Intermediate Cardiovascular Disease Risk Research Articles

Rapid access chest pain clinic; insights from 10 years of an australian experience

Abstract Introduction Rapid Access Chest Pain Clinic (RACPC) has been established in the UK as a safe and cost-effective model for managing low to intermediate Cardiovascular Disease (CVD) risk chest pain patients. In our institute, this service was established in 2012 based on the UK model. Purpose This study aimed to assess the safety, efficacy, and cost-effectiveness of the RACPC at a large metropolitan health service in Australia to inform future models of care. Patients and Methods: We conducted a retrospective analysis of consecutive patients who attended RACPC between 2012 and 2022. Patients aged 25-85 years with low to intermediate CVD risk chest pain and no previously known ischaemic heart disease were included. RACPC staff comprised of a multidisciplinary team of cardiologists, nurse practitioners, and cardiology liaison nurses. The primary outcome was to benchmark our clinic model against national peers. The secondary outcome was to examine the pattern and accuracy of requested cardiac imaging used in RACPC, identify the frequency of incidental findings resulting from imaging and determine the cost-effectiveness of RACPC. Results Over the ten-year study period, a total of 4,194 patients were seen. The median waiting time from referral to consultation was 15.5 days (5 - 21.5). Attendance rates gradually increased from 71% to 95% in the clinic's tenth year of operation. Furthermore, the number of missed appointments and cancellations decreased over the years, reaching 1% and 4%, respectively. A total of 1,758 CT Coronary Angiogram (CTCA); 1,629 functional assessments utilising either Transthoracic Stress Echocardiogram (TSE) or Myocardial Perfusion Scan (MPS), and 174 Invasive Angiography (IA) procedures were requested. 1.2% of the cohort had IA without any prior non-invasive cardiac imaging. CTCA was the most frequently requested modality and resulted in the highest rates of incidental findings (24%) such as pulmonary nodules and vascular anomalies, often leading to further investigations. The rate of non-invasive cardiac imaging resulting in IA for CTCA, TSE and MPS were 7.3%, 2.5%, and 6.4%, respectively. Revascularisation rate for positive IA, CTCA, TSE and MPS were 33.3%, 34.6%, 26.7% and 20% respectively. At our health service, and for the purpose of comparison, we encountered an average of 52 patients/year with low to intermediate CVD risk hospitalised for chest pain assessment with an average length of stay of 2.35 days at a cost of 250,000 Australian Dollars ($4808/patient). Whilst at RACPC, an average of 419 patients/year were seen with a total cost of around 62,400 A$ ($149/patient). Conclusion RACPC is a safe, efficient, and cost-effective model of care, with CTCA being the preferred modality of imaging due to its high diagnostic accuracy, high negative predictive value and high rate of significant incidental findings.

Multi-view carotid ultrasound is stronger associated with cardiovascular risk factors than presence of plaque or single carotid intima media thickness measurements in subclinical atherosclerosis

We aimed to explore the prevalence of atherosclerosis by using multi-view ultrasound examination of the carotid arteries and its association with clinical risk factors in a middle-aged population at low to intermediate risk of cardiovascular disease (CVD). Carotid vascular ultrasound was performed in 3532 participants in the VIPVIZA trial. Mean and maximal carotid intima media thickness (cIMT) at prespecified angles and plaque presence were examined on the left and right side. Associations between CVD risk factors and ultrasound variables were quantified by partial least squares (PLS) regression. A combined ultrasound variable was computed using weights of the first PLS component. Associations between CVD risk factors and the combined multi-view ultrasound variable, single cIMT and plaque measurements, respectively, were determined using linear regression modelling. The participants’ mean age was 55.7 years and 52.9% were women. Plaque prevalence was 51.1% in men and 39.0% in women. cIMT was higher in men than in women and in the left compared with the right carotid artery. The strongest association of CVD risk factors was observed with the combined multi-view ultrasound variable (R2 = 24%), compared with single cIMT variables (R2 = 14–18%) and plaque presence (R2 = 15%). The pattern was similar in both sexes. The association with CVD risk factors and the combined ultrasound variable was stronger in 40-year olds (R2 = 22%) compared with 50- or 60-year olds (R = 12%). CVD risk factors are stronger associated with a combined ultrasound variable than plaque presence or single cIMT measures suggesting that carotid multi-view ultrasonography better captures the focality of early atherosclerosis.Clinical Trial Registration: ClinicalTrials.gov, number NCT01849575. May 8, 2013.

