Estimating Risk of Cardiovascular Disease Among Long-Term Colorectal Cancer Survivors: A Nationwide Cohort Study

BackgroundConcerns about a growing number of colorectal cancer survivors have emerged regarding cardiovascular disease (CVD) risks. However, there is not yet a predictive tool that can estimate CVD risk and support the management of healthcare as well as disease prevention in terms of CVD risk among long-term colorectal cancer survivors.AimTo develop predictive tools to estimate individualized overall and each subtype of CVD risk using a nationwide cohort in South Korea.Methods and ResultsA total of 4,709 newly diagnosed patients with colorectal cancer who survived at least 5 years in the National Health Insurance System were analyzed. Cox proportional hazard regression was used for the identification of independent risk factors for the derivation of predictive nomograms, which were validated in an independent cohort (n = 3,957). Age, fasting serum glucose, γ-glutamyl transpeptidase, Charlson comorbidity index, household income, body mass index, history of chemotherapy, cigarette smoking, and alcohol consumption were identified as independent risk factors for either overall CVD or each subtype of CVD subtype. Based on the identified independent risk factors, six independent nomograms for each CVD category were developed. Validation by an independent cohort demonstrated a good calibration with a median C-index of 0.687. According to the nomogram-derived median score, relative risks of 2.643, 1.821, 4.656, 2.629, 4.248, and 5.994 were found for overall CVD, ischemic heart disease, myocardial infarction, total stroke, ischemic stroke, and hemorrhage stroke in the validation cohort.ConclusionsThe predictive tools were developed with satisfactory accuracy. The derived nomograms may support the estimation of overall and individual CVD risk for long-term colorectal cancer survivors.

Comparison of a Standardized High-Fat Meal versus a High-Fat Meal Scaled to Body Mass for Measuring Postprandial Triglycerides: A Randomized Crossover Study

Post-meal triglycerides are an independent cardiovascular disease (CVD) risk factor, but the ideal high-fat meal formulation has yet to be standardized and is one challenge prohibiting widespread clinical adoption of postprandial triglyceride assessment. Two general approaches often used are giving individuals a high-fat meal scaled to body weight or a standardized high-fat meal containing a set fat bolus. A recent expert panel statement has endorsed the latter, specifying 75 g of fat as an appropriate fat dosage. Despite this recommendation, no study to date has tested whether there is a difference in postprandial triglycerides or if risk classification is affected based on these different approaches. We recruited 16 generally healthy individuals with roughly equal distribution among body mass index (BMI)class (n = 5–6/per BMI category) and sex (n = 2–3 M/F) within each BMI class. Each participant underwent two abbreviated fat tolerance tests separated by ~1 week: one with a scaled to body weight high-fat meal (9 kcal/kg; 70% fat) and a standardized meal containing 75 g of fat (70% fat). Fasting, 4 h, and absolute change in triglycerides across the entire sample and within each BMI category were similar regardless of high-fat meal. Only one participant with obesity had discordant postprandial responses between the fat tolerance tests (i.e., different CVD risk classification). These findings suggest that, within a certain range of fat intake, generally healthy individuals will have a similar postprandial triglyceride response. Considering the greater convenience of utilizing standardized high-fat meals, our data suggest that a standardized high-fat meal may be acceptable for large-scale studies and clinical implementation.

Cardiovascular risk prediction in type 2 diabetes: a comparison of 22 risk scores in primary care settings

