Symptomatic Cardiovascular Disease Research Articles

Eccentric Muscle Strengthening Using Maximal Contractions Is Deleterious in Knee Osteoarthritis: A Randomized Clinical Trial.

Objectives: To show the superiority of eccentric versus concentric strengthening in terms of improving quadriceps strength in knee osteoarthritis (OA), a randomized controlled study was conducted to perform 12 sessions of either eccentric or concentric isokinetic muscle strengthening over 6 weeks. Methods: We recruited males and females, aged between 40 and 70 years, with predominantly unilateral femorotibial OA. Exclusion criteria were having a prosthesis, inflammatory arthritis or flare-up of OA, symptomatic patellofemoral OA, cardiovascular or pulmonary disease that could be a contraindication to the study treatment, and any pathology that could cause muscle weakness. The primary endpoint was the between-group difference in change in maximum concentric isokinetic knee extension peak torque (PT) at 60°/s on the OA side at 6 weeks. Secondary endpoints were between-group difference in change in concentric hamstring PT at 60°/s; eccentric quadriceps and hamstring PT at 30°/s; 10 m and 200 m walking speeds; pain and functional status (WOMAC score) at 6 weeks and 6 months. Results: The sample consisted of 11 females and 27 males, with a mean age of 57.7 ± 7.52 years and a body mass index (BMI) of 25.95 ± 3.93 kg/m2. Quadriceps strength increased more at 6 weeks in the concentric than the eccentric group with no statistical difference. There was a rate of 25% major adverse events in the eccentric group. Conclusions: Eccentric training resulted in a smaller improvement in quadriceps strength than concentric training and was associated with a high risk of muscle injury, particularly to the hamstring muscles.

Prevalence of cardiovascular risk factors, target organ damage, and subclinical and symptomatic cardiovascular disease in a national population of patients with chronic myeloid leukemia

Prevalence of cardiovascular risk factors, target organ damage, and subclinical and symptomatic cardiovascular disease in a national population of patients with chronic myeloid leukemia

Continuous glucose monitoring-derived time in range and CV are associated with altered tissue characteristics of the carotid artery wall in people with type 2 diabetes

Aims/hypothesisPrevious studies have suggested that glucose variability may accelerate atherosclerosis progression in people with type 2 diabetes. Current guidelines recommend assessing glycaemic control using continuous glucose monitoring (CGM), which provides a comprehensive glycaemic profile to supplement HbA1c measurement. However, the association between CGM-derived metrics and atherosclerosis progression is not entirely clear.MethodsThis exploratory study used baseline data and data obtained after 104 weeks from an ongoing prospective, multicentre, observational study. Six hundred study participants with type 2 diabetes and no apparent history of symptomatic cardiovascular disease underwent CGM and ultrasonographic atherosclerosis measurements of the carotid arteries, including the intima–media thickness (IMT) and grey-scale median (GSM), at baseline and 104 weeks. Non-invasive ultrasonic tissue characterisation of the carotid artery wall or plaque using the GSM reflects vascular composition. Multivariate regression models were used to analyse the association between CGM-derived indices, mainly time in range (TIR) and CV, and changes in carotid atherosclerosis index values.ResultsOver the 104-week study period, there were modest increases in mean IMT (from 0.759±0.153 to 0.773±0.152 mm, p<0.001) and thickened-lesion GSM (from 43.5±19.5 to 53.9±23.5 units, p<0.001), but no significant changes in common carotid artery maximum-IMT (from 1.109±0.442 to 1.116±0.469 mm, p=0.453) or mean GSM (from 48.7±19.3 to 49.8±20.8 units, p=0.092). In a linear regression model with adjustment for possible atherosclerotic risk factors, including HbA1c, TIR and CV at baseline were significantly associated with the annual change in mean GSM (regression coefficient per 10% increase in TIR 0.52; 95% CI 0.06, 0.98; Hochberg-adjusted p value 0.038; regression coefficient per 1% increase in CV −0.12; 95% CI −0.22, −0.02; Hochberg-adjusted p value 0.038). TIR and CV at baseline were also significantly associated with the annual change in thickened-lesion GSM (regression coefficient per 10% increase in TIR 0.95; 95% CI 0.12, 1.79; Hochberg-adjusted p value 0.038; regression coefficient per 1% increase in CV −0.19; 95% CI −0.36, −0.01; Hochberg-adjusted p value 0.038). Participants who achieved target CGM-derived metrics at baseline, as proposed by an international consensus, showed significant annual changes in mean GSM compared with those who did not (0.94±6.88 vs −0.21±6.19 units/year, p=0.007).Conclusions/interpretationTIR and CV were significantly associated with changes in the tissue characteristics of the carotid artery wall.Trial registrationUniversity Hospital Medical Information Network Clinical Trials Registry, number UMIN000032325Graphical

AI-integrated ocular imaging for predicting cardiovascular disease: advancements and future outlook.

