Yariv Gerber

Trends in Incidence, Severity, and Outcome of Hospitalized Myocardial Infarction

Background— In 2000, the definition of myocardial infarction (MI) changed to rely on troponin rather than creatine kinase (CK) and its MB fraction (CK-MB). The implications of this change on trends in MI incidence and outcome are not defined. Methods and Results— This was a community study of 2816 patients hospitalized with incident MI from 1987 to 2006 in Olmsted County, Minnesota, with prospective measurements of troponin and CK-MB from August 2000 forward. Outcomes were MI incidence, severity, and survival. After troponin was introduced, 278 (25%) of 1127 incident MIs met only troponin-based criteria. When cases meeting only troponin criteria were included, incidence did not change between 1987 and 2006. When restricted to cases defined by CK/CK-MB, the incidence of MI declined by 20%. The incidence of non–ST-segment elevation MI increased markedly by relying on troponin, whereas that of ST-segment elevation MI declined regardless of troponin. The age- and sex-adjusted hazard ratio of death within 30 days for an infarction occurring in 2006 (compared with 1987) was 0.44 (95% confidence interval, 0.30 to 0.64). Among 30-day survivors, survival did not improve, but causes of death shifted from cardiovascular to noncardiovascular (P=0.001). Trends in long-term survival among 30-day survivors were similar regardless of troponin. Conclusions— Over the last 2 decades, a substantial change in the epidemiology of MI occurred that was only partially mediated by the introduction of troponin. Non–ST-segment elevation MIs now constitute the majority of MIs. Although the 30-day case fatality improved markedly, long-term survival did not change, and the cause of death shifted from cardiovascular to noncardiovascular.

Central corneal thickness measurement with the Pentacam Scheimpflug system, optical low-coherence reflectometry pachymeter, and ultrasound pachymetry

PURPOSE: To assess the intraoperator repeatability and interoperator reproducibility of central corneal thickness measurements by the Pentacam Scheimpflug imaging system (Oculus) and the optical low‐coherence reflectometer (OLCR) pachymeter (Haag‐Streit) and to compare them with those of ultrasound (US) pachymetry. SETTING: Assaf Harofe Medical Center Ophthalmology Outpatient Clinic, Zerifin, Israel. METHODS: Repeatability was determined from 10 successive measurements in each of 4 healthy patients. Reproducibility for the Pentacam Scheimpflug system was determined from measurements by 2 operators in each of 24 patients; in these 24 patients, central corneal thickness measurements were compared between the Pentacam and US pachymetry. For the OLCR pachymeter, reproducibility was determined from measurements by 2 operators in each of 16 patients, in whom central corneal thickness was also measured with the Pentacam. RESULTS: Mean coefficient of repeatability was 0.84% for the Pentacam Scheimpflug system and 0.33% for the OLCR pachymeter. For the Pentacam, the coefficient of interoperator reproducibility was 1.10% and the 95% limits of agreement were −10.2 μm to +11.9 μm. Mean difference between Pentacam and US was 6.09 μm. For the OLCR pachymeter, the coefficient of interoperator reproducibility was 0.59% and the 95% limits of agreement were −5.4 μm to +7.0 μm. Mean difference between central corneal thickness values obtained with the OLCR pachymeter and Pentacam Scheimpflug system was 1.7 μm. CONCLUSIONS: Objective, noncontact measurement of central corneal thickness with the Pentacam Scheimpflug system and OLCR pachymeter was convenient and yielded excellent intraoperator repeatability and interoperator reproducibility. Central corneal thickness values obtained with the Pentacam were similar to those obtained with both the OLCR pachymeter and an US pachymeter. Further research is needed to corroborate whether central corneal thickness measurements by the Pentacam and OLCR devices can be used interchangeably and are more clinically useful than US pachymetry.

