Coronary artery disease prediction in women and men using chest pain characteristics and risk factors: an observational study in outpatient clinics

Objectives To assess the diagnostic value of non-acute chest pain characteristics for coronary artery disease in women and men referred to outpatient cardiology clinics. Design and setting This is an observational study performed at outpatient cardiology centres of the Netherlands. Participants The study population consisted of 1028 patients with non-acute chest pain (505 women). Analysis and results Twenty-four women (5%) and 75 men (15%) were diagnosed with coronary artery disease by invasive coronary angiography or CT angiography during regular care follow-up. Elastic net regression was performed to assess which chest pain characteristics and risk factors were of diagnostic value. The overall model selected age, provocation by temperature or stress, relief at rest and functional class as determinants and was accurate in both sexes (area under the curve (AUC) of 0.76 (95% CI 0.68 to 0.85) in women and 0.83 (95% CI 0.78 to 0.88) in men). Both sex-specific models selected age, pressuring nature, radiation, duration, frequency, progress, provocation and relief at rest as determinants. The female model additionally selected dyspnoea, body mass index, hypertension and smoking while the male model additionally selected functional class and diabetes. The sex-specific models performed better than the overall model, but more so in women (AUC: 0.89, 95% CI 0.81 to 0.96) than in men (AUC: 0.84, 95% CI 0.73 to 0.90). Conclusions In both sexes, the diagnostic value of non-acute chest pain characteristics and risk factors for coronary artery disease was high. Provocation, relief at rest and functional class of chest pain were the most powerful diagnostic predictors in both women and men. When stratified by sex the performance of the model improved, mostly in women

Mendelian randomization study of B-type natriuretic peptide and type 2 diabetes: evidence of causal association from population studies

<p>Background: Genetic and epidemiological evidence suggests an inverse association between B-type natriuretic peptide (BNP) levels in blood and risk of type 2 diabetes (T2D), but the prospective association of BNP with T2D is uncertain, and it is unclear whether the association is confounded.</p> <p>Methods and Findings: We analysed the association between levels of the N-terminal fragment of pro-BNP (NT-pro-BNP) in blood and risk of incident T2D in a prospective case-cohort study and genotyped the variant rs198389 within the BNP locus in three T2D case-control studies. We combined our results with existing data in a meta-analysis of 11 case-control studies. Using a Mendelian randomization approach, we compared the observed association between rs198389 and T2D to that expected from the NT-pro-BNP level to T2D association and the NT-pro-BNP difference per C allele of rs198389. In participants of our case-cohort study who were free of T2D and cardiovascular disease at baseline, we observed a 21% (95% CI 3%-36%) decreased risk of incident T2D per one standard deviation (SD) higher log-transformed NT-pro-BNP levels in analysis adjusted for age, sex, body mass index, systolic blood pressure, smoking, family history of T2D, history of hypertension, and levels of triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The association between rs198389 and T2D observed in case-control studies (odds ratio = 0.94 per C allele, 95% CI 0.91-0.97) was similar to that expected (0.96, 0.93-0.98) based on the pooled estimate for the log-NT-pro-BNP level to T2D association derived from a meta-analysis of our study and published data (hazard ratio = 0.82 per SD, 0.74-0.90) and the difference in NT-pro-BNP levels (0.22 SD, 0.15-0.29) per C allele of rs198389. No significant associations were observed between the rs198389 genotype and potential confounders.</p> <p>Conclusions: Our results provide evidence for a potential causal role of the BNP system in the aetiology of T2D. Further studies are needed to investigate the mechanisms underlying this association and possibilities for preventive interventions.</p&gt

Age at Menarche, the Leg Length to Sitting Height Ratio, and Risk of Diabetes in Middle-Aged and Elderly Chinese Men and Women

To evaluate the associations of age at menarche and the leg length-to-sitting-height ratio, markers of adolescent growth, with risk of diabetes in later life.Information from 69,385 women and 55,311 men, aged 40-74 years from the Shanghai Women's Health Study and Shanghai Men's Health Study, were included in the current analyses. Diabetes status was ascertained through biennial in person follow-up. Cox models, with age as the time scale, were used.There were 2369 cases of diabetes (1831 women; 538 men) during an average of 7.3 and 3.6 years of follow-up of the women and men, respectively. In females, menarche age was inversely associated with diabetes risk after adjustment for birth cohort, education, and income (HR = 0.95, 0.92-0.98). In both genders, leg length-to-sitting-height ratio was inversely related to diabetes (HR = 0.88, 0.80-0.97 for men; HR = 0.91, 0.86-0.96 for women) after adjustment for birth cohort, education, and income. Further adjustment for adult BMI at study enrollment completely eliminated the associations of age at menarche (HR = 0.99, 0.96-1.02) and the leg length-to-sitting-height ratio (HR = 1.00, 0.91-1.10 for men; HR = 1.01, 0.96-1.07 for women) with diabetes risk.Our study suggests that markers of an early age at peak height velocity, i.e. early menarche age and low leg-length-to-sitting height ratio, may be associated with diabetes risk later in life and this association is likely to be mediated through obesity

Cohort profile: the Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease (UCC-SMART) Study-an ongoing prospective cohort study of patients at high cardiovascular risk in the Netherlands

