Disease Management plus Recommended Care versus Recommended Care Alone for Ambulatory Patients with Chronic Obstructive Pulmonary Disease.

Rationale: The efficacy of disease management programs in the treatment of patients with chronic obstructive pulmonary disease (COPD) remains uncertain.Objectives: To study the effect of disease management (DM) added to recommended care (RC) in ambulatory patients with COPD.Measurements and Main Results: In this trial, 1,202 patients with COPD (age, ≥40 yr), with moderate to very severe airflow limitation were randomly assigned either to DM plus RC (study intervention) or to RC alone (control intervention). RC included follow-up by pulmonologists, inhaled long-acting bronchodilators and corticosteroids, smoking cessation intervention, nutritional advice and psychosocial support when indicated, and supervised physical activity sessions. DM, delivered by trained nurses during patients' visits to the designated COPD centers and by remote contacts with the patients between these visits, included patient self-care education, monitoring patients' symptoms and adherence to treatment, provision of advice in case of acute disease exacerbation, and coordination of care vis-à-vis other healthcare providers. The primary composite endpoint was first hospital admission for respiratory symptoms or death from any cause. During 3,537 patient-years, 284 patients (47.2%) in the control group and 264 (44.0%) in the study intervention group had a primary endpoint event. The median (range) time elapsed until a primary endpoint event was 1.0 (0-4.0) years among patients assigned to the study intervention and 1.1 (0-4.1) years among patients assigned to the control intervention; adjusted hazard ratio, 0.92 (95% confidence interval, 0.77-1.08).Conclusions: DM added to RC was not superior to RC alone in delaying first hospital admission or death among ambulatory patients with COPD.

Disease management in the treatment of patients with chronic heart failure who have universal access to health care: a randomized controlled trial.

BACKGROUND: The efficacy of disease management programs in improving the outcome of heart failure patients remains uncertain and may vary across health systems. This study explores whether a countrywide disease management program is superior to usual care in reducing adverse health outcomes and improving well-being among community-dwelling adult patients with moderate-to-severe chronic heart failure who have universal access to advanced health-care services and technologies. METHODS: In this multicenter open-label trial, 1,360 patients recruited after hospitalization for heart failure exacerbation (38%) or from the community (62%) were randomly assigned to either disease management or usual care. Disease management, delivered by multi-disciplinary teams, included coordination of care, patient education, monitoring disease symptoms and patient adherence to medication regimen, titration of drug therapy, and home tele-monitoring of body weight, blood pressure and heart rate. Patients assigned to usual care were treated by primary care practitioners and consultant cardiologists. The primary composite endpoint was the time elapsed till first hospital admission for heart failure exacerbation or death from any cause. Secondary endpoints included the number of all hospital admissions, health-related quality of life and depression during follow-up. Intention-to-treat comparisons between treatments were adjusted for baseline patient data and study center. RESULTS: During the follow-up, 388 (56.9%) patients assigned to disease management and 387 (57.1%) assigned to usual care had a primary endpoint event. The median (range) time elapsed until the primary endpoint event or end of study was 2.0 (0-5.0) years among patients assigned to disease management, and 1.8 (0-5.0) years among patients assigned to usual care (adjusted hazard ratio, 0.908; 95% confidence interval, 0.788 to 1.047). Hospital admissions were mostly (70%) unrelated to heart failure. Patients assigned to disease management had a better health-related quality of life and a lower depression score during follow-up. CONCLUSIONS: This comprehensive disease management intervention was not superior to usual care with respect to the primary composite endpoint, but it improved health-related quality of life and depression. A disease-centered approach may not suffice to make a significant impact on hospital admissions and mortality in patients with chronic heart failure who have universal access to health care. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00533013 . Trial registration date: 9 August 2007. Initial protocol release date: 20 September 2007.

Lipoprotein-associated phospholipase A2, and subsequent cardiovascular events and mortality among patients with coronary heart disease.

OBJECTIVE: The objective of this study is to evaluate the relevance of Lp-PLA2 to risk prediction among coronary heart disease (CHD) patients. METHODS: Lp-PLA2 activity was measured in 2538 CHD patients included in the Bezafibrate Infarction Prevention (BIP) study. RESULTS: Adjusting for patient characteristics and traditional risk factors, 1 standard deviation of Lp-PLA2 was associated with a hazard ratio (HR) of 1.12 (95% confidence interval (CI): 1.00-1.25) for mortality and 1.03 (0.93-1.14) for cardiovascular events. Lp-PLA2 did not significantly improve model discrimination, or calibration nor result in noteworthy reclassification. CONCLUSIONS: Our results do not support added value of Lp-PLA2 for predicting cardiovascular events or mortality among CHD patients beyond traditional risk factor.

