Glaucoma Prediction Models Based on Ocular and Systemic Findings.

INTRODUCTION: Our aim was to explore the impact of various systemic and ocular findings on predicting the development of glaucoma. METHODS: Medical records of 37,692 consecutive patients examined at a single medical center between 2001 and 2020 were analyzed using machine learning algorithms. Systemic and ocular features were included. Univariate and multivariate analyses followed by CatBoost and Light gradient-boosting machine prediction models were performed. Main outcome measures were systemic and ocular features associated with progression to glaucoma. RESULTS: A total of 7,880 patients (mean age 54.7 ± 12.6 years, 5,520 males [70.1%]) were included in a 3-year prediction model, and 314 patients (3.98%) had a final diagnosis of glaucoma. The combined model included 185 systemic and 42 ocular findings, and reached an ROC AUC of 0.84. The associated features were intraocular pressure (48.6%), cup-to-disk ratio (22.7%), age (8.6%), mean corpuscular volume (MCV) of red blood cell trend (5.2%), urinary system disease (3.3%), MCV (2.6%), creatinine level trend (2.1%), monocyte count trend (1.7%), ergometry metabolic equivalent task score (1.7%), dyslipidemia duration (1.6%), prostate-specific antigen level (1.2%), and musculoskeletal disease duration (0.5%). The ocular prediction model reached an ROC AUC of 0.86. Additional features included were age-related macular degeneration (10.0%), anterior capsular cataract (3.3%), visual acuity (2.0%), and peripapillary atrophy (1.3%). CONCLUSIONS: Ocular and combined systemic-ocular models can strongly predict the development of glaucoma in the forthcoming 3 years. Novel progression indicators may include anterior subcapsular cataracts, urinary disorders, and complete blood test results (mainly increased MCV and monocyte count).

Prevalence of common and rare ophthalmic findings in adults attending a medical survey institute.

PURPOSE: To examine the ophthalmic data from a large database of people attending a general medical survey institute, and to investigate ophthalmic findings of the eye and its adnexa, including differences in age and sex. METHODS: Retrospective analysis including medical data of all consecutive individuals whose ophthalmic data and the prevalences of ocular pathologies were extracted from a very large database of subjects examined at a single general medical survey institute. RESULTS: Data were derived from 184,589 visits of 3676 patients (mean age 52 years, 68% males). The prevalence of the following eye pathologies were extracted. Eyelids: blepharitis (n = 4885, 13.3%), dermatochalasis (n = 4666, 12.7%), ptosis (n = 677, 1.8%), ectropion (n = 73, 0.2%), and xanthelasma (n = 160, 0.4%). Anterior segment: pinguecula (n = 3368, 9.2%), pterygium (n = 852, 2.3%), and cataract or pseudophakia (n = 9381, 27.1%). Cataract type (percentage of all phakic patients): nuclear sclerosis (n = 8908, 24.2%), posterior subcapsular (n = 846, 2.3%), and capsular anterior (n = 781, 2.1%). Pseudophakia was recorded for 697 patients (4.6%), and posterior subcapsular opacification for 229 (0.6%) patients. Optic nerve head (ONH): peripapillary atrophy (n = 4947, 13.5%), tilted disc (n = 3344, 9.1%), temporal slope (n = 410, 1.1%), ONH notch (n = 61, 0.2%), myelinated nerve fiber layer (n = 94, 0.3%), ONH drusen (n = 37, 0.1%), optic pit (n = 3, 0.0%), and ON coloboma (n = 4, 0.0%). Most pathologies were more common in males except for ONH, and most pathologies demonstrated a higher prevalence with increasing age. CONCLUSIONS: Normal ophthalmic data and the prevalences of ocular pathologies were extracted from a very large database of subjects seen at a single medical survey institute.

Cardiovascular Risk Factors and Physical Fitness Among Subjects with Asymptomatic Colonic Diverticulosis.

