Prior History Of Cardiovascular Disease Research Articles

The added value of deep learning to submaximal exercise electrocardiogram for the 10-year prediction of major adverse cardiovascular and cerebrovascular events

Abstract Background The added value of exercise ECG data to traditional risk factors in predicting cardiovascular events remains unclear. Deep learning of ECG signals has demonstrated state-of-the-art performance in detecting subtle abnormalities indicative of cardiovascular disease. We investigated whether deep learning analysis of exercise ECGs could improve the prediction of major cardiovascular and cerebrovascular events (MACCE) with respect to established risk models in a large population-based cohort. Purpose To assess the added value of submaximal exercise ECG measurements to established cardiovascular risk prediction models. Methods We obtained ECG recordings from 41,076 UK Biobank participants without cardiovascular disease (CVD) who underwent a submaximal exercise ECG test. We obtained ECG recordings from 41,076 UK Biobank participants without cardiovascular disease (CVD) who underwent a submaximal exercise ECG test. We created two deep neural network ECG risk scores: one derived from conventional ECG parameters, measured at rest, peak exercise and late-stage recovery, and another based on the complete ECG (Q-ECG). We assessed the added value of conventional ECG parameters and Q-ECG risk scores to the UK's current prediction algorithm (QRISK3). We estimate the association between ECG parameters and MACCE, using Cox Proportional hazard models, following adjustment for traditional risk factors. All models were internally validated via 5-fold cross-validation and 1000 bootstrap iterations. Predictive performance was evaluated using Harrel's C-index, Net Reclassification Index (NRI) and net benefit. Findings: Incident MACCE was reported in 4,082 (9.9%) individuals in the study population and 3,463(9.7%) individuals with valid ECG parameters over a median follow-up period of 12.5 years. We found combined conventional ECG and Q-ECG scores were independently associated with MACCE, following adjustment for multiple testing: adjusted hazard ratio [HZ] = 1.76 (95% CI:1.63-1.91); HZ = 1.14 (95% CI:1.10-1.18), respectively, per standard deviation increase. Both conventional ECG parameters and Q-ECG were predictive of MACCE, independent of clinical risk factors, C-index = 0.64 (95%CI 0.63-0.65); net benefit = 0.09(95% CI 0.07 - 0.11) and C-index = 0.56 (95% CI 0.55-0.57); net benefit = 0.07(95% CI 0.05 - 0.09). ECG measurement's modestly improved model discrimination over the bassline QRISK3 risk score when combined with QRISK3 risk factors for conventional markers and Q-ECG score, respectively; ΔC-index 0.03 (95% CI: 0.02 – 0.04) and ΔC-index 0.03 (95% CI: 0.02 – 0.03); However, we observed no significant improvements in classification at the current recommended threshold of 10%. Conclusion In individuals without a history of prior cardiovascular disease, ECG measures independently predict the risk of MACCE. When combined with QRISK3, neural-network-derived ECG risk scores marginally improve cardiovascular risk prediction over QRISK3.

Combination of moderate-intensity statins and ezetimibe versus high-intensity statins alone for primary prevention of cardiovascular events

Abstract Background Combination of a moderate-intensity statin with ezetimibe can lead to similar reductions in cardiovascular events as monotherapy with a high-intensity statin in patients with established atherosclerotic cardiovascular disease (ASCVD). The comparative effectiveness of these two cholesterol-lowering strategies in the primary prevention setting is unknown. Purpose To compare incident ASCVD events associated with a combination of moderate-intensity statin and ezetimibe versus monotherapy with a high-intensity statin in adults without prior history of cardiovascular disease. Methods We conducted a new-user active comparator retrospective population-based cohort study in Canada. We included all adults aged ≥ 67 years (eligible for drug coverage) with a first prescription of either a combination of moderate-intensity statin with ezetimibe ("combination therapy") or high-intensity statin alone between January 2010 and December 2022. Patients were excluded if they had not received any prior lipid lowering therapies or had a history of myocardial infarction (MI), stroke, heart failure, peripheral vascular disease or prior coronary revascularisation at any time before or within 3 months of treatment initiation. The primary outcome was a composite of all-cause death, hospitalization for MI or stroke, or coronary revascularization. An inverse probability of treatment weighting propensity score was used to account for confounding (demographics, comorbidities, laboratory tests, other medications). Results Among 67,884 patients (mean age: 74.0±5.5y; 53% females), 8,798 (13%) initiated combination therapy and 59,086 (87%) initiated a high-intensity statin. At 1 year, after weighting, the mean achieved LDL-C was ~1.9 mmol/L in both groups. The median follow-up was 6.5 years. The cumulative incidence of the primary outcome at 10 years in the weighted cohort was 32.7% in the combination therapy group and 36.1% in the high-intensity statin group (HR: 0.87; 95% CI: 0.82 to 0.92; p<0.001; absolute risk reduction: 3.5%; 95% CI: 0.8 to 6.1; Figure 1). This result was primarily driven by a lower risk of all-cause death (HR: 0.85; 95% CI: 0.80 to 0.91; p<0.001; Figure 2) and stroke (cause-specific [cs] HR: 0.86; 95% CI 0.74 to 0.99; p=0.04), whereas no differences were observed in the risk of MI (csHR: 0.97; 95% CI: 0.82 to 1.15) or coronary revascularization (csHR: 0.97; 95% CI 0.85 to 1.11). Conclusion The combination of moderate-intensity statins with ezetimibe was associated with a lower risk of incident ASCVD compared with high-intensity statins alone among primary prevention patients in a real-world setting. These results were driven by a lower risk of all-cause death and stroke, but not coronary events. The influence of statin intolerance on the allocated strategy and adherence to therapy cannot be addressed in this analysis, which, along with verifying these estimates, may be best determined in a prospective randomized trial.

