10-year Cardiovascular Disease Mortality Research Articles

Abstract 4828: Effect of county-level income and rurality on cardiovascular disease mortality among Asian and Pacific Islander breast cancer survivors in the US, 2000-2018

Abstract Purpose: To examine differences in cardiovascular disease (CVD) mortality by county-level income and rurality for Asian versus Pacific Islander (PI) breast cancer survivors. Background: Asian and PI individuals experience varying cancer burden, and prior studies have reported disparities in treatment-related CVD mortality among breast cancer survivors by socioeconomic status and race and ethnicity. However, the impact of county-level income and rurality on CVD mortality among Asian and PI breast cancer survivors, separately, are not well described. Methods: We included 60,184 Non-Hispanic Asian and PI women diagnosed with first primary, invasive breast cancer between 2000-2017 in the U.S. Surveillance, Epidemiology, and End Results program (aged 18-84, survived 12+ months, and received initial surgery). We estimated the hazard ratio (HR) of CVD mortality using Cox proportional hazard models assessing the impact of county-level income (median household income: low = <$75,000; high [ref] = ≥$75,000) and rurality (urban [ref] = metropolitan counties, population ≥ 250,000; rural = nonmetropolitan counties), separately for Asian and PI breast cancer survivors. Models adjusted for continuous age, stage (localized, regional/distant), and year of breast cancer diagnosis (2000-2004, 2005-2009, 2010-2017). We calculated 10-year cumulative CVD mortality for Asian and PI women accounting for competing risks (e.g., non-CVD deaths). Results: Of 55,602 Asian and 4,582 PI breast cancer survivors, 1,114 Asian and 178 PI women died from CVD through 2018 (median follow-up, Asian = 6.0 years; PI = 5.5 years). PI women had a higher median age at breast cancer diagnosis (57 vs. 55 years) and more advanced stage (37% vs. 33%) than Asian women. Among Asian breast cancer survivors, low county-level income was associated with elevated CVD mortality (HR = 1.17, 95% CI = 1.04, 1.31), but not rurality (HR = 1.20, 95% CI = 0.91, 1.58). For PI breast cancer survivors, there were no significant associations observed for low county-level income (HR = 0.83, 95% CI = 0.60, 1.14) or rurality (HR = 1.11, 95% CI = 0.76, 1.61). At 10 years after breast cancer diagnosis, 1 in 40 Asian women and 1 in 20 PI women died of CVD. Conclusion: Asian breast cancer survivors living in low-income counties had heightened risk of CVD mortality compared with those living in higher income counties, highlighting potential healthcare access barriers to cancer survivorship care. Although PI women did not experience significant differences in CVD mortality across groups of county-level income and rurality, they had twice as high absolute risk of CVD mortality than Asian women, warranting further investigation. Future studies that disaggregate Asian and PI individuals into more diverse and granular ethnicity groups are needed to understand heterogeneity in breast cancer survivorship outcomes. Citation Format: Katherine L. Ho, Cody Ramin, Jaimie Z. Shing, Kekoa Taparra, Jacqueline B. Vo. Effect of county-level income and rurality on cardiovascular disease mortality among Asian and Pacific Islander breast cancer survivors in the US, 2000-2018 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4828.

High fish intake rich in n-3 polyunsaturated fatty acids reduces cardiovascular disease incidence in healthy adults: The ATTICA cohort study (2002-2022).

Background: The long-term effects of high fish intake rich in n-3 fatty acids for deterring cardiovascular disease (CVD) and related adverse outcomes in healthy individuals have not been yet elucidated. Purpose: To evaluate the association between total seafood, as well as small fish, intake on 10- and 20-year CVD incidence and mortality in healthy adults. Methods: A prospective cohort study (n = 2,020) was conducted in healthy community dwelling adults in Athens, Greece, selected following age- and sex-based random multistage sampling (mean ± SD age at baseline: 45.2 ± 14.0years). Seafood (high (>2 servings/week) vs. low (≤2 servings/week) intake), including small fish rich in n-3 fatty acids (high (>1 serving/week) vs. low (≤1 serving/week) intake), consumption was evaluated by semi-quantitative food frequency questionnaire at baseline. The occurrence of non-fatal and/or fatal CVD events (ICD-10) was assessed during 10- and 20-year follow-up periods. Results: Only 32.7% and 9.6% of participants had high seafood and small fish intakes, respectively. Participants with high seafood intake had 27% decreased 10-year CVD risk (adj. HR:0.73; 95% CI:0.55-0.98) and 74% lower attributable mortality (adj. HR:0.26; 95% CI:0.11-0.58). Participants with high seafood intake also sustained a 24% lower 20-year risk of CVD mortality (adj. HR: 0.76; 95% CI: 0.55-0.98). Moreover, participants with high small fish intake had a lower 10-year CVD risk and 76% decreased risk of 10-year CVD mortality (adj. HR:0.24; 95% CI:0.06-0.99), even among normotensive individuals (adj. HR:0.31; 95% CI:0.13-0.73). When analogous analyses focused on 20-year CVD incidence and mortality, similar but not significant associations were observed (all p-values >0.10). Conclusion: High intake of seafood, and particularly small fish rich in n-3 fatty acids, was associated with a lower risk of 10-year fatal and non-fatal CVD. Thus, public health interventions aimed at enhancing small fish consumption may most effectively deter long-term CVD outcomes, particularly among low risk normotensive individuals.