Inflammation and future risk of symptomatic heart failure in patients with stable coronary artery disease.

BACKGROUND: Heart failure (HF) carries poor prognosis in coronary artery disease (CAD) patients despite advances in therapy. Inflammation predicts recurrent cardiovascular events in CAD patients. It is unknown whether increased levels of inflammatory markers are associated with incident HF in these patients. AIM: The aims of this study were to evaluate the association between inflammatory markers and future HF risk in patients with stable CAD and to explore possible mediation by myocardial infarction (MI). METHODS: The study comprised 2,945 patients with stable CAD without HF at baseline during a median follow-up of 7.9 years. Inflammatory baseline markers were the basis of this study. RESULTS: Heart failure was diagnosed in 508 patients (17.2%). Patients who developed HF were older and had more often previous MI, diabetes, hypertension, and peripheral vascular disease. Baseline levels of C-reactive protein (CRP), fibrinogen, and white blood cells (WBCs) were significantly higher in patients who developed HF compared with those who did not. Age-adjusted incident HF rates were related to elevated baseline inflammatory markers in a dose-response manner. Adjusting for multiple confounders, the HF hazard ratios were 1.38 (95% CI 1.11-1.72), 1.33 (95% CI 1.07-1.66), and 1.36 (95% CI 1.10-1.68) for the third tertiles of CRP, fibrinogen, and WBC levels, respectively. Hazard ratio for the fifth quintile of a combined "inflammation score" was 1.83 (95% CI 1.40-2.39). Mediation by MI preceding the HF onset during follow-up accounted for 10.4%, 10.8%, and 8.6% of the association of subsequent HF with CRP, fibrinogen, and WBC, respectively. CONCLUSIONS: Increased levels of CRP, fibrinogen, and WBC are independently related to the incidence of HF in patients with stable CAD.

Arrhythmia Burden Among Adult Patients With Congenital Heart Disease: A Population-Based Study.

BACKGROUND: A significant percentage of patients with congenital heart disease surviving into adulthood will develop arrhythmias. These arrhythmias are associated with an increased risk of adverse events and death. We aimed to assess arrhythmia prevalence, risk factors, and associated health care usage in a large national cohort of patients with adult congenital heart disease. METHODS AND RESULTS: Adults with a documented diagnosis of congenital heart disease, insured by Clalit and Maccabi health services between January 2007 and December 2011, were included. We assessed the associations between arrhythmia and subsequent hospitalization rates and death with mixed negative binomial and Cox proportional hazard models, respectively. Among 11 653 patients with adult congenital heart disease (median age, 47 years [interquartile range, 31-62]), 8.7% had a tachyarrhythmia at baseline, 1.5% had a conduction disturbance, and 0.5% had both. Among those without a baseline arrhythmia, 9.2% developed tachyarrhythmias, 0.9% developed a conduction disturbance, and 0.3% developed both during the study period. Compared with no arrhythmia (reference group), arrhythmia in the previous 6 months was associated with a higher multivariable adjusted hospitalization rate, 1.33-fold higher than the rate of the reference group (95% CI, 1.00-1.76) for ventricular arrhythmia, 1.27-fold higher (95% CI, 1.17-1.38) for atrial arrhythmias, and 1.33-fold higher (95% CI, 1.04-1.71) for atrioventricular block. Atrial tachyarrhythmias were associated with an adjusted mortality hazard ratio (HR) of 1.65 (95% CI, 1.44-2.94), and ventricular tachyarrhythmias with a >2-fold increase in mortality risk (HR, 2.06 [95% CI, 1.44-2.94]). CONCLUSIONS: Arrhythmias are significant comorbidities in the adult congenital heart disease population and have a significant impact on health care usage and survival.

Socioeconomic status indicators and incidence of heart failure among men and women with coronary heart disease.