The Association between Adverse Pregnancy Outcomes and Laboratory Measures as Risk for Cardiovascular Disorders

Background; Due to the complicated etiology of cardiovascular illnesses, a thorough risk assessment is necessary for screening reasons. Many published studies relate the pregnancy complications and future cardiovascular disease (CVD) risk. Objective; Investigate the association between risk factors of the laboratory measures and adverse pregnancy outcomes (APOs) with level of cardiovascular disorders risk. Methods; Adult women were enrolled in a cross-sectional study, and they were divided into 2 groups according to whether they had a history of adverse pregnancy outcomes or not. Laboratory and clinical measurements were carried out, and The CVD risk was calculated according to Framingham risk score. Results; All women enrolled were over 40 years age, mostly obese, had predominantly A+ve and O+ve blood group phenotypes. As compared to the low risk category, women with a positive history of pregnancy-induced hypertension and preeclampsia were 7.5 times more likely to be in the intermediate group while those with a positive history of stillbirth were 17.2 times more likely to be in the high-risk group. Conclusion; With reference to the low risk category, a positive history of pregnancy-induced hypertension and preeclampsia was predictor for intermediate CVD risk, while a positive history of stillbirth was predictor for high CVD risk.

Abstract P3-03-17: The Impact of Cardiovascular Disease Risk on Cancer Progression among Female Breast Cancer Survivors: A Longitudinal Study within The Boss Cohort

Abstract Background Among breast cancer (BC) survivors, cardiovascular disease (CVD) is one of the most common comorbidities contributing to mortality. Data on to what extent CVD risk impacts disease progression and second cancers in younger women is limited. We conducted a prospective cohort study to examine whether CVD risk is associated with disease recurrence or new primary cancer among female BC survivors enrolled in a cohort of women with a family history of BC. Methods The study included 301 females with a first primary diagnosis of BC in the Breast and Ovarian Surveillance Service (BOSS) Cohort, after excluding those who had a history of recurrence or second primary cancer prior to enrollment (N=125), a diagnosis of ductal carcinoma in situ (DCIS) (N=66), and with missing CVD risk factors (N=3). A risk score based on 7 CVD risk factors (age 65 or older, diabetes, hypertension, high cholesterol, body mass index (BMI), smoking status, and physical activity) was assessed at baseline and updated 4 and 8 years after enrollment. Each risk factor was given a score (0, 1, or 2) and was summed and categorized into low (score=0 or 1), intermediate (score=2 or 3), and high (score >3) risk. The primary outcome was either BC progression or all second primary cancers. Analyses limited to BC progression and second BC only were also conducted. Outcomes were ascertained through active follow-up and confirmed by pathology records. Kaplan-Meier graphs and two different Cox regression models were used to compare risk groups: model 1 adjusted for participants’ age, race, BMI, time from diagnosis, education, tumor stage, and estrogen receptor (ER) status; model 2 included further adjustment of cancer treatments (chemotherapy, hormone therapy, radiation), statin use, baby aspirin use, and specifically cardiotoxic treatments. For subgroup analyses, a more parsimonious model was used including age, race, BMI, education, cancer treatments, and cardiotoxic treatment. Results Participants’ mean age of BC diagnosis was 47.4 years and the median follow-up time was 11.5 years. The incidence rate of recurrence or any second cancer was 21 cases per 1000 person-years. At baseline, there were 168, 130, and 84 survivors in the low, intermediate, and high CVD risk groups respectively, and their use of statins increased from 12.7%, 34.5% to 52.7%. In the multivariable model, BC survivors with an intermediate CVD risk score had a 2.23 times greater risk of recurrence or second primary cancer as compared to those with a low CVD risk score (95% CI=1.20- 4.17). After further adjusting for cancer and CVD treatment in model 2, the HR was attenuated but still significant to 2.01 (95% CI = 1.20- 4.17. Interestingly, the association was attenuated and non-significant in the high-risk group (model 2: HR=1.37, 95% CI = 0.54- 3.45). The positive association between intermediate CVD risk score and recurrence or second cancer was also observed among subgroups of BC survivors including those who were postmenopausal (HR = 2.23, 95% CI = 1.01-4.93), with ER-positive BC (HR=2.07, 95% CI=1.08-3.99), regional disease (HR = 2.74, 95% CI = 1.06-7.04), diagnosed 5 years or greater (HR = 4.85, 95% CI = 1.14-20.66). There was a significant interaction between intermediated CVD risk and diagnosis time of 5 years (P interaction = 0.033). Restricting the outcome to disease progression and second BC alone led to similar results. The HR comparing the intermediate risk group and low risk group was 2.65 (95% CI = 1.27-5.55) in model 1 and decreased to 2.28 (95% CI = 1.06-4.89) in model 2. Conclusion There was a significant association between CVD risk and subsequent cancer progression in female breast cancer survivors, particularly among long-term BC survivors. The non-significant results among the women with high CVD risk scores may reflect the fact that a greater proportion of these women compared to women in the intermediate group reported taking cardiac treatments that can favorably impact cancer progression. Citation Format: Xinyi Feng, Zhengyi Deng, Michelle McCollough, Betty May, Erica Selznick, Avonne Connor, Deborah K. Armstrong, Kala Visvanathan. The Impact of Cardiovascular Disease Risk on Cancer Progression among Female Breast Cancer Survivors: A Longitudinal Study within The Boss Cohort [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-17.