An office-based cardiovascular prediction model developed and validated in cohort studies of a middle-income country

ObjectivePrediction models for cardiovascular disease (CVD) mortality come from high-income countries, comprising laboratory measurements, not suitable for resource-limited countries. This study aims to develop and validate a non-laboratory model to predict CVD mortality in a middle-income setting. Study design and settingWe used data of population aged 40-80 years from three cohort studies: Tehran Lipid and Glucose Study (n = 5160), Isfahan Cohort Study (n = 4350), and Golestan Cohort Study (n = 45,500). Using Cox proportional hazard models, we developed prediction models for men and women, separately. Cross-validation and bootstrapping procedures were applied. The models’ discrimination and calibration were assessed by concordance statistic (C-index) and calibration plot, respectively. We calculated the models' sensitivity, specificity and net benefit fraction in a threshold probability of 5%. ResultsThe 10-year CVD mortality risks were 5.1% (95%CI: 4.8-5.5) in men and 3.1% (95%CI: 2.9%-3.3%) in women. The optimism-corrected performance of the model was c = 0.774 in men and c = 0.798 in women. The models showed good calibration in both sexes, with a predicted-to-observed ratio of 1.07 in men and 1.09 in women. The sensitivity was 0.76 in men and 0.66 in women. The net benefit fraction was higher in men compared to women (0.46 vs. 0.35). ConclusionA low-cost model can discriminate well between low- and high-risk individuals, and can be used for screening in low-middle income countries.

Obstructive sleep apnea predicts 10-year cardiovascular disease-related mortality in the Sleep Heart Health Study: a machine learning approach.

Obstructive sleep apnea (OSA) is considered to be an important risk factor for the development of cardiovascular disease (CVD). This study aimed to develop and evaluate a machine learning approach with a set of features for assessing the 10-year CVD mortality risk of the OSA population. This study included 2,464 patients with OSA who met study inclusion criteria and were selected from the Sleep Heart Health Study. We evaluated the importance of potential features by mutual information. The top 9 features were selected to develop a random forest model. We evaluated the model performance on a test set (n = 493) using the area under the receiver operating curve with 95% confidence interval and confusion matrix. A random forest model awarded the highest area under the receiver operating curve of 0.84 (95% confidence interval: 0.78-0.89). The specificity and sensitivity were 73.94% and 81.82%, respectively. Sixty-three years old was a threshold for increased risk of 10-year CVD mortality. Persons with severe OSA had higher risk than those with mild OSA. This study demonstrated that a random forest model can provide a quick assessment of the risk of 10-year CVD mortality. Our model may be more informative for patients with OSA in determining their future CVD mortality risk. Li A, Roveda JM, Powers LS, Quan SF. Obstructive sleep apnea predicts 10-year cardiovascular disease-related mortality in the Sleep Heart Health Study: a machine learning approach. J Clin Sleep Med. 2022;18(2):497-504.

