Prospective cohort study of retinal vessel diameters and risk of hypertension

Objective To examine the relation between diameters of the retinal arterioles and 10 year incidence of hypertension.Design Population based prospective cohort study.Setting Beaver Dam eye study.Participants 2451 normotensive people aged 43 to 84 years.Main outcome measures Diameters of retinal arterioles and venules measured from digitised photographs of the retina taken at baseline. Measurements summarised as the arteriole:venule ratio, with a lower ratio indicating smaller arteriolar diameters. Incident hypertension, defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or use of antihypertensive drugs during follow up.Results 721 participants developed hypertension over a 10 year period. Those with lower arteriole:venule ratio had a higher cumulative incidence of hypertension (incidences of 17.4%, 24.1%, 31.0%, and 45.1%, respectively, for decreasing quarters of distribution of arteriole:venule ratio). After adjustment for age and sex, participants with arteriole:venule ratios in the lowest quarter had a threefold higher risk of hypertension (odds ratio 2.95, 95% confidence interval 2.77 to 3.88) than those with ratios in the highest quarter. This association remained significant after further adjustment for baseline systolic and diastolic blood pressure and other risk factors (1.82, 1.39 to 2.40, for lowest versus highest ratio quarters).Conclusions Narrowed retinal arterioles are associated with long term risk of hypertension, suggesting that structural alterations of the microvasculature may be linked to the development of hypertension.     

Polygenic risk scores in cardiovascular risk prediction: A cohort study and modelling analyses

BackgroundPolygenic risk scores (PRSs) can stratify populations into cardiovascular disease (CVD) risk groups. We aimed to quantify the potential advantage of adding information on PRSs to conventional risk factors in the primary prevention of CVD.Methods and findingsUsing data from UK Biobank on 306,654 individuals without a history of CVD and not on lipid-lowering treatments (mean age [SD]: 56.0 [8.0] years; females: 57%; median follow-up: 8.1 years), we calculated measures of risk discrimination and reclassification upon addition of PRSs to risk factors in a conventional risk prediction model (i.e., age, sex, systolic blood pressure, smoking status, history of diabetes, and total and high-density lipoprotein cholesterol). We then modelled the implications of initiating guideline-recommended statin therapy in a primary care setting using incidence rates from 2.1 million individuals from the Clinical Practice Research Datalink. The C-index, a measure of risk discrimination, was 0.710 (95% CI 0.703–0.717) for a CVD prediction model containing conventional risk predictors alone. Addition of information on PRSs increased the C-index by 0.012 (95% CI 0.009–0.015), and resulted in continuous net reclassification improvements of about 10% and 12% in cases and non-cases, respectively. If a PRS were assessed in the entire UK primary care population aged 40–75 years, assuming that statin therapy would be initiated in accordance with the UK National Institute for Health and Care Excellence guidelines (i.e., for persons with a predicted risk of ≥10% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), then it could help prevent 1 additional CVD event for approximately every 5,750 individuals screened. By contrast, targeted assessment only among people at intermediate (i.e., 5% to <10%) 10-year CVD risk could help prevent 1 additional CVD event for approximately every 340 individuals screened. Such a targeted strategy could help prevent 7% more CVD events than conventional risk prediction alone. Potential gains afforded by assessment of PRSs on top of conventional risk factors would be about 1.5-fold greater than those provided by assessment of C-reactive protein, a plasma biomarker included in some risk prediction guidelines. Potential limitations of this study include its restriction to European ancestry participants and a lack of health economic evaluation.ConclusionsOur results suggest that addition of PRSs to conventional risk factors can modestly enhance prediction of first-onset CVD and could translate into population health benefits if used at scale.

Luanluan Sun and colleagues investigate whether adding polygenic risk scores to conventional risk factors of cardiovascular disease helps predict disease risk.     

