To evaluate the association of cardiorespiratory fitness with elevated intraocular pressure (IOP) in healthy adults.
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.
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).
Low cardiorespiratory fitness is independently associated with increased IOP among apparently healthy adults.
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.
Significance Inherited mutations in the tumor suppressor genes BRCA1 and BRCA2 predispose to very high risks of breast and ovarian cancer. For carriers of these mutations, risk-reducing surgery significantly reduces morbidity and mortality. General population screening for BRCA1 and BRCA2 mutations in young adult women could be feasible if accurate estimates of cancer risk for mutation carriers could be obtained. We determined that risks of breast and ovarian cancer for BRCA1 and BRCA2 mutation carriers ascertained from the general population are as high as for mutation carriers ascertained through personal or family history of cancer. General screening of BRCA1 and BRCA2 would identify many carriers who are currently not evaluated and could serve as a model for population screening for genetic predisposition to cancer.
Background Diabetes mellitus and impaired glucose metabolism are associated with increased risk for cardiovascular disease (CVD). However, it is still not clear whether glucose levels can predict CVD ...risk among patients without diabetes. The primary aim of this study is to assess whether normoglycemic fasting plasma glucose (FPG) is associated with increased risk of CVD outcomes in healthy patients. Methods We obtained blood measurements, data from physical examination, and medical and lifestyle information from 10,913 men and women who were evaluated in the Institute for Preventive Medicine of Sheba Medical Center. Enrolled were participants with FPG < 100 mg/dL as well as 100 to 125 mg/dL, who were free of diagnosis of CVD. The participants were actively screened for coronary disease using a stress test. Primary end points were coronary heart disease or self-reported cerebral vascular disease. Results A total of 1,119 incident cases of CVD occurred during a mean follow-up of 4.3 years. Subjects with fasting glucose levels in the high normal range (95-99 mg/dL) had an increased CVD risk when compared with levels < 80 mg/dL, (HR 1.53;CI 95% 1.22-1.91, P < .001). A multivariate model, adjusted for age, sex, family history of CVD, blood pressure, body mass index, smoking status, pharmacologic treatment, serum triglycerides, and high-density lipoprotein and low-density lipoprotein cholesterol levels, revealed an independent increased risk of CVD with rising FPG levels in the normal range. Conclusion Elevated CVD risk is strongly and independently associated with glucose levels within the normoglycemic range. Fasting plasma glucose may help in identifying apparently healthy persons with early metabolic abnormalities who are at increased risk for CVD before progression to prediabetes and overt diabetes mellitus.
Studies in different populations with high risk for cardiovascular disease (CVD) have shown an association between serum uric acid (SUA) and CVD. However, only a few studies have demonstrated such an ...association in healthy populations. The aim of this study was to investigate the association between SUA and CVD in a cohort of men and women without diabetes or CVD. A retrospective study was conducted, with a mean 4.8-year follow-up. The outcome was the occurrence of a cardiovascular event, defined as the diagnosis of ischemic heart disease, acute coronary syndrome, acute myocardial infarction, or ischemic stroke. Mean SUA levels were 6.2 ± 1.1 mg/dl for men (n = 6,580) and 4.4 ± 1.1 mg/dl for women (n = 2,559). For women, the rate of CVD occurrence was 11.6% for the highest quartile of SUA level, compared with 5.0% to 6.5% for the lower 3 quartiles. For men, the rate of CVD occurrence was 14.0% for the highest quartile of SUA level, compared with 10.8% for the lowest quartile. The hazard ratio for CVD, adjusted for age, serum creatinine level, body mass index, systolic blood pressure, low-density lipoprotein cholesterol level, triglyceride level, plasma fasting glucose, physical activity, cardiovascular family history, use of diuretics, and current smoking, was 1.24 (95% confidence interval 1.08 to 1.41) for women and 1.06 (95% confidence interval 1.00 to 1.13) for men (p for interaction = 0.04). In conclusion, the strong association of SUA levels with CVD in women, compared with the much lesser degree in men, highlights the necessity of stratifying by gender in investigations of cardiovascular risk factors and supports exploration of SUA as a marker of CVD risk in healthy populations.
