Established Cardiovascular Disease Research Articles

Dietary habits and compliance with dietary guidelines in patients with established cardiovascular disease.

Unhealthy dietary habits are an important risk factor for cardiovascular disease (CVD) and adopting a healthy diet is a central recommendation in CVD prevention. This study assessed the dietary habits of patients with established CVD, their compliance to dietary guidelines, and the relationship between guideline-compliance and recurrent cardiovascular event risk. 2656 patients with established CVD from the Utrecht Cardiovascular Cohort-Secondary Manifestations of ARTerial disease (UCC-SMART) prospective cohort study, were included between 1996 and 2022. Data on dietary intake was retrospectively collected for all participants in December 2022 using a 160-item food frequency questionnaire. Compliance with dietary guidelines was quantified using an amended version of the Dutch Healthy Diet 2015 (DHD-15) index (range: 0-135). Cox proportional hazard models were used to quantify the relationship with cardiovascular events (stroke and myocardial infarction). Among 2656 CVD patients (77% male, mean age 59 ± 9 years), median energy intake was 1922 [IQR: 1536-2351] kcal/day. The median DHD-15 index was 81.7 [IQR 71.2-92.0], with high compliance scores for recommendations on legumes and fish, and low scores for recommendations on whole grains, red meat, processed meat, and dairy. A higher DHD-15 score was associated with lower stroke risk (HR 0.78, 95% CI 0.66-0.92 per 10-point increase) but not with myocardial infarction. Compliance with dietary guidelines was suboptimal in patients with established CVD. High compliance was associated with a clinically significant reduction in stroke risk in patients with established CVD, emphasizing the importance of dietary counseling.

Evaluating the effectiveness of the cardiovascular assessment screening program with nurse practitioners and patients: results of a cluster randomised controlled trial

BackgroundThere is inconsistent utilisation of clinical practice guidelines (CPGs) for cardiovascular disease (CVD) screening and management by healthcare professionals to identify CVD risk factors early and to intervene using current recommendations. To address this issue, the Cardiovascular Assessment Screening Program (CASP) was developed, implemented, and evaluated. This manuscript reports on the second phase of an exploratory sequential mixed methods study that tested the effectiveness of the CASP with nurse practitioners (NPs) and patients in Canada.MethodsA two-armed, non-blinded, cluster randomised controlled trial (cRCT) compared the NP-led implementation of CASP with usual care by NPs in community practice clinics across one Canadian province. The NPs were the cluster variable as their screening practices could be affected by their educational training, resources, or other factors. NPs were eligible for inclusion in the study if they were located in different urban and rural community settings and could conduct follow-up visits with patients. NPs recruited and enrolled the patients from their own practices as participants if they were healthy individuals, aged 40–74 years, with no established CVD or vascular disease. Researchers randomly allocated the NPs (n = 10) to the intervention group (IG) or the control group (CG).ResultsEight (8) NPs and 167 patients participated in the cRCT study. Patient participant-level data were analysed by the originally assigned groups IG (n = 68) and CG (n = 99). Utilising GLM (generalized linear modeling) more IG patients (90%; n = 61) received comprehensive CVD screening compared to the CG patients (2%; n = 2), RR = 30.2, 95% CI [8.76, 103.9], p < .0001, controlling for the effect of NP and BP category.ConclusionNP implementation of CASP was effective for comprehensive screening compared to usual care and led to identifying previously unknown CVD risk factors, calculated FRS, heart health priorities and personalised goal-setting.Trial registrationClinicalTrial.gov ID#: NCT03170752, date of registration 2017/05/31.