Prospective breast cancer risk factors prediction in Saudi women

Women's health is affected by breast cancer worldwide and Saudi Arabia (SA) is no exception. Malignancy has enormous consequences for social, psychological and public health. The aim of this study was to examine the risk factors for Saudi women from breast cancer using logistic regression models. In 135 patient cases for different stages of breast cancer was used to study case management, 270 healthy women from King Abd Alla Medical City, Mecca, SA were taken to predict the probability of women developing breast cancer, logistic regression was analyzed taking factors such as age, marital status, family history, parity, age at first full-term pregnancy, menopausal status, body mass index (BMI) and breast feeding. The logistic regression model showed that there are important risk factors (age, marital status, family history, parity, age at first full-term pregnancy, menopausal status, body mass index, and breast feeding) in development of breast cancer. Fewer cases were observed in unmarried women, age ≤30, BMI ≤20. In contrast, more cases were found with women age 41–50 married, BMI > 30, a smaller number of children, not breast feeding, age of first pregnancy ≥30, menopausal status age at 46–50. Based on our data there is role of risk factors in developing breast cancer, less BMI, the increase number of children, breast feeding, which are playing as protective factor for breast cancer.     

The use of bioassays for the risk assessment of toxic leachates: an experimental study

Solid wastes from the oil-shale industry produce leachates containing toxic compounds such as heavy metals and persistent polycyclic aromatic hydrocarbons (PAH). The hazard to the environment represented by waste leachates depends not only on their chemical composition, but also on the mobility and bioavailability of toxic contaminants in soils. We evaluated the applicability of bioassays for toxicity assessment of the bioavailable fraction of heavy metals and PAH in soils, in experiments with samples of four different soil types (Rendzina, Brown pseudopodzolic, Typical brown, Sodpodzolic), the pH of which ranged from 6.2 to 7.2. The toxicity of the bioavailable fraction of the soil contaminants was assessed with the dehydrogenase enzyme activity assay, and with a Toxkit microbiotest with the crustacean, Thamnocephalus platyurus, after treatment of the soil samples with an artificial solution containing chromium (III), lead (II), copper (II), cadmium (II) and pyrene. The test results confirm those of earlier experiments, which characterised the sorption potential of investigated soils for the same compounds. Both tests turned out to be sufficiently sensitive, and hence can be recommended as effective and useful tools for the assessment of the bioavailable fraction of soil contaminants.     

Mortality risk prediction of high-sensitivity C-reactive protein in suspected acute coronary syndrome: A cohort study

BackgroundThere is limited evidence on the use of high-sensitivity C-reactive protein (hsCRP) as a biomarker for selecting patients for advanced cardiovascular (CV) therapies in the modern era. The prognostic value of mildly elevated hsCRP beyond troponin in a large real-world cohort of unselected patients presenting with suspected acute coronary syndrome (ACS) is unknown. We evaluated whether a mildly elevated hsCRP (up to 15 mg/L) was associated with mortality risk, beyond troponin level, in patients with suspected ACS.Methods and findingsWe conducted a retrospective cohort study based on the National Institute for Health Research Health Informatics Collaborative data of 257,948 patients with suspected ACS who had a troponin measured at 5 cardiac centres in the United Kingdom between 2010 and 2017. Patients were divided into 4 hsCRP groups (<2, 2 to 4.9, 5 to 9.9, and 10 to 15 mg/L). The main outcome measure was mortality within 3 years of index presentation. The association between hsCRP levels and all-cause mortality was assessed using multivariable Cox regression analysis adjusted for age, sex, haemoglobin, white cell count (WCC), platelet count, creatinine, and troponin.Following the exclusion criteria, there were 102,337 patients included in the analysis (hsCRP <2 mg/L (n = 38,390), 2 to 4.9 mg/L (n = 27,397), 5 to 9.9 mg/L (n = 26,957), and 10 to 15 mg/L (n = 9,593)). On multivariable Cox regression analysis, there was a positive and graded relationship between hsCRP level and mortality at baseline, which remained at 3 years (hazard ratio (HR) (95% CI) of 1.32 (1.18 to 1.48) for those with hsCRP 2.0 to 4.9 mg/L and 1.40 (1.26 to 1.57) and 2.00 (1.75 to 2.28) for those with hsCRP 5 to 9.9 mg/L and 10 to 15 mg/L, respectively. This relationship was independent of troponin in all suspected ACS patients and was further verified in those who were confirmed to have an ACS diagnosis by clinical coding. The main limitation of our study is that we did not have data on underlying cause of death; however, the exclusion of those with abnormal WCC or hsCRP levels >15 mg/L makes it unlikely that sepsis was a major contributor.ConclusionsThese multicentre, real-world data from a large cohort of patients with suspected ACS suggest that mildly elevated hsCRP (up to 15 mg/L) may be a clinically meaningful prognostic marker beyond troponin and point to its potential utility in selecting patients for novel treatments targeting inflammation.Trial registrationClinicalTrials.gov - {"type":"clinical-trial","attrs":{"text":"NCT03507309","term_id":"NCT03507309"}}NCT03507309

Amit Kaura and colleagues investigate whether mildly elevated high sensitivity C-reactive protein is associated with mortality risk in patients with suspected acute coronary syndromes.     