A Mediterranean diet microsimulation modeling in relation to cardiovascular disease burden: the ATTICA and GREECS epidemiological studies

To quantify the changes in 10-year cardiovascular disease (CVD) onset, recurrence, and mortality, in relation to transitioning from low to a higher level of adherence to the Mediterranean diet. An individual-level microsimulation was created based on ATTICA (2002-2012, n = 3042 subjects free-of-CVD) and GREECS (2004-2014, n = 2172 patients with acute coronary syndrome (ACS)) studies (in total n = 5214). Eight scenarios regarding the proportion of participants and the size of improvement of the level of adherence to the Mediterranean diet (corresponding to one to ten point increases in MedDietScore) were compared in terms of relative change in CVD incidence and mortality, as well as, the number of preventable CVD events and deaths. Improving adherence to the Mediterranean diet in at least 10% of the population, a significant relative percentage reduction could be observed in 10-year CVD onset, recurrence, and mortality. At least 851 first CVD events, 374 recurrent CVD events, and 205 CVD deaths per 100,000 of the population could be averted or delayed. In addition, Mediterranean diet clustering revealed that scoring higher in fruits, vegetables, whole wheat products, and legumes was more important than achieving higher scores in low consumption of meat and full-fat dairy products against CVD (all HRs in the former cluster were lower than the latter, indicating a stronger protective effect). This microsimulation process confirms the added value of the Mediterranean diet in primary and secondary CVD prevention having great achievements even with modifications in a small part of the population (10%), while challenges the orientation of Mediterranean-diet interventions giving higher weights to plant-based part.

Prior Oral Contraceptive Use and Longer Term Mortality Outcomes in Women with Suspected Ischemic Heart Disease.

Background: Previous Women's Ischemia Syndrome Evaluation (WISE) work demonstrated prior oral contraceptive (OC) use was associated with lower coronary artery disease (CAD) in women with suspected ischemia. The association of prior OC use with longer term all-cause and cardiovascular disease (CVD) mortality is unclear. Materials and Methods: WISE women undergoing coronary angiography for suspected ischemia (enrolled 1996-2001) with prior OC use history and 10-year follow-up data were analyzed. A blinded core laboratory assessed atherosclerotic CAD severity. Kaplan-Meier analyses evaluated prior OC use relative to all-cause and CVD mortality. Cox regression analyses adjusted for baseline differences. Mediation, interaction, and multicollinearity were analyzed. Results: Our 686 women had a mean age 62.5 ± 9.6 years, multiple cardiac risk factors, and 39% previously used OC. Prior OC users were younger, with less lipid-lowering medication use and lower atherosclerotic CAD severity scores (all p < 0.05). Prior OC use was associated with lower 10-year all-cause (p = 0.007) and CVD mortality (p = 0.019). After adjustment, this was no longer significant (p = 0.77 and p = 0.90, respectively). Atherosclerotic CAD severity score mediated one-third of the observed association. Prior OC use was associated with increased CVD mortality among women with very elevated menopausal systolic blood pressure (SBP). Conclusions: Unadjusted prior OC use was associated with lower longer-term all-cause and CVD mortality. One-third of this observed effect appears mediated by the atherosclerotic CAD severity score. Prior OC was adversely associated with CVD mortality in women with very elevated menopausal SBP. Additional investigation is needed to understand the potential benefits and harms of prior OC use. Clinical Trial Number: NCT00000554, or https://www.clinicaltrials.gov/ct2/show/NCT00000554.

Do the 2017 blood pressure cut-offs improve 10-year cardiovascular disease mortality risk prediction?

Background and aimsHigh blood pressure (BP) is a significant predictor for cardiovascular disease (CVD) mortality. The 2017 American College of Cardiology/American Heart Association guideline reclassified the BP categories; however, its impact on CVD mortality prediction is still unclear. Our study aimed to examine whether the application of new BP cut-offs could improve 10-year CVD mortality prediction among US adults. Methods and resultsThis population-based cohort study linked data from the US National Health and Nutrition Examination Survey (1988–1994 and 1999–2004) and National Death Index (up to December 31, 2015). We constructed original and modified, using new BP cut-offs, Systematic COronary Risk Evaluation models to predict 10-year CVD mortality. We measured model discrimination and calibration using the Harrell's C statistic and calibration plots, respectively. We calculated the net reclassification index to evaluate the reclassification. In addition, we compared the sensitivity, specificity, predictive values (PVs), and likelihood ratios (LRs). Among 28,964 adults (aged ≥ 20 years), 1493 have died of CVD within ten years of follow-up. The modified models had improvements in calibration and reclassification instead of discrimination compared to the original models. The modified models have higher sensitivity and negative PV; however, they have lower specificity, positive PV, positive LR, and negative LR. ConclusionsThe modified models failed to improve the discrimination of 10-year CVD mortality. However, they could increase the calibration and reclassification and capture more participants with high CVD risk. More studies are needed on the potential use of the new BP cut-offs in the CVD primary prevention.