#1299 The SGLT2 inhibitor canagliflozin, but not dapagliflozin or empagliflozin, ameliorates vascular calcification in a mouse model of nephrocalcinosis

Abstract Background and Aims Vascular calcification, defined as the abnormal deposition of minerals in blood vessels, is a major cardiovascular risk factor in patients with kidney failure. Sodium-glucose co-transporter 2 (SGLT2) inhibitors, commonly known as gliflozins, are a class of pharmaceutical compounds that have revolutionised the therapeutic management of type 2 diabetes. These drugs target the SGLT2 transporter, increasing glucose elimination through the urine, effectively lowering hyperglycaemia. In addition to their effect on blood sugar control, SGLT2 inhibitors have recently gained attention for potential cardiovascular benefits in patients with type 2 diabetes, chronic kidney disease (CKD) or established cardiovascular disease. Initially thought to be secondary to the promotion of urinary sodium and glucose excretion and weight loss, recent studies have also reported direct effects of gliflozins on the vascular compartment. Given the significant impact of vascular calcification on cardiovascular health in patients with kidney failure, the aim of this study was to investigate whether the three different SGLT2 inhibitors (canagliflozin, empagliflozin and dapagliflozin) could reduce the development of vascular calcification. Method Western blotting was used to investigate SGLT2 expression in mouse and human vascular smooth muscle cells (VSMC) and vascular explants. Human and mouse aortic VSMC and mouse aorta and human epigastric and iliac artery segments were treated with calcification medium supplemented with 1 or 5 µM of gliflozins. A nephrocalcinosis mouse model consisting of 2 weeks of high phosphorus diet (2%) in female DBA/2 mice was used in in vivo experiments. The animals were treated daily with the different gliflozins (3 mg/kg/j) by oral gavage. Calcium deposits were quantified using a quantitative colorimetric assay and alizarin red staining, blood and urine glucose levels were measured using a quantitative colorimetric assay and glomerular filtration rate (GFR) was measured using sinistrin-FITC excretion. Results We observed that SGLT2 is expressed in mouse and human vessels and vascular smooth muscle cells (VSMC). Treatment with canagliflozin, but not dapagliflozin or empagliflozin, reduced calcification in vitro, in human and mouse VSMC and ex vivo, in mouse aorta and human epigastric and iliac artery segments. The high phosphorus diet in mice led to nephrocalcinosis associated with impaired renal function as well as vascular calcification development in the aorta. In this model, although all 3 gliflozins showed efficacy in increasing urinary glucose excretion, blood glucose levels were not affected by gliflozins and renal function was not improved. However, canagliflozin, but not dapagliflozin or empagliflozin, significantly reduced vascular calcification in this nephrocalcinosis mouse model. Conclusion Our study demonstrated that canagliflozin reduces vascular calcification development, highlighting its potential as a therapeutic strategy. This protective effect was found to be drug-dependent and not class-dependent, as the other two SGLT2 inhibitors, dapagliflozin and empagliflozin, showed no significant effect on vascular calcification. Further studies are needed to understand the mechanisms and pathways involved and to determine whether the differential effect of the gliflozins is due to an off-target action of canagliflozin on other SGLT transporters.

#1479 Single nucleus RNA-sequencing indicates functional heterogeneity of renal endothelial cells in chronic kidney disease