Volume and Permeability of White Matter Hyperintensity on Cognition: A DCE Imaging Study of an Older Cohort With and Without Cognitive Impairment.

The impact of blood-brain barrier (BBB) leakage on white matter hyperintensity (WMH) subtypes (location) and its association with clinical factors and cognition remains unclear. To investigate the relationship between WMH volume, permeability, clinical factors, and cognition in older individuals across the cognitive spectrum. Prospective, cross-sectional. A total of 193 older adults with/without cognitive impairment; 128 females; mean age 70.1 years (standard deviation 6.8). 3 T, GE Dynamic contrast-enhanced, three-dimensional (3D) Magnetization-prepared rapid gradient-echo (MPRAGE T1WI), 3D fluid-attenuated inversion recovery (FLAIR). Periventricular WMH (PWMH), deep WMH (DWMH), and normal-appearing white matter (NAWM) were segmented using FMRIB automatic segmentation tool algorithms on 3D FLAIR. Hippocampal volume and cortex volume were segmented on 3D T1WI. BBB permeability (Ktrans) and blood plasma volume (Vp) were determined using the Patlak model. Vascular risk factors and cognition were assessed. Univariate and multivariate analyses were performed to identify factors associated with WMH permeability. Logistic regression analysis assessed the association between WMH imaging features and cognition, adjusting for age, sex, apolipoprotein E4 status, education, and brain volumes. A P-value <0.05 was considered significant. PWMH exhibited higher Ktrans (0.598 ± 0.509 × 10-3 minute-1) compared to DWMH (0.496 ± 0.478 × 10-3 minute-1) and NAWM (0.476 ± 0.398 × 10-3 minute-1). Smaller PWMH volume and cardiovascular disease (CVD) history were significantly associated with higher Ktrans in PWMH. In DWMH, higher Ktrans were associated with CVD history and cortical volume. In NAWM, it was linked to CVD history and dyslipidemia. Larger PWMH volume (odds ratio [OR] 1.106, confidence interval [CI]: 1.021-1.197) and smaller hippocampal volume (OR 0.069; CI: 0.019-0.253) were independently linked to worse global cognition after covariate adjustment. Elevated BBB leakage in PWMH was associated with lower PWMH volume and prior CVD history. Notably, PWMH volume, rather than permeability, was correlated with cognitive decline, suggesting that BBB leakage in WMH may be a consequence of CVD rather than indicate disease progression. 2 TECHNICAL EFFICACY: Stage 3.

12340 Cardiovascular Risks With Testosterone Replacement Therapy In Patients With Type 2 Diabetes Mellitus

Abstract Disclosure: A. Gupta: None. M. Nassar: None. H. Ghanim: None. Background: Concerns have been raised about testosterone replacement therapy (TRT) in hypogonadism patients, particularly regarding cardiovascular disease (CVD) risk. Despite some studies showing TRT's non-inferiority to placebo in men at high CVD risk, its impact on patients with type 2 diabetes mellitus (T2DM) remains uncertain. This study examines the incidence of cardiovascular events in patients with T2DM on TRT, with a focus on the first four years of treatment. Methods: Utilizing the TriNetX electronic health records network, this retrospective cohort study targeted patients with T2DM with testosterone levels &amp;lt;300 ng/dl or diagnosed hypogonadism. Patients were divided into two main groups based on their CVD history and TRT status. We conducted a comparative analysis between each cohort and a control group of patients who did not get testosterone replacement therapy (TRT). Matching for age, HbA1C, and BMI created balanced cohorts for comparison: 39,589 in each of the non-CVD event cohorts and 16,065 in each of the CVD event cohorts. Results: In patients without prior CVD, TRT significantly reduced the risk of acute myocardial infarction (MI) (risk ratio: 0.765, p &amp;lt;0.0001), with no significant difference in cerebral infarction risk. Conversely, TRT increased the risk of acute MI (risk ratio: 1.164, p &amp;lt; 0.0001) and cerebral infarction (risk ratio: 1.177, p &amp;lt; 0.0001) in patients with a history of CVD.Discussion: TRT may decrease acute MI risk in patients with T2DM without prior CVD but elevate acute MI and stroke risks in those with a CVD history. These findings suggest the need for cautious TRT consideration in patients with T2DM with differing cardiovascular histories. Conclusion: This analysis reveals that TRT is associated with a decreased risk of acute myocardial infarction in patients with T2DM without a history of CVD, suggesting a potential protective effect in this subgroup. However, TRT increases the risk of both myocardial infarction and stroke in patients with a prior history of CVD, indicating the need for careful patient selection and monitoring. These findings highlight the significance of personalized evaluation in the administration of TRT, particularly in patients with T2DM who have different cardiovascular backgrounds, to balance benefits against potential risks. Presentation: 6/2/2024

Association Between Neighborhood-Level Income and the Incidence of Cardiovascular Events Varies by Immigration Status: A Population-Based Cohort Study.