The recalibrated HellenicSCORE based on newly derived risk factors from the Hellenic National Nutrition and Health Survey (HNNHS); the HellenicSCORE II

BackgroundBecause of the increased burden of cardiovascular disease (CVD), country specific risk prediction models to forecast future CVD events and mortality are recommended, for primary prevention. The aim of this study was to recalibrate the HellenicSCORE, to accurately estimate the 10-year risk CVD mortality of Greek adults. MethodsData from the Hellenic National Nutrition and Health Survey (HNNHS) were used (N = 1012; 37.9% males). Information on age, smoking, systolic blood pressure (SBP), and total blood cholesterol from adults >40 years of age were derived following validated health survey protocols. Individual scores were calculated using these data and beta-coefficients derived from ESC SCORE. ResultsBoth updated HellenicSCORE II charts had lower risk estimates compared to the older version and were closer to the ESC SCORE charts, particularly at the extremes. No significant age difference by sex was observed (mean 59.5 (SD 13.1) years in total) in the population. Women had a significant higher mean total cholesterol compared to men [212.9 (39.5) vs 204.6 (41.2) mg/dl, respectively; p = 0.0343], but smoking prevalence and mean SBP was significantly higher in men [p for all, <0.001]. The mean population HellenicSCORE II score level was between 5.6% (0.2) and 7.9% (3.2) depending on the chart used, with no significant sex differences. ConclusionAlthough the HellenicSCORE II charts were lower, the mean population score was moderately high. This is of great importance because according to ESC guidelines, lifestyle intervention, and drug treatment should be based on an individuals’ total cardiovascular risk.

Association of predicted 10\xa0years cardiovascular mortality risk with duration of HIV infection and antiretroviral therapy among\xa0HIV-infected individuals\xa0in Durban, South Africa

BackgroundSouth Africa has the largest population of human immunodeficiency virus (HIV) infected patients on antiretroviral therapy (ART) realising the benefits of increased life expectancy. However, this population may be susceptible to cardiovascular disease (CVD) development, due to the chronic consequences of a lifestyle-related combination of risk factors, HIV infection and ART. We predicted a 10-year cardiovascular mortality risk in an HIV-infected population on long-term ART, based on their observed metabolic risk factor profile.MethodsWe extracted data from hospital medical charts for 384 randomly selected HIV-infected patients aged ≥ 30 years. We defined metabolic syndrome (MetS) subcomponents using the International Diabetes Federation definition. A validated non-laboratory-based model for predicting a 10-year CVD mortality risk was applied and categorised into five levels, with the thresholds ranging from very low-risk (< 5%) to very high-risk scores (> 30%).ResultsAmong the 384 patients, with a mean (± standard deviation) age of 42.90 ± 8.20 years, the proportion of patients that were overweight/obese was 53.3%, where 50.9% had low high-density lipoprotein (HDL) cholesterol and 21 (17.5%) had metabolic syndrome. A total of 144 patients with complete data allowed a definitive prediction of a 10-year CVD mortality risk. 52% (95% CI 44–60) of the patients were stratified to very low risk (< 5%) compared to 8% (95% CI 4–13) that were at a very high risk (> 30%) of 10-year CVD mortality. The CVD risk grows with increasing age (years), 57.82 ± 6.27 among very high risk and 37.52 ± 4.50; p < 0.001 in very low risk patients. Adjusting for age and analysing CVD risk mortality as a continuous risk score, increasing duration of HIV infection (p = 0.002) and ART (p = 0.007) were significantly associated with increased predicted 10 year CVD mortality risk. However, there was no association between these factors and categorised CVD mortality risk as per recommended scoring thresholds.ConclusionsApproximately 1 in 10 HIV-infected patients is at very high risk of predicted 10-year CVD mortality in our study population. Like uninfected individuals, our study found increased age as a major predictor of 10-year mortality risk and high prevalence of metabolic syndrome. Additional CVD mortality risk due to the duration of HIV infection and ART was seen in our population, further studies in larger and more representative study samples are encouraged. It recommends an urgent need for early planning, prevention and management of metabolic risk factors in HIV populations, at the point of ART initiation.