Abstract Background and Aims The burden of cardiovascular disease (CVD) in patients with chronic kidney disease (CKD) remains very high. Endothelial cell (EC) dysfunction is an important key player in the initiation and progression of both pathologies. More importantly, endothelial dysfunction occurs early in both disease courses and is potentially reversible, making it a promising target for effective preventive strategies. Recently, accumulating single-cell RNA sequencing-based evidence has highlighted EC heterogeneity in different pathophysiological contexts. However, while biological processes such as systemic inflammation, oxidative stress fibrosis are being defined as comm EC in CKD and CVD, a comprehensive understanding of at single-cell resolution is lacking. Here, we characterized renal EC subpopulations by single-nucleus RNA sequencing (snRNA-seq) to investigate alterations in CKD patients healthy controls and identify potential drivers of EC dysfunction in CKD. Method Droplet-based snRNA-seq (10X Genomics Chromium) was performed on cryopreserved kidney biopsy cores from 6 human patients with CKD (eGFR &amp;lt; 45 mL/min/1.73 m2) and 3 healthy controls. CKD patients included 2 patients with primary focal segmental glomerulosclerosis (FSGS) and 4 with secondary/maladaptive FSGS (2 patients with diabetes mellitus, 2 female patients in total); all patients had a Framingham 10-year cardiovascular risk score &amp;gt; 20, but no established CVD. Healthy control samples were pre-perfusion biopsies from patients undergoing living kidney donation (including 2 female patients). EC subclusters were annotated based on the expression of canonical EC marker genes. Differential gene expression analysis for patient samples vs. controls included all ECs and DEGs were filtered for log2FC &amp;gt; 0.25 or &amp;lt; −0.25 and adjusted P-value of &amp;lt; .05. Gene set enrichment analysis (GSEA) on the identified DEGs was performed using GO terms. Results A total of 4 081 ECs were present in the dataset, consisting of 5 EC subtypes in both the patient and control cohorts (Panel A). DEGs in CKD patients vs. controls included upregulated genes related to organogenesis and cell differentiation (MEF2C, MEIS2), vascular development (FLRT2), and angiogenesis regulators (VEGFC, PRCP, HDAC9) (Panel B). Notably, VEGFC and FLRT2, are involved in directing EC motility and vascular patterning. In accordance, GSEA showed enrichment for GO biological processes related to vascular endothelial growth factor signaling pathway, endothelial cell differentiation, endothelial development, regulation of angiogenesis, and endothelial cell migration (Panel C). This suggests a potential link between these genes and aberrant angiogenesis, analogous to previous findings in diabetic nephropathy. Some but not all of these changes were also reported for renal ECs of early diabetic nephropathy patients. Of note, the majority of patients studied in our cohort were non-diabetic, warranting further investigation into renal endothelial cell transcriptional alterations that are general to renal disease or specific to particular renal conditions such as diabetic nephropathy. Differential gene expression and GSEA analysis of the EC subclusters in CKD indicated involvement of the peritubular capillary and ascending vasa recta ECs in EC migration / angiogenesis-related responses, overlapping with the overall analysis described above. Glomerular capillary ECs showed upregulation of immune-related genes and processes, reflecting the inflammatory status of the kidney disease. Conclusion snRNA-seq analysis revealed heterogeneity and subtype-specific gene expression alterations of renal ECs from CKD patients compared to healthy controls. Differential functions include enhanced angiogenic (potentially compensatory) and immune-related responses. These findings suggest that specific biological functions may direct different roles of the renal EC subtypes in CKD and will be further validated for their cluster-specificity and for their therapeutic relevance.

Ten-Year Risk Equations for Incident Heart Failure in Established Atherosclerotic Cardiovascular Disease Populations.

Ten-year risk equations for incident heart failure (HF) are available for the general population, but not for patients with established atherosclerotic cardiovascular disease (ASCVD), which is highly prevalent in HF cohorts. This study aimed to develop and validate 10-year risk equations for incident HF in patients with known ASCVD. Ten-year risk equations for incident HF were developed using the United Kingdom Biobank cohort (recruitment 2006-2010) including participants with established ASCVD but free from HF at baseline. Model performance was validated using the Australian Baker Heart and Diabetes Institute Biobank cohort (recruitment 2000-2011) and compared with the performance of general population risk models. Incident HF occurred in 13.7% of the development cohort (n=31 446, median 63 years, 35% women, follow-up 10.7±2.7 years) and in 21.3% of the validation cohort (n=1659, median age 65 years, 25% women, follow-up 9.4±3.7 years). Predictors of HF included in the sex-specific models were age, body mass index, systolic blood pressure (treated or untreated), glucose (treated or untreated), cholesterol, smoking status, QRS duration, kidney disease, myocardial infarction, and atrial fibrillation. ASCVD-HF equations had good discrimination and calibration in development and validation cohorts, with superior performance to general population risk equations. ASCVD-specific 10-year risk equations for HF outperform general population risk models in individuals with established ASCVD. The ASCVD-HF equations can be calculated from readily available clinical data and could facilitate screening and preventative treatment decisions in this high-risk group.

