vs 1.20 per 100 person-years; P = .02), and a higher NCB (4.42 vs 1.78) than did patients treated with the low dose. CONCLUSION: A large proportion of elderly patients are not treated with OACs. We found that the NCB of OAC in the elderly is positive, with the highest benefit in elderly patients treated with warfarin who achieved TTR ≥ 60% or high dose of DOACs.

Comparing Management and Outcomes in Men and Women With Nonvalvular Atrial Fibrillation: Data From a Population-Based Cohort.

OBJECTIVES: This study sought to identify the differences in stroke, mortality, and bleeding between men and women with atrial fibrillation (AF). BACKGROUND: There are inconsistent data regarding the thromboembolic risk difference between men and women with AF. The authors assessed the risk of stroke, death, and bleeding in men and women with incident AF. METHODS: The authors employed a prospective historical cohort using an electronic database from a large health maintenance organization. All members with incident AF between 2004 and 2015 were included. Primary endpoints were ischemic stroke, death, and major bleeding. RESULTS: The authors identified 89,213 members with incident nonvalvular atrial fibrillation (NVAF), 52.3% of whom were women. Women were older, with a higher prevalence of hypertension, whereas more men had diabetes, heart failure, and ischemic heart disease than the women did. Ischemic stroke occurred in 6.4% of the patients: 7.0% of women and 5.8% of men. Sex did not affect adjusted stroke risk (hazard ratio [HR]: 0.91; 95% confidence interval [CI]: 0.77 to 1.06; p = 0.22). However, women 75 years of age and older were at an increased risk (HR: 1.25; 95% CI: 1.17 to 1.34). Mortality rates were higher among women (33.5% vs. 32%; p < 0.001); however, women had a significantly lower adjusted mortality risk (HR: 0.78; 95% CI: 0.71 to 0.86). Women had lower risk of intracranial hemorrhage (HR: 0.81; 95% CI: 0.76 to 0.87) and major gastrointestinal bleeding (HR: 0.78; 95% CI: 0.70 to 0.87). CONCLUSIONS: Men and women with AF had a similar risk of ischemic stroke, except for women 75 years of age or older, who had a higher risk. Our findings support using a similar anticoagulation strategy for prevention of stroke in men and women with a similar number of risk factors.

The association between eGFR in the normal or mildly impaired range and incident cadiovascular disease: Age and sex analysis.

BACKGROUND: Worse renal function, even in the normal or mildly impaired range, is associated with incident cardiovascular disease (CVD). Whether this association exists in both sexes across all ages is not known. METHODS: A population based cohort of individuals >22 years with no prior CVD and with an eGFR 60-130 ml/min/1.73 m2. eGFR was calculated using the CKD-EPI formula. Incident CVD was defined as either myocardial infarction, unstable angina pectoris, coronary revascularization, or cerebrovascular event. Incident CVD was examined separately in men and women in 3 age-groups (young, 22-40 years; middle-aged, 41-60 years; and elderly, ≥61 years), during a median follow-up of 96.0 months. RESULTS: Among 1,341,400 individuals (57% women, mean age 49.2 ±â€¯16.6 years), men had more incident CVD as compared to women (34,968 vs. 23,515 total incident CVD) in all age-groups (0.6% vs. 0.2% in young; 6.2% vs. 2.0% in middle-aged; 13.4% vs. 8.4% in elderly, respectively). After adjustment for CVD risk factors, an increment of 10 units in eGFR was independently associated with a decrease of 5.4%, 3.4% and 5.4% in incident CVD in young, middle-aged and elderly men (p < 0.001 for each) and a decrease of 6.3%, 3.4% and 6.8% in the same age-groups in women (p < 0.001 for each). There was no significant age-sex interaction in the association between eGFR and incident CVD. CONCLUSION: Although incident CVD differs in men and women, as well as in different age-groups, a higher eGFR even in the normal or mildly impaired range is associated with lesser incident CVD in men and women of all ages.

Symptoms of Depression and Anxiety as Barriers to Participation in Cardiac Rehabilitation Programs Among Arab and Jewish Patients in Israel.