BACKGROUND: The association between diverticular disease and atherosclerotic cardiovascular disease (ASCVD) has been demonstrated previously, mainly in symptomatic subjects. AIMS: To evaluate 10 years cardiovascular risk, exercise performance and association to ASCVD among subjects with asymptomatic diverticulosis. METHODS: A retrospective cross-sectional cohort of self-referred participants in a medical screening program, who underwent a screening colonoscopy. Demographics, clinical and laboratory variables, ASCVD score, and metabolic equivalents (METs) during treadmill stress test were compared between subjects with and without diverticulosis as diagnosed on screening colonoscopy. RESULTS: 4586 participants underwent screening colonoscopy; 799 (17.4%) had diverticulosis. Among 50-69 yo participants, diverticulosis subjects had a higher ASCVD score compared to non-diverticulosis subjects. Exercise performance was comparable between the groups, across all age groups. Using logistic regression analysis, advanced age group (50-59 yo Adjusted odds ratio (AOR) [95% confidence interval (CI)] 2.57 (1.52-4.34), p < 0.001; 60-69 yo, AOR 2.87 (2.09-3.95), p < 0.001; ≥ 70 yo AOR 4.81 (3.23-7.15), p < 0.001; compared to < 50 yo age group), smoking [AOR 1.27 (1.05-1.55), p = 0.016], HTN [AOR 1.27 (1.03-1.56), p = 0.022], obesity [AOR 1.36 (1.06-1.74), p = 0.014] and male sex [AOR 1.29 (1.02-1.64), p = 0.036] were associated with diverticular detection during screening colonoscopy. Among males, achieving METs score ≥ 10 was inversely associated with diverticular detection during screening colonoscopy [AOR 0.64 (0.43-0.95), p = 0.027]. CONCLUSIONS: Ten years probability for ASCVD estimated by the ASCVD score is higher among subjects with asymptomatic diverticulosis compared to subjects without diverticulosis. Improved exercise performance is demonstrated for the first time to correlate with decreased probability for diverticular disease in screening colonoscopy.

Yield of targeted genotyping for the recurring pathogenic variants in cancer susceptibility genes in a healthy, multiethnic Israeli population.

BACKGROUND: Several recurring pathogenic variants in BRCA1/BRCA2 and other cancer susceptibility genes are encountered in ethnically diverse Jewish populations. The yield of genotyping for these recurring pathogenic variants in healthy Israeli individuals unselected for ethnicity, sex, or a family history of cancer has not been previously reported. METHODS: Individuals voluntarily participating in annual medical surveillance at the Institute of Medical Screening of Sheba Medical Center were offered genotyping for predominant pathogenic variants in BRCA1/BRCA2 and recurring variants in CHEK2, MUTYH, APC, and the Lynch syndrome genes via a chip-based assay at the oncogenetic service of Sheba Medical Center from May 15, 2018, to December 15, 2020. All study participants were unrelated to one another. The study was approved by the Sheba ethics committee. RESULTS: Overall, 1764 individuals, including 1008 females (57%), with a mean age of 54.2 years (range, 25-86 years) were genotyped. The yield of the testing was 4% (71 of 1764), and it was higher in Ashkenazi Jews (AJs) and mixed AJ-non-AJ participants (4.75% [58 of 1222]; 1.8% for BRCA1/BRCA2 pathogenic variants) than non-AJ patients (2.2% [9 of 401]; 1% for BRCA1 pathogenic variants). When BRCA1/BRCA2 pathogenic variants were excluded, 2.44% carried low-penetrance variants, including CHEK2 c.1283C>T (n = 3), APC c.3920T>A (n = 36), and heterozygous MUTYH c.1187G>A (n = 4). A family history of cancer was not associated with a higher yield of pathogenic variant detection. CONCLUSIONS: The observed rates of positive genotyping in a healthy, unselected, multiethnic Israeli population warrant consideration of the inclusion of targeted genotyping of selected pathogenic variants in high-penetrance and perhaps lower penetrance cancer susceptibility genes for all Jewish individuals in Israel, regardless of their ethnicity or family history of cancer.

An impact of lipid profile and lipid lowering drugs on ≥70 year olds of an upper socioeconomic class: a retrospective cohort study.