Associations between specific volatile organic chemical exposures and cardiovascular disease risks: insights from NHANES

IntroductionAn increasing body of research has demonstrated a correlation between pollutants from the environment and the development of cardiovascular diseases (CVD). However, the impact of volatile organic chemicals (VOC) on CVD remains unknown and needs further investigation.ObjectivesThis study assessed whether exposure to VOC was associated with CVD in the general population.MethodsA cross-sectional analysis was conducted utilizing data from five survey cycles (2005–2006, 2011–2012, 2013–2014, 2015–2016, and 2017–2018) of the National Health and Nutrition Examination Survey (NHANES) program. We analyzed the association between urinary VOC metabolites (VOCs) and participants by multiple logistic regression models, further Bayesian Kernel Machine Regression (BKMR) models and Weighted Quantile Sum (WQS) regression were performed for mixture exposure analysis.ResultsTotal VOCs were found to be positively linked with CVD in multivariable-adjusted models (p for trend = 0.025), independent of established CVD risk variables, such as hypertension, diabetes, drinking and smoking, and total cholesterol levels. Compared with the reference quartile of total VOCs levels, the multivariable-adjusted odds ratios in increasing quartiles were 1.01 [95% confidence interval (CI): 0.78–1.31], 1.26 (95% CI: 1.05–1.21) and 1.75 (95% CI: 1.36–1.64) for total CVD. Similar positive associations were found when considering individual VOCs, including AAMA, CEMA, CYMA, 2HPMA, 3HPMA, IPM3 and MHBMA3 (acrolein, acrylamide, acrylonitrile, propylene oxide, isoprene, and 1,3-butadiene). In BKMR analysis, the overall effect of a mixture is significantly related to VOCs when all chemicals reach or exceed the 75th percentile. Moreover, in the WQS models, the most influential VOCs were found to be CEMA (40.30%), DHBMA (21.00%), and AMCC (19.70%).ConclusionThe results of our study indicated that VOC was all found to have a significant association with CVD when comparing results from different models. These findings hold significant potential for public health implications and offer valuable insights for future research directions.

Cardiovascular Risk Estimation Is Suboptimal in People With HIV.

Established cardiovascular disease (CVD) risk prediction functions may not accurately predict CVD risk in people with HIV. We assessed the performance of 3 CVD risk prediction functions in 2 HIV cohorts. CVD risk scores were calculated in the Mass General Brigham and Kaiser Permanente Northern California HIV cohorts, using the American College of Cardiology/American Heart Association atherosclerotic CVD function, the FHS (Framingham Heart Study) hard coronary heart disease function and the Framingham Heart Study hard CVD function. Outcomes were myocardial infarction or coronary death for FHS hard coronary heart disease function; and myocardial infarction, stroke, or coronary death for American College of Cardiology/American Heart Association and FHS hard CVD function. We calculated regression coefficients and assessed discrimination and calibration by sex; predicted to observed risk of outcome was also compared. In the combined cohort of 9412, 158 (1.7%) had a coronary heart disease event, and 309 (3.3%) had a CVD event. Among women, CVD risk was generally underestimated by all 3 risk functions. Among men, CVD risk was underestimated by the American College of Cardiology/American Heart Association and FHS hard CVD function, but overestimated by the FHS hard coronary heart disease function. Calibration was poor for women using the FHS hard CVD function and for men using all functions. Discrimination in all functions was good for women (c-statistics ranging from 0.78 to 0.90) and moderate for men (c-statistics ranging from 0.71 to 0.72). Established CVD risk prediction functions generally underestimate risk in people with HIV. Differences in model performance by sex underscore the need for both HIV-specific and sex-specific functions. Development of CVD risk prediction models tailored to HIV will enhance care for aging people with HIV.