Neighborhood-level income is inversely associated with cardiovascular events; however, it is uncertain whether this association varies with immigration status. We conducted a population-based cohort study of 5.2 million (53% women, 19% immigrants) urban-dwelling people aged ≥40 years without a prior history of cardiovascular disease in Ontario, Canada. Neighborhood-level income was measured in quintiles from quintile 1 (lowest) to quintile 5 (highest), and immigrants were defined as those born outside of Canada who moved to Canada after 1985. We estimated the association between neighborhood-level income and the rate of incident cardiovascular events (hospitalization for stroke or myocardial infarction, or cardiovascular death) using multivariable cause-specific hazards models and added an interaction term to see if the association varies by immigration status. The absolute difference in the rate of cardiovascular events across income quintiles was less pronounced in immigrants than in long-term residents: age- and sex-adjusted rate per 1000 person-years in quintile 1 versus quintile 5: 5.69 versus 4.10 in immigrants and 8.37 versus 5.87 in long-term residents. In adjusted models, the interaction between immigration status and neighborhoodl evel was significant (Pinteraction <0.001). The hazard of cardiovascular events declined with increasing income among long-term residents (hazard ratio [HR]Q1vsQ5, 1.46 to HRQ4vsQ5, 1.10) and immigrants, albeit with a smaller gradient (HRQ1vsQ5, 1.43 to HRQ4vsQ5, 1.20). The association between neighborhood-level income and cardiovascular disease incidence variesby immigration status. Understanding the social and structural factors associated with residing in low-income neighborhoods can help with the development of prevention programs that improve health for all.

The utility of pentraxin 3 and platelet-derived growth factor receptor beta as non-invasive biomarkers for prediction of cardiovascular risk in MAFLD patients

BackgroundMetabolic-associated fatty liver disease (MAFLD) has emerged as the predominant form of chronic liver disease globally linked with heightened cardiovascular disease (CVD) risk, the leading cause of mortality among affected individuals.AimThis study aims to assess serum PTX3 (pentraxin 3) and platelet-derived growth factor receptor beta (PDGFRβ) as potential non-invasive biomarkers for predicting cardiovascular risk (CVR) in MAFLD patients.MethodA case–control investigation encompassing 84 MAFLD patients without prior CVD history and 30 age- and gender-matched healthy controls was conducted. Both cohorts underwent comprehensive laboratory and radiological evaluations. CVR was evaluated through common carotid artery intima-media thickness (IMT), Framingham risk score, and QRISK 2 score. The efficacy of two ELISA biomarkers PTX3 and PDGFRβ was examined for correlation with CVR in MAFLD patients.ResultsMAFLD patients displayed significantly heightened levels of PTX3 and PDGFβ compared to healthy controls (P < 0.001, P = 0.016, respectively). PDGFβ exhibited a notably positive correlation with the Framingham score (P = 0.016), while no significant correlation was observed with pentraxin 3 (P = 0.061). Univariate and multivariate analyses identified diabetes mellitus (DM) (P < 0.001*), hypertension (P = 0.005), visceral fat (P < 0.001*), waist/hip circumference (P = 0.04), and PDGFβ (P = 0.03) as robust predictors of CVR, with PTX3 demonstrating limited prognostic utility.ConclusionPDGFβ emerged as a promising early non-invasive predictor of CVR in MAFLD patients, highlighting its potential role in guiding tailored preventive interventions, while PTX3 exhibited a modest impact warranting further investigation.

Progression of Coronary Artery Calcification and Risk of Clinical Events in CKD: The Chronic Renal Insufficiency Cohort Study

Coronary artery calcification (CAC) progresses rapidly in people with chronic kidney disease (CKD) compared with the general population. We studied the association between CAC progression and higher risks of atherosclerotic cardiovascular disease (CVD), congestive heart failure, and all-cause mortality among adults with CKD. Prospective cohort study. & Participants: 1,310 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study who had at least one CAC scan with no prior history of CVD and with observed or imputed data on changes in CAC over time. Observed or imputed CAC progression, categorized as incident CAC among participants with zero CAC on the baseline scan, or progressive CAC when the baseline scan demonstrated CAC and there was an increase in CAC ≥50 Agatston units per year. Atherosclerotic CVD (myocardial infarction or stroke), congestive heart failure, and all-cause mortality. Cause-specific Cox proportional hazards regression, stratified by presence of CAC at baseline. A total of 545 participants without and 765 with prevalent CAC at baseline were included. During a mean 3.3 years between CAC assessments, 177 (32.5%) participants without baseline CAC developed incident CAC while 270 participants (35.3%) with baseline CAC developed a ≥50 Agatston units per year increase in CAC. After multivariable adjustment, incident CAC was associated with 2.42-fold higher rate of atherosclerotic CVD (95% confidence interval [CI]: 1.23-4.79) and 1.82-fold higher rate of all-cause mortality (95% CI: 1.03-3.22). Progressive CAC (≥50 units per year) was not associated with atherosclerotic CVD (hazard ratio [HR]: 1.42; 95% CI: 0.85-2.35) but was associated with a 1.73-fold higher rate of all-cause mortality (95% CI: 1.31-2.28). Progressive CAC was not associated with incident heart failure. Residual confounding and limited statistical power for some outcomes. Among adults with CKD stages 2-4, CAC progression over a mean 3.3 years was associated with higher risk of atherosclerotic CVD and all-cause mortality. The associations were strongest among participants without CAC at baseline.

