Baseline Framingham Risk Score Research Articles

POS1079 ASSOCIATION OF C-REACTIVE PROTEIN AND NON-STEROIDAL ANTI-INFLAMMATORY DRUGS WITH CARDIOVASCULAR EVENTS IN PATIENTS WITH PSORIATIC ARTHRITIS: A TIME-DEPENDENT Cox REGRESSION ANALYSIS

Background:Psoriatic arthritis (PsA) is associated with accelerated atherosclerosis due to underlying inflammation. Whether inflammatory burden and drugs used to suppress inflammation over time are associated with cardiovascular (CV) events remains unclear.Objectives:This study aims to examine the time-varying effect of C-reactive protein (CRP) levels and the use of drugs including non-steroidal anti-inflammatory drugs (NSAIDs) on the risk of CV events independent of traditional CV risk factors in PsA patients.Methods:A retrospective cohort analysis was performed in patients with PsA who were recruited from 2008 to 2015 and followed till the end of 2019. The outcome was occurrence of a first CV event. Framingham risk score (FRS) was used to quantify the traditional CV risk. Cox proportional hazard models with time-varying CRP levels and drugs used were analyzed to identify the risk factors for CV events in PsA patients.Results:200 patients with PsA (median age: 47.5[40.0 – 56.0]; male: 119 [59.5%]) were recruited (Table 1. next page). After a mean follow-up of 8.8±3.8 years, 30 (15%) patients developed a first CV event. The Kaplan-Meier survival analysis indicated a significant difference in the CV event-free survival between patients with and without CRP level >3 mg/L (Figure 1A) and an inverse relationship between time-varying NSAIDs exposure and CV event-free survival (Figure 1B). The multivariable Cox regression model showed that time-varying CRP level (HR 1.02, 95% CI 1.00 to 1.04) and NSAIDs exposure (HR 0.30, 95% CI 0.15 to 0.95) were significantly associated with CV events after adjusting for baseline FRS (HR 5.04, 95% CI 1.83 to 13.85).Table 1.Baseline demographic and clinical characteristics, cardiovascular risk factors and treatments received.VariablesAll patientsn=200median (IQR) or n (%)CVD -ve,n=170median (IQR)or n (%)CVD +ve,n=30median (IQR)or n (%)p-valueNSAID -ve, n=61median (IQR)or n (%)NSAID +ve, n=139median (IQR) or n (%)p-valueMale, n (%)119 (59.5%)100 (58.6%)19 (63.3%)0.22839 (63.9%)80 (57.6%)0.397Age, years47.5 (40.0 – 56.0)46.5 (37.7 – 54.0)57.0 (45.3 – 65.8)<0.001*49.0 (44.0 – 56.5)46.0 (38.0 – 54.8)0.176Disease duration, years4.3 (1.8 – 7.9)4.1 (1.7 – 7.0)6.0 (2.1 – 8.6)0.0664.6 (1.5 – 8.7)4.3 (1.9 – 7.3)0.393Diabetes, n (%)45 (22.5%)30 (17.6%)15 (50.0%)<0.001*10 (16.4%)35 (25.2%)0.171Hypertension, n (%)68 (34.0%)46 (27.1%)22 (73.3%)<0.001*21 (34.4%)47 (33.9%)0.933CRP, mg/L4.9 (1.7 – 12.6)4.2 (1.5 – 12.0)11.3 (2.4 – 19.6)0.035*5.5 (1.7 – 15.1)7.2 (1.4 – 15.8)0.770ESR, mm/hr21 (10.0 – 38.0)20 (9 – 35)31 (14 – 60)0.038*21 (7 – 33)21 (11 – 43)0.291Systolic blood pressure, mmHg125 (115 – 140)124 (115 – 137)144 (129 – 160)<0.001*123 (118 – 137)125 (115 – 141)0.889Diastolic blood pressure, mmHg78 (70 – 85)78 (70 – 84)82 (72 – 90)0.19978 (72 – 86)78 (70 – 85)0.697FRS8.4 (4.0 – 17.0)7.5 (3.3 – 14.0)19.6 (13.4 – 43.0)<0.001*7.9 (3.5 – 15.5)8.7 (4.2 – 17.1)0.885Lipid-lowering drugs, n (%)30 (15.0%)25 (14.7%)5 (16.7%)0.7829 (14.8%)21 (15.1%)0.949MTX, n (%)99 (49.5%)81 (47.6%)18 (60.0%)0.21225 (41.0%)74 (53.2%)0.111bDMARDs, n (%)17 (8.5%)13 (7.6%)4 (13.3%)0.3036 (9.8%)11 (7.9%)0.654NSAIDs, n (%)139 (69.2%)119 (70.0%)20 (66.7%)0.715N/AN/AN/ASteroid, n (%)2 (1.0%)2 (1.2%)0 (0%)1.0001 (1.6%)1 (0.7%)0.518*statistically significant at p≤ 0.05CVD+ve, patients who developed cardiovascular events during subsequent follow-up;CVD-ve, patients who did not developed cardiovascular events during subsequent follow-up;NSAIDs, nonsteroidal anti-inflammatory drugs; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; FRS, Framingham Risk Score; MTX, methotrexate; bDMARDs, biological disease-modifying antirheumatic drugs.Conclusion:Increased inflammatory burden as reflected by elevated CRP level was associated with increased risk of CV events, while the risk was significantly reduced with NSAIDs use in PsA patients.Disclosure of Interests:None declared.