Effects of a Polypill, Aspirin, and the Combination of Both on Cognitive and Functional Outcomes

Vascular risk factors are associated with cognitive decline but studies addressing individual risk factors have not demonstrated an effect of risk factor management on the preservation of cognition. Few trials have examined the effect of vascular risk factor management on function. To determine if a polypill could reduce cognitive and functional decline in people with risk factors but without manifest cardiovascular disease. The International Polycap Study 3 (TIPS-3) was a 2 × 2 × 2 factorial randomized clinical trial. Hospital and community-based centers in 8 countries recruited and followed up participants between July 30, 2012, and September 30, 2020. A total of 5713 individuals were randomly assigned to treatment groups, and 2098 people 65 years or older at intermediate risk of cardiovascular disease completed a cognitive assessment and were included in the analyses. Polypill (antihypertensives and a statin), aspirin, or a combination of both treatments. Cognitive and functional assessments completed at baseline, 2 years, and study end. The primary outcome was the effect of a polypill compared with placebo and a polypill plus aspirin compared with double placebo on the composite outcome of the proportion of participants in each group who experienced a substantive decrease (>1.5 SD change) in cognitive or functional abilities. Of the 2389 study participants older than 65 years, a total of 2098 (88%; mean [SD] age, 70.1 [4.5] years; 1266 female individuals [60%]) completed the baseline and follow-up assessment. A total of 1796 participants (86%) had hypertension, and 680 participants (32%) had impaired fasting plasma glucose levels. Mean (SD) baseline systolic blood pressure was 146.1 (17.7) mm Hg, and mean (SD) low-density lipoprotein cholesterol (LDL-C) level was 124.3 (40.7) mg/dL and decreased by 5.7 mm Hg and 24 mg/dL, respectively, among those assigned to the polypill group. During a 5-year follow-up, there were no significant differences between treatment groups in the number of participants who experienced substantive cognitive decline (356 assigned polypill, 328 assigned placebo) or dementia (2 assigned polypill, 4 assigned placebo). Functional decline was reduced during follow-up for those assigned to polypill compared with placebo (mean [SD] country-standardized adjusted follow-up Standard Assessment of Global Everyday Activities [SAGEA] scores, 0.06 [0.03] vs 0.15 [0.03]; P = .01) and polypill plus aspirin compared with double placebo (mean [SD] country-standardized adjusted follow-up SAGEA scores, 0.01 [0.04] vs 0.14 [0.04]; P = .01). In this randomized clinical trial of patients 65 years or older with vascular risk factors, a polypill, with or without aspirin, was not associated with reduced cognitive outcomes but was associated with reduced functional decline.

Correlation of oxidative stress and metabolic risk factors in apparently healthy adults

Background: Diabetes, hypertension, obesity, and dyslipidemia, all are the risk factors of metabolic syndrome (MS). Various studies have shown that each risk factor is associated with increased inflammation. hsCRP is a non-specific, sensitive inflammatory marker that is raised in various inflammatory conditions. Similarly, glutathione is an antioxidant which binds with ROS produced during inflammation and reduces damage caused by ROS. Aims and Objectives: This study has been planned to find the correlation between oxidative stress and metabolic risk factors in apparently healthy adults. Materials and Methods: We recruited apparently healthy adults (n = 120) and measured waist circumference, blood pressure, lipid profile, Fasting blood sugar, serum GSH, and hsCRP in all the subjects. Seventy-seven subjects were found to have at least one or more metabolic risk factors (Group A) according to NCEP ATP III criteria with waist circumference >90 cm for male and >80 cm for female and 43 were without any metabolic risk factors (Group B). Thereafter, we compared the serum levels of hsCRP and serum GSH with persons having one or more risk factors for MS. Results: In this study, we observed that subjects with metabolic risk factors were having more oxidative stress indicated by increased hsCRP (4783.1 ± 2060.21) and low serum GSH (3.17 ± 0.81) in comparison to controls (1640.5 ± 547.47 and 4.79 ± 0.77, respectively). This increase in hsCRP and decrease in GSH in case group was statistically significant. We also found the higher basal hsCRP levels in control group as per AHA/CDC study. Conclusion: We observed in this study that Indians without any risk factors for MS have relatively higher CRP levels and are at intermediate risk for cardiovascular disease. It was also observed that as the number of metabolic risk factors increases, the levels of hsCRP increases, and serum GSH decreases. This indicates that more risk factors are associated with higher oxidative stress.

