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Evaluation of the Pooled Cohort Risk Equations for Cardiovascular Risk Prediction in a Multiethnic Cohort From the Women's Health Initiative.
Mora, S, Wenger, NK, Cook, NR, Liu, J, Howard, BV, Limacher, MC, Liu, S, Margolis, KL, Martin, LW, Paynter, NP, et al
JAMA internal medicine. 2018;(9):1231-1240
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Abstract
IMPORTANCE Atherosclerotic cardiovascular disease (ASCVD) kills approximately 1 in every 3 US women. Current cholesterol, hypertension, and aspirin guidelines recommend calculating 10-year risk of ASCVD using the 2013 Pooled Cohort Equations (PCE). However, numerous studies have reported apparent overestimation of risk with the PCE, and reasons for overestimation are unclear. OBJECTIVE We evaluated the predictive accuracy of the PCE in the Women's Health Initiative (WHI), a multiethnic cohort of contemporary US postmenopausal women. We evaluated the effects of time-varying treatments such as aspirin and statins, and ascertainment of additional ASCVD events by linkage with the Centers for Medicare and Medicaid Services (CMS) claims. DESIGN, SETTING, AND PARTICIPANTS The WHI recruited the largest number of US women (n = 161 808) with the racial/ethnic, geographic, and age diversity of the general population (1993-1998). For this study, we included women aged 50 to 79 (n = 19 995) participating in the WHI with data on the risk equation variables at baseline and who met the guideline inclusion and exclusion criteria. Median follow-up was 10 years. MAIN OUTCOMES AND MEASURES For this study, ASCVD was defined as myocardial infarction, stroke, or cardiovascular death. RESULTS Among the 19 995 women (mean [SD] age, 64 [7.3] years; 8305 [41.5%] white, 7688 [38.5%] black, 3491 [17.5%] Hispanic, 103 [0.5%] American Indian, 321 [1.6%] Asian/Pacific Islander, and 87 [0.4%] other/unknown), a total of 1236 ASCVD events occurred in 10 years and were adjudicated through medical record review by WHI investigators. The WHI-adjudicated observed risks were lower than predicted. The observed (predicted) risks for baseline 10-year risk categories less than 5%, 5% to less than 7.5%, 7.5% to less than 10%, and 10% or more were 1.7 (2.8), 4.4 (6.2), 5.3 (8.7), and 12.4 (18.2), respectively. Small changes were noted after adjusting for time-dependent changes in statin and aspirin use. Among women 65 years or older enrolled in Medicare, WHI-adjudicated risks were also lower than predicted, but observed (predicted) risks became aligned after including events ascertained by linkage with CMS for additional surveillance for events: 3.8 (4.3), 7.1 (6.4), 8.3 (8.7), and 18.9 (18.7), respectively. Similar results were seen across ethnic/racial groups. Overall, the equations discriminated risk well (C statistic, 0.726; 95% CI, 0.714-0.738). CONCLUSIONS AND RELEVANCE Without including surveillance for ASCVD events using CMS, observed risks in the WHI were lower than predicted by PCE as noted in several other US cohorts, but risks were better aligned after including CMS events. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00000611.
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Validation of a genetic risk score for atrial fibrillation: A prospective multicenter cohort study.
Muse, ED, Wineinger, NE, Spencer, EG, Peters, M, Henderson, R, Zhang, Y, Barrett, PM, Rivera, SP, Wohlgemuth, JG, Devlin, JJ, et al
PLoS medicine. 2018;(3):e1002525
Abstract
BACKGROUND Atrial fibrillation (AF) is the most commonly encountered arrhythmia and is associated with an elevated risk of stroke. Improving the identification of patients with the highest risk for AF to enable appropriate surveillance and treatment, if necessary, is critical to reducing AF-associated morbidity and mortality. Multiple common single nucleotide polymorphisms (SNPs) are unequivocally associated with the lifetime risk of AF. In the current study we aimed to prospectively validate an AF genetic risk score (GRS) in previously undiagnosed patients at risk for AF. METHODS AND FINDINGS Individuals 40 years of age or older with 1 clinical risk factor for AF, presenting with symptoms of AF, or with a first diagnosis of AF, were enrolled for genetic testing and ambulatory cardiac rhythm monitoring with an adhesive patch monitor or a long-term Holter monitor (mean wear time 10 days 21 hours and 13 days 18 hours, respectively). An AF event was the first diagnosis of AF by ECG, patch monitor, or long-term Holter monitor. The AF GRS was determined for each participant based on the weighted contribution of 12 genetic risk loci. Of 904 participants, 85 manifested AF. Their mean age was 66.2 (SD 11.8) years; 38% of participants were male. Participants in the highest quintile of AF GRS were more likely (odds ratio 3.11; 95% CI 1.27-7.58; p = 0.01) to have had an AF event than participants in the lowest quintile after adjusting for age, sex, smoking status, BMI, hypertension, diabetes mellitus, heart failure, and prior myocardial infarction. Study limitations included an ethnically homogenous population, a restricted rhythm monitoring period, and the evolving discovery of SNPs associated with AF. CONCLUSIONS Prospective assessment of a GRS for AF identified participants with elevated risk of AF beyond established clinical criteria. Accordingly, a GRS for AF could be incorporated into overall risk assessment to better identify patients at the highest risk of developing AF, although further testing in larger populations is needed to confirm these findings. TRIAL REGISTRATION ClinicalTrials.gov NCT01970969.