Pictorial information about subclinical atherosclerosis reduces the CVD risk: Results from the VIPVIZA RCT

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Region Västerbotten and the Swedish Research Council Background The VIPVIZA trial has previously shown beneficial effects on cardiovascular disease (CVD) risk scores 1 year after sending pictorial information of carotid ultrasound imaging (Picture 1) to individuals and their physicians Purpose To investigate whether the beneficial effects on CVD-risk observed at 1-year were sustained over three years Methods VIPVIZA is a pragmatic prospective open-label randomized controlled trial with blinded evaluators performed within a CVD prevention programme integrated in the regular primary health care in Västerbotten County, Sweden. Individuals aged 40, 50 or 60 years old with one CVD risk factor were enrolled and randomised 1:1 to intervention (n = 1749, pictorial information about subclinical atherosclerosis provided to participants and physicians, Picture 1) or control group(n = 1783, no information to participants or physicians). Intervention participants also recieved a follow-up phone call and the corresponding physicians written guideline-based information about the clinical significance of carotid ultrasound results. Participants were examined at baseline (2013-2016), after one and at three years Results A significant beneficial effect on cardiovascular risk was observed at the 3-year follow-up; Framingham Risk Score (FRS) was 13.38 for the intervention group and 14.08 for the control group(p = 0.047) and SCORE was 1.69 vs. 1.82(p = 0.022) respectively. The 3-year results adjusted for sex and educational level showed significant differences between the intervention and control group in FRS, SCORE, P-Total-Cholesterol, P-LDL-Cholesterol and waist circumference in favour of the intervention group. Analysis by sex showed difference in differences(DID) in FRS for men -1.19(95% CI -2.01 to -0.37) and -0.50(95% CI -0.93 to -0.07) for women and in SCORE for men -0.20(95% CI -0.33 to -0.06) and -0.08 (95% CI -0.13 to -0.04) for women, between the two groups over 3 years. Similarly, there were significant differences in DID in all educational groups. Further stratification by baseline FRS and SCORE risk category, showed a beneficial pattern of the intervention in all risk groups, however the DID at the 3-year follow-up was statistically significant only in the intermediate risk group for both FRS -1.34(95% CI -2.13 to -0.56) and SCORE -0.19(95% CI -0.32 to -0.05) Conclusions This study provides evidence of sustained effects over three years of pictorial information of subclinical carotid atherosclerosis on the reduction of cardiovascular risk regardless of sex and educational level. Importantly, a statistically significant intervention effect was seen in the intermediate risk group, where the majority of CVD events occur. Visualization of subclinical atherosclerosis may be one way to approach individuals at intermediate risk of CVD, a group where sufficient prevention is often overlooked. However, further studies are needed to investigate the intervention effect on hard end points as CVD-events and death. Abstract Figure. Picture 1

Association of C-reactive protein and non-steroidal anti-inflammatory drugs with cardiovascular events in patients with psoriatic arthritis: a time-dependent Cox regression analysis.

Aims:Psoriatic arthritis (PsA) is associated with accelerated atherosclerosis due to underlying inflammation. Whether inflammatory burden and drugs used to suppress inflammation over time are associated with cardiovascular (CV) events remained unclear. This study aims to examine the time-varying effect of C-reactive protein (CRP) levels and the use of drugs, including non-steroidal anti-inflammatory drugs (NSAIDs) and disease modifying anti-rheumatic drugs, on the risk of CV events independent of traditional CV risk factors in PsA patients.Methods:A retrospective cohort analysis was performed in patients with PsA who were recruited from 2008 to 2015 and followed until the end of 2019. The outcome was occurrence of a first CV event. Framingham risk score (FRS) was used to quantify the traditional CV risk. Cox proportional hazard models with time-varying CRP levels and drugs used were analysed to identify the risk factors for CV events in PsA patients.Results:Two hundred patients with PsA [median age: 47.5 (40.0–56.0); male: 119 (59.5%)] were recruited. After a mean follow-up of 8.8 ± 3.8 years, 30 (15%) patients developed a first CV event. The multivariable Cox regression model showed that time-varying CRP level [hazard ratio (HR) 1.02, 95% confidence interval (CI) 1.00–1.04] and NSAIDs exposure (HR 0.38, 95% CI 0.15–0.96) were significantly associated with CV events after adjusting for baseline FRS (HR 5.06, 95% CI 1.84–13.92).Conclusion:Increased inflammatory burden as reflected by elevated CRP level was associated with increased risk of CV events, while the risk was significantly reduced with NSAIDs use in PsA patients.