Death in Heart Failure: a Community Perspective

Background—Mortality in patients with heart failure (HF) remains high, but causes of death are incompletely defined. As HF is a heterogeneous syndrome categorized according to the ejection fraction (EF), the association between EF and causes of death is important, yet elusive. Methods and Results—Community subjects with HF were classified according to the preserved (≥50%) and the reduced EF (<50%). Deaths were classified as due to coronary heart disease and other cardiovascular and noncardiovascular diseases. Among 1063 persons with HF, 45% had preserved EF with fewer cardiovascular risk factors and less coronary disease than those with reduced EF. At 5 years, survival was 45% (95% CI, 43% to 49%), and 43% of the deaths were noncardiovascular. The leading cause of death in subjects with preserved EF was noncardiovascular disease (49%) versus coronary heart disease (43%) for subjects with reduced EF. The proportion of cardiovascular deaths decreased from 69% in 1979–1984 to 40% in 1997–2002 (P=0.007) among subjects with preserved EF, which is in contrast to a modest change among those with reduced EF (77% to 64%, P=0.08). Advanced age, male sex, diabetes, smoking, and kidney disease were associated with an increased risk of all-cause and cardiovascular deaths. After adjustment, preserved EF was associated with a lower risk of cardiovascular death but not all-cause death. Conclusions—Community subjects with HF experience a persistently high mortality, and a large proportion of deaths is noncardiovascular. Cardiovascular disease before death is less in subjects with preserved EF, and they are less likely to experience cardiovascular deaths compared with those with reduced EF. In those with preserved EF, the proportion of cardiovascular deaths declined over time.

A Contemporary Appraisal of the Heart Failure Epidemic in Olmsted County, Minnesota, 2000 to 2010

IMPORTANCE Heart failure (HF) is commonly referred to as an epidemic, posing major clinical and public health challenges. Yet, contemporary data on its magnitude and implications are scarce. OBJECTIVE To evaluate recent trends in HF incidence and outcomes overall and by preserved ejection fraction (HFpEF) or reduced ejection fraction (HFrEF). DESIGN, SETTING, AND PARTICIPANTS Incidence rates of HF in Olmsted County, Minnesota (population, approximately 144,248), between January 1, 2000, and December 31, 2010, were assessed. MAIN OUTCOMES AND MEASURES Patients identified with incident HF (n = 2762) (mean age, 76.4 years; 43.1% male) were followed up for all-cause and cause-specific hospitalizations (through December 2012) and death (through March 2014). RESULTS The age- and sex-adjusted incidence of HF declined substantially from 315.8 per 100,000 in 2000 to 219.3 per 100,000 in 2010 (annual percentage change, -4.6), equating to a rate reduction of 37.5% (95% CI, -29.6% to -44.4%) over the last decade. The incidence declined for both HF types but was greater (interaction P = .08) for HFrEF (-45.1%; 95% CI, -33.0% to -55.0%) than for HFpEF (-27.9%; 95% CI, -12.9% to -40.3%). Mortality was high (24.4% for age 60 years and 54.4% for age 80 years at 5 years of follow-up), frequently ascribed to noncardiovascular causes (54.3%), and did not decline over time. The risk of cardiovascular death was lower for HFpEF than for HFrEF (multivariable-adjusted hazard ratio, 0.79; 95% CI, 0.67-0.93), whereas the risk of noncardiovascular death was similar (1.07; 95% CI, 0.89-1.29). Hospitalizations were common (mean, 1.34; 95% CI, 1.25-1.44 per person-year), particularly among men, and did not differ between HFpEF and HFrEF. Most hospitalizations (63.0%) were due to noncardiovascular causes. Hospitalization rates for cardiovascular causes did not change over time, whereas those for noncardiovascular causes increased. CONCLUSIONS AND RELEVANCE Over the last decade, the incidence of HF declined substantially, particularly for HFrEF, contrasting with no apparent change in mortality. Noncardiovascular conditions have an increasing role in hospitalizations and remain the most frequent cause of death. These results underscore the need to augment disease-centric management approaches with holistic strategies to reduce the population burden of HF.

Secular trends in deaths from cardiovascular diseases: A 25-year community study

Background— Although age-adjusted cardiovascular disease (CVD) mortality has declined over the past decades, controversies remain about whether this trend was similar across locations of death and disease categories and about the existence of age and sex disparities. Methods and Results— We examined CVD mortality trends in Olmsted County, Minnesota, between 1979 and 2003 using the categories defined by the American Heart Association, including coronary heart disease (CHD), non-CHD diseases of the heart, and noncardiac circulatory diseases. Data on demographics, cause, and location of death of all 6378 residents who died of CVD were analyzed. Although decreases in the age-adjusted rates occurred in all groups, the magnitude of the decline varied widely. Lesser annual declines were noted in out-of-hospital than in-hospital deaths (1.8% versus 4.8%; P<0.001), in older than in younger persons (1.5% at age ≥85 years versus 3.9% for those ≤74 years of age; P<0.001), and in women relative to men (2.5% versus 3.3%; P=0.007). Furthermore, although CHD showed a marked annual decrease (3.3%), more modest decrements were found for non-CHD diseases of the heart (2.1%) and noncardiac circulatory diseases (2.4%) (P=0.02 and P=0.04 for the comparison with CHD decline, respectively). Conclusions— Over the past 25 years, CVD mortality declined markedly in the community, but there were large disparities in the magnitude of the decline, resulting in a shift in the distribution toward out-of-hospital and non-CHD deaths. Further reduction in CVD mortality will require strategies directed at elderly persons and women, in whom out-of-hospital rates have improved only minimally.