Clinical and experimental data support a critical role for inflammation in cardiovascular disease. The purpose of the current study was to examine the relation between an inflammatory marker, ...neutrophil-to-lymphocyte ratio (NLR), and incident atrial fibrillation (AF) in asymptomatic adults. We investigated 21,118 self-referred men and women who were annually screened in a tertiary medical center. All subjects were free of AF at baseline and had their serum NLR calculated at the first annual visit. Subjects were divided into 2 groups based on their baseline NLR: Low (<2.83; n = 17,524) and high (≥2.83; n = 3,594; Upper Sextile). The primary endpoint was new onset AF during follow-up. Mean age of study population was 48 ± 10 years and 72% were men. A total of 563 (2.7%) incident events occurred during an average follow-up of 7.5 ± 5 years. Unadjusted Cox regression analysis demonstrated that each 1 unit increase in NLR was associated with a significant 14% increase in risk of occurrence of a first AF event (95% confidence interval 1.06 to 1.23, p < 0.001) and 20% increased risk of death. Kaplan-Meier's survival analysis showed that the cumulative probability of incident AF was significantly higher among subjects with high NLR compared with low NLR group (p = 0.006). Interaction analysis with adjustment to clinical parameters showed that NLR-related risk was age-dependent, such that in the younger age-group (< =50 years) high NLR group had two folds increased risk for AF event compared with low NLR group (95% confidence interval 1.08 to 3.51; p = 0.027) whereas among older subjects the rate of events was similar between both NLR groups (p = NS; p for interaction = 0.024). In conclusion, our findings suggest that high NLR is associated with increased risk of new onset AF. This finding is more pronounced among young adults.
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. While cirrhosis is the main risk factor for HCC, the factors influencing progression from cirrhosis ...to HCC remain largely unknown. Gut microbiota plays a key role in liver diseases; however, its association with HCC remains elusive. This study aimed to elucidate microbial differences between patients with HCC-associated cirrhosis (HCC-cirrhosis) and cirrhotic patients without HCC and healthy volunteers and to explore the associations between diet, lifestyle, and the microbiome of these patients. Fecal samples and food frequency questionnaires were collected from 95 individuals (30 HCC-cirrhosis patients, 38 cirrhotic patients without HCC, and 27 age- and body mass index BMI-matched healthy volunteers). 16S rRNA gene sequencing was performed. Bacterial richness in cirrhosis and HCC-cirrhosis patients was significantly lower than in healthy controls. The HCC-cirrhosis group was successfully classified with an area under the curve (AUC) value of 0.9 based on the dysbiotic fecal microbial signature. The HCC-cirrhosis group had a significant overrepresentation of Clostridium and CF231 and reduced Alphaproteobacteria abundance compared to cirrhotic patients without HCC. Patients with HCC-cirrhosis who were overweight displayed significantly decreased bacterial richness and altered microbiota composition compared to their normal-weight counterparts. There was a significant correlation in the HCC-cirrhosis group between intake of artificial sweeteners and the presence of Akkermansia muciniphila. A unique microbial signature was observed in patients with HCC-cirrhosis, irrespective of cirrhosis stage, diet, or treatment. BMI, dietary sugar, and artificial sweeteners were significantly associated with alterations in the microbiome of HCC-cirrhosis patients. However, the increased abundance of Clostridium and CF231 observed in HCC-cirrhosis patients was not influenced by environmental factors, implying that this change was due to development of HCC. IMPORTANCE Development of hepatocellular carcinoma in patients with cirrhosis is associated with alterations in intestinal microbiota, including an escalation of dysbiosis and reduced bacterial richness. This study demonstrates that reduced bacterial richness and dysbiosis escalate with the progression of cirrhosis from compensated to decompensated cirrhosis and to HCC-associated cirrhosis (HCC-cirrhosis). Moreover, we report for the first time the effect of environmental factors on HCC-cirrhosis. Excess weight was associated with increased dysbiosis in patients with HCC compared to their normal-weight counterparts. Moreover, fatty liver, consumption of artificial sweeteners, and high-sugar foods were associated with altered microbial composition, including altered levels of Akkermansia muciniphila in HCC-cirrhosis. We have successfully determined that levels of Alphaproteobacteria and the two genera CF231 and Clostridium are significantly altered in cirrhotic patients who develop hepatocellular carcinoma, independently of cirrhosis severity and dietary habits.