Aims/hypothesis We aimed to compare the performance of risk prediction scores for CVD (i.e., coronary heart disease and stroke), and a broader definition of CVD including atrial fibrillation and heart failure (CVD+), in individuals with type 2 diabetes. Methods Scores were identified through a literature review and were included irrespective of the type of predicted cardiovascular outcome or the inclusion of individuals with type 2 diabetes. Performance was assessed in a contemporary, representative sample of 168,871 UK-based individuals with type 2 diabetes (age ≥18 years without pre-existing CVD+). Missing observations were addressed using multiple imputation. Results We evaluated 22 scores: 13 derived in the general population and nine in individuals with type 2 diabetes. The Systemic Coronary Risk Evaluation (SCORE) CVD rule derived in the general population performed best for both CVD (C statistic 0.67 [95% CI 0.67, 0.67]) and CVD+ (C statistic 0.69 [95% CI 0.69, 0.70]). The C statistic of the remaining scores ranged from 0.62 to 0.67 for CVD, and from 0.64 to 0.69 for CVD+. Calibration slopes (1 indicates perfect calibration) ranged from 0.38 (95% CI 0.37, 0.39) to 0.74 (95% CI 0.72, 0.76) for CVD, and from 0.41 (95% CI 0.40, 0.42) to 0.88 (95% CI 0.86, 0.90) for CVD+. A simple recalibration process considerably improved the performance of the scores, with calibration slopes now ranging between 0.96 and 1.04 for CVD. Scores with more predictors did not outperform scores with fewer predictors: for CVD+, QRISK3 (19 variables) had a C statistic of 0.68 (95% CI 0.68, 0.69), compared with SCORE CVD (six variables) which had a C statistic of 0.69 (95% CI 0.69, 0.70). Scores specific to individuals with diabetes did not discriminate better than scores derived in the general population: the UK Prospective Diabetes Study (UKPDS) scores performed significantly worse than SCORE CVD (p value <0.001). Conclusions/interpretation CVD risk prediction scores could not accurately identify individuals with type 2 diabetes who experienced a CVD event in the 10 years of follow-up. All 22 evaluated models had a comparable and modest discriminative ability. Graphical abstract

Factors Associated with Cardiovascular Disease Risk among Employees at a Portuguese Higher Education Institution

This study aimed to estimate the prevalence of risk factors for cardiovascular disease (CVD) and to assess the CVD risk (CVDRisk) in a sample of workers at a specific workplace: a higher education institution in Portugal. Data were collected using a questionnaire (e.cuidHaMUs.QueST®) with 345 HEI workers from June 2017–June 2018 with a high response rate (93.3%). Two constructs of risks for CVD were considered: (i) metabolic risk and hypertension (CVDRisk1); and (ii) modifiable behavioural risk (CVDRisk2). Logistic regression analyses were used to establish a relationship between risk indexes/constructs (CVDRisk1 and CVDRisk2) and groups of selected variables. The most prevalent CVD risk factor was hypercholesterolaemia (43.2%). Sixty-eight percent of participants were in the construct CVDRisk1 while almost half of the respondents were in CVDRisk2 (45.2%). The consumption of soft drinks twice a week or more contributed to a significantly increased risk of CVD in CVDRisk1. Lack of regular exercise and lack of daily fruit consumption significantly increased the risk of CVD in CVDRisk2. The challenge to decision makers and the occupational medical community is to incorporate this information into the daily practices of health surveillance with an urgent need for health promotional education campaigns in the workplace.

Cardiovascular Disease (CVD) Risk Assessment of HIV Medication Regimens using hematopoietic CD34+ progenitor cells

Background To determine the effects of integrase inhibitor (INSTI) in comparison to non INSTI based regimens such as non-nucleoside reverse transcriptase inhibitors (NNRTIs) based regimens on cardiovascular disease (CVD) risk in HIV+ patients without overt history of CVD or diabetes, with normal CD4:CD8 count. For CVD risk assessment we primarily used hematopoietic CD34+ progenitor cells, as a biomarker.Methods19 male subjects ages 32-61 years with BMI 21.0- 36.0, were enrolled. This was a single time point, cross-sectional, observational study. Subjects were enrolled under 2 groups (either on INSTI based regimen with 13 subjects or NNRTI (non-INSTI) based regimens with 6 subjects) who were taking stable doses of HAART. The medication regimens were a combination of one NRTI (typically tenofovir-emtricitabine) plus one INSTI or NNRTI. Our outcome measures were focused on cardiovascular and endothelial cell function and systemic inflammation. Our primary outcome measures were peripheral blood derived hematopoietic progenitor cell number (CD34 and CD133 positive), CD34+ cell function and gene expression studies. Our secondary outcomes were arterial stiffness measures and serum-based markers of inflammation. ResultsA significant increase in percentage number of progenitor cells, CD133+ cells (P=0.004) was noted along with an increase of double progenitor mark positive CD133+/CD34+ progenitor cell population was observed in INSTI group as compared to NNRTI group, by flow-cytometry. mRNA gene expression for antioxidant gene catalase was noted along with a trend towards a decrease in gene expression of inflammatory marker IL6 (p=0.06) was observed in CD34+ from INSTI group vs NNRTI group. The plasma IL-6 and CRP levels did not change significantly between the groups. Neutrophil-Lymphocyte ratio (NLR), an important marker of inflammation, was noted to be lower in INSTI group. A mean fasting glucose level was also lower in the INSTI group compared to NNRTI group (p=0.03). Interestingly, Urine- Microalbumin levels were higher in the INSTI group compared to NNRTI group (p=0.08), while eGFR levels were lower in the INSTI group (p=0.002). The arterial stiffness measures did not show statistically significant differences between the two groups. ConclusionWe conclude that the INSTI regimen may provide a better CVD risk profile compared to NNRTI based HAART regimen; however the increased albuminuria along with lower eGFR, noted in INSTI group is of concern. Because of the small size, these results would need replication in additional studies before changing clinical practice.Clinical Trial Registration https://clinicaltrials.gov/ct2/show/NCT03782142?cond=Hiv&spons=Sabyasachi+sen&cntry=US&state=US%3ADC&city=Washington&draw=2&rank=1ClinicalTrials.gov Identifier: NCT03782142