Baseline Framingham risk score does not predict future ECG-derived QRS duration over an average of 3.3\xa0years

BackgroundProlonged electrocardiogram (ECG) QRS duration has been associated with increased cardiovascular risk. It is unclear whether the main predictor of cardiovascular risk, the Framingham risk score also predicts short-term changes in ECG QRS duration. Our aim is to determine whether baseline Framingham risk score is associated with baseline or changes in QRS duration.MethodsA retrospective cross-sectional analysis was performed using observational data obtained from two hundred two participants. Framingham risk score was calculated using an online risk calculator. QRS duration was obtained using a 10 s trace from a Welch Allyn PC-based 12-lead ECG system.ResultsAverage follow-up duration was 3.3 ± 1.1 years. Mean QRS change was 1.8 ± 11.4 ms. Specifically, among two hundred two participants, there are 104 subjects with a greater QRS duration at follow-up, while 98 subjects had the same or a shorter follow-up QRS duration. Baseline Framingham risk score did not significantly predict an increase in QRSd with an odds ratio of 1.04 (P = 0.230). Regression analysis of QRS duration at baseline and Framingham risk at baseline had a weak association (R2 = 0.020; P = 0.043). The Framingham risk score at follow-up was likewise has a weak association with follow-up QRS duration (R2 = 0.045; P = 0.002).ConclusionsOur results do not demonstrate a statistically significant association between Framingham risk parameters and future QRS duration changes over longitudinal time. QRS duration had variable changes between baseline and follow-up. This might suggest that a longer period of follow-up is required to document more stable increases in QRS duration associated with ventricular pathology. A larger population study is needed to confirm our observations.

Effect of a Comprehensive Cardiovascular Risk Reduction Intervention in Persons With Serious Mental Illness

Persons with serious mental illness have a cardiovascular disease mortality rate more than twice that of the overall population. Meaningful cardiovascular risk reduction requires targeted efforts in this population, who often have psychiatric symptoms and cognitive impairment. To determine the effectiveness of an 18-month multifaceted intervention incorporating behavioral counseling, care coordination, and care management for overall cardiovascular risk reduction in adults with serious mental illness. This randomized clinical trial was conducted from December 2013 to November 2018 at 4 community mental health outpatient programs in Maryland. The study recruited adults with at least 1 cardiovascular disease risk factor (hypertension, diabetes, dyslipidemia, current tobacco smoking, and/or overweight or obesity) attending the mental health programs. Of 398 participants screened, 269 were randomized to intervention (132 participants) or control (137 participants). Data collection staff were blinded to group assignment. Data were analyzed on the principle of intention to treat, and data analysis was performed from November 2018 to March 2019. A health coach and nurse provided individually tailored cardiovascular disease risk reduction behavioral counseling, collaborated with physicians to implement appropriate risk factor management, and coordinated with mental health staff to encourage attainment of health goals. Programs offered physical activity classes and received consultation on serving healthier meals; intervention and control participants were exposed to these environmental changes. The primary outcome was the change in the risk of cardiovascular disease from the global Framingham Risk Score (FRS), which estimates the 10-year probability of a cardiovascular disease event, from baseline to 18 months, expressed as percentage change for intervention compared with control. Of 269 participants randomized (mean [SD] age, 48.8 [11.9] years; 128 men [47.6%]), 159 (59.1%) had a diagnosis of schizophrenia or schizoaffective disorder, 67 (24.9%) had bipolar disorder, and 38 (14.1%) had major depressive disorder. At 18 months, the primary outcome, FRS, was obtained for 256 participants (95.2%). The mean (SD) baseline FRS was 11.5% (11.5%) (median, 8.6%; interquartile range, 3.9%-16.0%) in the intervention group and 12.7% (12.7%) (median, 9.1%; interquartile range, 4.0%-16.7%) in the control group. At 18 months, the mean (SD) FRS was 9.9% (10.2%) (median, 7.7%; interquartile range, 3.1%-12.0%) in the intervention group and 12.3% (12.0%) (median, 9.7%; interquartile range, 4.0%-15.9%) in the control group. Compared with the control group, the intervention group experienced a 12.7% (95% CI, 2.5%-22.9%; P = .02) relative reduction in FRS at 18 months. An 18-month behavioral counseling, care coordination, and care management intervention statistically significantly reduced overall cardiovascular disease risk in adults with serious mental illness. This intervention provides the means to substantially reduce health disparities in this high-risk population. ClinicalTrials.gov Identifier: NCT02127671.

Peripheral endothelial function changes during HER2-directed therapy differ based on whether or not a patient receives anthracycline.