Abstract PO3-11-08: High Risk of Metabolic Dysfunction in Non-Obese Breast Cancer Survivors

Abstract Much literature already depicts the relationship between metabolic syndrome (MS), obesity, and breast cancer. Despite that, up to one-third of non-obese individuals may exhibit undiagnosed MS or metabolic dysfunction, posing an independent cancer risk and worse outcomes even for those with a body mass index (BMI) &amp;lt; 30kg/m². In that manner, our study aims to evaluate the metabolic profile of non-obese women with postmenopausal breast cancer compared to non-obese women without breast cancer. In this cross-sectional clinical study at the State University of São Paulo Medical School - UNESP. The study group (n=130) included women aged ≥ 45 and &amp;lt; 75 years, in amenorrhea for at least 12 months, BMI ≤ 30kg/m2, histological diagnosis of breast cancer, without metastatic disease, and without established cardiovascular disease (CVD). The control group (n=130) comprised women with all the same criteria except for breast cancer diagnosis. The groups were matched by age and menopause time in a ratio of one case to one control (1:1). We aimed to analyze their clinical, biochemical, and oncological data to establish relationships between these groups. We presented the data in tables 1 - 3. The groups showed homogeneity in age, time since menopause, BMI, waist circumference (WC), and cholesterol levels. There was a higher occurrence of MS and hypertension (HTN) among women treated for breast cancer compared to the control group (30.8% vs. 20.0% and 25.4% vs.14.6%, respectively) (p&amp;lt; 0.05). Similarly, a higher percentage of women treated for breast cancer had abnormal values for total cholesterol and glucose (56.2% vs. 43.1% and 29.2% vs. 15.4%, respectively) (p&amp;lt; 0.05). In the analysis of metabolic profile risk-adjusted for age time since menopause and BMI, women treated for breast cancer showed an increased risk for MS (OR=2.76, 95% CI 1.48-5.15), elevated glucose (OR=2.69, 95% CI 1.46-4.96), and HTN (OR=3.03, 95% CI 1.51-6.10). In the evaluation of factors influencing the metabolic profile, women with breast cancer had significantly higher mean values of WC (82.6±8.5 vs. 79.9±6.4 cm, p=0.048), systolic and diastolic blood pressure (129.2±17.1 and 77.7±8.8 mmHg vs. 118.2±15.1 and 73.6±8.8 mmHg, p=0.0002 and p=0.01, respectively), and glucose (99.7±32.5 vs. 86.6±7.6 mg/dL, p=0.0002) compared to control group. We conducted a sub-analysis among women with BMI &amp;lt; 25kg/m² from both groups. Women with breast cancer (n=64) had a higher occurrence of MS compared to women without breast cancer (n=53) (17.2% vs. 1.9%, respectively). Even though this sub-analysis did not reach the minimum number of patients with BMI &amp;lt; 25 kg/m² to achieve p value &amp;lt; 0,05, this analysis reveals a significant difference in MS incidence between the groups (p=0.007). This reinforces the hypothesis that oncological diagnosis substantially affects metabolic health, and therefore, breast cancer patients should receive special attention regarding their metabolic profile, regardless of their BMI. Conclusion: Non-obese women with breast cancer showed a higher risk of MS, HTN, and diabetes, with a worse metabolic profile than non-obese postmenopausal women without breast cancer. These findings suggest that postmenopausal women diagnosed with breast cancer, even in the absence of obesity, exhibit significant metabolic dysfunction characterized by a higher occurrence of MS and its components. The findings highlight the importance of a comprehensive assessment of metabolic health in women with breast cancer, regardless of their body mass index, to ensure appropriate and individualized care for these patients. Table 1 - Comparison of clinical and laboratory characteristics among 130 non-obese postmenopausal women with breast cancer and 130 non-obese postmenopausal women (control) (average values ± standard deviation). Table 2 - Comparison of categorized clinical and laboratory characteristics that influence the metabolic profile between 130 non-obese postmenopausal women with breast cancer and 130 non-obese postmenopausal women (control). Values expressed as number and percentage in parentheses. CA, cancer; WC, waist circumference; MS, metabolic syndrome; HDL, high-density lipoprotein, LDL, low-density lipoprotein; TG, triglycerides. *Significant difference p&amp;lt;0.05 (Chi-square Test). Table 3. Association between the presence of Metabolic Syndrome, and its clinical and laboratory components, among the 130 non-obese postmenopausal women with breast cancer and the 130 non-obese postmenopausal women (control). Values expressed as number and percentage in parentheses. CA, cancer; BP, blood pressure; WC, waist circumference; TG, triglycerides. *Odds ratio (OR) adjusted for age, menopause duration and BMI. **Significant difference if p&amp;lt;0.05 (Logistic Regression). Citation Format: Pedro Paulo Perroni Filho, Daniel Buttros, Eliana Aguiar Petri Nahas. High Risk of Metabolic Dysfunction in Non-Obese Breast Cancer Survivors [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-11-08.