Ten Years Risk Prediction of Cardiovascular Disease among Adults in Rural Area of Dakshina Kannada, Karnataka

Background: Cardiovascular disease (CVD), one of the non-communicable diseases, has become a major public health problem and it is a leading cause of morbidity and mortality in both developing and developed countries. The important CVD risk factors are obesity, hypertension, diabetes, hyperlipidaemia, unhealthy diet, physical inactivity and tobacco use. Cardiovascular risk approach is feasible and cost-effective tool, which helps to identify those at high risk for developing CVDs, so that immediate preventive measures or action can be taken to reduce the risk. Objectives: estimate the ten-year risk of developing cardiovascular disease using Framingham heart risk assessment score. Materials and Methods: A community-based, cross-sectional study was conducted among adults residing in a rural area of Dakshina Kannada District for a period of 6 months from July 2013 to December 2013. The data was collected using pretested semi structured questionnaire through interview methods. Anthropometric measurement and blood investigation (fasting blood sugar and lipid profile) was done. The Framingham Risk Score is a gender-specific algorithm used to estimate the 10-year cardiovascular risk of an individual Results: Among 712 study participants, 95 (13.3%) and 20 (2.8%) participants had intermediate and high risk of developing cardiovascular disease in 10 years respectively. The proportion of intermediate CVD risk prediction and high-risk predication was more in males as compared to females. Conclusion: The cardiovascular risk factors like obesity, physical inactivity, diabetes and hypertension are widely prevalent among adults in rural areas. The high-risk prediction for developing CVD among study participants in next 10 years was 2.8%. Keywords: Cardiovascular risk factors, Framingham risk score, 10 years CVD risk prediction, Prevalence

Is the Calcium Score Useful for Rheumatoid Arthritis Patients at Low or Intermediate Cardiovascular Risk?

Cardiovascular disease, particularly myocardial infarction, is the leading cause of death of rheumatoid arthritis (RA) patients. The usefulness of the coronary artery calcification score (CACS), determined using cardiac computed-tomography (CT)-scan images, was assessed as a part of a cardiovascular work-up of RA patients at low or intermediate cardiovascular disease risk. This descriptive, cross-sectional, single-center study was conducted on patients with stable RA or that which is in remission. Each patient’s work-up included a collection of cardiovascular risk factors, laboratory analyses, an electrocardiogram, a supra-aortic trunks (SATs) echo-Doppler test and a cardiac CT scan. The primary endpoint was to determine the frequency of patients with a CACS > 100, indicating notable atherosclerosis. Fifty patients were analyzed: mean ± standard deviation age was 53.7 ± 7.5 years, 82% women. The CACS exceeded 100 in 12 (24%) patients (11 were at intermediate risk) and 2 of them underwent angioplasty for silent myocardial ischemia. Cardiovascular risk was reclassified from intermediate to high for 5 patients. Age according to sex and smoking status were significantly associated with that increase; no association was found with RA characteristics or treatments.

The effect of vitamin D supplementation on cardiovascular risk in patients with prediabetes: A secondary analysis of the D2d study

AimsLow blood 25(OH)D level is associated with increased cardiovascular disease (CVD) risk. Additionally, individuals with prediabetes are at higher risk for CVD than individuals with normoglycemia. We investigated the effects of vitamin D supplementation on CVD outcomes in the vitamin D and type 2 diabetes (D2d) study, a large trial among adults with prediabetes. Methods2423 participants were randomized to 4000 IU/day of vitamin D3 or placebo and followed for median 3.0 years for new-onset diabetes. In pre-specified secondary analyses, we examined the effect of vitamin D supplementation on composite Major Adverse Cardiovascular Events (MACE); expanded MACE (MACE + revascularization); atherosclerotic CVD (ASCVD) risk score; and individual CVD risk factors (blood pressure, lipids, high-sensitivity C-reactive protein). Cox models compared hazard ratios (HR) between the two groups on MACE and expanded MACE. ResultsMean age was 60 years, 45 % were women, 13 % had history of CVD. Twenty-one participants assigned to vitamin D and 12 participants assigned to placebo met the MACE outcome (HR 1.81, 95%CI 0.89 to 3.69). There were 27 expanded MACE outcomes in each group (HR 1.02, 95%CI, 0.59 to 1.76). There were no significant differences between vitamin D and placebo in individual CVD risk factors, but change in ASCVD risk score favored the vitamin D group (−0.45 %, 95%CI -0.75 to −0.15). ConclusionsIn people with prediabetes not selected for vitamin D insufficiency and with intermediate CVD risk, vitamin D supplementation did not decrease MACE but had a small favorable effect on ASCVD risk score.Trial registration: D2d ClinicalTrials.gov number, NCT01942694, prospectively registered September 16, 2013.