1044 Background: Trastuzumab is well-demonstrated to be associated with cardiotoxicity (typically reduced ejection fraction), most commonly in patients who also receive anthracycline. The vascular effects of trastuzumab and anthracycline are understudied; we aimed to compare change in endothelial function during and after trastuzumab and to assess how anthracycline receipt affects this. Methods: This is an observational prospective study of women with newly diagnosed HER2-positive breast cancer. All participants underwent baseline evaluation of endothelial function testing by use of the EndoPAT2000 device approximately every three months over the subsequent 18 months after the initiation of HER2-directed therapy +/- anthracycline. The primary endpoint was change in endothelial function over time using the reactive hyperemia index (RHI). Framingham Risk Score (FRS) and lower RHI are both known to be independent predictors of future cardiovascular events in the general population. RHI deterioration was defined as a 20% reduction from baseline RHI to any available follow-up RHI assessment. Univariate analyses assessed if age, FRS, baseline RHI, and RHI deterioration differed between recipients and non-recipients of anthracycline using the Wilcoxon test. A multivariate logistic model evaluated FRS, age, and anthracycline receipt as possible independent predictors of RHI deterioration. Results: Among 38 eligible patients who consented and completed baseline assessments in addition to at least one follow-up assessment, 17 (45%) subsequently received anthracycline. 145 total follow-up RHI assessments were available overall (5 per patient on average). There were no differences between recipients and non-recipients of anthracyclines with regard to age [mean 49 years (SD 12) vs 53 years (SD 11); p=0.25], baseline FRS [mean 1.0 (SD 1.0) vs 1.5 (SD 1.4); p= 0.28] or baseline RHI [mean 2.4 (SD 0.6) vs 2.1 (SD 0.7); p=0.09]. RHI deterioration was more common for anthracycline recipients (mean 43% vs 21%; p=0.004), and in the multivariate model, anthracycline use was the only independent predictor of RHI deterioration (odds ratio: 2.8; 95% confidence interval: 1.35-6.07; p=0.006). Conclusions: This study suggests that endothelial dysfunction is more common after combined anthracycline and HER2-directed therapy than after HER2-directed therapy alone. RHI should be further studied as a possible early biomarker of cardiovascular toxicity in patients receiving treatment for breast cancer.

Effectiveness of blood pressure-lowering treatment by the levels of baseline Framingham risk score: A post hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT).

This was a post hoc analysis of Systolic Blood Pressure Intervention Trial (SPRINT), aimed to investigate whether intensive blood pressure treatment has differential therapeutic outcomes on patients with different baseline Framingham risk score (FRS). The 9298 SPRINT participants were categorized into low-risk (baseline FRS<10%), intermediate-risk (FRS=10%-20%), or high-risk (FRS>20%) arms. The primary outcome was a composite of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure, or death from cardiovascular causes. Serious adverse events were defined as hypotension, syncope, and bradycardia. Multiple Cox regression was used to calculate hazard ratios for study outcomes with intensive compared with standard SBP treatment between these three groups. After a median follow-up time of 3.26years, the primary outcome hazard ratio (HR) for intensive versus standard treatment was 0.73 (95% CI: 0.61-0.88, P=.0044) in the high-risk arm. And, for all-cause mortality, the hazard ratio with intensive SBP treatment was 1.58 (95% CI: 0.55-1.06), 0.9 (95% CI: 0.26-9.50), and 0.53 (95% CI: 0.34-0.82) in three arms (all P values for interaction>0.05). Effects of intensive versus standard SBP control on serious adverse events were similar among patients with different FRS. Our results suggested that regardless of the FRS level, the intensive blood pressure control was beneficial.

AB0323 CARDIOVASCULAR RISK ESTIMATION IN PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH BIOLOGICS OR C-DMARDS

Background Patients with Rheumatoid Arthritis (RA) are at increased risk of developing atherosclerotic cardiovascular (CV) disease. The impact of treatment with conventional or biological disease modifying drugs (c- or b-DMARDs) on inflammation of systemic circulation is an important question. Objectives The aim of this study is to determine the influence of therapy (c-DMARDs or b-DMARDs) on 10 year CV risk in patients with RA, over a period of 18 months. Methods A single center, observational study of 229 consecutive RA patients, who were treated with c-DMARDs or b-DMARDs mono/combination therapy for at least 18 months. The 10 year CV risk was calculated with Framingham risk score (FRS). Results A total of 229 patients were included, 111 received b-DMARDs and 194 c-DMARDs. The mean age was comparable between 2 groups (62.45±12.74 vs 64.56±12.48years, p: 0.1596) and 148 (64.63%) were female. Patients receiving b-DMARDs had longer disease duration compared to c-DMARDs group (14.34±9.89 vs 9.99±9.3 years respectively, p: 0.001) and comparable baseline FRS 10-year percent CV risk (10.74±8.88 vs 11.68±8.78 respectively, p: 0.3710). Baseline patient distribution across intermediate (9.6% vs 16.6%) and high (10.91% vs 16.16%) FRS 10-year CV risk categories was comparable between treatment groups (b-DMARDs vs c-DMARDs, p: 0.208), except low FRS category (27.51% vs 51.53% respectively, p Conclusion Patients treated with b-DMARDs had lower baseline and month 18 10-year CV risk. However, both treatment arms induced significant improvement of 10-year CV risk at 18 months.

SUN-055 Reduction of Mortality and Major Adverse Cardiovascular Events (MACE) in Men with Hypogonadism Treated with Long-Term Testosterone Therapy (TTh) with Testosterone Undecanoate Injections (TU): 10-Year Data from a Registry Study in a Urological Setting