Cardiovascular toxicity of fluoropyrimidines: Experience from a quaternary referral center.

e24028 Background: Fluoropyrimidines, including 5-fluorouracil (5-FU) and capecitabine, are widely used chemotherapeutic agents. Their use has been linked to various forms of cardiovascular (CV) toxicity. We sought to analyze the rate of CV events and associated factors in patients receiving fluoropyrimidines at our institution. Methods: We included all patients who received intravenous 5-FU or oral capecitabine at the Cleveland Clinic since 2000. Diagnosis data was obtained based on ICD-10 Codes. CV events included chest pain/angina, myocardial infarction, chronic ischemic heart disease, arrhythmias, conduction disorders, cardiac arrest, cardiomyopathy, and heart failure. CV events were accounted for if they occurred during treatment or within 30 days following the latest administration of the agent. Logistic regression was performed to identify predictors of CV events. Results: A total of 17,236 patients were included, of which 9,386 (54.5) received 5-FU and 7,850 (45.5) received capecitabine. Median age at treatment was 63. The most frequent malignancies were gastrointestinal (70%) and breast cancer (12.3%). A total of 2,283 patients (13.2%) experienced at least one CV event either during treatment or within 30 days following drug administration. The most frequent CV events were chest pain/angina (35.7% of all events). On multivariable logistic regression, factors associated with increased risk of CV events were black race, smoking history, hypertension, and obesity (Table). A prior history of CV disease was also associated with increased risk of CV events (OR 1.22; 95% CI [1.09 - 1.33]). Finally, intravenous 5-FU was linked to higher odds of CV events compared to oral capecitabine (OR 1.48; 95% CI [1.34 - 1.63]). Conclusions: This large-scale cohort study provides pivotal insights into the cardiovascular risks associated with fluoropyrimidine therapy. Besides traditional risk factors, black patients were more likely to suffer from CV events. Additionally, capecitabine may offer better CV outcomes compared to 5-FU. These findings underscore the need for refined risk assessment and enhanced cardiovascular monitoring in patients treated with fluoropyrimidines. [Table: see text]

Association between blood pressure levels and premature atrial contractions in patients with hypertension

BackgroundHigh blood pressure (BP) induces left atrial structural and functional remodeling that increases susceptibility to atrial arrhythmia. We hypothesized that lower systolic BP (SBP) levels are associated with a lower prevalence of premature atrial contractions (PACs) in patients with hypertension. MethodsThis analysis included 4,697 participants (mean age 62±13.1 years, 50% women, 25.6% blacks) with hypertension from the Third National Health and Nutrition Examination Survey who did not have a prior history of cardiovascular disease (CVD). Multivariable logistic regression was used to examine the cross-sectional association between SBP and prevalence of PACs ascertained from 12-lead resting electrocardiograms. Multivariable Cox proportional hazard analysis was used to examine the association between baseline PACs and CVD mortality. ResultsApproximately 1.6% (n=74) of participants had baseline PACs. Patients with SBP ≤140 mmHg had a lower prevalence of PACs than those with SBP ≥140 mmHg (1.1% vs. 1.9%, p-value=0.01). In a multivariable logistic regression model, each 10 mmHg decrease in SBP was associated with a 12% lower odds of PACs (OR (95%CI): 0.88 (0.77-0.99)). During 14 years of follow-up, 645 CVD deaths occurred. In a multivariable-adjusted Cox model, presence of PACs was associated with a 78% increased risk of CVD mortality (HR (95%CI): 1.78 (1.23-2.60)). ConclusionsIn patients with hypertension, lower SBP levels are associated with a lower prevalence of PACs, and presence of PACs is associated with a higher risk of CVD mortality risk. These findings highlight the potential role of BP lowering in the management of cardiac arrhythmias.

Comparison of β-blocker agents and mortality in maintenance hemodialysis patients: an international cohort study.