PURPOSE: The Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease (UCC-SMART) Study is an ongoing prospective single-centre cohort study with the aim to assess important determinants and the prognosis of cardiovascular disease progression. This article provides an update of the rationale, design, included patients, measurements and findings from the start in 1996 to date. PARTICIPANTS: The UCC-SMART Study includes patients aged 18-90 years referred to the University Medical Center Utrecht, the Netherlands, for management of cardiovascular disease (CVD) or severe cardiovascular risk factors. Since September 1996, a total of 14 830 patients have been included. Upon inclusion, patients undergo a standardised screening programme, including questionnaires, vital signs, laboratory measurements, an ECG, vascular ultrasound of carotid arteries and aorta, ankle-brachial index and ultrasound measurements of adipose tissue, kidney size and intima-media thickness. Outcomes of interest are collected through annual questionnaires and adjudicated by an endpoint committee. FINDINGS TO DATE: By May 2022, the included patients contributed to a total follow-up time of over 134 000 person-years. During follow-up, 2259 patients suffered a vascular endpoint (including non-fatal myocardial infarction, non-fatal stroke and vascular death) and 2794 all-cause deaths, 943 incident cases of diabetes and 2139 incident cases of cancer were observed up until January 2020. The UCC-SMART cohort contributed to over 350 articles published in peer-reviewed journals, including prediction models recommended by the 2021 European Society of Cardiology CVD prevention guidelines. FUTURE PLANS: The UCC-SMART Study guarantees an infrastructure for research in patients at high cardiovascular risk. The cohort will continue to include about 600 patients yearly and follow-up will be ongoing to ensure an up-to-date cohort in accordance with current healthcare and scientific knowledge. In the near future, UCC-SMART will be enriched by echocardiography, and a food frequency questionnaire at baseline enabling the assessment of associations between nutrition and CVD and diabetes

The PROgnostic Value of unrequested Information in Diagnostic Imaging (PROVIDI) Study: rationale and design

We describe the rationale for a new study examining the prognostic value of unrequested findings in diagnostic imaging. The deployment of more advanced imaging modalities in routine care means that such findings are being detected with increasing frequency. However, as the prognostic significance of many types of unrequested findings is unknown, the optimal response to such findings remains uncertain and in many cases an overly defensive approach is adopted, to the detriment of patient-care. Additionally, novel and promising image findings that are newly available on many routine scans cannot be used to improve patient care until their prognostic value is properly determined. The PROVIDI study seeks to address these issues using an innovative multi-center case-cohort study design. PROVIDI is to consist of a series of studies investigating specific, selected disease entities and clusters. Computed Tomography images from the participating hospitals are reviewed for unrequested findings. Subsequently, this data is pooled with outcome data from a central population registry. Study populations consist of patients with endpoints relevant to the (group of) disease(s) under study along with a random control sample from the cohort. This innovative design allows PROVIDI to evaluate selected unrequested image findings for their true prognostic value in a series of manageable studies. By incorporating unrequested image findings and outcomes data relevant to patients, truly meaningful conclusions about the prognostic value of unrequested and emerging image findings can be reached and used to improve patient-care

An epidemiological model for prediction of endometrial cancer risk in Europe

Endometrial cancer (EC) is the fourth most frequent cancer in women in Europe, and as its incidence is increasing, prevention strategies gain further pertinence. Risk prediction models can be a useful tool for identifying women likely to benefit from targeted prevention measures. On the basis of data from 201,811 women (mostly aged 30–65 years) including 855 incident EC cases from eight countries in the European Prospective Investigation into Cancer and Nutrition cohort, a model to predict EC was developed. A step-wise model selection process was used to select confirmed predictive epidemiologic risk factors. Piece-wise constant hazard rates in 5-year age-intervals were estimated in a cause-specific competing risks model, five-fold-cross-validation was applied for internal validation. Risk factors included in the risk prediction model were body-mass index (BMI), menopausal status, age at menarche and at menopause, oral contraceptive use, overall and by different BMI categories and overall duration of use, parity, age at first full-term pregnancy, duration of menopausal hormone therapy and smoking status (specific for pre, peri- and post-menopausal women). These variables improved the discriminating capacity to predict risk over 5 years from 71 % for a model based on age alone to 77 % (overall C statistic), and the model was well-calibrated (ratio of expected to observed cases = 0.99). Our model could be used for the identification of women at increased risk of EC in Western Europe. To achieve an EC-risk model with general validity, a large-scale cohort-consortium approach would be needed to assess and adjust for population variation

Estrogen receptor α polymorphisms and postmenopausal breast cancer risk

Item does not contain fulltextBACKGROUND: The estrogen receptor alpha (ESR1) is a mediator of estrogen response in the breast. The most studied variants in this gene are the PvuII and XbaI polymorphisms, which have been associated to lower sensitivity to estrogen. We evaluated whether these polymorphisms were associated with breast cancer risk by means of an association study in a population of Caucasian postmenopausal women from the Rotterdam study and a meta-analysis of published data. METHODS: The PvuII and XbaI polymorphisms were genotyped in 3,893 women participants of the Rotterdam Study. Baseline information was obtained through a questionnaire. We conducted logistic regression analyses to assess the risk of breast cancer by each of the ESR1 genotypes. Meta-analyses of all publications on these relations were done by retrieving literature from Pubmed and by further checking the reference lists of the articles obtained. RESULTS: There were 38 women with previously diagnosed breast cancer. During follow-up, 152 were additionally diagnosed. The logistic regression analyses showed no difference in risk for postmenopausal breast cancer in carriers of the PvuII or XbaI genotypes neither in overall, incident or prevalent cases. No further evidence of a role of these variants was found in the meta-analysis. CONCLUSIONS: Our results suggest that the ESR1 polymorphisms do not play a role in breast cancer risk in Caucasian postmenopausal women