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Critical review of methods for risk ranking of food-related hazards, based on risks for human health.
Van der Fels-Klerx, HJ, Van Asselt, ED, Raley, M, Poulsen, M, Korsgaard, H, Bredsdorff, L, Nauta, M, D'agostino, M, Coles, D, Marvin, HJP, et al
Critical reviews in food science and nutrition. 2018;(2):178-193
Abstract
This study aimed to critically review methods for ranking risks related to food safety and dietary hazards on the basis of their anticipated human health impacts. A literature review was performed to identify and characterize methods for risk ranking from the fields of food, environmental science and socio-economic sciences. The review used a predefined search protocol, and covered the bibliographic databases Scopus, CAB Abstracts, Web of Sciences, and PubMed over the period 1993-2013. All references deemed relevant, on the basis of predefined evaluation criteria, were included in the review, and the risk ranking method characterized. The methods were then clustered-based on their characteristics-into eleven method categories. These categories included: risk assessment, comparative risk assessment, risk ratio method, scoring method, cost of illness, health adjusted life years (HALY), multi-criteria decision analysis, risk matrix, flow charts/decision trees, stated preference techniques and expert synthesis. Method categories were described by their characteristics, weaknesses and strengths, data resources, and fields of applications. It was concluded there is no single best method for risk ranking. The method to be used should be selected on the basis of risk manager/assessor requirements, data availability, and the characteristics of the method. Recommendations for future use and application are provided.
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Sports Practices and Cardiovascular Risk in Teenagers.
Scherr, C, Fabiano, LCC, Guerra, RL, Belém, LHJ, Câmara, ACG, Campos, A
Arquivos brasileiros de cardiologia. 2018;(3):248-255
Abstract
BACKGROUND Cardiovascular diseases are the leading cause of deaths in the world, and many events could be prevented by healthy life habits. OBJECTIVES To compare the occurrence of cardiovascular risk factors in adolescents enrolled at public schools in the city of Rio de Janeiro, including a renowned school for sport practices. METHODS Cross-sectional study, convenience sampling of 422 students enrolled at the Experimental Olympic Gymnasium (EOG) and at Figueiredo Pimentel School (FP). Using descriptive analyses, continuous variables were expressed as mean and standard deviation or median and interquartile ranges, and the Student's t-test or the chi-square test, respectively, was used for comparisons. The sports were classified according to the metabolic equivalent of task (MET) (below or above 5). RESULTS We included 274 students enrolled at the EOG and 148 at FP. Mean age was similar between schools -12.5 ± 1.6 years at FP and 12.6 ± 0.9 at the EOG; 65.5% of the students at FP and 43.8% of the students at the EOG were female (p < 0.01). Significant differences in the prevalence of hypertension (20% vs. 6.3%, p < 0.01) and borderline cholesterol levels (27.7% vs. 17.3%, p = 0.01) were found between FP and EOG students, respectively. CONCLUSION High prevalence of hypertension, overweight/obesity and altered blood lipid profile was found in this group of adolescents. Regular sports training program combined with little influence of their eating habits outside school may contribute to a better metabolic profile and reduction in cardiovascular risk factors in students. Public health measures are also need.
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Tobacco smoking and the risk of atrial fibrillation: A systematic review and meta-analysis of prospective studies.