Cardiovascular disease (CVD) remains the leading cause of death worldwide. Assessing of CVD risk plays an essential role in identifying individuals at higher risk and enables the implementation of targeted intervention strategies, leading to improved CVD prevalence reduction and patient survival rates. The ocular vasculature, particularly the retinal vasculature, has emerged as a potential means for CVD risk stratification due to its anatomical similarities and physiological characteristics shared with other vital organs, such as the brain and heart. The integration of artificial intelligence (AI) into ocular imaging has the potential to overcome limitations associated with traditional semi-automated image analysis, including inefficiency and manual measurement errors. Furthermore, AI techniques may uncover novel and subtle features that contribute to the identification of ocular biomarkers associated with CVD. This review provides a comprehensive overview of advancements made in AI-based ocular image analysis for predicting CVD, including the prediction of CVD risk factors, the replacement of traditional CVD biomarkers (e.g., CT-scan measured coronary artery calcium score), and the prediction of symptomatic CVD events. The review covers a range of ocular imaging modalities, including colour fundus photography, optical coherence tomography, and optical coherence tomography angiography, and other types of images like external eye images. Additionally, the review addresses the current limitations of AI research in this field and discusses the challenges associated with translating AI algorithms into clinical practice.

Low-Dose Aspirin for Primary Prevention of Cardiovascular Events Comparing East Asians With Westerners: A Meta-Analysis

BackgroundEast Asians have shown different risk profiles for both thrombophilia and bleeding than Western counterparts. ObjectivesThe authors sought to evaluate the effect of low-dose aspirin for primary prevention between these populations. MethodsWe searched randomized clinical trials (RCTs) for intervention with low-dose aspirin (≤100 mg once daily) in participants without symptomatic cardiovascular disease until December 31, 2021. The number of events between the arms was extracted for analysis. Pooled risk ratios (RRs) and risk differences (RDs) were analyzed in each population. Outcomes included a major adverse cardiovascular event (MACE), cardiovascular death, myocardial infarction, stroke, and major bleeding (intracranial hemorrhage and major gastrointestinal bleeding). ResultsTwo RCTs included 17,003 East Asians, and 9 RCTs had 117,467 Western participants. Aspirin treatment showed a similar effect in reducing the MACE rate (RR of East Asians: 0.87; 95% CI: 0.71-1.05; RR of Westerners: 0.90; 95% CI: 0.85-0.95) (Pinteraction = 0.721). In contrast, the risk of major bleeding during aspirin vs control was greater in the East Asian population (RR: 2.48; 95% CI: 1.86-3.30) compared with the Western population (RR: 1.45; 95% CI: 1.26-1.66) (Pinteraction = 0.001), which was driven by more frequent gastrointestinal bleeding (RR of East Asians: 3.29; 95% CI: 2.26-4.80 vs RR of Westerners: 1.56; 95% CI: 1.29-1.88) (Pinteraction < 0.001). The net RDs (RD of MACE plus RD of major bleeding) were 8.04 and 0.72 per 1,000 persons in East Asian and Western participants, indicating 124 and 1,389 of the net number needed to harm, respectively. ConclusionsLow-dose aspirin for primary prevention in East Asians must be cautiously prescribed because of the increased risk of major bleeding relative to Western counterparts.

O.2.3-11 Light standing work and high intensity occupational physical activities predict baseline and 8-year progression of carotid atherosclerosis among women

Abstract Purpose Recent reviews link higher levels of occupational physical activity (OPA) to cardiovascular disease (CVD). However, the evidence for women is inconsistent and studies of activity-limiting symptomatic CVD are prone to healthy worker selection effect. To address these limitations, this study investigated OPA effects on asymptomatic carotid artery intima-media thickness (IMT), a proxy for atherosclerosis, among women. Methods Participants include 905 women from the population-based Kuopio Ischemic Heart Disease Risk Factor Study with baseline (1998-2001) data on self-reported OPA and sonographic measurement of IMT. Linear mixed models with adjustment for 15 potential confounders estimated and compared mean baseline IMT and 8-year IMT progression for five levels of self-reported OPA. Analyses stratified by cardiovascular health and retirement status were planned because strong interactions between pre-existing CVD and OPA intensity have previously been reported. Results Light standing work, moderately heavy active work, and heavy or very heavy physical work were all consistently associated with greater baseline IMT and 8-year IMT progression than light sitting work, being hazardous for cardiovascular health. The greatest baseline IMT was observed for heavy or very heavy physical work (1.21 mm), and the greatest 8-year IMT progression for light standing work and moderately heavy active work (both 0.13 mm), 30% above sitting work (0.10 mm). Stratified analyses showed that these differences were driven by much stronger OPA effects among women with baseline carotid artery stenosis. Retired women experienced slower IMT progression than those still working at baseline. Conclusions Light standing work and higher levels of OPA intensity predict higher baseline IMT and 8-year IMT progression, especially among women with baseline stenosis. This study suggests that inconsistent findings regarding the effects of OPA on cardiovascular diseaes and mortality outcomes may be due to healthy worker selection and exposure misclassification biases including the failure to distinguish between standing and sitting work postures in many cohort studies. Funding Source This project is funded by the Danish taxpayers, via the Danish Work Environment Research Foundation, grant number 20195100247.