BACKGROUND: Life expectancy has greatly increased, generating an improvement in screening programs for disease prevention, lifesaving drugs and medical devices. The impact of lowering low-density lipoprotein cholesterol (LDL-C) in the very elderly is not well-established. Our aim was to explore the association of LDL-C, high density lipoprotein cholesterol (HDL-C) and lipid lowering drugs (LLDs) on cognitive decline, malignancies and overall survival. METHODS: This was a retrospective cohort study. Our study comprised 1498 (72.7%) males and 561 (27.3%) females, aged ≥70 who had attended the Institute for Medical Screening (IMS), Sheba Medical Center, Israel at least twice during 2013-2019. Data were obtained from the computerized database of the IMS. A manual quality control to identify potential discrepancies was performed. RESULTS: Overall, 6.3% of the subjects treated with LLDs (95/1421) versus 4.2% not treated (28/638), cognitively declined during the study years. No statistically significant effects of LDL-C, HDL-C and LLDs on cognitive decline were observed after correcting for age, prior stroke and other vascular risk factors. With regard to cancer, after adjusting for confounders and multiple inferences, no definite relationships were found. CONCLUSIONS: This analysis of an elderly, high socioeconomic status cohort suggests several relationships between the use of LLDs and health outcomes, some beneficial, especially, with regard to certain types of cancer, but with a higher risk of cognitive decline. Further studies are warranted to clarify the health effects of these medications in the elderly.

Physical fitness mediates the association between age and cognition in healthy adults.

BACKGROUND: Physical fitness is an important contributor to healthy aging that improves cognition. Older adults who engage in cardiorespiratory fitness activities show less cognitive decline. AIMS: To examine whether physical fitness acts as a potential protective mechanism shielding against the negative associations between age and cognition. Specifically, we examined whether physical fitness mediates the relationship between age and processing speed. METHODS: 114 (M = 63.80, SD = 10.63) senior executives completed a computerized cognitive battery composed of four processing speed tasks. Level of physical fitness was assessed on a treadmill stress test and reported in metabolic equivalents (METs). RESULTS: Older age was associated with slower processing speed (r = 0.25, p = 0.007), whereas greater physical fitness was associated with faster processing speed (r = -0.30, p = 0.001). Path analysis indicated that the association between age and processing speed was fully mediated by the level of physical fitness (Indirect effect: ß = 0.10, p = 0.008; Direct effect: ß = 0.16, p = 0.20). CONCLUSIONS AND DISCUSSION: The findings indicate that physical fitness is a strong mediator of the relationship between age and processing speed and imply that physical fitness makes a major contribution to cognitive reserve during the aging process. The results may suggest that the decrease in physical fitness during aging may partially account for slower cognitive processing.

Correction: Population screening for BRCA1/BRCA2 founder mutations in Ashkenazi Jews: proactive recruitment compared with self-referral.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Clinically significant incidental QTc prolongation is subject to within-individual variability.

BACKGROUND: Prolonged QTc interval observed in daily practice is often deemed to be drug induced and might result in drug discontinuation, with possible therapeutic consequences. However, whether clinically significant prolonged QTc may be due to within-individual variability occurs has yet to be described. METHODS: A retrospective cohort study documenting within-individual QTc variability in subjects attending annual routine medical evaluation. At each visit, QT interval was measured and corrected for heart rate using Bazett and three other commonly used formulae. Outcome measures were rates of ΔQTc ≥60 msec, absolute QTc ≥500 msec and QTc ≥25% from baseline. RESULTS: A total of 188 subjects [54 (29%)] females were recruited. Mean age at first ECG was 54 ± 12.8 years with mean time interval of 12.2 ± 1.1 months between measurements. Mean Bazett QTc was higher compared to the other 3 formulae: 412 ± 20 vs. 400 ± 16 msec. Using Bazett formula, 18/188 (9.6%) and 5/188 (2.7%) subjects showed at least one measurement with ΔQTc ≥60 msec and QTc ≥500 msec, respectively. Of the former, 5/18 (27.8%) showed QTc ≥25% prolongation. In multivariate analysis, QTc ≥500 msec was significantly associated with number of measurements (HR: 5.01, 95%CI: 1.21-20.78, p = .026) with no effect of other known confounders. Lower rates were demonstrated with the other three formulae. CONCLUSION: In clinical practice, significant prolonged QTc may be attributed to within-individual variability, particularly when adjusting the QT interval with Bazett correction. This should be taken into consideration when decisions on changing current drug regimens are to be made.