Despite a lack of clinical trial data, β-blockers are widely prescribed to dialysis patients. Whether specific β-blocker agents are associated with improved long-term outcomes compared with alternative β-blocker agents in the dialysis population remains uncertain. We analyzed data from an international cohort study of 10125 patients on maintenance hemodialysis across 18 countries that were newly prescribed a β-blocker medication within the Dialysis Outcomes and Practice Patterns Study (DOPPS). The following β-blocker agents were compared: metoprolol, atenolol, bisoprolol and carvedilol. Multivariable Cox proportional hazards models were used to estimate the association between the newly prescribed β-blocker agent and all-cause mortality. Stratified analyses were performed on patients with and without a prior history of cardiovascular disease. The mean (standard deviation) age in the cohort was 63 (15) years and 57% of participants were male. The most commonly prescribed β-blocker agent was metoprolol (49%), followed by carvedilol (29%), atenolol (11%) and bisoprolol (11%). Compared with metoprolol, atenolol {adjusted hazard ratio (HR) 0.77 [95% confidence interval (CI) 0.65-0.90]} was associated with a lower mortality risk. There was no difference in mortality risk with bisoprolol [adjusted HR 0.99 (95% CI 0.82-1.20)] or carvedilol [adjusted HR 0.95 (95% CI 0.82-1.09)] compared with metoprolol. These results were consistent upon stratification of patients by presence or absence of a prior history of cardiovascular disease. Among patients on maintenance hemodialysis who were newly prescribed β-blocker medications, atenolol was associated with the lowest mortality risk compared with alternative agents.

Abstract 6291: Changes in physical activity and ischemic stroke risk after cancer diagnosis: A nationwide cohort study

Abstract Background: Physical inactivity is prevalent after cancer treatment, which may pose a greater risk of ischemic stroke in cancer survivors. Objective: To investigate the association between physical activity change from pre- to post-diagnosis and ischemic stroke risk among cancer survivors. Methods: Cancer survivors without prior history of cardiovascular disease were identified. Pre- and Post-adherence to physical activity was determined within two years from cancer diagnosis. The primary outcome was incident ischemic stroke. Using the Fine-Gray model, sub-distribution hazard ratios (sHRs) and 95% confidence intervals (CIs) for ischemic stroke risk were calculated, considering death as a competing risk. Results: Among 269,943 cancer survivors (mean [SD] age 56.3 [12.1] years, 45.7% male), 10.1% remained active, 11.4% became inactive, and 16.6% became active post-diagnosis. During 1,109,566.68 person-years[YMP1] , remaining active both pre- and post-diagnosis was associated with 15% decreased risk of ischemic stroke (sHR 0.85, 95% CI 0.75-0.96), compared to those who remained inactive. Cancer survivors who became active, and inactive post-diagnosis showed a 16%, and 11% lower risk of ischemic stroke (sHR 0.84, 95% CI 0.75-0.93; sHR 0.89, 95% CI 0.79-0.99) than those who remained inactive. Conclusions: Our findings suggest that staying physically active is associated with a reduced risk of ischemic stroke among cancer survivors. Notably, these advantages are not limited to individuals who were physically active before their diagnosis, and it is not too late to start post-diagnosis. Preventive strategies against ischemic stroke in cancer survivors should emphasize the incorporation of regular physical activity at any stage of their cancer journey. Citation Format: Dong Wook Shin, Wonyoung Jung, In Young Cho, Jinhyung Jung, Mihee Cho, Hye Yeon Koo, Be-Long Cho, Jin Ho Park, Hyuk Tae Kwon, Kyungdo Han, Yong-Moon Mark Park. Changes in physical activity and ischemic stroke risk after cancer diagnosis: A nationwide cohort study [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 6291.

Effects of prior reproductive losses on risk of cardiovascular diseases within six months of a first live birth

ObjectiveThere is emerging evidence suggesting that pregnancy loss (induced or natural) is associated with an increased risk of cardiovascular diseases (CVD). This prospective longitudinal study investigates the effect of prior pregnancy losses on CVD risk during the first six months following a first live birth. MethodsMedicaid claims of 1,002,556 low-income women were examined to identify history of pregnancy losses, CVD, diabetes, and hyperlipidemia prior to first live birth. The study population was categorized into five groups: A: women with no pregnancy loss or CVD history prior to first live birth; B: women with pregnancy loss and no CVD prior to first live birth. C: women with a first CVD diagnosis after a first pregnancy ending in a loss and before their first live birth. D: women with CVD prior to first live birth and no history of pregnancy loss. E: women with both CVD and pregnancy loss prior to their first live birth. ResultsAfter controlling for age, race, state of residence, and history of diabetes and hyperlipidemia, the risk of CVD in the six-month period following a first live birth were 15%, 214%, 79% and 129% more common for Groups B, C, D and E, respectively, compared to Group A. ConclusionsPregnancy loss is an independent risk factor for CVD risk following a first live birth, both for women with and without a prior history of CVD. The risk is highest when CVD is first diagnosed after a pregnancy loss and prior to a first live birth.

The heart-mind relationship in women cardiovascular primary prevention: the role of depression, anxiety, distress and Type-D personality in the 10-years cardiovascular risk evaluation.