Low-Dose Aspirin and the Risk of Stroke and Intracerebral Bleeding in Healthy Older People

Low-dose aspirin has been widely used for primary and secondary prevention of stroke. The balance between potential reduction of ischemic stroke events and increased intracranial bleeding has not been established in older individuals. To establish the risks of ischemic stroke and intracranial bleeding among healthy older people receiving daily low-dose aspirin. This secondary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized, double-blind, placebo-controlled trial of daily low-dose aspirin was conducted among community-dwelling people living in Australia or the US. Participants were older adults free of symptomatic cardiovascular disease. Recruitment took place between 2010 and 2014, and participants were followed up for a median (IQR) of 4.7 (3.6-5.7) years. This analysis was completed from August 2021 to March 2023. Daily 100-mg enteric-coated aspirin or matching placebo. Stroke and stroke etiology were predetermined secondary outcomes and are presented with a focus on prevention of initial stroke or intracranial bleeding event. Outcomes were assessed by review of medical records. Among 19 114 older adults (10 782 females [56.4%]; median [IQR] age, 74 [71.6-77.7] years), 9525 individuals received aspirin and 9589 individuals received placebo. Aspirin did not produce a statistically significant reduction in the incidence of ischemic stroke (hazard ratio [HR], 0.89; 95% CI, 0.71-1.11). However, a statistically significant increase in intracranial bleeding was observed among individuals assigned to aspirin (108 individuals [1.1%]) compared with those receiving placebo (79 individuals [0.8%]; HR, 1.38; 95% CI, 1.03-1.84). This occurred by an increase in a combination of subdural, extradural, and subarachnoid bleeding with aspirin compared with placebo (59 individuals [0.6%] vs 41 individuals [0.4%]; HR, 1.45; 95% CI, 0.98-2.16). Hemorrhagic stroke was recorded in 49 individuals (0.5%) assigned to aspirin compared with 37 individuals (0.4%) in the placebo group (HR, 1.33; 95% CI, 0.87-2.04). This study found a significant increase in intracranial bleeding with daily low-dose aspirin but no significant reduction of ischemic stroke. These findings may have particular relevance to older individuals prone to developing intracranial bleeding after head trauma. ISRCTN.org Identifier: ISRCTN83772183.

Occupational physical activity predicts baseline and 8-year progression of carotid atherosclerosis among women.

Recent reviews link higher levels of occupational physical activity (OPA) to cardiovascular disease (CVD). However, the evidence for women is inconsistent and studies of activity-limiting symptomatic CVD are prone to healthy worker survivor effect. To address these limitations, this study investigated OPA effects on asymptomatic carotid artery intima-media thickness (IMT) among women. Participants include 905 women from the population-based Kuopio Ischemic Heart Disease Risk Factor Study with baseline (1998-2001) data on self-reported OPA and sonographic measurement of IMT. Linear mixed models with adjustment for 15 potential confounders estimated and compared mean baseline IMT and 8-year IMT progression for five levels of self-reported OPA. Analyses stratified by cardiovascular health and retirement status were planned because strong interactions between preexisting CVD and OPA intensity have previously been reported. Light standing work, moderately heavy active work, and heavy or very heavy physical work were all consistently associated with greater baseline IMT and 8-year IMT progression than light sitting work. The greatest baseline IMT was observed for heavy or very heavy physical work (1.21 mm), and the greatest 8-year IMT progression for light standing work and moderately heavy active work (both 0.13 mm), 30% above sitting work (0.10 mm). Stratified analyses showed that these differences were driven by much stronger OPA effects among women with baseline carotid artery stenosis. Retired women experienced slower IMT progression than those working at baseline. Higher levels of OPA predict higher baseline IMT and 8-year IMT progression, especially among women with baseline stenosis.

Response to a low-energy meal replacement plan on glycometabolic profile and reverse cardiac remodelling in type 2 diabetes: a comparison between South Asians and White Europeans.