COMPARISON OF A FRAILTY INDEX WITH CARDIOVASCULAR RISK SCORES IN PREDICTING CARDIOVASCULAR DISEASE MORTALITY

We compared the predictive and discriminative ability of frailty with traditional cardiovascular risk scores to estimate 10-year cardiovascular disease (CVD) mortality risk. Individuals aged 20-79 years old from the National Health and Nutrition Examination Survey who were free from CVD were included (n= 32,066). A 33-item frailty index (FI) which excluded CVD and diabetes-related variables was calculated. We calculated the Framingham Disease Risk (FDR) Hard Coronary Heart Disease and General CVD risk scores, the American Heart Association/American College of Cardiology (AHA/ACC) atherosclerotic cardiovascular disease risk equation, and the European Systematic Coronary Risk Estimation tool. A total of 322 individuals died (1.0%) from CVD. There was a low correlation between the FI and CVD risk scores (spearman’s r= 0.19-0.33; p<0.0001) and a weak to strong correlation between CVD risk scores (spearman’s r=0.19-0.88; p<0.0001). The competing-risks hazard ratio for CVD mortality for every 1% increase in the FI was 1.040 (95% CI: 1.032-1.048; p<0.0001) in an age and sex-adjusted model. The FI was independently predictive of CVD mortality when the other CVD risk scores were added to the model. The area under the receiving operating characteristic (ROC) curve was 0.800 (95% CI: 0.789-0.808; p<0.0001) for the FI. ROC values for the CVD risk scores ranged from 0.710 (95% CI: 0.700-0.721; p<0.0001) for the AHA/ACC risk score to 0.779 (95% CI: 0.770-0.789; p<0.0001) for the FDR General CVD risk score. An FI calculated with non-CVD and diabetes variables can predict 10-year CVD mortality risk independently of traditional CVD risk scores.

Trends in all-cause and cardiovascular mortality in patients with incident rheumatoid arthritis: a 20-year follow-up matched case-cohort study.

To examine all-cause and cardiovascular disease (CVD) mortality in consecutive cohorts of patients with incident RA, compared with population comparators. The Oslo RA register inclusion criteria were diagnosis of RA (1987 ACR criteria) and residency in Oslo. Patients with disease onset 1994-2008 and 10 matched comparators for each case were linked to the Norwegian Cause of Death Registry. Hazard ratios for all-cause and CVD mortality were calculated for 5, 10, 15 and 20 years of observation using stratified cox-regression models. Mortality trends were estimated by multivariate cox-regression. 443, 479 and 469 cases with disease incidence in the periods 94-98, 99-03 and 04-08 were matched to 4430, 4790 and 4690 comparators, respectively. For cases diagnosed between 1994 and 2003, the all-cause mortality of cases diverged significantly from comparators after 10 years of disease duration [hazard ratio (95% CI) 94-98 cohort 1.42 (1.15-1.75): 99-03 cohort 1.37 (1.08-1.73)]. CVD related mortality was significantly increased after 5 years for the 94-98 cohort [hazard ratio (95% CI) 1.86 (1.16-2.98) and after 10 years for the 99-03 cohort 1.80 (1.20-2.70)]. Increased mortality was not observed in the 04-08 cohort where cases had significantly lower 10-year all-cause and CVD mortality compared with earlier cohorts. All-cause and CVD mortality were significantly increased in RA patients diagnosed from 1994 to 2003, compared with matched comparators, but not in patients diagnosed after 2004. This may indicate that modern treatment strategies have a positive impact on mortality in patients with RA.

Validation of the Systematic COronary Risk Evaluation - Older Persons (SCORE-OP) in the EPIC-Norfolk prospective population study

BackgroundThe Systematic COronary Risk Evaluation – Older Persons (SCORE-OP) algorithm is developed to assess 10-year risk of death due to cardiovascular disease (CVD) in individuals aged ≥65 years. We studied the performance of SCORE-OP in the European Prospective Investigation of Cancer Norfolk (EPIC-Norfolk) prospective population cohort. Methods10-year CVD mortality as predicted by SCORE-OP was compared with observed CVD mortality among individuals in the EPIC-Norfolk cohort. Persons aged 65–79 years without known CVD were included in the analysis. CVD mortality was defined as death due to ischemic heart disease, cardiac failure, cerebrovascular disease, peripheral-artery disease or aortic aneurysm. Predicted 10-year CVD mortality was calculated by the SCORE-OP algorithm, and compared to observed mortality rates. The area under the receiver operator characteristics curve (AUROC) was calculated to evaluate discriminative power. Calibration was evaluated by calculating ratios of predicted vs observed mortality and by Hosmer-Lemeshow tests. ResultsA total of 6590 individuals (45.8% men), mean age 70.2 years (standard deviation 3.3) were included. The predicted mortality by SCORE-OP was 9.84% (95% confidence interval (CI) 9.76–9.92) and observed mortality was 10.2% (95% CI 9.52–11.04), ratio 0.96. AUROC was 0.63 (95% CI 0.60–0.65), and X2 was 3.3 (p = 0.92). ConclusionSCORE-OP overall accurately estimates the rate of CVD mortality in a general population aged 65–79 years. However, while calibration is excellent, the discriminative power of the SCORE-OP is limited, and as such cannot be readily implemented in clinical practice for this population.