High fitness might be associated with the development of new-onset atrial fibrillation in obese non-athletic adults.

BACKGROUND: Data on the association between AF and fitness are conflicting. OBJECTIVES: The aim of this analysis was to investigate the association between fitness, obesity and incidence of atrial fibrillation (AF) among apparently healthy non-athlete adults. METHODS: We investigated 20 410 self-referred subjects who were annually screened in a tertiary medical centre. All subjects were free of AF and completed maximal exercise stress test according to the Bruce protocol at baseline. Fitness was categorised into age- and sex-specific quintiles (Q) according to the treadmill time. Subjects were categorised to low (Q1-Q2) and high fitness (Q3-5) groups. The primary end point was new-onset AF during follow-up. RESULTS: Mean age was 48 ± 10 years and 72% were men. A total of 463 (2.3%) events occurred during an average follow-up of 8 ± 5 years corresponding to an AF event rate of 0.3% per person year. Univariate and multivariate models showed that AF risk was similar in both fitness groups. However, AF event rate was 0.55% per person year among high fitness obese subjects, compared with 0.31% for low fitness obese subjects (P < .01). Subgroup interaction analysis showed that AF risk is obesity-dependent, such that in the obese group (≥30 kg/m2 ) high fitness was independently associated with a significant 79% increased AF risk (95% CI 1.15-2.78; P = .01), whereas among non-obese subjects the rate of events was similar between both fitness groups (P for interaction = (.02)). CONCLUSIONS: Our findings suggest that high fitness might be associated with increased AF risk among obese subjects.

The association of total cholesterol with processing speed is moderated by age in mid- to late-age healthy adults.

OBJECTIVES: To investigate the nature of the association of normal levels of total cholesterol with cognitive function and the contribution of age to this association. METHODS: A sample of 61 senior executives, who were summoned for an annual medical examination with approximately four measurements of total cholesterol during 4 years, were examined with a computerized cognitive battery assessing mental processing speed as a sensitive measure of cognitive decline. We examined the association of total cholesterol with processing speed and the moderating effect of age on this association. RESULTS: A multiple regression analysis yielded a significant interaction between cholesterol and age for processing speed (p = .045). In order to examine the source of the interaction, simple slope analysis was performed. A significant negative high correlation was found for young subjects (p = .021), while no significant correlation was observed at middle (p = .286) or older (p = .584) age. The difference in slopes was robust to adjustment for potential confounding factors, including body mass index, and fasting glucose. CONCLUSIONS: Within the normal range, higher total cholesterol levels were associated with better processing speed in younger ages and this association diminished with increasing age. Our findings highlight the important role of brain cholesterol in good cognitive functioning.

Population screening for BRCA1/BRCA2 founder mutations in Ashkenazi Jews: proactive recruitment compared with self-referral.

PURPOSE: Population screening of three common BRCA1/BRCA2 mutations in Ashkenazi Jews (AJ) apparently fulfills screening criteria. We compared streamlined BRCA screening via self-referral with proactive recruitment in medical settings. METHODS: Unaffected AJ, age ≥25 years without known familial mutations, were either self-referred or recruiter-enrolled. Before testing, participants received written information and self-reported family history (FH). After testing, both non-carriers with significant FH and carriers received in-person genetic counseling. Psychosocial questionnaires were self-administered 1 week and 6 months after enrollment. RESULTS: Of 1,771 participants, 58% were recruiter-enrolled and 42% were self-referred. Screening uptake was 67%. Recruited enrollees were older (mean age 54 vs. 48, P < 0.001) and had less suggestive FH (23 vs. 33%, P < 0.001). Of 32 (1.8%) carriers identified, 40% had no significant FH. Post-test counseling compliance was 100% for carriers and 89% for non-carrier women with FH. All groups expressed high satisfaction (>90%). At 6 months, carriers had significantly increased distress and anxiety, greater knowledge, and similar satisfaction; 90% of participants would recommend general AJ BRCA screening. CONCLUSION: Streamlined BRCA screening results in high uptake, very high satisfaction, and no excess psychosocial harm. Proactive recruitment captured older women less selected for FH. Further research is necessary to target younger women and assess other populations.Genet Med advance online publication 08 December 2016.