South Asians (SA) constitute a quarter of the global population and are disproportionally affected by both type 2 diabetes (T2D) and heart failure. There remains limited data of the acceptability and efficacy of low-energy meal replacement plans to induce remission of T2D in SA. The objective of this exploratory secondary analysis of the DIASTOLIC study was to determine if there was a differential uptake, glycometabolic and cardiovascular response to a low-energy meal replacement plan (MRP) between SA and White European (WE) people with T2D. Obese adults with T2D without symptomatic cardiovascular disease were allocated a low-energy (~810 kcal/day) MRP as part of the DIASTOLIC study (NCT02590822). Comprehensive multiparametric cardiovascular magnetic resonance imaging, echocardiography, cardiopulmonary exercise testing and metabolic profiling were undertaken at baseline and 12 weeks. A comparison of change at 12 weeks between groups with baseline adjustment was undertaken. Fifteen WE and 12 SAs were allocated the MRP. All WE participants completed the MRP versus 8/12 (66%) SAs. The degree of concentric left ventricular remodelling was similar between ethnicities. Despite similar weight loss and reduction in liver fat percentage, SA had a lower reduction in Homeostatic Model Assessment for Insulin Resistance [-5.7 (95% CI: -7.3, -4.2) versus -8.6 (-9.7, -7.6), p = 0.005] and visceral adiposity compared to WE [-0.43% (-0.61, -0.25) versus -0.80% (-0.91, -0.68), p = 0.002]. Exercise capacity increased in WE with no change observed in SA. There was a trend towards more reverse remodelling in WE compared to SAs. Compliance to the MRP was lower in SA versus WE. Overall, those completing the MRP saw improvements in weight, body composition and indices of glycaemic control irrespective of ethnicity. Whilst improvements in VAT and insulin resistance appear to be dampened in SA versus WE, given the small sample, larger studies are required to confirm or challenge this potential ethnic disparity. NCT02590822.

Prevalence of abnormal left ventricular geometry and predictors of left ventricular hypertrophy in patients with rheumatoid arthritis

Abstract Background Rheumatoid arthritis (RA) patients have an excess risk of cardiovascular morbidity and mortality. Left ventricular hypertrophy (LVH) is generally considered a target organ damage of hypertensive patients, but it is an overlooked condition in the RA. In addition, LVH is one-sixth prevalence in RA patients and reflects a greater risk of cardiovascular events. Purpose We aimed to study the prevalence of LVH in patients with RA without symptomatic cardiovascular disease and explore the associated factors of LVH. Methods A cross-sectional study was conducted among adult RA patients and a retrospectively review of echocardiography from the database in non-RA participants. LVH was defined as LV mass index greater than 115 g/m2 in males or 95 g/m2 in females. The prediction model for LVH was constructed by stepwise logistic regression. The prediction model's performance on the test data is evaluated using receiver operator characteristic (ROC) curves to predict the presence of LVH and optimal cut-off point determined by the Youden index. Results This study included 109 RA patients and 119 age- and sex-matched non-RA participants. RA participants showed a significantly greater CV risk factor profile; hypertension, diabetes, and dyslipidemia than non-RA participants. Fifty two of 109 (47.7%) RA patients had abnormal LV geometry; eccentric hypertrophy, concentric remodeling, and concentric hypertrophy were 8/109 (7.3%), 28/109 (25.7%), and 16/109 (14.7%), respectively. The prevalence of LVH in RA patients was comparable to non-RA participants 24/109 (22%) and 28/119 (23.5%), p=0.91, respectively. However, there was significantly higher relative wall thickness in RA than non-RA participants 0.4±0.1 and 0.3±0.1, p&amp;lt;0.001, respectively. The diagnostic performance of the score prediction [(0.025×systolic blood pressure) + (non-steroidal anti-inflammatory drug × (0 or 1)) + (0.141×Troponin T level) ≥3.948] was to predict LVH in RA patients showed 91% sensitivity and 39% specificity (AUC = 0.689, 95% CI 0.564–0.814). Conclusion RA was associated with higher abnormal LV geometry compared to the non-RA participant. LVH is not uncommon in RA patients, and we could consider it as a target organ damage despite no obvious cardiovascular risk factors. The risk predictor score may be applied for fundamental screening tool for LVH in RA patients before sending the patients for echocardiography. Funding Acknowledgement Type of funding sources: None.

Nighttime hemodynamic phenotype. A novel risk factor for cardiovascular disease, especially heart failure: the practitioner-based nationwide JAMP study.

Non-dipper and riser patterns of nocturnal blood pressure (BP) are risk factors for cardiovascular disease (CVD), including heart failure (HF). However, the risk associated with a disrupted nocturnal pattern of heart rate is not well known. To investigate whether the nighttime heart rate is a risk factor for HF, alongside nighttime BP phenotype. The practitioner-based, nationwide, prospective Japan Ambulatory Blood Pressure Monitoring Prospective (JAMP) study included patients with ≥ 1 CVD risk factor but without symptomatic CVD at baseline. All patients underwent 24-h ambulatory BP monitoring at baseline and were followed annually. Nocturnal heart rate dipping (%) was calculated as 100•[1 - nighttime/daytime heart rate]. During a mean 4.5years' follow-up in 6,359 patients (mean age 68.6years), there were 306 CVD events (119 stroke, 99 coronary artery disease, and 88 HF). A 10-beats/min increase in nighttime heart rate was significantly associated with a 36-47% increase in the risk of total CVD, stroke and HF events independently of office SBP and nighttime SBP (all p < 0.005). The CVD and HF risk associated with nocturnal heart rate dipping status was independent of office and 24-h systolic BP and nocturnal BP dipping status (p < 0.001). Performance of the final model for predicting HF including BP parameters was significantly improved by the addition of nocturnal heart rate dipping patterns (p = 0.038; C-statistic 0.852). Nighttime non-dipper and riser patterns of heart rate were associated with CVD especially HF, independently and additively of nocturnal BP dipping status, indicating the importance of antihypertensive strategies targeting nighttime hemodynamics. URL: https://www.umin.ac.jp/ctr/ ; Unique identifier: UMIN000020377.