Trends in the risk of cardiovascular disease in women with breast cancer in a Dutch nationwide cohort study

ObjectivesTo investigate trends in cardiovascular disease (CVD) risk following breast cancer using national registry data.MethodsA nationwide cohort study was conducted, comprising 163 881 women with in situ (7.6%) or invasive...

Cardiovascular Mortality Among CML Patients in the Pre-TKI and TKI Eras: A SEER Analysis 1992-2004

Background:Since the US Food and Drug Administration (FDA) approved the first BCR-ABL1-targeted tyrosine kinase inhibitor (TKI) imatinib in 2002 as the first line therapy1, chronic phase chronic myeloid leukemia (CML-CP), once a uniformly fatal disease, now has become a disease that is controlled in >90% patients2. Conventional treatment for CML before TKIs included hydroxyurea, interferon alpha with or without cytarabine, busulfan, as well as stem cell transplantation3. Currently, there are five TKIs approved by FDA for chronic-phase CML treatment: imatinib, nilotinib, dasatinib, bosutinib, and ponatinib4.Studies have suggested that CML patients have higher baseline cardiovascular comorbidities than general US population5. Moreover, TKIs, especially later generation, are associated with cardiovascular toxicities including myocardial infarction, ischemic heart disease, cerebrovascular disease, peripheral arterial disease, QT prolongation, hypertension, and venous thrombosis1,4,6-9. As patients may need life-long (or minimum of several years') therapy, the cardiovascular safety profile of TKI treatment warrants utmost attention. Thus, we examined the effect of TKIs on cardiovascular mortality using the SEER database.Methods:Data were extracted from the Surveillance, Epidemiology and End Results (SEER) 18 program 1992-2004. Cardiovascular diseases were defined as diseases of the heart, hypertension, cerebrovascular disease, atherosclerosis, aortic aneurysm and dissection, and other disease of arteries, arterioles, and capillaries. Time of diagnosis between 1992-2002 was defined as pre-TKI era and 2003-2014 as TKI era. Patients had BCR/ABL negative CML or any other cancer before CML were excluded.T-test and chi-square test were used to analyze the baseline characteristics. Multivariable Cox proportional hazards regression was used to calculate the hazard ratio (HR). Sub-distribution hazard ratios (SHRs) for cardiovascular disease (CVD) specific mortality were calculated by using Fine and Gray competing-risks model. All above statistical tests were performed assuming a 2-sided alpha of 0.05 by using SAS 9.4. CVD standard mortality ratio (SMR) and absolute excess risk (AER) were calculated by using SEER*Stat 8.3.5 software MP-SIR Matrix comparing to the total U.S. population (1969-2016 Counties).Results:A total of 10,502 patients were included (Table 1). Table 2 shows that as expected, increased age was associated with higher CVD mortality. Females had a 20% decreased risk of overall CVD mortality compared to males. Notably, those diagnosed in the TKI era had better cardiovascular outcome than the pre-TKI diagnosis, HR=0.78 (95%CI: 0.64-0.94), which was also illustrated in Figure 1. In the adjusted model (Table 3), the significantly decreased mortality in the TKI era was mostly observed at 10-year follow up and among the youngest age group 15-44 years. The 10-year cardiovascular mortality also differed by gender, especially after age 54 (Fig. 2). In the TKI era, males had a 58% increased 10-year CVD mortality (p<0.01) compared to females (Table 4). In comparison to US general population (Fig. 3), CML patients had higher cardiovascular mortality, regardless of year of diagnosis. However, the overall CVD was higher in the pre-TKI era: 1.69 (95% CI: 1.51-1.89) vs. 1.45 (95%CI: 1.24-1.69) in the TKI era. Additionally, the AERs in the TKI era across all age groups were significantly lower compared to the pre-TKI era (Figure 4).Conclusions:Though TKIs appear to be associated with increased cardiovascular toxicity, we herein report an observed decreased cardiovascular mortality among CML patients diagnosed in the TKI era relative to the pre-TKI era. One potential explanation is that TKIs might be less cardiotoxic than conventional chemotherapies such as busulfan, cytarabine, or interferon; additionally these findings could be due to overall decreased CVD mortality since 200010. While CVD mortality among CML patients improved after 2002, it was still higher than the general US population. Besides the cardiovascular toxicities of TKIs, underlying CML associated factors could also be a potential driver for increased CVD mortality11. Our results argue for aggressive management, in general, of CVD risk factors among CML patients, especially elderly and males, and further investigation into specific mechanisms, factors and predictors of risk in TKI-treated CML. [Display omitted] DisclosuresMauro:Takeda: Consultancy; Pfizer: Consultancy; Novartis: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy.