BACKGROUND: Low socioeconomic status (SES) is associated with increased coronary heart disease (CHD) risk. Little is known about the relationship between SES and heart failure (HF) incidence among CHD patients. METHODS AND RESULTS: The association among education, occupation, and HF risk was studied in 2,951 CHD patients, free of HF at baseline, participating in a clinical trial, correcting for the competing risk of death. Over 8 years of close follow-up, 511 patients developed HF. These patients were older, and had higher frequency of metabolic risk factors and advanced CHD than HF-free counterparts. Age-adjusted HF incidence rate/1,000 person-years increased from 20.4 to 30.0 among patients with academic and elementary education, respectively. The rate for "blue collar" occupation was 25.1 compared with 18.5 among "academic"/"white collar" occupations combined. Adjusting for sex, obesity, diabetes, metabolic syndrome, peripheral vascular disease, hypertension, and myocardial infarction number, the HF hazard ratios [HRs] were 0.85 (95% confidence interval [CI] 0.70-1.03) and 0.76 (95% CI 0.58-0.99) for high-school and academic education versus elementary education, respectively. HR for "blue collar" compared with "academic"/"white collar" occupations was 1.30 (95% CI 0.97-1.74). CONCLUSIONS: SES indicators (mainly education) are associated with HF incidence among CHD patients. The association is only marginally explained by possible confounders or known mediators such as hypertension and myocardial infarction.

The relatively good outcome of cerebellum-brainstem ischemic strokes.

BACKGROUND: Our clinical experience suggests that the outcome of cerebellum-brainstem ischemic strokes is better than that of hemispheric ischemic strokes. METHODS: Within the setting of 2 national Israeli prospective stroke surveys, we analyzed risk factors, etiology, severity at presentation, and prognosis of first ischemic cerebellum-brainstem stroke (259 patients), comparing with strokes within the anterior circulation (1,029 patients). RESULTS: Patients with cerebellum-brainstem strokes were younger and had less frequently atrial fibrillation and congestive heart failure. Cardioembolic etiology was significantly less prevalent (p < 0.001). Severity at presentation was milder (p < 0.001). At discharge, worsening of the modified Rankin Scale was present in a smaller number of patients (p < 0.001); more returned to their home (p < 0.001). Six-month and 1-year mortality were lower (p < 0.001 for both). Adjusted logistic regression models showed that patients with cerebellum-brainstem strokes had 50% smaller chances of dying (OR 0.55; 95% CI 0.31-0.98) and a smaller chance of worsening of the modified Rankin Scale at discharge (OR 0.61; 95% CI 0.46-0.82). CONCLUSIONS: Cerebellum-brainstem strokes are less frequently cardioembolic, have a less severe presentation, and carry a better immediate and long-term prognosis.

Mortality in heart failure with worsening anemia: a national study.

BACKGROUND: Anemia is common in heart failure (HF), but there is controversy regarding its contribution to morbidity and mortality. OBJECTIVE: To examine the association of mild and severe anemia with acute HF severity and mortality. METHODS: Data were prospectively collected for patients admitted to all departments of medicine and cardiology throughout the country during 2 months in 2003 as part of the Heart Failure Survey in Israel. Anemia was defined as hemoglobin (Hb) < 12 g/dl for women and < 13 g/dl for men; Hb < 10 g/dl was considered severe anemia. Mortality data were obtained from the Israel population registry. Median follow-up was 33.6 months. RESULTS: Of 4102 HF patients, 2332 had acute HF and available hemoglobin data. Anemia was common (55%) and correlated with worse baseline HF. Most signs and symptoms of acute HF were similar among all groups, but mortality was greater in anemic patients. Mortality rates at 6 months were 14.9%, 23.7% and 26.3% for patients with no anemia, mild anemia and severe anemia, respectively (P < 0.0001), and 22.2%, 33.6% and 39.9% at one year, respectively (P < 0.0001). Compared to patients without anemia, multivariable adjusted hazard ratio was 1.35 for mild anemia and 1.50 for severe anemia (95% confidence interval 1.20-1.52 and 1.27-1.77 respectively). CONCLUSIONS: Anemia is common in patients with acuteHF and is associated with increased mortality correlated with the degree of anemia.

Longitudinal bidirectional link between socioeconomic position and health: a national panel survey analysis.