Gender disparities in the functional significance of anemia among apparently healthy adults.

BACKGROUND: Data on the functional impact of anemia on cardiorespiratory fitness (CRF) and survival in healthy individuals are limited. Our aim was to evaluate the association between anemia thresholds, low CRF, and survival in otherwise healthy adults. METHODS: Study population included 16 334 apparently healthy subjects attending annual periodic health screening examinations (71 200 annual visits), including exercise stress testing (EST). Anemia was defined by the World Health Organization (WHO) or Beutler and Waalens' (BW) criteria. Low CRF was defined as the lowest fitness quintile according to the Bruce protocol. RESULTS: The mean age was 46±10 years, and 70% were men. Mean Hb levels were 13±1 and 15±1 among women and men, respectively, with higher proportion of anemia among women. The majority of anemic subjects had mild anemia. When analyzing repeated annual visits, anemia was associated with a significant 39% and 64% increased risk of low CRF according the WHO and BW criteria only in women (n=18 672). Baseline anemia at first visit was associated with 2.6- and 1.9-fold increased risk of all-cause mortality using the WHO and BW criteria, exclusively in men (n=11 511). CONCLUSIONS: Overall, the functional and prognostic impact of anemia is gender dependent, based on the WHO and BW arbitrary criteria, suggesting differing mechanism and responses.

Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2.

In the Ashkenazi Jewish (AJ) population of Israel, 11% of breast cancer and 40% of ovarian cancer are due to three inherited founder mutations in the cancer predisposition genes BRCA1 and BRCA2. For carriers of these mutations, risk-reducing salpingo-oophorectomy significantly reduces morbidity and mortality. Population screening for these mutations among AJ women may be justifiable if accurate estimates of cancer risk for mutation carriers can be obtained. We therefore undertook to determine risks of breast and ovarian cancer for BRCA1 and BRCA2 mutation carriers ascertained irrespective of personal or family history of cancer. Families harboring mutations in BRCA1 or BRCA2 were ascertained by identifying mutation carriers among healthy AJ males recruited from health screening centers and outpatient clinics. Female relatives of the carriers were then enrolled and genotyped. Among the female relatives with BRCA1 or BRCA2 mutations, cumulative risk of developing either breast or ovarian cancer by age 60 and 80, respectively, were 0.60 (± 0.07) and 0.83 (± 0.07) for BRCA1 carriers and 0.33 (± 0.09) and 0.76 (± 0.13) for BRCA2 carriers. Risks were higher in recent vs. earlier birth cohorts (P = 0.006). High cancer risks in BRCA1 or BRCA2 mutation carriers identified through healthy males provide an evidence base for initiating a general screening program in the AJ population. General screening would identify many carriers who are not evaluated by genetic testing based on family history criteria. Such a program could serve as a model to investigate implementation and outcomes of population screening for genetic predisposition to cancer in other populations.

Use of exercise capacity to improve SCORE risk prediction model in asymptomatic adults.

