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

Lavie, Gil; Hoshen, Moshe; Leibowitz, Morton; Benis, Arriel; Akriv, Amichay; Balicer, Ran; Reges, Orna
PURPOSE/OBJECTIVE: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.
PMID: 33217370
ISSN: 1555-7162
CID: 4770762

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

Dicker, Dror; Greenland, Philip; Leibowitz, Morton; Hoshen, Moshe; Senderey, Adi Berliner; Rasmussen-Torvik, Laura J; Balicer, Ran D; Reges, Orna
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/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/CONCLUSIONS: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.
PMID: 33150480
ISSN: 1708-0428
CID: 4689262

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

Vilchinsky, Noa; Reges, Orna; Leibowitz, Morton; Khaskia, Abdulrahim; Mosseri, Morris; Kark, Jeremy D
PURPOSE/OBJECTIVE: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/CONCLUSIONS:Symptoms of distress may serve as barriers to CPRP participation, regardless of ethnic origin.
PMID: 29485526
ISSN: 1932-751x
CID: 3052582

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

Reges, Orna; Greenland, Philip; Dicker, Dror; Leibowitz, Morton; Hoshen, Moshe; Gofer, Ilan; Rasmussen-Torvik, Laura J; Balicer, Ran D
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.
PMCID:5833565
PMID: 29340677
ISSN: 1538-3598
CID: 2915522

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

Reges, Orna; Leibowitz, Morton; Hoshen, Moshe; Leventer-Roberts, Maya; Greenland, Philip; Balicer, Ran
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.
PMID: 28387143
ISSN: 2047-4881
CID: 2521682

Association Between Achieved Low-Density Lipoprotein Levels and Major Adverse Cardiac Events in Patients With Stable Ischemic Heart Disease Taking Statin Treatment

Leibowitz, Morton; Karpati, Tomas; Cohen-Stavi, Chandra J; Feldman, Becca S; Hoshen, Moshe; Bitterman, Haim; Suissa, Samy; Balicer, Ran D
Importance: International guidelines recommend treatment with statins for patients with preexisting ischemic heart disease to prevent additional cardiovascular events but differ regarding target levels of low-density lipoprotein cholesterol (LDL-C). Trial data on this question are inconclusive and observational data are lacking. Objective: To assess the relationship between levels of LDL-C achieved with statin treatment and cardiovascular events in adherent patients with preexisting ischemic heart disease. Design, Setting, and Participants: Population-based observational cohort study from 2009 to 2013 using data from a health care organization in Israel covering more than 4.3 million members. Included patients had ischemic heart disease, were aged 30 to 84 years, were treated with statins, and were at least 80% adherent to treatment or, in a sensitivity analysis, at least 50% adherent. Patients with active cancer or metabolic abnormalities were excluded. Exposures: Index LDL-C was defined as the first achieved serum LDL-C measure after at least 1 year of statin treatment, grouped as low (
PMID: 27322095
ISSN: 2168-6114
CID: 2159042

Reduction in myocardial infarction incidence: Focus on socioeconomic disparities

Reges, Orna; Leibowitz, Morton; Hoshen, Moshe; Rabi, Yardena; Gluzman, Irit; Cohen, Chandra J; Balicer, Ran D
PMID: 24794958
ISSN: 0167-5273
CID: 1051702

Marital satisfaction and depression among couples following men's acute coronary syndrome: Testing dyadic dynamics in a longitudinal design

Dekel, Rachel; Vilchinsky, Noa; Liberman, Gabriel; Leibowitz, Morton; Khaskia, Abed; Mosseri, Morris
OBJECTIVES: The current study examined the contribution of marital satisfaction to symptoms of depression among patients with acute coronary syndrome (ACS) and their partners. METHOD: The sample comprised of 91 ACS male patients and their female partners. Data were collected at the time of initial hospitalization and 6 months later. Patients' and partners' assessments of marital satisfaction were measured using the ENRICH scale. Symptoms of depression were measured using the Brief Symptoms Inventory (BSI). Dyadic analysis applying the Actor-Partner Inter-dependence Model (APIM) was used. RESULTS: Different patterns emerged for the two phases. In the acute phase, only the Actor effect was significant: for both patients and partners, one's greater marital satisfaction was associated with one's lower levels of depression. In the chronic phase, both Actor and Partner effects were significant, while different trends were found for patients and partners. Partners' marital satisfaction was associated with their own and the patients' decreased depression symptoms, whereas among patients, higher levels of marital satisfaction were associated with elevated levels of depression both for themselves and for their partners. CONCLUSIONS: A dyadic perspective and phases of illness have to be taken into account in understanding adjustment and developing interventions following ACS. STATEMENT OF CONTRIBUTION: What is already known on this subject? The contribution of marital satisfaction to psychological adjustment following cardiac illness has been explored, but mainly from the perspective of one partner only. Different phases of an illness present different challenges for both patients and family members. What does this study add? A dyadic perspective on recovery from cardiac illness. The partner's contribution during the different phases of the illness.
PMID: 23552169
ISSN: 1359-107x
CID: 722392