Background: 3 studies reported an increased cardiovascular risk with TTh while hundreds of studies have demonstrated cardiovascular benefits of TTh in men with hypogonadism. Material and Methods: A prospective, cumulative registry study to investigate long-term effectiveness and safety of depot TU to treat hypogonadism was established in 2004 in a urological setting. Of 805 hypogonadal men, 412 received parenteral TU 1000 mg/12 weeks following an initial 6-week interval (T-group) for up to 12 years. 393 men opted against TTh and served as controls (CTRL). Mean changes over time between groups were compared by mixed effects model for repeated measures with random effect for intercept and fixed effects for time, group and their interaction and adjusted for age, weight, waist circumference, fasting glucose, blood pressure and lipids to account for baseline differences between groups. Results: Baseline age: 57.7±7.4 (T-group), 63.7±4.8 years (CTRL) (p<0.001). Total follow-up time comprised approximately 6.500 patient-years. Testosterone levels at baseline were 9.7 nmol/L in both groups (p=0.841). Anthropometry: 66.3% (T-group) and 48% (CTRL) were obese. Waist circumference decreased by 9.9 cm (T-group) and increased by 4.4 cm (CTRL). Weight decreased by 16.6% (T-group) and increased by 4.6% (CTRL). Glycemic control: 34.2% (T-group) and 43.3% (CTRL) had type 2 diabetes. HbA1c decreased by 2.1% (T-group) and increased by 2.1% (CTRL). Lipids: HDL increased by 1.5 mmol/L (T-group) and by 0.9 mmol/L (CTRL). LDL decreased by 1.6 mmol/L (T-group) and increased by 0.9 mmol/L (CTRL). Non-HDL decreased by 4.1 mmol/L (T-group) and increased by 3.3 mmol/L (CTRL). Blood pressure (BP): systolic BP decreased by 21.2 mmHg (T-group) and increased by 9 mmHg (CTRL), diastolic BP decreased by 11.3 mmHg (T-group) and increased by 5.2 mmHg (CTRL). In the T-group, 45 patients (10.9%) had had a previous myocardial infarction (MI), in CTRL, 43 patients (10.9%) (p=0.993). 162 men (39.3%) had been smokers at baseline, 145 (36.9%) in CTRL (p=0.359). The mean baseline Framingham risk score was 15.5 in the T-group and 15.8 in CTRL (p<0.05). The mean 10-year risk was 22.7% in the T-group and 23.5% in CTRL (p=0.11). The risk declined in the T-group to 17% after 1 year and 13% after 2 years and remained stable thereafter. In CTRL, risk remained unchanged during the first 4 years and then increased to 29% for the remaining observation period. During the entire observation, there were 16 deaths (3.9%) in the T-group. In CTRL, there were 74 deaths (18.8%), 70 MIs (17.8%) and 59 strokes (15%). The reduction of cardiovascular events by TTh after applying a linear mixed effect model was 24.7% and 15.5% after applying a random effect longitudinal model. Medication adherence in the T-group was 100 per cent as all TU-injections were performed in the office and documented. Conclusions: In hypogonadal men, long-term TTh reduces MACE and mortality.

PO562 Baseline Framingham Risk Score Does Not Predict Future ECG Derived QRS Duration Changes In an Australian Rural Population

PO562 Baseline Framingham Risk Score Does Not Predict Future ECG Derived QRS Duration Changes In an Australian Rural Population

EFFECT OF INTENSIVE BLOOD PRESSURE TREATMENT ACCORDING TO BASELINE FRAMINGHAM RISK SCORE: RESULTS FROM SYSTOLIC BLOOD PRESSURE INTERVENTION TRIAL (SPRINT)

To determine whether the effects of intensive (<120 mmHg) compared with standard (<140 mmHg) systolic blood pressure (SBP) treatment are different among those with different baseline Framingham risk score (FRS) in the Systolic Blood Pressure Intervention Trial (SPRINT). De-identified SPRINT

A methodology review on the incremental prognostic value of computed tomography biomarkers in addition to Framingham risk score in predicting cardiovascular disease: the use of association, discrimination and reclassification

BackgroundComputed tomography (CT) biomarkers claim to improve cardiovascular risk stratification. This review focuses on significant differences in incremental measures between adequate and inadequate reporting practise.MethodsStudies included were those that used Framingham Risk Score as a baseline and described the incremental value of adding calcium score or CT coronary angiogram in predicting cardiovascular risk. Searches of MEDLINE, EMBASE, Web of Science and Cochrane Central were performed with no language restriction.ResultsThirty five studies consisting of 206,663 patients (men = 118,114, 55.1%) were included. The baseline Framingham Risk Score included the 1998, 2002 and 2008 iterations. Selective reporting, inconsistent reference groupings and thresholds were found. Twelve studies (34.3%) had major and 23 (65.7%) had minor alterations and the respective Δ AUC were significantly different (p = 0.015). When the baseline model performed well, the Δ AUC was relatively lower with the addition of a CT biomarker (Spearman coefficient = − 0.46, p < 0.0001; n = 33; 76 pairs of data). Other factors that influenced AUC performance included exploration of data analysis, calibration, validation, multivariable and AUC documentation (all p < 0.05). Most studies (68.7%) that reported categorical NRI (n = 16; 46 pairs of data) subjectively drew strong conclusions along with other poor reporting practices. However, no significant difference in values of NRI was found between adequate and inadequate reporting.ConclusionsThe widespread practice of poor reporting particularly association, discrimination, reclassification, calibration and validation undermines the claimed incremental value of CT biomarkers over the Framingham Risk Score alone. Inadequate reporting of discrimination inflates effect estimate, however, that is not necessarily the case for reclassification.