Aune, D, Schlesinger, S, Norat, T, Riboli, E
European journal of preventive cardiology. 2018;(13):1437-1451
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Abstract
Background Epidemiological studies on smoking and atrial fibrillation have been inconsistent, with some studies showing a positive association while others have found no association. It is also unclear whether there is a dose-response relationship between the number of cigarettes smoked or pack-years and the risk of atrial fibrillation. We conducted a systematic review and meta-analysis to clarify the association. Design Systematic review and meta-analysis. Methods We searched the PubMed and Embase databases for studies of smoking and atrial fibrillation up to 20 July 2017. Prospective studies and nested case-control studies within cohort studies reporting adjusted relative risk estimates and 95% confidence intervals (CIs) of atrial fibrillation associated with smoking were included. Summary relative risks (95% CIs) were estimated using a random effects model. Results Twenty nine prospective studies (22 publications) were included. The summary relative risk was 1.32 (95% CI 1.12-1.56, I2 = 84%, n = 11 studies) for current smokers, 1.09 (95% CI 1.00-1.18, I2 = 33%, n = 9) for former smokers and 1.21 (95% CI 1.12-1.31, I2 = 80%, n = 14) for ever smokers compared to never smokers. Comparing current versus non-current smokers the summary relative risk was 1.33 (95% CI 1.14-1.56, I2 = 78%, n = 10). The summary relative risk was 1.14 (95% CI 1.10-1.20, I2 = 0%, n = 3) per 10 cigarettes per day and 1.16 (95% CI 1.09-1.25, I2 = 49%, n = 2) per 10 pack-years and there was no evidence of a non-linear association for cigarettes per day, Pnon-linearity = 0.17. Conclusions The current meta-analysis suggests that smoking is associated with an increased risk of atrial fibrillation in a dose-dependent matter, but the association is weaker among former smokers compared to current smokers.
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Circulating microRNA-132 levels improve risk prediction for heart failure hospitalization in patients with chronic heart failure.
Masson, S, Batkai, S, Beermann, J, Bär, C, Pfanne, A, Thum, S, Magnoli, M, Balconi, G, Nicolosi, GL, Tavazzi, L, et al
European journal of heart failure. 2018;(1):78-85
Abstract
AIMS: Non-coding microRNAs (miRNAs) are critically involved in cardiovascular pathophysiology. Since they are measurable in most body fluids, they have been proposed as circulating biomarkers. We examined the prognostic value of a specific candidate miRNA in a large cohort of patients with chronic heart failure (HF) enrolled in a multicentre clinical trial. METHODS AND RESULTS Plasma levels of miR-132 were measured using miRNA-specific PCR-based technologies at randomization in 953 patients with chronic, symptomatic HF from the GISSI-Heart Failure trial. The association with fatal (all-cause and cardiovascular death) and non-fatal events (time to first admission to hospital for cardiovascular reasons or worsening of HF) and the incremental risk prediction were estimated in adjusted models. Higher circulating miR-132 levels were independently associated with younger age, better renal filtration, ischaemic aetiology of HF, more severe HF symptoms, higher diastolic blood pressure, higher cholesterol, and male sex. After extensive adjustment for demographic, clinical, and echocardiographic risk factors and baseline NT-proBNP concentrations, miR-132 remained associated only with HF hospitalizations (hazard ratio 0.79, 95% confidence interval 0.66-0.95, P = 0.01) and improved its risk prediction with the continuous net reclassification index (cNRI 0.205, P = 0.001). CONCLUSION In well characterized patients with chronic HF, circulating miR-132 levels rise with the severity of HF. Lower circulating miR-132 levels improved risk prediction for HF readmission beyond traditional risk factors, but not for mortality. MiR-132 may be helpful to intensify strategies aimed at reducing re-hospitalization, which has a substantial health and economic burden in HF.
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Use of the Kidney Failure Risk Equation to Determine the Risk of Progression to End-stage Renal Disease in Children With Chronic Kidney Disease.