Defining Optimal Health Range for Thyroid Function Based on the Risk of Cardiovascular Disease.

Reference ranges of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) are defined by their distribution in apparently healthy populations (2.5th and 97.5th percentiles), irrespective of disease risk, and are used as cutoffs for defining and clinically managing thyroid dysfunction. To provide proof of concept in defining optimal health ranges of thyroid function based on cardiovascular disease (CVD) mortality risk. In all, 9233 participants from the Rotterdam Study (mean age, 65.0 years) were followed up (median, 8.8 years) from baseline to date of death or end of follow-up period (2012), whichever came first (689 cases of CVD mortality). We calculated 10-year absolute risks of CVD mortality (defined according to the SCORE project) using a Fine and Gray competing risk model per percentiles of TSH and FT4, modeled nonlinearly and with sex and age adjustments. Overall, FT4 level >90th percentile was associated with a predicted 10-year CVD mortality risk >7.5% (P = 0.005). In men, FT4 level >97th percentile was associated with a risk of 10.8% (P < 0.001). In participants aged ≥65 years, absolute risk estimates were <10.0% below the 30th percentile (∼14.5 pmol/L or 1.10 ng/dL) and ≥15.0% above the 97th percentile of FT4 (∼22 pmol/L or 1.70 ng/dL). We describe absolute 10-year CVD mortality risks according to thyroid function (TSH and FT4) and suggest that optimal health ranges for thyroid function can be defined according to disease risk and are possibly sex and age dependent. These results need to be replicated with sufficient samples and representative populations.

Validation of a Cardiovascular Disease Policy Microsimulation Model Using Both Survival and Receiver Operating Characteristic Curves.

Despite some advances, cardiovascular disease (CVD) remains the leading cause of death and healthcare costs in the United States. We therefore developed a comprehensive CVD policy simulation model that identifies cost-effective approaches for reducing CVD burden. This paper aims to: 1) describe our model in detail; and 2) perform model validation analyses. The model simulates 1,000,000 adults (ages 35 to 80 years) using a variety of CVD-related epidemiological data, including previously calibrated Framingham-based risk scores for coronary heart disease and stroke. We validated our microsimulation model using recent National Health and Nutrition Examination Survey (NHANES) data, with baseline values collected in 1999-2000 and cause-specific mortality follow-up through 2011. Model-based (simulated) results were compared to observed all-cause and CVD-specific mortality data (from NHANES) for the same starting population using survival curves and, in a method not typically used for disease model validation, receiver operating characteristic (ROC) curves. Observed 10-year all-cause mortality in NHANES v. the simulation model was 11.2% (95% CI, 10.3% to 12.2%) v. 10.9%; corresponding results for CVD mortality were 2.2% (1.8% to 2.7%) v. 2.6%. Areas under the ROC curves for model-predicted 10-year all-cause and CVD mortality risks were 0.83 (0.81 to 0.85) and 0.84 (0.81 to 0.88), respectively; corresponding results for 5-year risks were 0.80 (0.77 to 0.83) and 0.81 (0.75 to 0.87), respectively. The model is limited by the uncertainties in the data used to estimate its input parameters. Additionally, our validation analyses did not include non-fatal CVD outcomes due to NHANES data limitations. The simulation model performed well in matching to observed nationally representative longitudinal mortality data. ROC curve analysis, which has been traditionally used for risk prediction models, can also be used to assess discrimination for disease simulation models.

Risk estimates of cardiovascular diseases in a Sri Lankan community.