Recommendations from the EGAPP Working Group: Genomic profiling to assess cardiovascular risk to improve cardiovascular health

Summary of RecommendationsThe Evaluation of Genomic Applications in Practice and Prevention Working Group (EWG) found insufficient evidence to recommend testing for the 9p21 genetic variant or 57 other variants in 28 genes (listed in Table 1) to assess risk for cardiovascular disease (CVD) in the general population, specifically heart disease and stroke. The EWG found that the magnitude of net health benefit from use of any of these tests alone or in combination is negligible. The EWG discourages clinical use unless further evidence supports improved clinical outcomes. Based on the available evidence, the overall certainty of net health benefit is deemed “Low.” RationaleIt has been suggested that an improvement in CVD risk classification (adjusting intermediate risk of CVD into high- or low-risk categories) might lead to management changes (e.g., earlier initiation or higher rates of medical interventions, or targeted recommendations for behavioral change) that improve CVD outcomes. In the absence of direct evidence to support this possibility, this review sought indirect evidence aimed at documenting the extent to which genomic profiling alters CVD risk estimation, alone and in combination with traditional risk factors, and the extent to which risk reclassification improves health outcomes. Analytic validityAssay-related evidence on available genomic profiling tests was deemed inadequate. However, based on existing technologies that have been or may be used and on data from two of the companies performing such testing, the analytic sensitivity and specificity of tests for individual gene variants might be at least satisfactory. Clinical validityTwenty-nine gene candidates were evaluated, with 58 different gene variant/disease associations. Evidence on clinical validity was rated inadequate for 34 of these associations (59%) and adequate for 23 (40%). Inadequate grades were based on limited evidence, poor replication, existence of possible biases, or combinations of these factors. For heart disease (25 combined associations) and stroke (13 combined associations), profiling provided areas under the receiver operator characteristics curve of 66% and 57%, respectively. Only the association of 9p21 variants with heart disease had convincing evidence of a per-allele odds ratio of between 1.2 and 1.3; this was the highest effect size for any variant/disease combination with at least adequate evidence. Although the 9p21 association seems to be independent of traditional risk factors, there is adequate evidence that the improvement in risk prediction is, at best, small. Clinical utilityClinical utility was not formally evaluated in any of the studies reported to date, including for 9p21. As a result, no evidence was available on the balance of benefits and harms. Also, there was no direct evidence available to assess the health benefits and harms of adding these markers to traditional risk factors (e.g., Framingham Risk Score). However, the estimated additional benefit from adding genomic markers to traditional risk factors was found to be negligible. Contextual IssuesPrevention of CVD is a public health priority. Improvements in outcomes associated with genomic profiling could have important impacts. Traditional risk factors such as those used in the Framingham Risk Scores have an advantage in clinical screening and risk assessment strategies because they measure the actual targets for therapy (e.g., lipid levels and blood pressure). To add value, genomic testing should lead to better outcomes than those achievable by assessment and treatment of traditional risk factors alone. Some issues important for clinical utility remain unknown, such as the biological mechanism underlying the most convincing marker's (9p21) association with CVD; the level of risk that changes intervention; whether long-term disease outcomes will improve; how individuals ordering direct to consumer tests will understand/respond to test results and interact with the health care system; and whether direct to consumer testing will motivate behavior change or amplify potential harms.

Association of traditional risk factors with carotid intima-media thickness and carotid plaque in asymptomatic individuals with a family history of premature cardiovascular disease.