Winnicki, E, McCulloch, CE, Mitsnefes, MM, Furth, SL, Warady, BA, Ku, E
JAMA pediatrics. 2018;(2):174-180
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Abstract
IMPORTANCE The kidney failure risk equation (KFRE) has been shown to accurately estimate progression to kidney failure in adults with chronic kidney disease (CKD). Use of the KFRE in children with CKD, if accurate, would help to optimize planning for end-stage renal disease (ESRD) care. OBJECTIVE To determine whether the KFRE adequately discriminates the risk of ESRD in children with CKD. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study included 603 children with an estimated glomerular filtration rate of less than 60 mL/min/1.73 m2 in the Chronic Kidney Disease in Children study, a national multicenter observational study. Data were collected from January 1, 2005, through July 31, 2013, and analyzed from September 30, 2016, through September 8, 2017. EXPOSURES The primary predictive factors were the 4-variable (age, sex, bedside Schwartz estimated glomerular filtration rate, and ratio of albumin to creatinine levels) and 8-variable (4 variables plus serum calcium, phosphate, bicarbonate, and albumin levels) KFREs, which provide 1-, 2-, and 5-year estimates of the risk of progression to ESRD. MAIN OUTCOMES AND MEASURES Time to ESRD. The Cox proportional hazards model was used to examine the association between the KFRE score and time to ESRD. C statistics were used to discriminate ESRD risk by the KFRE, with a value of greater than 0.80 indicating strong discrimination. RESULTS Of the 603 children included in the study, 378 were boys (62.7%) and 225 were girls (37.3%); median age at study entry was 12 years (interquartile range, 8-15 years). Median estimated glomerular filtration rate was 44 mL/min/1.73 m2. Four hundred fifty-seven participants (75.8%) had a nonglomerular cause of CKD. Median observation time was 3.8 years (interquartile range, 1.7-6.2 years); 144 (23.9%) developed ESRD within 5 years of enrollment. The 4-variable KFRE scores discriminated risk of ESRD, with C statistics of 0.90, 0.86, and 0.81 for the 1-, 2-, and 5-year risk scores, respectively. Results were similar using the 8-variable equation. CONCLUSIONS AND RELEVANCE The KFRE is a simple tool that provides excellent discrimination of the risk of ESRD. Results suggest that the KFRE could be incorporated into the clinical care of children with CKD to aid in anticipatory guidance, timing of referral for transplant evaluation, and planning for dialysis access.
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TIMI-AF score and cardiovascular events in vitamin K antagonists-naïve outpatients with atrial fibrillation.
Pérez Cabeza, AI, Bravo Marques, R, Chinchurreta Capote, PA, Ruiz Mateas, F, Fanola, CL, Rosas Cervantes, G, González Correa, JA, Valle Alberca, A, Mesa Prado, F, López Tejero, S, et al
Clinical cardiology. 2018;(9):1252-1258
Abstract
BACKGROUND The TIMI-AF score predicts poor outcomes in patients with atrial fibrillation (AF) and guides selection of anticoagulant therapy by identifying clinical benefit of direct oral anticoagulants (DOACs) or vitamin K antagonists (VKA). HYPOTHESIS Our objective was to determine the ability to predict cardiovascular events according to the TIMI-AF score in a real-world population. METHODS Retrospective observational study of VKA-naïve patients with AF was seen at a cardiology outpatient clinic in Spain between November 2012 and August 2014. We recorded adverse events (myocardial infarction, systemic embolism or stroke, major bleeding, and death). RESULTS The study population comprised of 426 patients (50.7% men, mean age, 69 ± 14 years). The TIMI-AF score identified 372 patients (87.3%) with a low risk, 50 patients (11.7%) with an intermediate risk, and 4 patients (0.9%) with a high risk. After a mean follow-up of 423.4 ± 200.1 days, 37 patients (9%) experienced an adverse event. Patients with a TIMI-AF score ≥ 7 had a poorer cardiovascular prognosis (HR, 6.1; 95%CI, 3.2-11.7; P < 0.001). The area under the ROC curve of TIMI-AF was 0.755 (95%CI, 0.669-0.840; P < 0.001), which was greater than that of CHA2 DS2 VASc (0.641; 95%CI, 0.559-0.724; P = 0.004), HAS-BLED (0.666; 95%CI, 0.578-0.755; P < 0.001), and SAMeTT2 R2 (0.529; 95%CI, 0.422-0.636; P = 0.565). Similar results were obtained in relation to the net clinical outcome (life-threatening bleeding, disabling stroke, or all-cause mortality). CONCLUSIONS The TIMI-AF risk score can identify patients who are at greater risk of cardiovascular events and a poor net clinical outcome with a better diagnostic yield than CHA2 DS2 VASc, HAS-BLED, and SAMeTT2 R2 .