Weight gain and 10-year cardiovascular risk with sustained tobacco abstinence in smokers with serious mental illness: a subgroup analysis of a randomized trial.

People with serious mental illness die earlier than those without mental illness, largely from cardiovascular disease due to high rates of smoking and obesity. The objective of this study was to determine whether the metabolic effects of postcessation weight gain among smokers with serious mental illness attenuated the cardiovascular benefit of tobacco abstinence. A subgroup analysis was conducted of 65 outpatient smokers with DSM-IV diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder from 10 community mental health centers in 6 states who enrolled between March 2008-April 2012 and completed a trial of varenicline for tobacco abstinence. The intervention included a 12-week open-label phase with varenicline followed by a 40-week randomized, placebo-controlled phase in 87 participants who achieved 12-week abstinence. Main outcome measures were smoking status and change from baseline in weight and 10-year Framingham cardiovascular risk score at end of intervention (week 52). At week 52, 65 participants completed follow-up (33 abstinent; 32 relapsed). At baseline, the 2 groups did not differ in body mass index (mean = 31 kg/m(2)), blood pressure, serum glucose, or diagnoses of diabetes (31%) and hypertension (34%). Abstinent participants were older and had a higher mean baseline Framingham risk score (14.2% vs 10.3%, P = .002). At week 52, abstinent participants gained more weight than relapsed participants (4.8 vs 1.2 kg, P = .048) and, as a result of quitting smoking, had a greater reduction in Framingham risk score (-7.6% vs 0.0%, P < .001). There was no effect of study drug assignment on weight or Framingham risk score. Sustained tobacco abstinence reduced 10-year cardiovascular risk in outpatients with serious mental illness despite significant postcessation weight gain and high prevalence of obesity, diabetes, and hypertension. Clinicaltrials.gov identifier: NCT00621777.

Is an unfavourable cardiovascular risk profile a risk factor for vasomotor menopausal symptoms? Results of a population-based cohort study

Evidence suggests an association between vasomotor menopausal symptoms (VMSs), i.e. hot flushes and night sweats, and cardiovascular disease. However, the causal pathway is unclear. We investigated whether an unfavourable cardiovascular risk profile is a risk factor for VMS later in life. Retrospective cohort study. Women aged 50-70 from the general population. The Prospect-European Prospective Investigation into Cancer and Nutrition (Prospect-EPIC) cohort is a population-based cohort of women who enrolled between 1993 and 1997. Follow-up questionnaires were sent at 5-year intervals for 15 years. Women who returned the third questionnaire, answered questions regarding lifetime VMS and did not report VMS prior to baseline were included in this study (n = 1295). At baseline, the Framingham Risk Score (FRS) was determined. We used logistic regression analysis to calculate odds ratios (ORs) for the association between baseline FRS and incident VMS. Incident VMS. At baseline (mean age ± standard deviation, 52.2 ± 3.6 years), 21.2% had a FRS > 10%. During follow-up, 40.2% of women reported the onset of VMS. Adjusted for body mass index, physical activity, education and alcohol consumption, each point increase in FRS was associated with a decreased incidence of VMS [OR, 0.94 (95% CI, 0.91-0.97)]. Additional adjustment for menopausal status attenuated the OR to null [OR, 0.98 (95% CI, 0.95-1.01)]. None of the separate FRS variables were associated with VMS after adjustment for age. In our cohort, an unfavourable cardiovascular risk profile was not associated with VMS, and therefore we found no evidence for the involvement of a vascular mechanism in the etiology of VMS.

Cardiovascular risk in obese diabetic patients is significantly reduced one year after gastric bypass compared to one year of diabetes support and education.

Roux-en-Y gastric bypass (RYGB) reduces most of the obesity-related comorbidities known to increase the cardiovascular risk in obese subjects. The Framingham risk score (FRS) is designed to be independent of body weight and estimates the 10-year risk for coronary heart disease (CHD), myocardial infarction, stroke, cardiovascular disease (CVD), death from CHD, and death from CVD. Our aim was to evaluate the effectiveness of RYGB on improving the FRS when compared to a matched control group who underwent diabetes support and education program (DSE). In a prospective cohort study, we evaluated preoperatively and at 12 months, 61 morbidly obese subjects with diabetes. Thirty underwent laparoscopic RYGB, and 31 received 1 year of DSE, consisting of educational sessions on diet, nutrition, and exercise. Groups were matched for gender, age, weight, blood pressure, and cholesterol and triglyceride levels. Strict gender-specific FRS was used to assess the cardiovascular risk. Excess weight-loss percentages (%EWL) were 55.6 ± 15.1 in the RYGB group and 1.2 ± 10.8 in the DSE group (P < 0.001). The two groups were matched for baseline FRS. RYGB patients experienced a significant decrease in all FRS, whereas control subjects did not show a significant decrease for the 10-year risk for CHD, CVD and death from CVD. The between-group differences for changes from baseline to 12 months in all FRS were significant. The 10-year risk reductions for CHD, MI, stroke, CVD, death from CHD, and death from CVD in the RYGB group relative to the DSE group were, respectively, 42, 48, 30, 39, 50, and 50%. No correlations between reduction in FRS and %EWL were found after RYGB. A significant improvement in the 10 year estimated cardiovascular risk is observed in patients undergoing RYGB, but not in those who were offered usual medical therapy plus DSE. However, the effects of RYGB on FRS are independent of weight loss.