Perspectives on the use of multiple sclerosis risk genes for prediction

Objective

A recent collaborative genome-wide association study replicated a large number of susceptibility loci and identified novel loci. This increase in known multiple sclerosis (MS) risk genes raises questions about clinical applicability of genotyping. In an empirical set we assessed the predictive power of typing multiple genes. Next, in a modelling study we explored current and potential predictive performance of genetic MS risk models.

Materials and Methods

Genotype data on 6 MS risk genes in 591 MS patients and 600 controls were used to investigate the predictive value of combining risk alleles. Next, the replicated and novel MS risk loci from the recent and largest international genome-wide association study were used to construct genetic risk models simulating a population of 100,000 individuals. Finally, we assessed the required numbers, frequencies, and ORs of risk SNPs for higher discriminative accuracy in the future.

Results

Individuals with 10 to 12 risk alleles had a significantly increased risk compared to individuals with the average population risk for developing MS (OR 2.76 (95% CI 2.02–3.77)). In the simulation study we showed that the area under the receiver operating characteristic curve (AUC) for a risk score based on the 6 SNPs was 0.64. The AUC increases to 0.66 using the well replicated 24 SNPs and to 0.69 when including all replicated and novel SNPs (n = 53) in the risk model. An additional 20 SNPs with allele frequency 0.30 and ORs 1.1 would be needed to increase the AUC to a slightly higher level of 0.70, and at least 50 novel variants with allele frequency 0.30 and ORs 1.4 would be needed to obtain an AUC of 0.85.

Conclusion

Although new MS risk SNPs emerge rapidly, the discriminatory ability in a clinical setting will be limited.     

Cancer risk associated with the use of valsartan in Korea: A nationwide cohort study

BackgroundDespite valsartan’s widespread use, few studies have explored its potential carcinogenicity. We evaluated the association between valsartan and cancer.MethodsWe conducted a retrospective cohort study using data from 2002 to 2015 gathered from the National Health Insurance database. Patients with hypertension aged ≥ 30 who used valsartan or other angiotensin II receptor blockers (ARBs) were included. Eligible patients were those with no prior history of the use of any ARBs, diagnosis of cancer, or organ transplantation in the 4 years predating their first use of the drugs of interest. The primary and secondary outcomes included the occurrence of all cancers and site-specific solid cancers, respectively. After applying propensity score (PS) matching, Cox regression was used to calculate the hazard ratios (HRs) and 95 % confidence intervals (CIs).ResultsA total of 1,550,734 individuals were identified as new users of valsartan or other ARBs. Of the 153,047 valsartan users, 16,047 were diagnosed with cancer. No increased risk of overall cancer was observed in valsartan users as compared to other ARB users (aHR = 1.00; 95 % CI, 0.98–1.02). Valsartan was, however, associated with a slightly elevated risk of liver (aHR = 1.09; 95 % CI, 1.01–1.16) and kidney cancer (aHR = 1.11; 95 % CI, 1.02–1.22).ConclusionCompared with other ARBs, valsartan did not increase the risk of overall cancer. A slightly increased risk for some solid cancers was associated with valsartan use, though the absolute rate difference was small.     

Prospective assessment of cardiovascular risk parameters in patients with rheumatoid arthritis

Background

The study presents a prospective follow-up assessment of cardiovascular (CV) risk parameters in patients with rheumatoid arthritis (RA) in comparison with control subjects.

Methods

The study group consisted of 41 RA patients. The following parameters were assessed at subsequent visits [initial (T0), follow-up after 6 years (T6)]: traditional CV risk factors, carotid intima media thickness (cIMT), QTc duration, serum concentration of amino-terminal pro-brain natriuretic peptide (NT-proBNP). A comparative cIMT assessment was performed on 23 healthy controls of comparable age.