Fibro-inflammatory recovery and type 2 diabetes remission following a low calorie diet but not exercise training: A secondary analysis of the DIASTOLIC randomised controlled trial.

AimsTo investigate the relationship between fibro‐inflammatory biomarkers and cardiovascular structure/function in people with Type 2 Diabetes (T2D) compared to healthy controls and the effect of two lifestyle interventions in T2D.MethodsData were derived from the DIASTOLIC randomised controlled trial (RCT) and includes a comparison between those with T2D and the matched healthy volunteers recruited at baseline. Adults with T2D without cardiovascular disease (CVD) were randomized to a 12‐week intervention either: (1) exercise training, (2) a low‐energy (∼810 kcal/day) meal‐replacement plan (MRP) or (3) standard care. Principal Component and Fisher's linear discriminant analysis were used to investigate the relationships between MRI acquired cardiovascular outcomes and fibro‐inflammatory biomarkers in cases versus controls and pre‐ and post‐intervention in T2D.ResultsAt baseline, 83 people with T2D (mean age 50.5 ± 6.4; 58% male) and 36 healthy controls (mean age 48.6 ± 6.2; 53% male) were compared and 76 people with T2D completed the RCT for pre‐ post‐analysis. Compared to healthy controls, subjects with T2D had adverse cardiovascular remodelling and a fibro‐inflammatory profile (20 differentially expressed biomarkers). The 3D data visualisations showed almost complete separation between healthy controls and those with T2D, and a marked shift towards healthy controls following the MRP (15 biomarkers significantly changed) but not exercise training.ConclusionsFibro‐inflammatory pathways and cardiovascular structure/function are adversely altered before the onset of symptomatic CVD in middle‐aged adults with T2D. The MRP improved the fibro‐inflammatory profile of people with T2D towards a more healthy status. Long‐term studies are required to assess whether these changes lead to continued reverse cardiac remodelling and prevent CVD.

FC 122: Effects of Canagliflozin on Cardiovascular and Kidney Events in Patients With Chronic Kidney Disease With and Without Peripheral Vascular Disease: Integrated Analysis From the Canvas Program and Credence Trial

Abstract BACKGROUND AND AIMS Type 2 diabetes mellitus (T2DM) is associated with comorbidities, such as chronic kidney disease (CKD) and peripheral vascular disease (PVD), which may increase risk of cardiovascular (CV) and kidney events. Canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, reduced the risk of CV and kidney events in patients with T2DM and high CV risk or nephropathy in the CANVAS Program and CREDENCE trial, respectively. The effects of canagliflozin on CV and kidney outcomes in patients with CKD with and without PVD remain unknown. METHOD This post hoc analysis included integrated, pooled data from the CANVAS Program and the CREDENCE trial. The effects of canagliflozin compared with placebo on CV and kidney outcomes were assessed in patients with CKD with and without PVD at baseline. CKD was defined as estimated glomerular filtration rate (eGFR) &amp;lt;60 mL/min/1.73 m2 and PVD was defined based on investigator classification on the electronic case report form without requirement for specific clinical evaluation or imaging. Propensity score (PS) matching was used to balance patient demographics and baseline clinical characteristics between groups. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using Cox regression models. RESULTS A total of 14 543 participants from the CANVAS Program (N = 10 142) and CREDENCE (N = 4401) were included. Of these, 3514 had CKD alone (canagliflozin, n = 1792; placebo, n = 1722; mean eGFR, 46 mL/min/1.73 m2; symptomatic CV disease history, 49%; insulin use, 64%) and 1156 had CKD + PVD (canagliflozin, n = 626; placebo, n = 530; mean eGFR, 46 mL/min/1.73 m2; symptomatic CV disease history, 96%; insulin use, 74%) at baseline. Canagliflozin was associated with a reduced risk of major adverse cardiovascular events (MACE), the composite of hospitalization for heart failure (HHF) or CV death (HHF/CV death), doubling of serum creatinine (dSCr), end-stage kidney disease (ESKD) and the composite of ESKD or dSCr compared with placebo in patients with CKD with and without PVD (Figure 1A). After matching, 3210 patients had CKD alone (mean eGFR, 46 mL/min/1.73 m2; symptomatic CV disease history, 49%; insulin use, 64%) and 966 had CKD + PVD (mean eGFR, 46 mL/min/1.73 m2; symptomatic CV disease history, 98%; insulin use, 74%), with equal numbers in the canagliflozin and placebo groups. In the PS-matched groups, canagliflozin was associated with a reduced risk of MACE, HHF/CV death, dSCr, ESKD and the composite of ESKD or dSCr compared with placebo in patients with CKD with and without PVD (Figure 1B). CONCLUSION Canagliflozin significantly reduced the risk of MACE, HHF/CV death, dSCr, ESKD, and the composite of ESKD or dSCr in patients with CKD with and without PVD, suggesting that the beneficial effects of canagliflozin on CV and kidney outcomes are consistent and can be seen in patients regardless of these comorbidities.