BACKGROUND: Health inequities can stem from socioeconomic position (SEP) leading to poor health (social causation) or poor health resulting in lower SEP (health selection). We aimed to examine the longitudinal bidirectional SEP-health associations and identify inequity risk factors. METHODS: Longitudinal Household Israeli Panel survey participants (waves 1-4), age ≥25 years, were included (N=11 461; median follow-up=3 years). Health rated on a 4-point scale was dichotomised as excellent/good and fair/poor. Predictors included SEP parameters (education, income, employment), immigration, language proficiency and population group. Mixed models accounting for survey method and household ties were used. RESULTS: Examining social causation, male sex (adjusted OR 1.4; 95% CI 1.1 to 1.8), being unmarried, Arab minority (OR 2.4; 95% CI 1.6 to 3.7, vs Jewish), immigration (OR 2.5; 95% CI 1.5 to 4.2, reference=native) and less than complete language proficiency (OR 2.22; 95% CI 1.50 to 3.28) were associated with fair/poor health. Higher education and income were protective, with 60% lower odds of subsequently reporting fair/poor health and 50% lower disability likelihood. Accounting for baseline health, higher education and income were associated with lower likelihood of health deterioration, while Arab minority, immigration and limited language proficiency were associated with higher likelihood. Regarding health selection, longitudinal income was lower among participants reporting poor baseline health (85%; 95% CI 73% to 100%, reference=excellent), disability (94%; 95% CI 88% to 100%), limited language proficiency (86%; 95% CI 81% to 91%, reference=full/excellent), being single (91%; 95% CI 87% to 95%, reference=married), or Arab (88%; 95% CI 83% to 92%, reference=Jews/other). CONCLUSION: Policy aimed at reducing health inequity should address both social causation (language, cultural, economic and social barriers to good health) and health selection (protecting income during illness and disability).

The "obesity paradox": does it persist among Israeli patients with decompensated heart failure? A subanalysis of the Heart Failure Survey in Israel (HFSIS).

BACKGROUND: Earlier studies among heart failure (HF) patients reported a paradox of reduced mortality rates in those with increased body mass index (BMI). Recently, however, it has been shown that obesity was not associated with better prognosis in certain groups. The aim of this study was to evaluate the "obesity paradox" among patients included in the Heart Failure Survey in Israel (HFSIS). METHODS AND RESULTS: Clinical, demographic, and laboratory characteristics of 2,323 patients hospitalized with a diagnosis of acute or decompensated chronic HF in 25 public Israeli hospitals between March 1 and April 30, 2003, were categorized by BMI as: normal weight (18.5-24.9 kg/m(2); n = 837), overweight (25.0-29.9 kg/m(2); n = 877), or obese (≥30.0 kg/m(2); n = 574), excluding 35 patients with BMI <18.5 kg/m(2). Survival over 15 months was inversely related to BMI category. Age-adjusted mortality hazard ratio (HR) was 0.95 (95% confidence interval [CI] 0.79-1.14) for overweight patients and 0.70 (95% CI 0.55-0.88) for obese patients compared with normal-weight patients. After further adjustment for gender, ejection fraction, New York Heart Association functional class, ischemic heart disease, diabetes, hypertension, dyslipidemia, renal function, and medications (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, ß-blocker, spironolactone), obesity was associated with a nonsignificant HR of 0.79 (95% CI 0.59-1.05). Hypertension and dyslipidemia were also paradoxically associated with better survival in our model (HR 0.74, CI 0.59-0.92; and HR 0.77, CI 0.63-0.94; respectively; both P < .05). CONCLUSIONS: Our study falls in line with the obesity paradox observation (in obese but not overweight patients) in a large survey of HF patients, although this finding was not statistically significant on multivariate adjustment analysis.

Fighting a pandemic: sociodemographic disparities and coronavirus disease-2019 vaccination gaps-a population study.