Abstract P010: Cardiac Risk Factors and 6-Year Change in high-sensitivity Cardiac Troponin-T.

Introduction: Troponin measured with a highly sensitive assay (hs-cTNT) can detect subclinical myocardial injury and may be useful for risk stratification. However, little is known about temporal changes in hs-cTNT in the general population. Hypothesis: Traditional cardiac risk factors will predict change in hs cTNT. Methods: We analyzed data from 8698 ARIC Study participants, free of cardiovascular disease, who had hs-cTNT measured at visit 2 (1990-1992) and visit 4 (1996-1998). Hs-cTNT was categorized as: undetectable (&lt;5 ng/L), detectable (5-14 ng/L), and elevated (≥14 ng/L). We examined the association of baseline Framingham Risk Score (FRS) groups (low &lt;10%, intermediate 10-20%, high &gt;20%) and individual cardiac risk factors with change across hs-cTNT categories using Poisson regression and with absolute 6-year change using robust linear regression. Results: Over 6 years, 2124 study participants went from undetectable to detectable or elevated hs-cTNT and 353 went from detectable to elevated hs-cTNT. The mean crude 6-year hs-cTNT change (SD) within FRS groups were; low (+1.3 (6.0) ng/L), intermediate (+2.3 (9.3) ng/L), and high (+3.7 (8.3) ng/L). Higher baseline FRS was associated with an increase in hs-cTNT over 6 years ( Table ). This association was stronger for incident detectable hs-cTNT than for progression from detectable to elevated. Major predictors of change were baseline age, male gender, diabetes and hypertension. Black race/ethnicity and obesity were also associated with categorical hs-cTNT change. In addition to HDL-c, baseline hypercholesterolemia and smoking may be associated with downwards hs-cTNT change. Conclusions: Framingham Risk Score was positively associated with 6-year hs-cTNT change in middle-age adults. The modifiable risk factors primarily driving this association were diabetes, hypertension, and obesity. Additional studies are needed to evaluate if modifying these risk factors can prevent progression of subclinical myocardial damage.

Critical Review of High-Sensitivity C-Reactive Protein and Coronary Artery Calcium for the Guidance of Statin Allocation

Statins have been shown to be effective in primary prevention even among patients at low cardiovascular risk.1 However, statins are associated with moderate medical costs and have potential side effects.2 As a result, various biomarkers have been proposed for use in a tailored treatment strategy aimed at decreasing the number needed to treat (NNT), increasing the number needed to harm, and maximizing the cost-effectiveness of statin therapy. High-sensitivity C-reactive protein (hsCRP) and coronary artery calcium (CAC) are the leading novel markers of cardiovascular risk and are most commonly suggested for use in a tailored treatment approach. Despite the theoretical benefits of these 2 biomarkers, there has been a dearth of definitive randomized trials specifically designed to test the efficacy of these, or any, novel biomarker for statin allocation. To date, only 2 randomized control trials have explored the potential use of these tests in improving outcomes with statin therapy: hsCRP in the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial2a and CAC in the St. Francis Heart trial (Table).2b View this table: Table. Systematic Comparison of the JUPITER and the St. Francis Heart Trials In this article, we perform a comprehensive review of these trials from several different viewpoints: study rationale, study design, funding source, study population, pharmacological intervention, overall trial result, and overall trial interpretation. Our goal is to critically assess the level of evidence that these 2 randomized control trials provide, to suggest additional secondary analyses of the existing trial data, and to lay out a framework for performing true biomarker randomized control trials in the future. ### JUPITER Trial hsCRP is an acute phase inflammatory protein shown to predict the likelihood of future cardiovascular events regardless of baseline Framingham risk score, low-density lipoprotein-cholesterol (LDL-C) level, or presence of metabolic syndrome.5, …

Changes in lifestyle modestly reduce the estimated cardiovascular disease risk in one-year follow-up of the Finnish diabetes prevention program (FIN-D2D)

The purpose of this study was to assess whether changes in self-rated physical activity and diet during a type 2 diabetes (T2D) prevention program were associated with changes in estimated 10-year risk for cardiovascular disease (CVD) events and mortality in people at high risk for T2D. Individuals were identified and offered lifestyle counseling as part of the Finnish diabetes prevention program. Ten-year risk for estimated CVD events and mortality were calculated with Framingham Risk Score (FRS) and Systematic Coronary Risk Evaluation (SCORE) formula. FRS was available for 774 men and 1474 women and SCORE for 961 men and 1766 women. During the one-year follow-up, 9.6% of the men reported both an increase in physical activity and improved dietary pattern, 4.1% an increase in physical activity, 39.3% an increase in improved dietary pattern, while 47.0% reported no lifestyle changes. Corresponding numbers for women were 14.2%, 3.8%, 39.2% and 42.7%. Estimated 10-year risk for CVD events decreased 3.5% in men and 1.5% in women reporting an increase in physical activity and improvement in diet, compared to an increase of 0.15% in men (p<0.001, between groups) and decrease of 0.43% (p=0.027, between groups) in women with no lifestyle changes after adjustment for age and baseline FRS. Numbers needed to treat to prevent one CVD event by lifestyle changes were 25 for men and 59 for women. Lifestyle changes had no effect on estimated CVD mortality risk. Lifestyle counseling offered in primary health care for one year results in favorable changes in lifestyle, and lowered the estimated 10-year risk for CVD events.