Distribution of Coronary Artery Calcium by Age, Sex, and Race Among Patients 30-45 Years Old

BackgroundCoronary artery calcium (CAC) is a measure of atherosclerotic burden and is well-validated for risk stratification in middle- to older-aged adults. Few studies have investigated CAC in younger adults, and there is no calculator for determining age-, sex-, and race-based percentiles among individuals aged <45 years. ObjectivesThe purpose of this study was to determine the probability of CAC >0 and develop age-sex-race percentiles for U.S. adults aged 30-45 years. MethodsWe harmonized 3 datasets—CARDIA (Coronary Artery Risk Development in Young Adults), the CAC Consortium, and the Walter Reed Cohort—to study CAC in 19,725 asymptomatic Black and White individuals aged 30-45 years without known atherosclerotic cardiovascular disease. After weighting each cohort equally, the probability of CAC >0 and age-sex-race percentiles of CAC distributions were estimated using nonparametric techniques. ResultsThe prevalence of CAC >0 was 26% among White males, 16% among Black males, 10% among White females, and 7% among Black females. CAC >0 automatically placed all females at >90th percentile. CAC >0 placed White males at the 90th percentile at age 34 years compared with Black males at age 37 years. An interactive webpage allows one to enter an age, sex, race, and CAC score to obtain the corresponding estimated percentile. ConclusionsIn a large cohort of U.S. adults aged 30-45 years without symptomatic atherosclerotic cardiovascular disease, the probability of CAC >0 varied by age, sex, and race. Estimated percentiles may help interpretation of CAC scores among young adults relative to their age-sex-race matched peers and can henceforth be included in CAC score reporting.

Selected Articles from This Issue

Racial/ethnic disparities in cancer mortality are well-described and are partly attributable to later stage of diagnosis. It is unclear to what extent reductions in the incidence of late-stage cancer could narrow these relative and absolute disparities. To better understand the potential of enhanced cancer screening in the population at large, Clarke and colleagues previously assessed the population-level potential of earlier detection of common cancer types by examining current rates of diagnosis after metastasis and hypothesizing reductions in deaths that could occur if cancers were diagnosed at earlier stages. Here, that assessment is expanded by estimating these absolute and relative reductions separately for eight contemporary U.S. population subgroups defined by race/ethnicity and sex. Across population subgroups, non-Hispanic Black males have the highest burden of stage IV cancer and would have the most deaths averted from improved detection of cancer before metastasis. Detecting cancer before metastasis could meaningfully reduce deaths in all populations, but especially in non-Hispanic Black populations.This study by Lipshultz and colleagues assessed the burden of potentially modifiable cardiometabolic risk factors among childhood cancer survivors previously treated with anthracycline-containing regimens, compared with population-matched controls. Overall, survivors had similar cardiometabolic profiles compared with general population controls. Survivors had higher rates of pre-hypertension/hypertension, reinforcing the importance of close attention to blood pressure management, even in early adulthood. With more favorable lifestyle habits in this cohort, survivors had a lower predicted cardiovascular risk when applying general population risk factor models, but nonetheless a moderate or greater risk of subsequent symptomatic cardiovascular disease predicted by childhood cancer survivor-specific risk models. Further strategies supporting optimal cardiometabolic risk factor control and risk assessment are warranted in survivors.Breast cancers in recently postpartum women may have worse outcomes, but studies examining tumor molecular features by pregnancy recency have shown conflicting results. This analysis used Carolina Breast Cancer Study data to examine clinical and molecular tumor features among women <50 years of age who were recently (≤10 years prior), or remotely (>10 years prior) postpartum, or nulliparous. Prevalence odds ratios (PORs) and 95% confidence intervals (CIs) were estimated using multivariable models. The results suggest a dominant effect of parity (vs. nulliparity) and a lesser effect of pregnancy recency on tumor molecular features, although tumor immune microenvironments were altered in association with pregnancy recency. This study by Vohra and colleagues is unique in examining tumor immune microenvironment and RNA-based markers according to time since last childbirth.Asian Americans (AA) are the fastest growing and highly diverse population group in the U.S., yet few studies have examined cancer mortality burden by AA ethnicity. Using SEER cancer registry data, Karia and colleagues examined differences in gynecologic cancer mortality between White and AA women by ethnicity (Filipino, Chinese, Japanese, Korean, Vietnamese, Indian/Pakistani). AA women had a lower risk of ovarian and cervical cancer mortality and a higher risk of uterine cancer mortality than White women, with substantial heterogeneity across AA ethnicity. These findings underscore the importance of disaggregation of data by ethnicity to fully understand cancer burden among the diverse AA population.