Results

The mean (SD) cIMT value in RA patients was significantly higher at T6 than at T0 [0.87 (0.21) vs 0.76 (0.15) mm, p?<?0.001], the increase in patients with atherosclerotic plaques was noted. Patients with plaques were significantly older, had higher inflammatory parameters. The mean cIMT was significantly higher in RA patients than in controls at both T6, T0 visits. Certain traditional CV risk factors exacerbated during follow up. Unfavorable metabolic parameters and significantly higher cIMT were found in male patients than in female patients at T6. During follow-up, no significant differences in NT-proBNP, QTc were found. There were no significant relationships between cIMT, NT-proBNP, QTc and parameters of disease activity at T6.

Conclusions

During the 6-year course of established RA, significant exacerbation of atherosclerosis was found, revealed by higher cIMT. A careful monitoring should be applied to patients with atherosclerotic plaques and of male gender due to higher burden of CV risk. In long-standing disease, traditional CV risk factors seem to play a key role, beyond the inflammatory activity.

     

Noncancer risk assessment of arsenic safe and unsafe water uses: Bayesian estimation on cohort study

Cancer and noncancer risk of arsenic exposure depends on arsenic intake through drinking water and diets. The present study evaluated the probability of noncancer effects of arsenic exposure from drinking water and diets in a cohort of 82 participants in arsenic-endemic rural areas, considering arsenic-safe and arsenic-unsafe water uses for three consecutive years. The risk assessment included the collection of last 24 hours' diet replica and urine of the participants followed by total arsenic analysis of the same. Toxic dose emerging from exposure duration is a nonlinear variable. So, Bayesian estimation of the data for noncancer risk assessment of the variable arsenic consumption was performed. In spite of using arsenic-safe water, we observed arsenic consumption and release. Participants with skin lesions had more arsenic in urine than participants without skin lesions. Future risk for participants without skin lesions was twice due to less arsenic release in urine. For the first time, Bayesian simulation was used to assess noncancer risk on a cohort for a consecutive three-year study. A significant finding was the higher assessed noncancer risk of the participants without skin lesions than the participants with skin lesions.     

On the use of ordinal scoring scales in social life cycle assessment

The International Journal of Life Cycle Assessment -     

Modelling population exposure-response functions for use in environmental risk assessment

Effective environmental management requires accurate prediction of the probable individual, population, and ecosystem responses associated with environmental hazards. While much is known about the short-term physiological impacts of toxicants at the individual level, little is known about the long-term responses of populations. This occurs, in part, because of the costs and difficulties associated with completing long-term studies. In the absence of such field data it is argued that modelling both bridges the existing information gap and provides a credible means of predicting long-term population responses. An individuals-based Atlantic salmon (Salmo salar) population dynamics model, adjusted to include laboratory-derived acute toxicity data, is used to measure recovery time in a population subjected to concentrations and durations of copper exposure characteristic of an accidental release of mine tailings. Selected recovery criteria are proposed and discussed in terms of their suitability for use in environmental risk assessment. The resulting model data are used to estimate population exposure-response functions and, for purposes of environmental risk assessment, to describe the cumulative probability distribution ofin-situ environmental damage. The output of the model suggests a recovery time of 15 to 20 years and significant increases in the variability of post-perturbation population levels.     

基于土地利用变化的长春市生态风险评价

基于长春市1985年、2000年和2015年的Landsat TM遥感影像, 提取3个时相的土地利用类型数据, 通过构建网格尺度下的生态风险指数, 借助空间分析、地统计分析等方法定量评价长春市土地利用变化下的生态风险时空演变特征, 并应用地理探测器对其影响因子进行探测。结果表明: (1)1985—2015年, 长春市土地利用变化明显, 建设用地持续扩张, 耕地波动式收缩; 土地利用中耕地转为建设用地、林地与耕地间的相互转换是地类转移的主要形式; (2)长春市土地利用生态风险呈小幅下降趋势, 在地域内呈现西高东低的分异特征, 生态风险热、冷点区空间分布相对稳定并具有一定程度扩张趋势; (3)生态风险快速增长时期, 经济、人口与发展活力的空间格局成为长春市生态风险的主导因子, 而海拔与三者的协同作用进一步增强了生态风险的解释力。总体来看, 建设用地扩张会加剧中心城区生态风险, 但与区域整体生态风险增高并不存在必然联系; 为防止高风险区持续扩张, 城市应设定“增长边界”、转变空间发展方式、高效集约利用建设用地, 加强城市生态系统自然保育、防止景观破碎化, 实现城市可持续发展。     

Prospective study of cigarette smoking,alcohol use,and the risk of diabetes in men.