ASSESSMENT OF CARDIOVASCULAR RISK IN PATIENTS WITH RHEUMATOID ARTHRITIS ACCORDING TO CURRENT HYPERTENSION GUIDELINES

Objective: Patients with rheumatoid arthritis (RA) are at increased risk of cardiovascular disease (CVD) by as much as 50% compared to the general population. Considering that disease-specific calculators have failed to provide more accurate CVD risk stratification in RA, CVD risk calculation in RA patients is challenging, especially for those who are not by definition at high risk based on concomitant established CVD or its equivalents. The presence of an immune-mediated inflammatory disease (e.g., RA) has been considered as a CVD risk modifier by the previous 2018 European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines. Nevertheless, current 2023 ESH/ESC guidelines recommend assessment in RA using general CVD risk calculators. Design and method: We aimed to calculate CVD risk in RA patients using the most frequently applied CVD risk calculators in the general population. We only stratified patients free from established CVD (heart disease, stroke) or its equivalents (diabetes mellitus, chronic kidney disease) aged 40-74 years. The following algorithms were applied: (i) SCORE2 (Systemic Coronary Risk Estimation-2), (ii) Framingham Risk Score-Adult Treatment Panel (FRS-ATP) CVD risk calculator, and (iii) the American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort Equation. We further correlated the estimated CVD risk by each algorithm with surrogate CVD markers, i.e. arterial stiffness and carotid atherosclerosis. For this purpose, carotid-femoral pulse wave velocity (cfPWV) was measured using applanation tonometry (Sphygmocor ®), and carotid intima-media thickness (cIMT) was estimated using carotid ultrasound. Results: A total of 91 patients aged 60.3±8.1 years were included (78% females). Using the FRS-ATP algorithm, more patients were classified as high risk and fewer as low risk compared to the other calculators (Table 1). Moreover, CVD risk calculated with FRS-ATP correlated stronger with both cfPWV and cIMT, compared to CVD risk calculated with the other algorithms (Table 2). Conclusions: In RA patients without established CVD, diabetes, or chronic kidney disease, the FRS-ATP algorithm may be applied as a useful tool for CVD risk stratification. Prospective, large-scale studies are warranted to determine the most reliable CVD risk prediction model for patients with RA.

COMPARATIVE ANALYSIS OF ERGOSPYROMETRIC VARIABLES BETWEEN SEDENTARY AND NON-SEDENTARY PATIENTS WITH METABOLIC SYNDROME AND ESTABLISHED CARDIOVASCULAR DISEASE