Pneumococcal vaccine targeting strategy for the older adults: Customized risk profiling

Balicer, Ran D; Cohen, Chandra J; Leibowitz, Morton; Feldman, Becca S; Brufman, Ilan; Roberts, Craig; Hoshen, Moshe
BACKGROUND: Current pneumococcal vaccine campaigns take a broad, primarily age-based approach to immunization targeting, overlooking many clinical and administrative considerations necessary in disease prevention and resource planning for specific patient populations. We aim to demonstrate the utility of a population-specific predictive model for hospital-treated pneumonia to direct effective vaccine targeting. METHODS: Data was extracted for 1,053,435 members of an Israeli HMO, age 50 and older, during the study period 2008-2010. We developed and validated a logistic regression model to predict hospital-treated pneumonia using training and test samples, including a set of standard and population-specific risk factors. The model's predictive value was tested for prospectively identifying cases of pneumonia and invasive pneumococcal disease (IPD), and was compared to the existing international paradigm for patient immunization targeting. RESULTS: In a multivariate regression, age, co-morbidity burden and previous pneumonia events were most strongly positively associated with hospital-treated pneumonia. The model predicting hospital-treated pneumonia yielded a c-statistic of 0.80. Utilizing the predictive model, the top 17% highest-risk within the study validation population were targeted to detect 54% of those members who were subsequently treated for hospitalized pneumonia in the follow up period. The high-risk population identified through this model included 46% of the follow-up year's IPD cases, and 27% of community-treated pneumonia cases. These outcomes were compared with international guidelines for risk for pneumococcal diseases that accurately identified only 35% of hospitalized pneumonia, 41% of IPD cases and 21% of community-treated pneumonia. CONCLUSIONS: We demonstrate that a customized model for vaccine targeting performs better than international guidelines, and therefore, risk modeling may allow for more precise vaccine targeting and resource allocation than current national and international guidelines. Health care managers and policy-makers may consider the strategic potential of utilizing clinical and administrative databases for creating population-specific risk prediction models to inform vaccination campaigns.
PMID: 24384054
ISSN: 0264-410x
CID: 722372

Defining the Role of Medication Adherence in Poor Glycemic Control among a General Adult Population with Diabetes

Feldman, Becca S; Cohen-Stavi, Chandra J; Leibowitz, Morton; Hoshen, Moshe B; Singer, Shepherd R; Bitterman, Haim; Lieberman, Nicky; Balicer, Ran D
AIMS: This study assesses the attributable impact of adherence to oral glucose medications as a risk factor for poor glycemic control in population subgroups of a large general population, using an objective medication adherence measure. METHODS: Using electronic health records data, adherence to diabetes medications over a two-year period was calculated by prescription-based Medication Possession Ratios for adults with diabetes diagnosed before January 1, 2010. Glycemic control was determined by the HbA1c test closest to the last drug prescription during 2010-2012. Poor control was defined as HbA1c>75 mmol/mol (9.0%). Medication adherence was categorized as "good" (>80%), "moderate" (50-80%), or "poor" (<50%). Logistic regression models assessed the role medication adherence plays in the association between disease duration, age, and poor glycemic control. We calculated the change in the attributable fraction of glucose control if the non-adherent diabetic medication population would become adherent by age-groups. RESULTS: Among 228,846 diabetes patients treated by oral antiglycemic medication, 46.4% had good, 28.8% had moderate, and 24.8% had poor adherence. Good adherence rates increased with increasing disease duration, while glycemic control became worse. There was a strong inverse association between adherence level and poor control (OR = 2.50; CI = 2.43-2.58), and adherence was a significant mediator between age and poor control. CONCLUSIONS: A large portion of the diabetes population is reported to have poor adherence to oral diabetes medications, which is strongly associated with poor glycemic control in all disease durations. While poor adherence does not mediate the poorer glycemic control seen in patients with longer-standing disease, it is a significant mediator of poor glycemic control among younger diabetes patients. A greater fraction of poorly controlled younger patients, compared to older patients, could be prevented if at least 80% adherence to their medications was achieved. Therefore, our results suggest that interventions to improve adherence should focus on this younger sub-group.
PMCID:4178119
PMID: 25259843
ISSN: 1932-6203
CID: 1283632