BACKGROUND: Data suggest lower coronavirus disease-2019 (COVID-19) vaccination coverage among minority and disadvantaged groups. We aimed to identify interactions between sociodemographic factors associated with vaccination gaps. METHODS: This population study used Israeli National COVID-19 data (extracted: 10 May 2021). The analysis comprised 6 478 999 individuals age ≥15 years with aggregated area-level data on sex and age distribution and no COVID-19 history. We estimated vaccination hazard and cumulative incidence using the Fine and Gray competing risk model. RESULTS: Older age and higher socioeconomic status (SES) were associated, with stepwise higher cumulative vaccination rates (age 20-24: 67%, age ≥ 75: 96%; SES 1-3: 61%, 4-5: 74.2%, 6-7: 82%, 8-10: 87%). We found the lowest vaccination rates in Arab (65%) and Ultra-Orthodox Jewish (54%) areas. SES modified the association in Arab neighbourhoods, with higher coverage than in the non-Orthodox Jewish reference group in SES 1-3 [adjusted hazard ratio (HR) = 1.06; 95% confidence interval (CI): 1.02-1.11], and gradually lower coverage in higher SES classes (SES 6-7: HR = 0.83; 95% CI: 0.79-0.87). Vaccination rates were also higher among younger Arabs (≤45 years) compared with age counterparts in the reference population group (age 25-34: HR = 1.18; 95% CI: 1.12-1.28) and lower than the reference group among Arabs age ≥45 years. Among Ultra-Orthodox Jews, vaccination HRs remained below one across age and SES classes. CONCLUSIONS: Age and SES modified the association between population group and vaccination coverage. Identifying the interplay between sociodemographic characteristics and the underlying explanations may improve targeted efforts, aimed at closing vaccination coverage gaps and mitigating COVID-19.

Sex related differences in the characteristics and outcomes of heart failure: A sub analysis of heart failure disease management study.

Aims: This is a sub-analysis of a randomized controlled trial on heart failure (HF) disease management (DM) in which patients with HF (N = 1,360; 27.5% women) were assigned randomly to DM (N = 682) or usual care (UC) (N = 678). Study intervention did not significantly affect the rate of hospital admissions or mortality. This study evaluates sex-related differences in baseline characteristics, clinical manifestations, adherence to treatment and outcomes among the study cohort. Methods: Association between sex and hospital admissions and mortality was tested in multivariable models adjusted for the patients' baseline characteristics. The primary composite outcome of the study included time to first HF hospitalization or all-cause mortality. Secondary composite outcome included number of hospital admissions and days of hospitalization, for HF and all other causes. Results: Compared to males, females recruited in the study were on average 3 years older [median age 72 (62, 78) vs. 75 (65, 82), p = 0.001], with higher prevalence of preserved left ventricular function (LVEF ≥50%) and lower frequency of ischemic heart disease (IHD) (p ≤ 0.001). Females had shorter 6-min walking distance and worse quality of life and depression scores at baseline (p < 0.001). The proportion of patients receiving HF recommended medical treatment was similar among females and males. During a median follow-up of 2.7 years (range: 0-5), there were no significant differences between females and males with respect to the time elapsed until the study primary endpoint and its components in univariate analysis [557 (56.5%) males and 218 (58.3%) females were hospitalized for HF or died for any cause; p > 0.05]. Multivariable analysis showed that females were significantly less likely than males to experience the primary outcome [adjusted hazard ratio (HR) = 0.835, 95% CI: 0.699, 0.998] or to die from any cause [adjusted HR = 0.712; 95%CI: 0.560, 0.901]. The sex-related mortality differences were especially significant among patients with non-preserved EF, with IHD or with recent HF hospitalization. Females also had lower rates of all-cause hospital admissions [adjusted rate ratio = 0.798; 95%CI: 0.705, 0.904] and were more likely to adhere to HF medical therapy compared to males. Conclusion: Females with HF fare better than men. Sex related differences were not explained by baseline and morbidity-related characteristics or adherence to medical treatment.

Health Service Utilization Patterns Among Adults With Congenital Heart Disease: A Population-Based Study.

Background Several studies have examined hospitalizations among patients with adult congenital heart disease (ACHD). Few investigated other services or utilization patterns. Our aim was to study service utilization patterns and predictors among patients with ACHD. Methods and Results We identified 11 653 patients with ACHD aged ≥18 years (median, 47 years), through electronic records of 2 large Israeli healthcare providers (2007-2011). The association between patient, disease, and sociogeographic characteristics and healthcare resource utilization were modeled as recurrent events accounting for the competing death risk. Patients with ACHD had high healthcare utilization rates compared with the general population. The highest standardized service utilization ratios (SSRs) were found among patients with complex congenital heart disease including primary care visits (SSR, 1.53; 95% CI, 1.47-1.58), cardiology outpatient visits (SSR, 5.17; 95% CI, 4.69-5.64), hospitalizations (SSR, 6.68; 95% CI, 5.82-7.54), and days in hospital (SSR, 15.37; 95% CI, 14.61-16.12). Adjusted resource utilization hazard increased with increasing lesion complexity. Hazard ratios (HRs) for complex versus simple disease were: primary care (HR, 1.14; 95% CI, 1.06-1.23); cardiology outpatient visits (HR, 1.40; 95% CI, 1.24-1.59); emergency department visits (HR, 1.19; 95% CI, 1.02-1.39); and hospitalizations (HR, 1.75; 95% CI, 1.49-2.05). Effects attenuated with age for cardiology outpatient visits and hospitalizations and increased for emergency department visits. Female sex, geographic periphery, and ethnic minority were associated with more primary care visits, and female sex (HR versus men, 0.89 [95% CI, 0.84-0.94]) and periphery (HR, 0.72 [95% CI, 0.58-0.90] for very peripheral versus very central) were associated with fewer cardiology visits. Arab minority patients also had high hospitalization rates compared with the majority group of Jewish or other patients. Conclusions Healthcare utilization rates were high among patients with ACHD. Female sex, geographic periphery, and ethnicity were associated with less optimal service utilization patterns. Further research should examine strategies to optimize service utilization in these groups.