The use of imaging to detect subclinical atherosclerosis helps to inform decision-making in people classified as having intermediate risk for cardiovascular disease (CVD). This study sought to use carotid plaque as an alternative to carotid intima media thickness (cIMT). Carotid ultrasound for assessment of cIMT and plaque was obtained in 1031 people (53years, 61% female) with a family history of atherosclerotic CVD. The association of baseline characteristics and standard atherosclerotic risk factors (RFs) were sought with abnormal cIMT and plaque. The strongest association of plaque was a history of hypertension (odds ratio [OR] 1.87 (1.02-3.42), followed by age (OR 1.08 [95% CI 1.02-1.13]). For cIMT, the strongest association was smoking history (OR 1.57 [1.13-2.19]). The area under the receiver operator curve for the presence of plaque was 0.74 (95% CI 0.68-0.81, p < 0.001) and 0.65 (95% CI 0.61-0.70, p < 0.001) for cIMT elevation. Isolated elevation of cIMT (n = 178) was associated with increased total cholesterol, body mass index (BMI) and systolic blood pressure (SBP). Plaque only (n = 29) was associated with hypertension, male sex and older age. The presence of both markers abnormal (n = 22) was associated with a history of smoking. The absence of either abnormal cIMT or plaque (n = 773), was inversely associated with current or past smoking, SBP and BMI. Abnormalities in carotid vessels are present in a minority of intermediate risk patients with familial premature disease. The associations with RFs differ and are more closely associated with plaque.

Thoracic Aorta Calcium Detection and Quantification Using Convolutional Neural Networks in a Large Cohort of Intermediate-Risk Patients.

Arterial calcification is an independent predictor of cardiovascular disease (CVD) events whereas thoracic aorta calcium (TAC) detection might anticipate extracoronary outcomes. In this work, we trained six convolutional neural networks (CNNs) to detect aortic calcifications and to automate the TAC score assessment in intermediate CVD risk patients. Cardiac computed tomography images from 1415 patients were analyzed together with their aortic geometry previously assessed. Orthogonal patches centered in each aortic candidate lesion were reconstructed and a dataset with 19,790 images (61% positives) was built. Three single-input 2D CNNs were trained using axial, coronal and sagittal patches together with two multi-input 2.5D CNNs combining the orthogonal patches and identifying their best regional combination (BRC) in terms of lesion location. Aortic calcifications were concentrated in the descending (66%) and aortic arch (26%) portions. The BRC of axial patches to detect ascending or aortic arch lesions and sagittal images for the descending portion had the best performance: 0.954 F1-Score, 98.4% sensitivity, 87% of the subjects correctly classified in their TAC category and an average false positive TAC score per patient of 30. A CNN that combined axial and sagittal patches depending on the candidate aortic location ensured an accurate TAC score prediction.

Polypill for primary prevention in individuals with intermediate risk for cardiovascular disease.

Polypill for primary prevention in individuals with intermediate risk for cardiovascular disease.

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

Objective evaluation of improved image quality with application of novel noise reduction filter in dynamic myocardial CT perfusion

Abstract Funding Acknowledgements Type of funding sources: None. Background Dynamic myocardial CT perfusion (CTP) is a non-invasive imaging technique able to depict cardiac ischemia. It is expected that the application of a new dynamic perfusion image noise reducing filter, the similarity filter (4DSF) would improve the image quality of CTP, resulting in clear visualization of perfusion deficits and hypo-perfused tissue and allowing for a substantial reduction in the radiation dose in dynamic myocardial CTP. Purpose To evaluate image quality before and after the application of a novel noise reducing filter on dynamic myocardial CT perfusion images reconstructed with deep learning-based algorithm. Methods The image datasets of patients with stable chest pain at intermediate risk of cardiovascular disease, who underwent stress dynamic CTP scanning as clinically indicated were retrospectively collected. The images were acquired with a 320-slice CT system, reconstructed using a deep learning-based algorithm (8 mm slice thickness) and filtered with the 4DSF. For each case, the signal-to-noise ratio (SNR) and the contrast-to-noise ratio (CNR) in six regions-of-interest (ROIs, 33-38 mm2) were computed, before and after filtering. The signal ROIs were located midventricular, in both four-chamber and short-axis views in the left ventricle blood pool, and the background ROIs in the cardiac septum and lateral wall. Differences in the SNR and CNR values were compared using paired t-tests. Results As a part of an ongoing study, twenty five cases were analysed to date. The following results (means for AiCE and AiCE + 4DSF, and corresponding p-values) were obtained in short axis view: septum SNR: 3.46 vs 6.25 (p = 0.007), lateral wall SNR: 3.66 vs 6.52 (p = 0.000), septum CNR: 13.35 vs 23.85 (p = 0.005), lateral wall CNR: 13.16 vs 23.57 (p = 0.010); and in four-chamber view: septum SNR: 3.67 vs 7.44 (p = 0.003), lateral wall SNR: 3.97 vs 7.65 (p = 0.001) and septum CNR: 13.92 vs 29.97 (p = 0.016), lateral wall CNR: 13.63 vs 29.75 (p = 0.018). All results are statistically significant. Conclusions We confirmed that the similarity filter decreases noise and therefore improves the objective image quality in both short axis and four chamber views. Therefore, the improved tissue texture depiction and improved visualization of perfusion defects may facilitate detection of ischemia and lead to reduction in radiation dose necessary for dynamic CTP, maintaining image quality. Abstract Figure. Region-of-interests (ROIs) location

New carotid plaque, but not the progression of intima-media thickness, predicts the progression of high-risk coronary plaque.