Cardiovascular diseases are the leading cause of death among women. Prevention programmes underscore the need to address women-specific risk factors. Additionally, mental well-being is a significant aspect to consider when grappling with cardiovascular disease in women, particularly depression, anxiety, distress, and personality traits. This study aimed to create "at-risk" psychological profiles for women without prior cardiovascular disease history and to evaluate the association between anxiety, depression, distress, and Type-D personality traits with increased cardiovascular risk over 10 years. 219 women voluntarily participated in the "Monzino Women's Heart Centre" project for primary prevention and early diagnosis of cardiovascular diseases. Psychological profiles were developed utilising cluster analysis. The primary finding indicating that belonging to the "at-risk" psychological cluster was associated with a surge in the 10-year cardiovascular risk prediction score, despite the number of comorbid risk factors (Psychological "at-risk" cluster: β = .0674; p = .006; Risk factors: β = .0199; p = .242). This finding suggests that psychological well-being of women should be assessed from the very beginning of cardiovascular prevention programmes.

Clinical Outcomes in Hospitalized Patients with Cancer and New versus Preexistent Atrial Fibrillation.

There is limited information on the prognostic impact of new onset versus preexistent atrial fibrillation (AF) in hospitalized patients with cancer. We sought to determine the clinical impact of new onset AF (NOAF) compared with preexistent AF in hospitalized patients with cancer. All patients with cancer hospitalized over the course of one year with clinically manifest new or preexistent AF were enrolled in the Memorial Sloan Kettering Cancer Center (MSKCC) AF registry. The relationship of NOAF to the primary composite outcome of all cause death, cardiovascular (CV) rehospitalization or cerebrovascular event (CVE), as well as secondary CV endpoints, were analyzed using proportional hazards regression. Where applicable, the competing risk of death was accounted for using methodology described by Fine and Gray. Among 606 patients included in the analysis, 313 (51.7%) had NOAF and 293 (48.3%) had preexistent AF. Patients with NOAF were younger and had less frequent prior history of CV disease compared with patients with preexistent AF. At follow up, patients with NOAF had a higher adjusted hazard for the primary composite outcome versus patients with prior AF (HR 1.64, 95% CI 1.27, 2.13, p=0.002), as well as the secondary CV composite outcome of clinical AF recurrence, CV death, CV rehospitalization or CVE (HR 2.17, 95% CI 1.57, 2.99, P<0.0001). In hospitalized patients with cancer and electrocardiographically manifest new versus preexistent AF, NOAF was associated with a higher risk for the primary composite outcome of all-cause death, CV rehospitalization or CVE.

Is Glycemic Control the Primary Goal in Diabetes Treatment?

The prevalence of Diabetes is steadily increasing, raising public health concerns. Hyperglycemia leads to microvascular and macrovascular diseases through several metabolic and biochemical pathways. Previous clinical trials and observational studies have demonstrated that tight glycemic control can reduce the incidence of diabetic complications, with the greatest benefit shown in younger patients with diabetes of shorter duration and those who have no prior history of cardiovascular disease. Moreover, previous studies highlight the concept of metabolic memory and legacy effect, since controlling diabetes early can have an impact on long-term prognosis of the disease. As to whether it is time to consider shifting the treatment focus for patients with type 2 diabetes from a glucose-centric to a weight-centric or a cardio-centric approach, the dilemma remains theoretical; glucose control, weight loss and effective treatment of metabolic and cardio-vascular co-morbidities are interrelated components of an integrated plan of care that should be addressed simultaneously and effectively.

Association of low muscle mass and obesity with increased all-cause and cardiovascular disease mortality in US adults.

Sarcopenic obesity, defined as the coexistence of low muscle mass and high adiposity, is associated with cardiovascular disease (CVD) and mortality. However, to what extent sarcopenia contributes to these risks independently or in conjunction with other cardiovascular risk factors remains unclear. This study aimed to investigate the association of low muscle mass, central obesity (COB), metabolic abnormalities, and their combinations with CVD and mortality risk. This cross-sectional analysis used data from the National Health and Nutrition Examination Survey 1999-2006 and 2011-2018. Participants aged >20years and with reported whole-body dual X-ray absorptiometry data were included. Participants were divided into eight groups based on low muscle mass, metabolic abnormalities, and COB status. The mean age of participants was 55years, and 50.4% of participants were male. Low muscle mass was observed in 2472 (14.6%) out of 16839 participants. Among the eight groups, the metabolically unhealthy COB group with low muscle mass had the highest hazard ratio (HR) for all-cause mortality (HR, 2.00; 95% CI, 1.56-2.56; P<0.001), whereas the metabolically healthy COB group with low muscle mass had the highest HR for CVD mortality (HR, 3.18; 95% CI, 1.53-6.65; P=0.001). The mediation analysis showed that low muscle mass directly increased the risk of both all-cause mortality (HR, 1.56; 95% CI, 1.35-1.79; P<0.001) and CVD mortality (HR, 1.80; 95% CI, 1.40-2.31; P<0.001). Additionally, subgroup analysis revealed that low muscle mass significantly increased the risk of all-cause and CVD mortality in participants without a prior CVD history and those with diabetes mellitus. Low muscle mass is an independent risk factor for all-cause and CVD mortality, especially in individuals with metabolic abnormalities and COB.

An analysis of published cases of cutting balloon use in spontaneous coronary artery dissection.