AIMS: The SCORE risk estimation system is used for cardiovascular risk stratification in apparently healthy adults and is based on known cardiovascular risk factors. The purpose of the current study was to evaluate whether exercise capacity can improve the accuracy of the SCORE overall survival risk estimation. METHODS AND RESULTS: We investigated 22 878 asymptomatic men and women who were annually screened in a tertiary medical centre. All subjects were free of known ischaemic heart disease, and had completed maximal exercise stress test according to the Bruce protocol. The SCORE risk estimation system was used to evaluate individual cardiovascular risk for all subjects. The primary endpoint was mortality, after exclusion of patients with metastatic cancer during follow-up. The incremental contribution of exercise capacity in predicting the risk of death was evaluated by net reclassification improvement (NRI) and area under the receiver operating curve (AUROC). Mean age of the study population was 47.4 ± 10.3, and 71.6% were men. There were 505 (2.21%) deaths during a mean follow-up of 9.2 ± 4.1 years. Kaplan-Meier survival analysis showed that both SCORE and low exercise capacity were associated with reduced survival. When added to the SCORE risk prediction, exercise capacity allowed more accurate risk stratification: NRI analysis showed an overall improvement of 56.8% in the accuracy of classification and the AUROC increased (0.782 vs. 0.766). CONCLUSION: Both SCORE and exercise capacity are strong independent predictors of all-cause mortality. The addition of exercise capacity to the SCORE risk model can improve the accuracy of the model.

Body mass index and the risk of new-onset atrial fibrillation in middle-aged adults.

BACKGROUND: Increased body mass index (BMI) and obesity are associated with increased risk of new-onset atrial fibrillation (AF) among middle-aged adults. OBJECTIVES: The objective of the study is to investigate the association between BMI and the risk for new-onset AF among middle-aged adults. METHODS: We investigated 18,290 men and women who were annually screened in a tertiary medical center. Participants were divided at baseline into 3 groups: normal weight (BMI ≥18 and <25 kg/m(2), n = 7,692), overweight (BMI ≥25 and <30 kg/m(2), n = 8,032), and obese (BMI ≥30 kg/m(2), n = 2,566). The primary end point was new-onset AF during follow-up. RESULTS: Mean age of study population was 49 ± 11 years, and 73% were men. A total of 288 incident events (1.6%) occurred during 6 ± 4 years. Kaplan-Meier survival analysis showed that the cumulative probability of AF at 6 years was highest among obese participants, intermediate among overweight participants, and lowest among participants with normal weight (2.1%, 1.7%, and 0.8% respectively, P < .001). Multivariable Cox regression analysis showed that overweight and obesity were independently associated with increased AF risk (hazard ratio 1.54 [P = .004] and 2.41 [P < .001], respectively). Assessment of BMI change as a time-dependent covariate in the multivariable model showed that each 1 kg/m(2) reduction in BMI during follow-up was associated with a significant 7% reduction in the risk for the occurrence of a first AF event (hazard ratio 0.93, 95% CI 0.88-0.99, P = .019). Consistently, similar analysis showed that each 5-kg weight loss during follow-up was independently associated with a significant 12% reduced risk of new-onset AF (95% CI 0.81-0.98, P = .02). CONCLUSIONS: Our findings suggest that overweight and obesity are associated with increased AF risk, whereas weight reduction is independently associated with reduced risk of de novo AF.

Rarity of adenomatous polyps in ulcerative colitis and its implications for colonic carcinogenesis.