Guidelines for the Prevention of Symptomatic Cardiovascular Disease, Based upon the Presence of Coronary Artery Calcified Plaque—Provided by the Society for the Prevention of Symptomatic Heart Disease

Introduction: The epidemic of atherosclerotic cardiovascular disease in the Western World accounts for the majority of morbidity and mortality in adults. This disease is on the increase, and previous recommendations using “risk equations” to prescribe preventive treatment have not been successful in reducing the prevalence of cardiovascular disease. Furthermore, compliance with statin medication has been limited, with approximately 50% of individuals being non-compliant within five years. This situation is unacceptable since atherosclerosis is both preventable and reversible. Methods: The guidelines presented in this article utilize coronary artery calcium scanning as the basis for preventative therapeutic decisions and identifying the presence of asymptomatic cardiovascular disease. This radiographic technique is superior to “risk equations” in predicting future cardiovascular events. It provides a comprehensive assessment of the lifelong insults to the coronary artery vascular endothelium and the resulting inflammation. Coronary artery calcium scanning is widely available, inexpensive, safe, and reproducible. It has the major advantage of increasing treatment compliance in patients with positive coronary artery calcium scores. Results: All suggested guidelines are supported by published scientific data. Citations are provided to allow the reader to obtain further information. The authors are available for further consultation. Each guideline provides specific recommendations that the primary caregiver can discuss with the patient. Patient involvement in decision-making is strongly recommended. Both treatment costs and adverse effects are minimal. Conclusion: It is anticipated that the early identification of asymptomatic cardiovascular disease and its aggressive treatment will result in regression of subclinical atherosclerosis. Adoption of these guidelines will stop the epidemic of symptomatic heart disease and result in healthier and more satisfied patients.

The activity of the renin-angiotensin-aldosterone system before and after parathyroidectomy in patients with primary hyperparathyroidism

Background. The relationships between renin-angiotensin-aldosterone system (RAAS) and elevated parathyroid hormone levels in primary hyperparathyroidism (PHPT) is being actively discussed. But the way how parathyroid hormone interacts with renin and aldosterone currently is not clear.&#x0D; Materials and methods. Forty patients aged 18 to 70 years with a confirmed diagnosis of PHPT were involved in the study. All patients were tested for the main parameters of phosphorus-calcium metabolism and the RAAS parameters (plasma renin, plasma aldosterone) before and 2 weeks after parathyroidectomy.&#x0D; Results. Sixty percent of patients had any cardiovascular disease (CVD) and hypertension was the most common. Patients CVD in comparison with patients without CVD were older (61 and 41 years, respectively; p0.001), had a higher body mass index (28.9 and 21.9 kg/m2, respectively; p0.001) and had a lower aldosterone-to-renin ratio ARR (1.78 and 5.42, respectively; p=0.030). Patients with hypertension were older than patients with normal blood pressure (63 and 41 years, respectively; p0.001), had a higher body mass index (28.1 and 23.5 kg/m2, respectively; p=0.005), a lower ARR (1.46 and 5.82, respectively; p=0.001), as well higher levels of plasma renin (109.2 and 20.3 pg/ml, respectively; p=0.007) and serum total calcium (2.84 and 2.71 mmol/l, respectively; p=0.041). Correlation analysis showed that in patients with PHPT and CVD, the concentration of aldosterone is associated with the level of 24-hour urinary calcium (r=0.829, p=0.042), and in patients with symptomatic PHPT and CVD, the level of aldosterone correlated with the level of ionized calcium (r=-0.812, p=0.05). We found no significant differences between the levels of renin, aldosterone and ARR before and 2 weeks after parathyroidectomy. However, in the postoperative period, there were no differences in the levels of renin and ARR among patients with hypertension and without hypertension.&#x0D; Conclusion. In our study we found that the levels of plasma renin and serum total calcium were higher in patients with PHPT and hypertension compared to patients with normal blood pressure. Also, we found the associations between plasma aldosterone and levels of ionized calcium and 24-hour urinary calcium. But the relationships between RAAS parameters and parameters of phosphorus-calcium metabolism need further investigations.

Uric Acid Variability as a Predictive Marker of Newly Developed Cardiovascular Events in Type 2 Diabetes.