SCAD involves a sudden tear or separation within the layers of the coronary artery wall, resulting in blood flow obstruction and subsequent myocardial ischemia. A comprehensive literature search was conducted to identify relevant published cases of cutting balloon use in patients diagnosed with spontaneous coronary artery dissection. Electronic databases including PubMed, MEDLINE, Embase, Cochrane Library and Google Scholar were systematically searched from inception until the present using terms "cutting balloon," "SCAD," "acute coronary syndrome," "intramural hematoma," and "angioplasty." A total of 32 published cases of cutting balloon use in spontaneous coronary artery dissection were analyzed in this study. The majority of the patients included in the analysis were female without prior history of cardiovascular disease. The median age of the SCAD population was approximately 46 years. The most frequently affected artery in SCAD cases was the Left Anterior Descending artery. Intravascular ultrasound was utilized more frequently than other modalities of adjunctive imaging techniques. The most frequent complication was the distal propagation of hematoma. Despite the successful dilation achieved with the cutting balloon, in some cases stenting was required to provide additional support. The results of this analysis demonstrate that cutting balloon use in SCAD cases yields favorable outcomes.

Association of pulse pressure with risk of major adverse cardiovascular events among cardiovascular outcome trial participants

Abstract Background Hypertension is a well-established risk factor for the development for cardiovascular (CV) disease and accumulating evidence also implicates elevated pulse pressure (PP), a surrogate marker for arterial stiffness, as an independent risk factor for major adverse cardiovascular events (MACE). Purpose The study aimed to assess the association of PP with MACE among participants in multiple CV outcome clinical trials. It also aimed to determine if the presence of various CV comorbidities impacts the association between PP and MACE. Methods Adult patients between the ages of 19-98 years (n = 65,382, mean age 63) enrolled in five large CV outcome trials (ACCELERATE, STRENGTH, PRECISION, ALECARDIO, and LIGHT) with independently adjudicated clinical end points were identified. Baseline demographics, medical history, blood pressures, and CV medications were collected. Univariate and multivariate analyses were generated and analyzed for temporal trends, risk, and adjusted survival. Results Participants had a mean baseline blood pressure of 128 /76 mm Hg and a mean PP of 52 mm Hg. Forty-five percent were women, 31% had coronary artery disease, 51% had type 2 diabetes mellitus, 84% had hypertension, 25% had history of myocardial infarction (MI), and 35% had a history of an acute coronary syndrome. The composite MACE end point included CV death, myocardial infarction, or stroke and occurred in 3712 participants (5.7%).The composite end point of all cause death, myocardial infarction, and stroke occurred in 4513 participants (6.9%). For every 10 mm Hg increase in PP there was an increased risk of MACE (unadjusted hazard ratio (HR) 1.20, 95% CI 1.17 to 1.23). Similarly, a PP &amp;gt; 60 mmHg demonstrated an unadjusted HR of 1.53 (95% CI 1.43 to 1.64) compared with PP &amp;lt; 60 mm Hg. Although increased PP was a risk factor in both men and women, every 10 mm Hg increase in PP was associated with higher risk of MACE in women (adjusted HR 1.17, 95%CI 1.17, 1.12 to 1.22) compared with men (adjusted HR 1.09, 95% CI, 1.05 to 1.12). Table 1 displays the adjusted HR for patients grouped by race, history of prior CV disease, or the presence of CV risk factors (diabetes and chronic kidney disease.) While most subgroups demonstrated an increased risk of MACE with increasing PP, PP was not associated with MACE among individuals with a history of stroke (HR 1.00, 95% CI 0.92 to 1.08). Kaplan-Meier survival curves comparing PP greater than or less than 60 mm Hg are seen in Figure 1. Conclusions Among CV outcome clinical trial participants, with independently adjudicated end points, baseline PP is associated with an increased risk for future MACE. The association stands for most participant subgroups except for participants with a prior history of stroke.Table 1Figure 1

Incidence of major cardiovascular outcomes in patients with chronic kidney disease by severity: a United States population-based study using electronic medical records