Carotid intima-media thickness (CIMT) is regarded as a controversial risk marker for cardiovascular disease (CVD). We aimed to evaluate the role of CIMT and carotid plaque progression as predictors for the progression of coronary plaque and compositions. In the Garlic 4 study, asymptomatic patients with intermediate CVD risk (Framingham risk score 6-20%) were recruited for a serial carotid ultrasound, and coronary artery calcium score (CAC)/coronary computed tomography angiography (CCTA) studies for subclinical atherosclerosis at a baseline and 1 year. The association between progression of quantitatively measured coronary plaque compositions and the progression of CIMT/carotid plaque was analyzed. A P value <0.05 is considered as statistically significant. Forty-seven consecutive patients were included. The mean age was 58.5 ± 6.6 years, and 69.1 % were male. New carotid plaque appeared in 34.0 % (n = 16) of participants, and 55.3 % (n = 26) of subjects had coronary plaque progression. In multilinear regression analysis, adjusted by age, gender, and statin use, the development of new carotid plaque was significantly associated with an increase in noncalcified coronary plaque [β (SE) 2.0 (0.9); P = 0.025] and necrotic core plaque (1.7 (0.6); P = 0.009). In contrast, CIMT progression was not associated with the progression of coronary plaque, or coronary artery calcium (CAC) (P = NS). Compared to CIMT, carotid plaque is a better indicator of coronary plaque progression. The appearance of a new carotid plaque is associated with significant progression of necrotic core and noncalcified plaque, which are high-risk coronary plaque components.

Abstract 13510: Impact of Adverse Pregnancy Outcomes on Indication for Lipid Therapy in Women

Introduction: Lifetime risk for cardiovascular disease (CVD) is higher in women who experience adverse pregnancy outcomes (APOs) including pre-eclampsia, preterm birth, gestational hypertension, and gestational diabetes. APOs are risk-enhancing factors for atherosclerotic cardiovascular disease (ASCVD) in contemporary cholesterol guidelines. Hypothesis: History of APOs impacts consideration for lipid therapy in a significant proportion of women with borderline to intermediate CVD risk . Methods: A single center retrospective chart review of new patients who presented to the University of Florida Women’s Heart Health Clinic between July 2017 - July 2019 was performed. New female patients were routinely screened for pregnancy history with an obstetrics questionnaire, and cardiovascular history and lipid profiles were collected where available. Patients were stratified by age and calculated 10-yr risk of a cardiovascular event using the ACC/AHA Pooled Cohort Equation. APO history within age and risk categories in addition to pregnancy history documentation in electronic health records were then assessed. Results: Of the 182 new patients who presented to the University of Florida Women’s Heart Health Clinic between July 2017 - July 2019, average age was 49 years old and 71.3% were Caucasian. 25% of the study population had history of APO, and of patients with history of APO, only 55% had documented lipid profiles, 46% had pregnancy history documented in the obstetrics section of the electronic health record, and 17% had pregnancy history documented in their past medical history section. For patients aged 40-75 y/o with borderline-intermediate 10-yr CV event risk, risk-enhancing factors influenced consideration of potential statin therapy, with 20% of patients in the intermediate risk group having history of APO. Conclusions: Pregnancy history impacts potential statin therapy in a significant percentage of women aged 40-75 y/o with borderline-intermediate 10-yr ASCVD risk. However, APOs are often under-recognized and poorly documented as non-traditional CVD risk factors in women. Efforts to improve recognition of APOs in clinical practice should be promoted to improve CVD risk reduction efforts, particularly in young women.