Background: Cardiovascular disease (CVD) is associated with morbidity and mortality in patients with type 2 diabetes mellitus (T2D). However, the role of serum uric acid as a risk factor for developing cardiovascular disease is controversial. This study investigated whether uric acid variability was associated with new-onset symptomatic CVD in patients with T2D, requiring percutaneous coronary intervention.Methods: A total of 1,071 patients were enrolled in this retrospective cross-sectional study after propensity score matching. Patients with T2D and new-onset symptomatic CVD who received percutaneous coronary intervention for the first time, and with at least three consecutive 6-monthly measurements of serum uric acid were recruited from Severance Hospital between January 2015 and December 2019. Uric acid variability was measured by average successive variability (ASV) and analyzed to evaluate a possible correlation with the risk of developing CVD.Results: The patients were divided into quartiles based on the uric acid variability. Patients in the highest quartile were older and presented lower renal function and a higher mortality from CVD. There was a linear association between a high uric acid variability and the development of CVD. Compared to the lowest quartile, patients in the higher quartiles had a higher risk of CVD [quartile 3: adjusted odds ratio (aOR) = 1.76; 95% confidence interval (CI), 1.20–2.82; P = 0.019; quartile 4 aOR = 2.89; 95% CI, 1.74–4.80; P < 0.001].Conclusion: High uric acid variability is independently associated with an increased risk of new-onset symptomatic CVD requiring percutaneous coronary intervention in patients with T2D. Thus, maintaining serum uric acid in a narrow range by prescribing effective medications is essential to prevent new-onset CVD in patients with T2D. Nonetheless, the potential use of uric acid variability as a predictive marker of CVD in patients with T2D needs further validation.

Cardiovascular risk stratification in the noncardiac solid organ transplant candidate.

Solid organ transplantation (SOT) has become a widely accepted therapy for end-stage disease across the spectrum of thoracic and abdominal organs. With contemporary advances in medical and surgical therapies in transplantation, candidates for SOT are increasingly older with a larger burden of comorbidities, including cardiovascular disease (CVD). CVD, in particular, is a leading cause of morbidity and mortality in SOT candidates with end-stage disease of noncardiac organs [1]. Identification of coronary artery disease (CAD), heart failure, and valvular disease are important in noncardiac SOT to ensure both appropriate peri-transplant management and equitable organ allocation. Although the American College of Cardiology (ACC) and the American Heart Association (AHA) have published guidelines and recommendations for the perioperative cardiovascular evaluation of patients undergoing noncardiac surgery, the implications of both symptomatic and asymptomatic CVD differ in patients with end-stage organ failure being considered for SOT when compared to the general population. Herein, we review the epidemiology, diagnosis, and evidence for the management of CVD in kidney and liver transplantation, combining current guidelines from the 2012 ACC/AHA scientific statement on cardiac disease evaluation in SOT with more contemporary evidenced-based algorithms.

Vascular stiffness in children born after frozen or fresh embryo transfer. A cardiac magnetic resonance imaging study of 8 to 9 year old children

Abstract Background Vascular stiffness increases during childhood, and increased vascular stiffness is associated with symptomatic cardiovascular disease in adults with metabolic syndrome. In comparison with naturally conceived children (NC), children conceived after in-vitro fertilization by frozen (FET) or fresh embryo transfer (Fresh ET) are at risk of being large- and small-for-gestational-age, respectively. Epigenetic modulation during assisted reproductive technologies (ART) is suggested to influence cardiovascular risk factors, and recent literature suggests that children conceived after ART are at increased risk of insulin resistance, endothelial dysfunction and arterial hypertension. Such changes may be associated with increased vascular stiffness, but it is not yet been examined directly. Purpose We investigated if ART children are at increased risk of aortic distensibility and pulse-wave velocity. Methods 150 children aged 8–9 years conceived after FET (n=50), Fresh ET (n=50) or by natural conception (NC, n=50) were studied with magnetic resonance imaging. Conductance artery stiffness was determined from aortic distensibility and aortic pulse-wave velocity (PWV). Data were analyzed with blinding according to treatment group. Based on a conservative estimate for the common SD for the difference between groups of 1.5 mm2/mmHg, 36 children were required in each group to detect a difference in aortic distensibility of 10%, which corresponds to a 5 year age difference, with an alpha of 0.05 (double-sided) and a beta of 0.80. We aimed for 50 children in each group to allow for dropouts and non-analyzable scans, and to allow for further determinations. The effects of potential confounders on the effect of conception method on ascending aorta distensibility and total aortic PWV were tested stepwise in four linear regression models (Figure 1). Results Child groups were comparable with respect to anthropometric measures (Table 1). No differences were observed in systolic or diastolic blood pressure, cardiac output, total peripheral resistance, or in aortic distensibility (Ascending aorta distensibility: FET, ascending aorta 11.12±3.55 10–3 mm2/mmHg; Fresh ET 11.77±2.97 10–3 mm2/mmHg; NC 11.43±2.82 10–3 mm2/mmHg) (ANOVA-p=0.58) or aortic PWV (PWV of total aorta: FET, 3.69±0.75 m/s; Fresh ET, 3.49±0.31 m/s; NC, 3.59±0.61 m/s) (ANOVA-p=0.26). The effect of ART remained non-significant after adjustment for child sex, maternal BMI at early pregnancy, and maternal educational level (Figure 1). Conclusion The effects of ART on aortic distensibility were not statistically significant, but in the direction of the hypothesis of stiffer conductance arteries from frozen embryo transfer. The confidence interval was relatively wide, and the results suggest that the difference between frozen and fresh embryo transfer may in fact correspond to an age difference of more than 5 years. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Novo Nordisk Foundation Table 1Figure 1