Comparison Between ASCVD Versus WHO Risk Score in Predicting of 10-Year Cardiovascular Risk in an Iranian Adult: A Hospital-Based Cross-Sectional Study

Cardiovascular disease (CVD) mortality has increased in the Iranian population. Word Health Organization (WHO) risk score was recently used in Iranian prevention and control of non-communicable disease programs for risk assessment. The purpose of the study was to compare the 10-year cardiovascular risk using atherosclerotic cardiovascular disease (ASCVD) and WHO risk score. In a cross-sectional study, data from patients with cardiac symptoms without any documents related to CVD were collected from the outpatient clinic. The proportion of subjects with high CVD risk according to ASCVD and WHO risk score and also agreement between two scores was presented. The sensitivity and specificity of ASCVD according to the WHO risk score as a national risk assessment tool were calculated. The study included 284 subjects with a mean age of 53.80 (8.78) years and 68 % of women. The frequency of subjects with high CVD risk based on ASCVD and WHO was 35% and 6%, respectively. The agreement between the two scores was moderate (κ=0.45), with the most agreement in identifying low-risk subjects. The sensitivity and specificity of ASCVD according to the WHO risk score was 95.3% and 75.1%, respectively. The present finding showed that Agreement between two risk scores was moderated, especially in stratifying low-risk subjects. But, the ASCVD risk score categorized more people as a high risk rather than the WHO tool. Assessment of the accuracy of the WHO risk score with comparing predicted risk with observed risk in a cohort study for the Iranian population is necessary.

Does Adding Adverse Pregnancy Outcomes Improve the Framingham Cardiovascular Risk Score in Women? Data from the Tehran Lipid and Glucose Study

Background Limited and conflicting evidence is available regarding the predictive value of adding adverse pregnancy outcomes (APOs) to established cardiovascular disease (CVD) risk factors. Hence, the objective of this study was to determine whether adding APOs to the Framingham risk score improves the prediction of CVD events in women. Methods and Results Out of 5413 women who participated in the Tehran Lipid and Glucose Study, 4013 women met the eligibility criteria included for the present study. The exposure and the outcome variables were collected based on the standard protocol. Cox proportional hazard model was used to evaluate the association of APOs and CVDs. The variant of C‐statistic for survivals and reclassification of subjects into Framingham risk score categories after adding APOs was reported. Out of the 4013 eligible subjects, a total of 1484 (36.98%) women reported 1 APO, while 395 (9.84%) of the cases reported multiple APOs. Univariate proportional hazard Cox models showed the significant relations between CVD events and APOs. The enhanced model had a higher C‐statistic indicating more acceptable discrimination as well as a slight improvement in discrimination (C‐statistic differences: 0.0053). Moreover, we observed a greater risk of experiencing a CVD event in women with a history of multiple APOs compared with cases with only 1 APO (1 APO: hazard ratio [HR] = 1.22; 2 APOs: HR; 1.94; ≥3 APOs: HR = 2.48). Conclusions Beyond the established risk factors, re‐estimated CVDs risk by adding APOs to the Framingham risk score may improve the accurate risk estimation of CVD. Further observational studies are needed to confirm our findings.