BACKGROUND AND STUDY AIMS: Despite ample research on the dysplasia to carcinoma risk in ulcerative colitis, there are scant data on the prevalence of adenomatous polyps in this population. METHODS: The number and histology of all polyps detected at colonoscopies of ulcerative colitis patients aged > 50 during 2006 - 2012 were compared with similarly aged controls undergoing screening colonoscopy. RESULTS: There were 206 patients with ulcerative colitis and 624 controls included in the study (mean age 61.7 ±â€Š8.7 vs. 60.8 ±â€Š6.1, respectively; P = 0.15). Adenomatous polyps were detected in only 13/206 colonoscopies for ulcerative colitis compared with 162 /624 controls (6.3 % vs. 25.9 %, respectively; odds ratio [OR] 0.19, 95 % confidence interval [CI] 0.1 - 0.34; P < 0.0001). When also considering all prior colonoscopies performed over 7.7 ±â€Š4.6 years of follow-up (mean 4.1 ±â€Š2.9 colonoscopies/patient, range 1 - 15, total 832 colonoscopies), the risk of ever finding an adenoma in ulcerative colitis patients was still significantly lower compared with controls (14.1 % vs. 25.9 %, respectively; OR 0.47, 95 %CI 0.3 - 0.72; P = 0.0005). On multivariable analysis, adenomas were positively associated with advanced age (OR 1.07/year, 95 %CI 1.03 - 1.1; P < 0.0001) and with increasing body mass index (BMI; OR 1.06/kg/m(2), 95 %CI 1.01 - 1.1; P = 0.01) and negatively associated with having ulcerative colitis (OR 0.15, 95 %CI 0.09 - 0.44; P = 0.0005). Among 115 Crohn's disease patients aged > 50 years, the rate of ever-adenomas in small-bowel Crohn's disease was similar to the controls (P = 0.8) and not influenced by 5-aminosalicylic acid use, whereas patients with colonic Crohn's disease had a significantly lower rate of adenomas compared with the controls (3.9 % vs. 25.9 %; P = 0.002). CONCLUSION: Unlike patients with small-bowel Crohn's disease, patients with ulcerative colitis or with colonic Crohn's disease seldom develop sporadic adenomatous polyps. These data may provide novel clues to a possible role for colonic immune activation in restricting the adenoma to carcinoma sequence while propagating the dysplasia to carcinoma pathway.

The association between cardiorespiratory fitness and cardiovascular risk may be modulated by known cardiovascular risk factors.

BACKGROUND: We aimed to evaluate whether reduced cardiovascular fitness has a direct or indirect effect for the development of cardiovascular disease. METHODS: We investigated 15,595 men and women who were annually screened in a tertiary medical center. All subjects were free of ischemic heart disease and had completed maximal exercise stress test according to the Bruce protocol at their first visit. Fitness was categorized into age- and sex-specific quintiles (Q) according to Bruce protocol treadmill time with Q1 as lowest fitness. Subjects were categorized at baseline into 3 groups: low fitness (Q1), moderate fitness (Q2-Q4), and high fitness (Q5). The primary end point of the current analysis was the development of a first cardiovascular event during follow-up. RESULTS: Mean age of study patients was 48 ± 10 years, and 73% were men. A total of 679 events occurred during 92,092 person-years of follow-up. Kaplan-Meier survival analysis showed that the cumulative probability of cardiovascular events at 6 years was significantly higher among subjects with low fitness (P < .001). Low fitness was associated with known cardiovascular risk factors, including hypercholesterolemia (odds ratio [OR] 1.58, 95% CI 1.31-1.89), diabetes mellitus (OR 2.32, 95% CI 1.58-3.41), and obesity (OR 10.46, 95% CI 8.43-12.98). The effect of low fitness on cardiovascular events was no longer significant when including diabetes mellitus, hypercholesterolemia, and obesity as mediators (hazard ratio 0.99, 95% CI 0.82-1.19). CONCLUSIONS: The association between cardiovascular fitness and adverse cardiovascular outcomes may be modulated through traditional cardiovascular risk factors. These findings need to be further validated in prospective clinical trials.

Impaired fasting glucose and left ventricular diastolic dysfunction in middle-age adults: a retrospective cross-sectional analysis of 2971 subjects.