Retinal vessel analysis as a novel screening tool to identify childhood acute lymphoblastic leukemia survivors at risk of cardiovascular disease

BACKGROUND Microvascular endothelial dysfunction is central to the pathogenesis of cardiovascular disease (CVD). The eye offers direct access for endothelial health assessment via the retinal microvasculature. The aim of the study was to investigate whether image-based retinal vessel analysis is a feasible method of assessing endothelial health in survivors of childhood acute lymphoblastic leukemia (cALL). MATERIALS AND METHODS Cardiovascular risk factors (CRFs) were estimated using the 30-year Framingham Risk Score in 73 childhood leukemia survivors (median age: 25; median years from diagnosis: 19) and 78 healthy controls (median age: 23). Radial arterial stiffness was measured using pulse wave analyzer, while endothelial activation markers were measured by soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1). Retinal fundus images were analyzed for central retinal artery/vein equivalents (CRAE/CRVE) and arteriolar-venular ratio (AVR). RESULTS cALL survivors had higher CRF (P<0.0001), arterial stiffness (P=0.001), and sVCAM-1 (P=0.007) compared with controls. Survivors also had significantly higher CRVE (P=0.021) while AVR was significantly lower (P=0.026) in survivors compared with controls, compatible with endothelial dysfunction. In cALL survivors with intermediate risk for CVD, CRAE, and AVR are significantly lower, while sVCAM-1 and sICAM-1 are significantly higher when compared with survivors with low CVD risk after adjusting with covariates (age, sex, and smoking status). CONCLUSIONS cALL survivors have an increased risk of CVD compared with age-matched peers. The survivors demonstrated microvasculopathy, as measured by retinal vascular analysis, in addition to physical and biochemical evidence of endothelial dysfunction. These changes predate other measures of CVD. Retinal vessel analysis may be utilized as a robust screening tool for identifying survivors at increased risk for developing CVD.

Use of low-dose acetylsalicylic acid for cardiovascular disease prevention: A practical, stepwise approach for pharmacists.

Low-dose acetylsalicylic acid (ASA) is recommended in patients with established cardiovascular disease. However, the role of ASA in those without cardiovascular disease (i.e., primary prevention) is less clear, which has led to discordance among Canadian guidelines. In 2018, 3 double-blind, randomized controlled trials were published that evaluated ASA 100 mg daily versus placebo in patients without established cardiovascular disease. In the ASPREE trial, ASA did not reduce the risk of all-cause death, dementia, or persistent physical disability in patients ≥70 years of age but increased the risk of major bleeding. In the ARRIVE trial, ASA failed to lower the risk of a composite of cardiovascular events but increased any gastrointestinal bleeding in patients at intermediate risk of cardiovascular disease. In the ASCEND trial, ASA significantly reduced the primary composite cardiovascular outcome in patients with diabetes for a number needed to treat of 91 over approximately 7.4 years. Yet major bleeding was increased with ASA for a number needed to harm of 112. Therefore, in most situations, ASA should not be recommended for primary cardiovascular prevention. However, there are additional indications for ASA beyond cardiovascular disease. Thus, a sequential algorithm was developed based on contemporary evidence to help pharmacists determine the suitability of ASA in their patients and play an active role in educating their patients about the potential benefits (or lack thereof) and risks of ASA. Can Pharm J (Ott) 2020;153:xx-xx.

Feasibility and Acceptability of Using a Telehealth Platform to Monitor Cardiovascular Risk Factors in Hematopoietic Cell Transplantation Survivors at Risk for Cardiovascular Disease.

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in hematopoietic cell transplantation (HCT) survivors. In these patients, such risk factors as hypertension, diabetes, obesity, and physical inactivity are important modifiers of CVD risk. However, the period when HCT survivors are at greatest risk of developing these risk factors, and in turn CVD, coincides with a drop in engagement in survivorship care. We examined the feasibility and acceptability of a 4-week remote risk-based monitoring (blood pressure monitor, weight scale, pulse oximeter, glucometer) and management program in 18 (11 allogeneic and 7 autologous) HCT survivors at intermediate-high risk of CVD. The median patient age was 66 years (range, 53 to 74 years), 67% had hypertension, 22% had diabetes, 11% were obese (body mass index ≥30 kg/m2), 56% were at intermediate risk of CVD, and 44% were at high risk of CVD. Weekly compliance with the remote monitoring schedule (≥3 readings/week using all devices) ranged from 72% in week 1 to 83% in weeks 2 to 4. Fifteen participants (83%) generated 86 alerts that were outside the predetermined range of normal; 63 of these readings (73%) normalized without intervention, and 23 (27%) necessitated triage by the study research nurse. Nearly all participants reported that the study kept them motivated and involved in their healthcare, and >85% agreed that the study supported their healthcare goals, helped them learn and manage their health conditions, and increased their access to healthcare. These findings may set the foundation for innovative risk-based and remote interventions to reduce the burden of CVD in this growing population of patients.