Ten‐Year Cardiovascular Disease Risk Trajectories by Obstetric History: A Longitudinal Study in the Norwegian HUNT Study

Background Women with a history of obstetric complications are at increased risk of cardiovascular disease, but whether they should be specifically targeted for cardiovascular disease (CVD) risk screening is unknown. Methods and Results We used linked data from the Norwegian HUNT (Trøndelag Health) Study and the Medical Birth Registry of Norway to create a population‐based, prospective cohort of parous women. Using an established CVD risk prediction model (A Norwegian risk model for cardiovascular disease), we predicted 10‐year risk of CVD (nonfatal myocardial infarction, fatal coronary heart disease, and nonfatal or fatal stroke) based on established risk factors (age, systolic blood pressure, total and high‐density lipoprotein cholesterol, smoking, antihypertensive use, and family history of myocardial infarction). Predicted 10‐year CVD risk scores in women aged between 40 and 60 years were consistently higher in those with a history of obstetric complications. For example, when aged 40 years, women with a history of preeclampsia had a 0.06 percentage point higher mean risk score than women with all normotensive deliveries, and when aged 60 years this difference was 0.86. However, the differences in the proportion of women crossing established clinical thresholds for counseling and treatment in women with and without a complication were modest. Conclusions Findings do not support targeting parous women with a history of pregnancy complications for CVD screening. However, pregnancy complications identify women who would benefit from primordial and primary prevention efforts such as encouraging and supporting behavioral changes to reduce CVD risk in later life.

The bisphenol F and bisphenol S and cardiovascular disease: results from NHANES 2013–2016

Background Bisphenol F (BPF) and bisphenol S (BPS) have replaced bisphenol A (BPA) in the manufacturing of products containing polycarbonates and epoxy resins; however, the effects of these substitutes on the risk of cardiovascular disease (CVD), including congestive heart failure, coronary heart disease, angina pectoris, heart attack, and stroke, have not been assessed. Objective To examine the association of urinary BPS and BPF with CVD risk in a U.S. representative U.S. population. Methods Cross-sectional data from 1267 participants aged 20–80 years from the 2013–2016 National Health and Nutrition Examination Survey (NHANES) were analyzed. Survey-weighted multiple logistic regression was used to assess the association between BPA, BPF, BPS and CVD. The Bayesian kernel machine regression (BKMR) model was applied to assess the mixture effect. Results A total of 138 patients with CVD were identified. After adjusting for potential confounding factors, the T3 tertile concentration of BPS increased the risk of total CVD (OR: 1.99, 95% CI 1.16–3.40). When stratified by age, we found that BPS increased the risk of CVD in the 50–80 age group (OR: 1.40, 95% CI 1.05–1.87). BPS was positively associated with the risk of coronary heart disease, and the T3 tertile concentration of BPS increased the coronary heart disease risk by 2.22 times (95% CI 1.04–4.74). No significant association was observed between BPF and CVD. Although the BKMR model did not identify the mixed exposure effect of BPS, the risk of CVD increased with increasing compound concentration. Conclusion Our results suggest that BPS may increase the risk of total CVD and coronary heart disease in the US population, and prospective studies are needed to confirm the results.

Prevalence and factors associated with hypertension among adults with and without HIV in Western Kenya

Introduction The burden of cardiovascular disease (CVD) is increasing in sub-Saharan Africa with untreated hypertension being a major contributing factor. Understanding the magnitude of the problem and risk factors associated with HIV and long-term antiretroviral therapy (ART) is critically important for designing effective programs for diagnosing and treating hypertension in Kenya. Methods In this cross-sectional study, we enrolled 300 persons with HIV (PWH) on long term ART (≥6 months) and 298 HIV-negative adults seeking care at the Kisumu County Hospital between September 2017 and May 2018. Hypertension was defined as blood pressure of ≥140/90mmHg or a previous hypertension diagnosis. Multivariate regression was used to assess the association between hypertension and HIV adjusting for age, sex, and known CVD risk factors. Results Overall prevalence of hypertension was 22%. PWH had a lower prevalence of hypertension than HIV-negative persons (16% vs 27% respectively; p<0.002). In multivariate analyses, persons with HIV were 37% less likely to have hypertension compared to HIV-negative individuals (adjusted prevalence ratio 0.63; 95% confidence interval: 0.46–0.86). Other factors that were associated with hypertension in all participants included older age >40 years, body mass index (BMI) >25 kg/m2 and low-density lipoproteins ≥130mg/dL. Among PWH, being older than 40 years and higher BMI >30 kg/m2 were associated with hypertension. Conclusion Prevalence of hypertension was high, affecting nearly one in every 4 adults, and associated with older age, higher BMI and high low-density lipoproteins. PWH on long-term ART had significantly lower prevalence of hypertension compared to HIV-negative individuals, potentially due to increased access to healthcare services and interaction with prevention messaging. Interventions to increase screening for and prevention of hypertension in the community for all adults are warranted.