BACKGROUND: Left ventricular (LV) diastolic dysfunction (LVDD) is a well-established and early echocardiographic characteristic of diabetic cardiomyopathy. However, there are limited data on the association between impaired fasting glucose (IFG) and LVDD. OBJECTIVE: To determine whether IFG is associated with LVDD among middle age adults. METHODS: Amongst 3781 subjects screened in an annual health survey program and referred for an echocardiogram, 2971 individuals without LV systolic dysfunction or valvular heart disease were selected. Mean age of study population was 59 ± 12 years and 75% were men. The subjects were categorized into three groups: euglycemia (N = 2025), IFG (N = 534) and diabetes mellitus (DM; N = 412). Doppler echocardiography readers were blinded to glycemic state. Subjects with impaired LV relaxation, pseudo-normal or restrictive filling patterns were defined as having LVDD. RESULTS: LVDD was diagnosed in 574 (19 %) of subjects and it was more prevalent among patients with IFG and DM than in euglycemic individuals (27, 30 and 15%, respectively; p < 0.001). Patients with IFG and DM had lower ratios of early (E) to late (A) trans-mitral flow (0.9 ± 0.3 and 0.9 ± 0.3 vs. 1.1 ± 0.4, respectively, p < 0.001). LV hypertrophy (LVH) was also more prevalent among patients with IFG and DM (11 and 18%, respectively, vs. 9%; p < 0.001). Multivariate binary logistic regression model adjusted to age, gender, obesity, LVH, renal function, total, high and low density lipoprotein cholesterol, triglycerides, ischemic heart disease, hypertension and LV ejection fraction showed that patients with IFG were 43% more likely to have LVDD compared with euglycemic subjects (95% confidence interval 1.12-1.83, p = 0.004). CONCLUSIONS: IFG is independently associated with a significant increase in the likelihood for the presence of LVDD in middle aged adults.

Cardiac stress test is normal in pre-motor Parkinson's disease.

Cardiac sympathetic denervation is an early nonmotor feature of Parkinson's disease (PD). The aim of the current study was to trace evidence for cardiac dysfunction abnormalities in the premotor phase of PD. We retrospectively reviewed treadmill ergometric tests of a large cohort (n = 16,841) between 2000 and 2012, that attended the Executive Screening Survey (ESS) at Sheba Medical Center. Heart rate and blood pressure profiles as well as exercise capacity were compared between subjects who later developed PD and age- and sex-matched subjects (ratio 1:2) who did not. We identified 28 subjects (24 males) who developed PD at follow-up. The PD group was older than the group of subjects who did not develop PD on first ergometric test (64.82 ± 8.82 vs. 48.91 ± 10.60 years, P < 0.001). The time between the first ergometric test and motor symptoms onset was 4.64 ± 2.86 years. Patients who later developed PD had lower maximal heart rate (P < 0.001) and lower heart rate reserve than healthy controls (P < 0.001); however, compared with age- and sex-matched subjects, subjects who developed PD had similar exercise capacity and heart rate profile during rest, exercise, and recovery, even 1 year before diagnosis. In this study, we did not detect significant signs of sympathetic dysfunction during the premotor phase of PD.

Low cardiorespiratory fitness is associated with elevated intraocular pressure among apparently healthy adults.

PURPOSE: To evaluate the association of cardiorespiratory fitness with elevated intraocular pressure (IOP) in healthy adults. METHODS: In this cross-sectional study, we evaluated 17,990 asymptomatic self-referred adults free of diabetes or cardiovascular disease who were screened in a preventive healthcare setting. All subjects underwent measurement of IOP and completed a maximal exercise stress test according to the Bruce protocol. Fitness was categorized into age and sex-specific quintiles according to the treadmill time and dichotomized to low (lowest quintile) and non-low fitness groups. Elevated IOP was defined as ≥ 21 mmHg. RESULTS: Median age was 45 (IQR 39-52) years and 12,073 (67%) were men. There were 3,351 (19%) subjects in the low fitness group. Median IOP was 14 mmHg (IQR 12-16) with elevated IOP documented in 188 (1%) subjects. Univariate binary logistic regression model demonstrated that compared with non-low fitness group, subjects in the low fitness group were 2.2 times more likely to have elevated IOP (95% CI 1.598-2.95, p<0.001). Multivariate binary logistic regression with adjustment to known cardiovascular risk factors (age, sex, hypertension, smoking, overweight, regular physical activity, low HDL cholesterol, high triglycerides, and fasting glucose levels) successfully demonstrated that lower fitness was independently and significantly associated with a 90% increased likelihood of elevated IOP (95% CI 1.37-2.61, p<0.001). Subgroup analysis revealed that the association was more pronounced among women compared with men (OR 3.8 vs. 1.6, p for interaction = 0.069). CONCLUSIONS: Low cardiorespiratory fitness is independently associated with increased IOP among apparently healthy adults.