Abstract Background and Aims Data on the incidence of cardiovascular (CV) events by stage of chronic kidney disease (CKD) and the effect of previous CV history on future events in CKD patients (pts) is limited. We aimed to analyze a large US electronic medical record (EMR) database and evaluate incidence of new major adverse CV events (MACE) per CKD stage over a 5-year follow-up. Methods A retrospective cohort study was conducted using IBM® Explorys EMR data (&amp;gt;53 million patients) from Jan 2010 to Dec 2019. Two cohorts of CKD patients were created: Cohort 1 based on diagnostic codes (n = 810,987 pts), and Cohort 2 on KDIGO screening/staging criteria (n = 953,396). Sub-cohorts were created for each CKD stage (1-5). CKD classification was not mutually exclusive (individual pts could contribute to multiple main and sub-cohorts). Pts in Cohort 1 were required to have an ICD 9/10 code for a specific CKD stage while pts in Cohort 2 required two consecutives abnormal eGFR, uACR/uPCR results within 3-18 months to determine KDIGO CKD stage. Pts were required to have at least 12-months lookback period. Index date was the date of diagnosis or second abnormal test. We followed up each patient individually until the occurrence of a composite of MACE including death, coronary artery disease (CAD) events, any stroke, hospitalization for heart failure, or loss to follow-up, or for up to 5 years. Results Most patients in Cohort 1 (DxC) and 2 (KDIGO) were Caucasian and had stage 3 CKD at baseline. Mean age was 70y and 71y in Cohort 1 and 2 respectively, with 49% and 40% males. The prevalence of pre-existing CV diseases increased with CKD stage. The proportion of pts from Cohort 2 receiving a diagnosis of CKD at least once during their study period increased from 34% in stage 1 to 86% and 83% in stage 4 and 5, respectively. The 5-year incidence of the composite of MACE increased with stage in both cohorts: 40.3% to 66.0% in Cohort 1 and 25.1% to 65.8% in Cohort 2. These incidences were higher in pts with a CV history (Table 1). DxC pts tended to have a higher incidence of MACE, especially in the early stages. Death was the most frequent event at 5y in both cohorts across all stages (27.8% and 19.7% respectively at stage 3). It occurred in half of pts with a prior history of CV disease in both Cohorts in stages 4-5 CKD. Stroke was the most frequent event in the early stages (21.6% and 19.5% respectively at stage 3) and CAD events the most frequent in the late stages (27.6% and 29.5% respectively at stage 5). Conclusion CKD pts have a high risk of MACE at 5 years, with incidence 2-3 times higher in patients with pre-existing CV disease. There are differences in MACE incidences between CKD definitions, that were higher in coded diagnoses vs. lab results, especially in stages 1-3, warranting further investigation. Aggressive treatment of CV disease and risk factors should be considered for all CKD pts due to high 5-year MACE rates, regardless of CKD stage.Table 1.

Clonal Hematopoiesis, Inflammation, Hemostasis, and Cardiometabolic Biomarkers: The Reasons for Geographic and Racial Differences in Stroke Study

CONCLUSIONS Clonal hematopoiesis (CH) is implicated in the pathogenesis of multiple age-associated disorders including malignancy, cardiovascular disease (CVD), chronic kidney disease, and mortality. Some of these adverse outcomes may be mediated by CH-driven inflammatory dysregulation, but the association of CH with biomarkers in other pathways related to these outcomes has not been studied. We studied the association between CH and biomarkers of inflammation, hemostasis and cardiometabolic risk in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. REGARDS is a prospective study that enrolled 30,239 Black and White individuals ≥45 years across United States between 2003 and 2007, and collected extensive health data by telephone and in-person exams. Biomarkers listed in Table 2, and CH were measured in baseline blood samples in an age-, sex-, and race-stratified cohort random sample (CRS). We excluded participants with prior history of CVD. Sequencing was performed at &amp;gt;500x depth to identify somatic mutations in 24 of the most common CH genes, capturing &amp;gt;95% of CH observed in the general population. CH was categorized based on variant allele frequency (VAF) of the dominant mutation as 0%, &amp;gt;0-&amp;lt;2%, 2-10% and &amp;gt;10%. Linear regression was used to calculate the age-, sex-, and race-adjusted difference in mean biomarker level for those with versus those without CH. The study included 781 participants (mean age at enrollment: 66 years [SD 12.1], 46% male, 50% Black individuals). The prevalence of CH at varying VAF was: VAF 0% - 43.3%; VAF &amp;gt;0 to &amp;lt;2% - 32.5%; 2 to 10% - 18.4%; &amp;gt;10% - 5.8%. Mutations were most prevalent in DNMT3A (60.3%), then TET2 (13.8%) and ASXL1 (10.1%). The mean age was higher in participants with CH (73 years, SD 10) than in those without CH (61 years, SD 11). Distributions of the most common CH mutations at VAF ≥2% by age, sex and race are shown in Table 1. Mutations in DNMT3A were overrepresented in Black participants and women, whereas mutations in TET2 and ASXL1 were more common in White participants. Associations of CH with inflammation, hemostasis and cardiometabolic biomarkers were presented in Table 2. Mean Log IL-8 was 0.23 (95% CI 0.05-0.41) units higher in those with high VAF CH (&amp;gt;10%) versus those without CH, with no association among other inflammation biomarkers.Among hemostasis biomarkers, mean log D-dimer was 0.26 (95% CI 0.01-0.52) units higher in those with high VAF CH versus those without CH. There was a non-significant trend towards an association between CH and lower Factor VIII and higher fibrinogen (Table 2). Among cardiometabolic biomarkers, mean log Adiponectin was 0.32 (95% CI 0.04-0.61) units higher in those with high VAF CH versus no CH. We did not identify a statistically significant association between CH and other cardiometabolic markers. CH is prevalent in the general population, especially at low VAF. In addition to inflammatory dysregulation, findings here suggest possible other pathways for deleterious effects of CH on health via hemostasis and cardiometabolic pathways. Since our study was cross-sectional, we could not ascertain if CH leads to abnormal biomarker levels or if pathways represented by the above biomarkers predispose to CH. Studying associations of CH with serial biomarkers in a larger population, by specific mutations, and by sex and race will provide mechanistic insights on CH associated adverse outcomes.