OBJECTIVE--To examine the association between smoking, alcohol consumption, and the incidence of non-insulin dependent diabetes mellitus in men of middle years and older. DESIGN--Cohort questionnaire study of men followed up for six years from 1986. SETTING--The health professionals'' follow up study being conducted across the United States. SUBJECTS--41,810 male health professionals aged 40-75 years and free of diabetes, cardiovascular disease, and cancer in 1986 and followed up for six years. MAIN OUTCOME MEASURE--Incidence of non-insulin dependent diabetes mellitus diagnosed in the six years. RESULTS--During 230,769 person years of follow up 509 men were newly diagnosed with diabetes. After controlling for known risk factors men who smoked 25 or more cigarettes daily had a relative risk of diabetes of 1.94 (95% confidence interval 1.25 to 3.03) compared with non-smokers. Men who consumed higher amounts of alcohol had a reduced risk of diabetes (P for trend < 0.001). Compared with abstainers men who drank 30.0-49.9 g of alcohol daily had a relative risk of diabetes of 0.61 (95% confidence interval 0.44 to 0.91). CONCLUSIONS--Cigarette smoking may be an independent, modifiable risk factor for non-insulin dependent diabetes mellitus. Moderate alcohol consumption among healthy people may be associated with increased insulin sensitivity and a reduced risk of diabetes.     

Visit-to-visit blood pressure variability and the risk of stroke in the Netherlands: A population-based cohort study

BackgroundApart from blood pressure level itself, variation in blood pressure has been implicated in the development of stroke in subgroups at high cardiovascular risk. We determined the association between visit-to-visit blood pressure variability and stroke risk in the general population, taking into account the size and direction of variation and several time intervals prior to stroke diagnosis.Methods and findingsFrom 1990 to 2016, we included 9,958 stroke-free participants of the population-based Rotterdam Study in the Netherlands. This is a prospective cohort study including participants aged 45 years and older. Systolic blood pressure (SBP) variability was calculated as absolute SBP difference divided by mean SBP over 2 sequential visits (median 4.6 years apart). Directional SBP variability was defined as SBP difference over 2 visits divided by mean SBP. Using time-varying Cox proportional hazards models adjusted for age, sex, mean SBP, and cardiovascular risk factors, hazard ratios (HRs) for stroke up to January 2016 were estimated per SD increase and in tertiles of variability. We also conducted analyses with 3-, 6-, and 9-year intervals between variability measurement and stroke assessment. These analyses were repeated for diastolic blood pressure (DBP). The mean age of the study population was 67.4 ± 8.2 years and 5,776 (58.0%) were women. During a median follow-up of 10.1 years, 971 (9.8%) participants had a stroke, including 641 ischemic, 89 hemorrhagic, and 241 unspecified strokes. SBP variability was associated with an increased risk of hemorrhagic stroke (HR per SD 1.27, 95% CI 1.05–1.54, p = 0.02) and unspecified stroke (HR per SD 1.21, 95% CI 1.09–1.34, p < 0.001). The associations were stronger for all stroke subtypes with longer time intervals; the HR for any stroke was 1.29 (95% CI 1.21–1.36, p < 0.001) at 3 years, 1.47 (95% CI 1.35–1.59, p < 0.001) at 6 years, and 1.38 (95%CI 1.24–1.51, p < 0.001) at 9 years. For DBP variability, we found an association with unspecified stroke risk. Both the rise and fall of SBP and the fall of DBP were associated with an increased risk for unspecified stroke. Limitations of the study include that, due to an average interval of 4 years between visits, our findings may not be generalizable to blood pressure variability over shorter periods.ConclusionsIn this population-based study, we found that visit-to-visit blood pressure variation was associated with an increased risk of unspecified and hemorrhagic stroke, independent of direction of variation or mean blood pressure.

In a population-based cohort study, Alis Heshmatollah and colleagues investigate the associations between blood pressure variability and risk of stroke among adults in the Netherlands.     

A versatile microrespirometer for routine use

A new design of microrespirometer suitable for routine laboratory work has been described.