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Sodium-glucose co-transporter 2 inhibitors and cardiovascular outcomes: A systematic review and meta-analysis.
Usman, MS, Siddiqi, TJ, Memon, MM, Khan, MS, Rawasia, WF, Talha Ayub, M, Sreenivasan, J, Golzar, Y
European journal of preventive cardiology. 2018;(5):495-502
Abstract
Background The risks and benefits of sodium-glucose co-transporter 2 (SGLT2) inhibitors on cardiovascular outcomes have not been well established. We pooled evidence from all available clinical trials to assess the cardiovascular effects of this drug. Design A systematic review and meta-analysis of randomised controlled trials. Methods We queried electronic databases (MEDLINE, Scopus, CENTRAL and clinicaltrials.gov) from their inception to July 2017 for published and unpublished placebo controlled trials of SGLT2 inhibitors. Only studies with a follow-up period of at least 24 weeks and reporting at least one cardiovascular outcome were included. Results from trials were presented as odds ratios (ORs) with 95% confidence intervals (CIs) and were pooled using a random-effects model. Results Thirty-five eligible studies (canagliflozin, nine; empagliflozin, eight; dapagliflozin, 18), consisting of 34,987 patients with type 2 diabetes mellitus were included. Pooled results show that SGLT2 inhibitors, when compared to placebo, significantly reduce all-cause mortality (OR 0.79, 95% CI 0.70-0.89; P < 0.001), major adverse cardiac events (OR 0.8, 95% CI 0.76-0.92; P < 0.001), non-fatal myocardial infarction (OR 0.85, 95% CI 0.73-0.98; P = 0.03) and heart failure/hospitalisation for heart failure (OR 0.67, 95% CI 0.59-0.76; P < 0.001) in patients with type 2 diabetes mellitus. No significant difference was noted in the occurrence of stroke (OR 1.02, 95% CI 0.85-1.21; P = 0.87), atrial fibrillation (OR 0.61, 95% CI 0.31-1.19; P = 0.15) or unstable angina (OR 0.95, 95% CI 0.73-1.25; P = 0.73). In addition, there was no heterogeneity between different drugs in the SGLT2 inhibitor class for all of the clinical outcomes studied ( I2 = 0). Conclusions SGLT2 inhibitors significantly reduce the incidence of mortality, major adverse cardiac events, non-fatal myocardial infarction and heart failure in patients with type 2 diabetes mellitus. Subtypes of SGLT2 inhibitors appear to have similar cardiovascular effects.
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Cardiovascular risk goes up as your mood goes down: Interaction of depression and socioeconomic status in determination of cardiovascular risk in the CONSTANCES cohort.
Wiernik, E, Meneton, P, Empana, JP, Siemiatycki, J, Hoertel, N, Vulser, H, Nabi, H, Limosin, F, Czernichow, S, Goldberg, M, et al
International journal of cardiology. 2018;:99-105
Abstract
BACKGROUND Recent evidence suggests that the association of psychological variables with the risk of coronary heart disease (CHD) might depend upon socioeconomic status (SES). However, it is unclear whether the association between depressive symptoms and CHD risk might differ according to three SES indicators (education, occupational status and household monthly income). METHODS Among 34,836 working participants of the French CONSTANCES cohort (16,221 men, mean age [SD]: 44.0 [10.4] years) without history of cardiovascular disease, depressive symptoms were assessed with the Center of Epidemiologic Studies Depression scale (CES-D). The Framingham risk equation calibrated to the French population estimated the participant's 10-year risk of CHD. Associations between depressive symptoms and CHD risk were estimated using linear regression models in SES strata. RESULTS The estimated 10-year risk of CHD was 16.9% in men and 1.8% in women. In men, the increased CHD risk in those with (versus without) depressive symptoms was more pronounced as occupational status decreased, being 0.65% (-0.57; 1.88), 1.58% (0.50; 2.66) and 3.19% (1.30; 5.07) higher in individuals of high, medium and low occupational status, respectively (p for interaction: 0.01). In contrast, effect modification by education or household income was less evident, despite similar trends. In women, no effect modification was found whatever the SES indicator. CONCLUSIONS Depressive symptoms and 10-year estimated CHD risk were more tightly linked in individuals of lower SES, at least in men. Occupational status was the SES indicator that displays the most obvious effect modification on this association.