Factors associated with disparities in out-of-pocket expenditure on dental care: results from two cross-sectional national surveys.

BACKGROUND: Socioeconomic differences in oral health and dental care utilization are a persistent problem in many high-income countries. We evaluated demographic, geographic and socioeconomic factors associated with disparities in households' out-of-pocket expenditure (OOPE) on dental care, and the effect of ongoing dental health reform on these disparities. METHODS: This cross-sectional analysis used data collected in two Israeli Household Expenditure Surveys conducted in 2014 and 2018. OOPE for dental care was estimated using a two-part multivariable model. A logistic regression was used to examine the likelihood of reporting any OOPE, and a log-transformed linear regression model examined the level of expenditure among those who reported any OOPE. RESULTS: In 2018, OOPE on dental care accounted for 22% of total health expenditure for all households, whereas among those who reported dental OOPE it reached 43%. Households with children up to age 14 years reported lower OOPE, regardless of ownership of supplementary health insurance. Owning supplementary health insurance had a heterogeneous effect on the level of OOPE, with a significant increase among those with 0-8 years of education, compared to households without such insurance, but not among those of higher educational level. In 2014, Arab ethnic minority and residence in the country periphery were associated with a greater likelihood for any OOPE and higher amounts of OOPE on dental care. While the gaps between Jewish and Arab households persisted into 2018, those between peripheral and non-peripheral localities seem to have narrowed. CONCLUSIONS: The burden of dental OOPE on Israeli households remains heavy and some disparities still exist, even after the implementation of the dental health reform. Expanding the dental health reform and addressing barriers to preventive dental care, especially among Arabs and those of lower educational level, may help in reducing households' private expenses on dental care.

Apolipoproteins and long-term prognosis in coronary heart disease patients.

BACKGROUND: Apolipoproteins have been recently suggested as an alternative to lipoproteins in prediction of cardiovascular risk. Data regarding their added value in predicting the prognosis of coronary heart disease (CHD) patients are scarce. Our aim was to examine the association between lipoprotein cholesterol and related apolipoproteins with long-term mortality among CHD patients. METHODS: Patients (4,472 men; 624 women, 40-74 years old) with total cholesterol <270 mg/dL (<7.0 mmol/L), high-density lipoprotein cholesterol (HDL-C) <45 mg/dL (<1.16 mmol/L), and triglycerides <300 mg/dL (< or =3.39 mmol/L); excluded from the Bezafibrate Infarction Prevention study; or included in the placebo arm were followed up for a median of 12.3 years. RESULTS: Among both men and women, the association of apolipoproteins A-I and B with mortality was comparable to their corresponding lipids (HDL-C, non-HDL-C respectively). Adjusting for age, disease history, comorbidities, smoking and baseline glucose, the risk associated with the upper versus the lower tertile (lower vs upper for HDL-C and apolipoprotein A-I) among men were 1.04 (95% CI 0.91-1.19) for non-HDL-C; 1.11 (0.97-1.27) for apolipoprotein B; 1.24 (1.09-1.41) for HDL-C; and 1.30 (1.14-1.49) for apolipoprotein A-I. Atherogenic to nonatherogenic particle ratios (lipids or apolipoproteins) were in line with the results of their individual components pointing to a less atherogenic profile among women. Models including either apolipoprotein or cholesterol subfractions had similar predictive power. CONCLUSION: Lipoprotein cholesterol and associated apolipoprotein have comparable ability to predict long-term mortality. The measurement of apolipoproteins constitutes an acceptable alternative to the use of blood lipids in assessing prognosis for CHD patients.