Risk Stratification in Dialysis Patients: Coronary Artery Calcification Score Combined with High Sensitive C-Reactive Protein and Framingham Score for Cardiovascular Risk Prediction in Asymptomatic Subjects

Introduction: Vascular calcification independently predicts cardiovascular disease, the major cause of death in Chronic Kidney Disease (CKD) patients. Coronary Artery Calcium Score (CACS) is a marker for atherosclerotic plaque burden, vascular calcification and has been shown to be a predictor of incidence of myocardial infarction and death from Cardiovascular (CV) disease. Objectives: The aim of the study was to evaluate factors influencing CV mortality in a group of Peritoneal Dialysis (PD) patients during a six year observation period. Patients and methods: The study included 53 patients with no symptoms of CV disease (25 women, 28 men; mean age of 52 ± 12 years) treated with PD for a median period of 24 months. Baseline Framingham Risk Score (FRS) was assessed and CACS was measured using Multi-Row Spiral Computed Tomography (MSCT). Laboratory measurements included high sensitive C-reactive protein (hsCRP), osteoprotegerin (OPG), fibroblast growth factor 23 (FGF23), osteopontin (OPN), osteocalcin (OC), intact parathyroid hormone (iPTH), total calcium (Ca) and phosphates (Pi). The data concerning mortality was collected over a 6 year period. Results: During the six year observation period, 24 (45%) patients died, including 19 due to CV causes. Median overall survival was 72 months (lower quartile, 17 months). CACS was a significant predictor of all-cause and CV mortality both in simple analysis (HR=1.03 per 100 Agatston units, p=0.02 and HR=1.05, p=0.003), as well as in a multiple model adjusted for age of patients, dialysis duration, weekly creatinine clearance, Ca x Pi, iPTH, OPG, hsCRP and FRS (HR=1.04, p=0.02 and HR=1.05, p=0.01). The value of 800 Agatston units significantly differentiated the group into those with higher and lower risk for CV death (p=0.04). Age and FGF23 concentration were independent predictors of CACS. Also, hsCRP and FRS significantly predicted all-cause and CV mortality in simple Cox regression (HR=1.04, p=0.002 and HR=1.04, p=0.003; HR=1.14, p=0.047 and HR=1.23, p=0.01) as well as in a multiple model (HR=1.05, p=0.002 and HR=1.05, p=0.01; HR=1.23, p=0.01 and HR=1.33, p=0.004). Adding CACS to FRS and hsCRP significantly improved the prediction of cardiovascular mortality (p=0.02). Conclusions: Coronary calcium imaging is a non-invasive method of CV risk stratification that can accurately identify high-risk asymptomatic dialysis patients at the start of dialysis. The assessment of CACS together with inflammatory markers and conventional CV risk factors (FRS) may contribute to early diagnosis, prevention and reduction of deaths from CV disease in dialysis patients. Among the markers of bone disease, FGF-23 (a regulator of phosphorus metabolism) may be an early predictor of vascular calcification among dialysis patients.

A Novel Approach to Cardiovascular Health By Optimizing Risk Management (ANCHOR): Behavioural Modification in Primary Care Effectively Reduces Global Risk

Primary care is well positioned to facilitate cardiovascular risk improvement and reduce future cardiovascular disease (CVD) burden. The efficacy of risk factor screening, behavioural counselling, and pharmacological treatment to lower CVD risk was assessed via a prospective pre- and postintervention health risk assessment, individualized intervention with behaviour modification, risk factor treatment, and linkage to community programs, with 1-year follow-up and final health risk assessment. Primary outcome was the proportion of subjects with moderate and high baseline Framingham Risk Score (FRS) reducing their risk by 10% and 25%, respectively; the secondary end point was the proportion dropping ≥ 1 risk category. Patients were enrolled (N = 1509) from March 2006 through October 2008 and 72% completed the study. This analysis focuses on 563 subjects with moderate or high baseline FRS, and excluded 325 low-risk patients and 205 with established CVD or diabetes mellitus. Median age was 56 years, 57.7% were female. The primary outcome was achieved in 31.8% (N = 112; 95% confidence interval [CI], 26.9%-36.6%) of moderate risk FRS participants and 47.9% (N = 101; 95% CI, 41.2%-54.6%) of high-risk participants. The secondary outcome was achieved by 37.2% (N = 210; 95% CI, 33.2%-41.2%). Prevalence of metabolic syndrome fell from 79.2% (N = 446; 95% CI, 75.9%-82.6%) at entry to 52.8% (N = 303; 95% CI, 48.7%-56.9%) at study end. Significant improvements in all modifiable risk factors occurred through lifestyle modification. Global cardiovascular risk can be effectively decreased via lifestyle changes informed by readiness to change assessment and individualized counselling targeting specific behaviours. ClinicalTrials.gov number NCT01620996.