PURPOSE: Despite its proven efficacy, low participation rates in cardiac prevention and rehabilitation programs (CPRPs) prevail worldwide, especially among ethnic minorities. This is strongly evident in Israel's Arab minority. Since psychological distress has been found to be associated with CPRP participation and minorities are subjected to higher levels of distress, it is plausible that distress may be an important barrier for CPRP participation among minority patients. The current prospective study assessed the contribution of depression and anxiety symptoms to participation in a CPRP after acute coronary syndrome, both in the enrollment phase and when considering adherence over time, among Jewish (majority) and Arab (minority) patients in Israel. METHODS: Patients were interviewed during hospitalization about their emotional status and at a 6-mo follow-up concerning participation in a CPRP. Analyses were performed on 397 patients. The Brief Symptom Inventory was used. Logistic regression modeling was applied. RESULTS: Symptoms of depression, but not anxiety, were frequently observed among Arab patients compared with their Jewish counterparts. In analyses adjusted for age, sex, ethnicity, and sociodemographic and clinical characteristics, having symptoms of anxiety was associated with less participation in a CPRP, evident for both Jews and Arabs; this association was less evident for symptoms of depression. Multivariable adjusted models did not show a significant association of symptoms of anxiety or depression with adherence in a CPRP. Accounting for psychological distress did not reduce the sharp difference between Jews and Arabs in CPRP participation. CONCLUSION: Symptoms of distress may serve as barriers to CPRP participation, regardless of ethnic origin.

Association of Bariatric Surgery Using Laparoscopic Banding, Roux-en-Y Gastric Bypass, or Laparoscopic Sleeve Gastrectomy vs Usual Care Obesity Management With All-Cause Mortality.

Importance: Bariatric surgery is an effective and safe approach for weight loss and short-term improvement in metabolic disorders such as diabetes. However, studies have been limited in most settings by lack of a nonsurgical group, losses to follow-up, missing data, and small sample sizes in clinical trials and observational studies. Objective: To assess the association of 3 common types of bariatric surgery compared with nonsurgical treatment with mortality and other clinical outcomes among obese patients. Design, Setting, and Participants: Retrospective cohort study in a large Israeli integrated health fund covering 54% of Israeli citizens with less than 1% turnover of members annually. Obese adult patients who underwent bariatric surgery between January 1, 2005, and December 31, 2014, were selected and compared with obese nonsurgical patients matched on age, sex, body mass index (BMI), and diabetes, with a final follow-up date of December 31, 2015. A total of 33 540 patients were included in this study. Exposures: Bariatric surgery (laparoscopic banding, Roux-en-Y gastric bypass, or laparoscopic sleeve gastrectomy) or usual care obesity management only (provided by a primary care physician and which may include dietary counseling and behavior modification). Main Outcomes and Measures: The primary outcome, all-cause mortality, matched and adjusted for BMI prior to surgery, age, sex, socioeconomic status, diabetes, hyperlipidemia, hypertension, cardiovascular disease, and smoking. Results: The study population included 8385 patients who underwent bariatric surgery (median age, 46 [IQR, 37-54] years; 5490 [65.5%] women; baseline median BMI, 40.6 [IQR, 38.5-43.7]; laparoscopic banding [n = 3635], gastric bypass [n = 1388], laparoscopic sleeve gastrectomy [n = 3362], and 25 155 nonsurgical matched patients (median age, 46 [IQR, 37-54] years; 16 470 [65.5%] women; baseline median BMI, 40.5 [IQR, 37.0-43.5]). The availability of follow-up data was 100% for all-cause mortality. There were 105 deaths (1.3%) among surgical patients during a median follow-up of 4.3 (IQR, 2.8-6.6) years (including 61 [1.7%] who underwent laparoscopic banding, 18 [1.3%] gastric bypass, and 26 [0.8%] sleeve gastrectomy), and 583 deaths (2.3%) among nonsurgical patients during a median follow-up of 4.0 (IQR, 2.6-6.2) years. The absolute difference was 2.51 (95% CI, 1.86-3.15) fewer deaths/1000 person-years in the surgical vs nonsurgical group. Adjusted hazard ratios (HRs) for mortality among nonsurgical vs surgical patients were 2.02 (95% CI, 1.63-2.52) for the entire study population; by surgical type, HRs were 2.01 (95% CI, 1.50-2.69) for laparoscopic banding, 2.65 (95% CI, 1.55-4.52) for gastric bypass, and 1.60 (95% CI, 1.02-2.51) for laparoscopic sleeve gastrectomy. Conclusions and Relevance: Among obese patients in a large integrated health fund in Israel, bariatric surgery using laparoscopic banding, gastric bypass, or laparoscopic sleeve gastrectomy, compared with usual care nonsurgical obesity management, was associated with lower all-cause mortality over a median follow-up of approximately 4.5 years. The evidence of this association adds to the limited literature describing beneficial outcomes of these 3 types of bariatric surgery compared with usual care obesity management alone.