Depression and anxiety are associated with high health care utilization and mortality among adults with congenital heart disease.

BACKGROUND: The significance of depression/anxiety among ACHD patients in terms of health care utilization is unknown and data on the association with mortality are scarce. METHODS: Analyses comprised 8334 ACHD patients, age ≥ 18 years, insured by a large healthcare organization (2007-2011). Depression/anxiety were determined by diagnoses and treatments recorded in the organization database. Adjusted utilization relative rates (RRs) were estimated with negative binomial models and mortality hazard ratios (HRs) with the Cox proportional hazard model. RESULTS: ACHD patients with depression/anxiety (N = 2950, 35%) were more likely to be older (mean ±â€¯SD: 54 ±â€¯17 vs. 45 ±â€¯18 years), women (61% vs. 45%), and have comorbidities than counterparts without depression/anxiety. Following multivariable adjustment, patients with depression/anxiety had more primary care and cardiology clinic visits, more emergency department visits and more hospitalizations. RRs (95% confidence interval) were: 1.31 (1.27-1.35); 1.07 (1.01-1.13); 1.60 (1.46-1.77); and 1.18 (1.08-1.29) respectively, for diagnosis before the study period, and 1.36 (1.31-1.42); 1.22 (1.14-1.30); 1.43 (1.24-1.60) and 1.47 (1.33-1.64), respectively, for diagnosis during the study. Stratifying by age, the highest adjusted primary care and cardiology visit RRs were found among 18-24 years old patients and the lowest among patients ≥65 years. Between 2007 and 2017, 905 patients died. Depression/anxiety were associated with increased mortality risk with adjusted HRs: 1.10 (95% CI: 0.94-1.29) for past diagnosis and 1.40 (1.17-1.67) for study period depression/anxiety diagnosis. CONCLUSIONS: Depression/anxiety in ACHD patients is associated with increased health-care utilization and a higher risk of death. The efficacy of addressing patients' psychosocial needs in optimizing health-care utilization and improving prognosis needs further evaluation.

Beta-blockers for coronary heart disease in chronic kidney disease.

BACKGROUND: Limited data exist on whether the cardioprotective benefit of beta-blockers is modified by the presence of chronic kidney disease (CKD). METHODS: A post hoc analysis of the data from the Bezafibrate Infarction Prevention (BIP) study was performed. CKD was defined according to the Modification of Diet in Renal Disease (MDRD) equation as an estimated glomerular filtration rate (GFR) <60 mL/min/1.73 m(2). The Cox proportional hazard model, including adjustment for propensity score, was used to estimate the hazard ratios (HR) for the composite endpoint combining acute myocardial infarction (AMI) or sudden cardiac death (SCD). RESULTS: In this cohort of 3075 coronary heart disease (CHD) patients, 568 (18.5%) had CKD and 1185 (38.5%) were treated with beta-blockers. A total of 245 (43.1%) CKD patients received beta-blockers at baseline. The mean (+/- SD) estimated GFR in the CKD and non-CKD subgroups was 55 (+/- 4) and 73 (+/- 9) mL/min/1.73 m(2), respectively. After a median follow-up of 6.2 years, the crude incidence rates of AMI or SCD/1000 person years (PY) were 25.6, 21.9, 34.6 and 27.5 for the beta-blockers-/CKD-, beta-blockers+/CKD-, beta-blockers-/CKD+ and beta-blockers+/CKD+ groups, respectively. Compared to patients with beta-blockers-/CKD-, the adjusted HR of AMI or SCD was 0.87 (90% CI 0.71-1.06) for the beta-blockers+/CKD-, 1.35 (90% CI 1.05-1.73) for the beta-blockers-/CKD+ and 1.06 (90% CI 0.76-1.46) for the beta-blockers+/CKD+. CONCLUSIONS: These analyses suggest that the use of beta-blockers is associated with a reduction in event risk in patients with CHD regardless of the presence or absence of CKD.

Effects of peroxisome proliferator-activated receptor ligands, bezafibrate and fenofibrate, on adiponectin level.