Long-term persistence with statin treatment in a not-for-profit health maintenance organization: a population-based retrospective cohort study in Israel.

BACKGROUND Although discontinuing lipid-lowering treatment can cause preventable morbidity, previously published reports have indicated considerable variability in persistence with statin use. In general, such reports have been limited by short follow-up periods and modest study populations. OBJECTIVES The aims of this study were to assess long-term persistence with statins and to identify the sociodemographic, clinical, and pharmacotherapy-related factors associated with long-term persistence with statin treatment in first-time users in Israel. METHODS This retrospective cohort study used data from adult enrollees of a not-for-profit health maintenance organization and from death certificates in Israel. Eligible patients initiated statin treatment between 1998 and 2006. Persistence was assessed separately in patients with no indication of a cardiovascular disease (primary prevention) or coronary artery disease (secondary prevention). Treatment persistence and proportion of days covered (PDC) were measured using the interval between the date of the first prescription dispensation (index date) and the point of discontinuation. RESULTS Data from 229,918 patients were included (primary prevention, 136,052; secondary prevention, 93,866). The PDC was significantly higher in the secondary-prevention group compared with the primary-prevention group (59% vs 45%; P < 0.001). In both cohorts, persistence continually diminished from the index date through follow-up, with > or = 75% of patients discontinuing statin therapy by 2 years. Baseline predictors of discontinuation of statin treatment included younger age, female sex, lower socioeconomic status (SES), absence of diabetes or hypertension, no concurrent use of beta-blockers or angiotensin-converting enzyme inhibitors, and less health service utilization. New immigrants and patients in the primary-prevention group who had a baseline low-density lipoprotein cholesterol concentration <130 mg/dL were at increased risk for treatment discontinuation. CONCLUSION In this study in these patients receiving first-time statin treatment in Israel, we found poor persistence with statins among both the primary- and secondary-prevention cohorts, especially among new immigrants and patients with low SES despite low out-of-pocket prescription costs and free access to health services.

Smoking status and long-term survival after first acute myocardial infarction a population-based cohort study.

OBJECTIVES We compared long-term survival after acute myocardial infarction (AMI) of never-smokers, pre-AMI quitters, post-AMI quitters, and persistent smokers and assessed whether cigarette reduction among persistent smokers is associated with lower mortality. BACKGROUND Quitting smoking has been shown to improve outcome after AMI. However, longitudinal cohort data with repeated assessments of smoking and information on multiple confounders are lacking. Moreover, little is known about the importance, if any, of reductions in the amount smoked. METHODS Consecutive patients < or = 65 years of age, discharged from 8 hospitals in central Israel after first AMI in 1992 to 1993, were followed through 2005. Extensive data, including self-reported smoking habits, were obtained at baseline and 4 times during follow-up. Cox proportional hazards regressions were used to assess the hazard ratios (HRs) for death associated with smoking categories modeled as time-dependent variables. RESULTS At baseline, smokers were younger, more likely to be male, and had a lower prevalence of hypertension and diabetes than nonsmokers. Over a median follow-up of 13.2 years, 427 deaths occurred in 1,521 patients. The multivariable-adjusted HRs for mortality were 0.57 (95% confidence interval [CI]: 0.43 to 0.76) for never-smokers, 0.50 (95% CI: 0.36 to 0.68) for pre-AMI quitters, and 0.63 (95% CI: 0.48 to 0.82) for post-AMI quitters, compared with persistent smokers. Among persistent smokers, upon multivariable adjustment including pre-AMI intensity, each reduction of 5 cigarettes smoked daily after AMI was associated with an 18% decline in mortality risk (p < 0.001). CONCLUSIONS Smoking cessation either before or after AMI is associated with improved survival. Among persistent smokers, reducing intensity after AMI appears to be beneficial.