Quantifying the risk of cardiovascular disease (CVD) in a community is important in planning preventive strategies, but such data are limited from developing countries, especially South Asia. We aimed to estimate the risks of coronary heart disease (CHD), total CVD, and CVD mortality in a Sri Lankan community. A community survey was conducted in an urban health administrative area among individuals aged 35-64 years, selected by stratified random sampling. Their 10-year CHD, total CVD, and CVD mortality risks were estimated using three risk prediction tools: National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III), Systematic Coronary Risk Evaluation (SCORE), and World Health Organisation/ International Society of Hypertension (WHO/ISH) charts. Among study participants (n=2985), 54.5% were females, and mean age (SD) was 52.4 (7.8) years. According to NCEP-ATP III ('hard' CHD risk), WHO/ISH (total CVD risk), and SCORE (CVD mortality risk) criteria, 25.4% (95% CI 23.6-27.2), 8.2% (95% CI 7.3-9.2), and 11.8 (95% CI 10.5-13.1) respectively were classified as at 'high risk'. The proportion of high risk participants increased with age. 'High risk' was commoner among males (30.3% vs 20.6%, p<0.001) according to NCEPATP III criteria, but among females (9.7% vs. 6.7%, p<0.001) according to WHO/ISH criteria. No significant gender difference was noted in SCORE risk categories. A large proportion of individuals in this community are at risk of developing cardiovascular diseases, especially in older age groups. Risk estimates varied with the different prediction tools, and were comparatively higher with NCEP-ATP III charts.

Estimated 10-year cardiovascular mortality seriously underestimates overall cardiovascular risk

ObjectiveThe European Society of Cardiology's prevention guideline suggests that the risk of total (fatal plus non-fatal) cardiovascular disease (CVD) may be calculated from the risk of CVD mortality using a...

The Systematic COronary Risk Evaluation (SCORE) in a large UK population: 10-year follow-up in the EPIC-Norfolk prospective population study

The European Society of Cardiology endorses cardiovascular disease (CVD) risk stratification using the Systematic COronary Risk Evaluation (SCORE) algorithm, with separate algorithms for high-risk and low-risk countries. In the 2012 European Guidelines on CVD Prevention in Clinical Practice, the UK has been reclassified as a low-risk country. However, the performance of the SCORE algorithm has not been validated in the UK. We compared CVD mortality as predicted by SCORE with the observed CVD mortality in the European Prospective Investigation of Cancer-Norfolk (EPIC-Norfolk) prospective population study, a cohort representative of the general population. Individuals without known CVD or diabetes mellitus, aged 39-65 years at baseline, were included in our analysis. CVD mortality was defined as death due to ischaemic heart disease, cardiac failure, cerebrovascular disease, peripheral artery disease and aortic aneurysm. Predicted CVD mortality was calculated at baseline using the SCORE high-risk and low-risk algorithms. A total of 15,171 individuals (57.1% female) with a mean age of 53.9 (SD 6.2) years were included. Predicted CVD mortality was 2.85% (95% confidence interval (CI) 2.80-2.90) with the SCORE high-risk algorithm and 1.55% (95% CI 1.52-1.58) with the low-risk algorithm. The observed 10-year CVD mortality was 1.25% (95% CI 1.08-1.44). Similar results were observed across sex and age subgroups. In the large EPIC-Norfolk cohort representative of the UK population, the SCORE low-risk algorithm performed better than the high-risk algorithm in predicting 10-year CVD mortality. Our findings indicate that the UK has been correctly reclassified as a low-risk country.

Depression and mortality: Artifact of measurement and analysis?

BackgroundPrevious research demonstrates various associations between depression, cardiovascular disease (CVD) incidence and mortality, possibly as a result of the different methodologies used to measure depression and analyse relationships. This analysis investigated the association between depression, CVD incidence (CVDI) and mortality from CVD (MCVD), smoking related conditions (MSRC), and all causes (MALL), in a sample data set, where depression was measured using items from a validated questionnaire and using items derived from the factor analysis of a larger questionnaire, and analyses were conducted based on continuous data and grouped data. MethodsData from the PRIME Study (N=9798 men) on depression and 10-year CVD incidence and mortality were analysed using Cox proportional hazards models. ResultsUsing continuous data, both measures of depression resulted in the emergence of positive associations between depression and mortality (MCVD, MSRC, MALL). Using grouped data, however, associations between a validated measure of depression and MCVD, and between a measure of depression derived from factor analysis and all measures of mortality were lost. LimitationsLow levels of depression, low numbers of individuals with high depression and low numbers of outcome events may limit these analyses, but levels are usual for the population studied. ConclusionsThese data demonstrate a possible association between depression and mortality but detecting this association is dependent on the measurement used and method of analysis. Different findings based on methodology present clear problems for the elucidation and determination of relationships. The differences here argue for the use of validated scales where possible and suggest against over-reduction via factor analysis and grouping.