Background:
Screening with colonoscopy for all average-risk population is probably not cost-effective due to the limited sources and over-generalization of the risk, and risk stratification can be ...used to optimize colorectal cancer screening.
Objectives:
We aimed to assess risk factors for advanced neoplasia (AN) and a classification tree algorithm to predict the risk.
Design:
This is a retrospective cross-sectional study.
Methods:
This study was composed of consecutive asymptomatic average-risk individuals undergoing first screening colonoscopy between 2008 and 2019. Detailed characteristics including background diseases, habits, and medications were collected. We used multivariable logistic regression to investigate the associations between clinical variables and the presence of AN and built a classification algorithm to predict AN.
Results:
A total of 3856 patients were included (73.2% male, median age 55). Adenoma and AN detection rate were 15.8% and 3.4%, respectively. On multivariable analysis, predictors of AN odds ratio (OR), 95% confidence interval (CI) were age (1.04, 1.01–1.06, p = 0.003), male sex (2.69, 1.56–4.64, p < 0.001), and smoking (1.97, 1.38–2.81, p < 0.001). A classification tree algorithm showed that smoking was the most important risk factor for prediction of AN (4.9% versus 2.4%, p < 0.001), followed by age with a cutoff value of 60 in the smokers (8.4% versus 3.8%, p = 0.001) and 50 in the non-smokers (2.9% versus 0.9%, p = 0.004).
Conclusion:
Smoking habits, old age, and male gender are highly associated with an increased risk for AN and should be incorporated in the individualized risk-assessment to adapt a screening program.
Background: Heart rate variability (HRV) is an accepted and reliable means for assessing autonomic nervous system dysfunction. A 5‐minute measurement of HRV is considered methodologically adequate. ...Several studies have attempted to use shorter recordings of 1–2 minutes or 10 seconds. The aim of this study was to determine the reliability of HRV parameters calculated from ultra‐short electrocardiogram recordings.
Methods: Seventy healthy volunteers were recruited for the study. HRV was evaluated for 5 minutes according to accepted procedures. Thereafter, HRV parameters were recalculated from randomly selected 1‐minute and 10‐second intervals. The standard and ultra‐short measurements were correlated using intraclass correlation coefficients.
Results: Good correlations between the 5‐minute electrocardiograms (ECGs) and both the 1‐minute and 10‐second ECGs were noted for average RR interval, and root mean square of successive differences in RR intervals (RMSSD). No correlation was noted for standard deviation of the RR interval (SDNN) and several other HRV parameters.
Conclusions: RMSSD, but not SDNN, seem a reliable parameter for assessing HRV from ultra‐short (1 minute or 10 seconds) resting electrocardiographic recordings. Power spectral analysis and evaluation of other HRV parameters require longer recording periods. Further research is required to evaluate the importance of ultra‐short RMSSD for cardiovascular risk stratification.
Ann Noninvasive Electrocardiol 2011;16(2):117–122
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/m2 , n = 7,692), overweight (BMI ≥25 and <30 kg/m2 , n = 8,032), and obese (BMI ≥30 kg/m2 , 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/m2 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.
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:
β
= 0.10,
p
= 0.008; Direct effect:
β
= 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.
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