Lipoprotein-Associated Phospholipase A2 and Prognosis After Myocardial Infarction in the Community

Objective—We evaluated the role of lipoprotein-associated phospholipase A2 (Lp-PLA2), an inflammatory biomarker, in defining risk after myocardial infarction (MI). Methods and Results—Olmsted County, Minn, residents who experienced an MI meeting standardized criteria between 2003 and 2005 (n=271) were prospectively identified and followed. Lp-PLA2 levels were measured at baseline and evaluated along with traditional risk indicators. Lp-PLA2 was modestly associated with total and low-density lipoprotein cholesterol, smoking, and age (inversely) but not with MI characteristics or severity, comorbidities, C-reactive protein, or the time from symptom onset to blood sampling. During the first year of follow-up, 42 deaths occurred. The survival estimates (95% confidence intervals [CI]) at 1 year were 92% (86% to 98%), 85% (78% to 93%), and 74% (65% to 84%) in the lowest, middle, and upper Lp-PLA2 tertiles, respectively (P=0.007). After adjustment for age and sex, the hazard ratios for death in the middle and upper Lp-PLA2 tertiles were 2.20 (95% CI: 0.88 to 5.54) and 4.93 (95% CI: 2.10 to 11.60), compared with the lowest tertile, respectively (Ptrend<0.001). Further adjustment for other risk indicators resulted in even stronger associations. Lp-PLA2 also contributed to risk discrimination as indicated by the increases in the area under the receiver operating characteristic curves obtained in each of the models examined (all P≤0.05). Conclusions—Among community subjects presenting with MI, increased Lp-PLA2 levels measured early after MI are strongly and independently associated with mortality and provide incremental value in risk discrimination over traditional predictors.

Effect of diabetes mellitus on biomechanical parameters of the cornea.

PURPOSE: To compare parameters of biomechanical response of the human cornea measured as corneal hysteresis (CH) and corneal resistance factor (CRF) in patients with diabetes mellitus and healthy control subjects. SETTING: Department of Ophthalmology, Assaf Harofeh Medical Center, Zerifin, Israel. METHODS: In the right eye of each participant, the CH, CRF, Goldmann‐correlated intraocular pressure (IOPg), and corneal‐compensated intraocular pressure (IOPcc) were measured with the Ocular Response Analyzer. Central corneal thickness (CCT) was measured by ultrasonic pachymetry and intraocular pressure by Goldmann applanation tonometry (IOP GAT). Findings were compared between the 2 groups (control and diabetic). RESULTS: Forty diabetic patients (17 women, 23 men) and 40 healthy subjects (19 women, 21 men) were prospectively recruited. The mean CH was 9.3 mm Hg ± 1.4 (SD) and 10.7 ± 1.6 mm Hg and the mean CRF was 9.6 ± 1.6 mm Hg and 10.9 ± 1.7 mm Hg in the control group and diabetic group, respectively (both P < .0001). Diabetic corneas were significantly thicker (P = .019); the mean CCT was 530.3 ± 35.9 μm in the control group and 548.7 ± 33.0 μm in the diabetic group. The CH and CRF remained significantly different in multivariate analysis that included CCT. There was no statistically significant difference between the 2 groups in IOPcc, IOPg, or IOP GAT measurements. CONCLUSIONS: Diabetes mellitus affected biomechanical parameters of the human corneas, including increased CH, CRF, and CCT. Whether this observation has implications in the clinical management and understanding of corneal ectasia and glaucoma requires further study.

Multimorbidity in Heart Failure: A Community Perspective

BACKGROUND Comorbidities are a major concern in heart failure, leading to adverse outcomes, increased health care utilization, and excess mortality. Nevertheless, the epidemiology of comorbid conditions and differences in their occurrence by type of heart failure and sex are not well documented. METHODS The prevalence of 16 chronic conditions defined by the US Department of Health and Human Services was obtained among 1382 patients from Olmsted County, Minn. diagnosed with first-ever heart failure between 2000 and 2010. Heat maps displayed the pairwise prevalences of the comorbidities and the observed-to-expected ratios for occurrence of morbidity pairs by type of heart failure (preserved or reduced ejection fraction) and sex. RESULTS Most heart failure patients had 2 or more additional chronic conditions (86%); the most prevalent were hypertension, hyperlipidemia, and arrhythmias. The co-occurrence of other cardiovascular diseases was common, with higher prevalences of co-occurring cardiovascular diseases in men compared with women. Patients with preserved ejection fraction had one additional condition compared with those with reduced ejection fraction (mean 4.5 vs 3.7). The patterns of co-occurring conditions were similar between preserved and reduced ejection fraction; however, differences in the ratios of observed-to-expected co-occurrence were apparent by type of heart failure and sex. In addition, some psychological and neurological conditions co-occurred more frequently than expected. CONCLUSION Multimorbidity is common in heart failure, and differences in co-occurrence of conditions exist by type of heart failure and sex, highlighting the need for a better understanding of the clinical consequences of multiple chronic conditions in heart failure patients.