Targeting LDL Cholesterol: Beyond Absolute Goals Toward Personalized Risk.

PURPOSE OF REVIEW: The aim of this study was to review and assess the evidence for low-density lipoprotein cholesterol (LDL-C) treatment goals as presented in current guidelines for primary and secondary prevention of cardiovascular disease. RECENT FINDINGS: Different sets of guidelines and clinical studies for secondary prevention have centered on lower absolute LDL-C targets [<70 mg/dL (<1.8 mmol/L)], greater percent reductions of LDL-C (≥50%), or more intense treatment to achieve greater reductions in cardiovascular risk. Population-based risk models serve as the basis for statin initiation in primary prevention. Reviews of current population risk models for primary prevention show moderate ability to discriminate [with c-statistics ranging from 0.67 to 0.77 (95% CIs from 0.62 to 0.83) for men and women] with poor calibration and overestimation of risk. Individual clinical trial data are not compelling to support specific LDL-C targets and percent reductions in secondary prevention. Increasing utilization of electronic health records and data analytics will enable the development of individualized treatment goals in both primary and secondary prevention.

Diabetes control: Incidence of acute myocardial infarction and all-cause mortality among patients with 3-6 years' disease duration.

Background Optimal glycated haemoglobin (HbA1c) concentrations to minimize large vessel complications and prolong life in diabetes patients are not well established. Design A retrospective cohort study from 2010 to 2012 using data from the Clalit Health Service (Clalit) integrated healthcare system's electronic data warehouse. Patients included had newly incident diabetes, had at least two HbA1c measurements during the 3 years prior to 1 January 2010 without any disruption(s) in Clalit membership between 2010 and 2014. Methods Time-dependent variables were utilized for HbA1c concentration exposure at three time periods. Diabetes control was evaluated taking average HbA1c measures per time period. Unadjusted and adjusted extended Cox regression analyses assessed the association between time-dependent average HbA1c level and acute myocardial infarction and all-cause mortality. Results Among our 61,971 participants, 2.0% experienced acute myocardial infarction and 6.9% died. Compared to patients with HbA1c 7.0 to < 7.5%, a higher risk of myocardial infarction was found with 8.5 to < 9.0% (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.05-1.91) and ≥9.0% (HR 1.87, 95% CI 1.50-2.33) groups; a lower risk was found among <6.0% (HR 0.74, 95% CI 0.59-0.93), 6.0 to < 6.5% (HR 0.77, 95% CI 0.64-0.94) and 6.5 to < 7.0% (HR 0.73, 95% CI 0.60-0.88) groups. The association with all-cause mortality was J-shaped, demonstrating a higher risk in those <6.0% (HR 1.20, 95% CI 1.06-1.34), 7.5 to < 8.0% (HR 1.17, 95% CI 1.02-1.35), 8.0 to < 8.5% (HR 1.38, 95% CI 1.16-1.64), 8.5 to < 9.0% (HR 1.36, 95% CI 1.10-1.67) and ≥9.0% (HR 1.74, 95% CI 1.49-2.04) groups. Conclusions HbA1c concentration below 6.0% may be associated with an excess risk for all-cause mortality. Clinicians must be aware of this association when treating individual patients.