OBJECTIVE: Adiponectin is adipose-specific secretory protein and acts as anti-diabetic and anti-atherosclerotic molecule. We previously found peroxisome proliferators response element in adiponectin promoter region, suggesting that peroxisome proliferator-activated receptor (PPAR) ligands elevate adiponectin. Fibrates are known to be PPARalpha ligands and were shown to reduce risks of diabetes and cardiovascular disease. Effect of fibrates on adiponectin has not been clarified, whereas thiazolidinediones enhance adiponectin. Thus, we explored the possibility and mechanism that fibrates enhance adiponectin in humans, mice, and cells. METHODS AND RESULTS: Significant increase of serum adiponectin was observed in bezafibrate-treated subjects compared with placebo group in patients enrolled in The Bezafibrate Infarction Prevention study. Higher baseline adiponectin levels were strongly associated with reduced risk of new diabetes. Fibrates, bezafibrate and fenofibrate, significantly elevated adiponectin levels in wild-type mice and 3T3-L1 adipocytes. Such an effect was not observed in PPARalpha-deficient mice and adipocytes. Fibrates activated adiponectin promoter but failed to enhance its activity when the point mutation occurred in peroxisome proliferators response element site and the endogenous PPARalpha was knocked down by PPARalpha-RNAi. CONCLUSIONS: Our results suggest that fibrates enhance adiponectin partly through adipose PPARalpha and measurement of adiponectin might be a useful tool for searching subjects at high risk for diabetes.

Update on the use of fibrates: focus on bezafibrate.

Low-density lipoprotein-cholesterol (LDL-C) is a well established coronary heart disease (CHD) risk factor. However, the ability of this metabolic risk factor alone to identify individuals at rigk for future CHD events is limited. The raised triglycerides-low high-density lipoprotein-cholesterol (HDL-C) dyslipidaemia was shown to be an important cardiovascular risk factor independently of LDL-C levels. Fibric acid derivatives (fibrates) have been used in clinical practice for more than 2 decades as a class of agents known to decrease triglyceride levels while substantially increasing HDL-C levels. Through peroxisome proliferator-activated alpha-receptors, fibrates have a significant impact on the synthesis of several apolipoproteins and enzymes of lipoprotein metabolism as well as on the expression of several genes involved in fibrinolysis and inflammation. Data from recent primary and secondary prevention clinical trials demonstrate the efficacy of fibrate therapy in patients with the raised triglycerides-low HDL-C dyslipidaemia. This review summarizes current data regarding mechanism of action and the metbolic effects of fibrates, as well as results from major clinical trials on the efficacy of this mode of lipid lowering therapy. In addition, recent data from subgroup analyses of the Bezafibrate Infarction Prevention trial, demonstrating several important metabolic and long-term cardiovascular effects of bezafibrate therapy, are detailed.

C-reactive protein, bezafibrate, and recurrent coronary events in patients with chronic coronary heart disease.

BACKGROUND: Elevated C-reactive protein (CRP) levels are related to increased coronary risk in healthy subjects and in patients with acute coronary syndromes. The aims of the present study were to assess the following: (1) the association between CRP and subsequent coronary risk in patients with chronic coronary heart disease (CHD), (2) the effect of long-term bezafibrate treatment on CRP levels, and (3) to evaluate the consequences of change in CRP level over time on subsequent risk. METHODS: Patients with chronic CHD (n = 3122) were recruited to a secondary prevention study that assessed the efficacy of bezafibrate versus placebo. C-reactive protein was measured in plasma samples collected at prerandomization and after 2 years of follow-up. Mean follow-up time was 6.2 years. Primary end point was fatal and nonfatal myocardial infarction and sudden cardiac death. RESULTS: Increased baseline CRP levels were associated with increased risk (hazard ratios [HRs] per unit of log-transformed CRP level change) of myocardial infarction (HR 1.17, 95% CI 1.03-1.33), the primary end point (HR 1.19, 95% CI 1.06-1.34), total death (HR 1.19, 95% CI 1.02-1.40) and cardiac death (HR 1.28, 95% CI 1.04-1.59). After 2 years, CRP levels increased by 3.0% (from a mean level of 3.44 mg/L) in the bezafibrate group and by 3.7% (from 3.49 mg/L) in the placebo group. C-reactive protein levels after 2 years were associated with increased subsequent cardiovascular risk. CONCLUSIONS: Baseline CRP and 2-year CRP levels were associated with subsequent risk of myocardial infarction and death in patients with chronic CHD. Bezafibrate did not reduce CRP levels as compared with placebo.