Objective: To analyze the ergospirometric prognostic variables of VO2MAX, OUES, SLOPE VE/VCO2, and ventilatory class, between sedentary and non-sedentary patients with metabolic syndrome all suffering from any kind of established cardiovascular disease. Design and method: From November 2022 to September 2023, 99 patients, with an average age of 70 years, 51.5% women and 48.5% men, underwent an ergospirometry study. They were divided into two groups: sedentary (SP) and non-sedentary (NSP) according to the responses obtained from the IPAQ survey. Subsequently, the ergospirometric variables that measure cardiorespiratory and cardiovascular capacity related to maximum exercise capacity O2 metabolism (VO2MAX), the increase in oxygen consumption according to minute ventilation (OUES) and the response to ventilation according to CO2 production (slope VE/VCO2) were analyzed in both groups. For statistical analysis, the Student's t test and the Fisher exact test were used. The R v4.0.3 software was used. Results: The level of exercise was low in 56 (56.6%) and moderate or high in 43 patients. (43.4%). The NSP group presented higher levels of maximum oxygen consumption (18.3 vs 12.7, p=0.001), higher mean percentage of OUES (92 vs 63.9, p=0.001) and lower mean VE/VCO2 SLOPE ratio (26 vs 31, p=0.001). Among the NSP, 14% were found in ventilatory class 2 and 86% in class 3 and in the SP, 25% were found in class 1, 21.4% in class 2, and 48.2% in class 3. Although that a high percentage of NSP were in functional class 3 (86%) the same presented better values than those SP with better ventilatory class. We did not obtain statistical differences between both groups with respect to their underlying cardiovascular pathologies. Conclusions: A sedentary lifestyle is associated with higher erogospirometric variables risk in patients with metabolic syndrome and established cardiovascular disease. The level of physical activity is a factor that modifies this cardiovascular risk. Ergospirometry is an effective tool to measure cardiovascular prognosis.

Nocturnal Heart Rate Response to Spontaneous Arousals Following Sleep Restriction

Short sleep duration is associated with future cardiovascular disease including hypertension, especially in females, but mechanistic evidence is largely lacking. Experimental sleep restriction has been shown to cause short sleep-mediated tachycardia and reduced heart rate variability, indicative of autonomic cardiac instability, in some but not all studies. Heart rate (HR) response to spontaneous cortical arousals can be regarded as an index of autonomic cardiac control given its characteristic temporal pattern. Whether the HR response to cortical arousals is altered during experimental sleep restriction remains unknown. We hypothesized that sleep restriction would result in augmented HR reactivity to spontaneous arousals, and that this response would be more marked in females. We studied 19 young, healthy subjects (eight females, age: 23.5 ± 5 years, body mass index [BMI]: 24.5 ± 3.6 kg/m2). In a randomized, crossover design, participants were tested during a normal sleep (NS, 9 hr sleep opportunity) or sleep restriction (SR, 4 hr sleep opportunity) study arm. Each 16-day study visit consisted of a 4-day study acclimation phase, 9-day experimental sleep perturbation segment, followed by a 3-day recovery period. An overnight polysomnography (PSG) study was conducted on study days 2, 5 and 11 (at baseline and after 1 and 7 days of restricted versus control sleep). A registered PSG technician provided sleep staging and spontaneous arousal scoring, which was confirmed by an investigator with sleep expertise (IMG). For each identified spontaneous arousal, the HR change was quantified for 30 cardiac cycles post-arousal onset and compared to a pre-arousal baseline (average HR 5 – 10 cardiac cycles prior to arousal). An arousal was considered valid for analysis if at least one minute of stage N2 or rapid eye movement (REM) sleep occurred following sleep stage transition and was at least 30 seconds apart from other sleep disturbance-related events (e.g., limb movement, apneic event, etc.). Given low prevalence of slow wave sleep (SWS) arousals, arousals occurring in that sleep stage were excluded from present analysis. Statistical analysis, including repeated measures ANOVA (RMANOVA, p &lt; 0.05) with condition and time (cardiac cycles) as within-subjects factors and sex as the between-subjects factor, was conducted to compare the beat-to-beat HR response to arousal between study conditions. Additionally, average and peak HR responses to spontaneous arousals were compared via RMANOVA with condition and time (study days) as within-subjects and sex as between-subjects factors. HR response to spontaneous arousal in stage two and REM sleep was similar between NS and SR on study day 5 or day 11 (condition × time: p = 0.943, 0.865). Secondary analysis of average and peak HR responsiveness to spontaneous arousals in stage two and REM sleep between conditions and study days was also not statistically different (condition × time: p = 0.193, 0.185). Last, no significant sex differences were detected across comparisons (condition × time × sex: p &gt; 0.05 for all). These findings suggest that a 9-day sleep restriction paradigm may not alter cardiac autonomic function in otherwise healthy adults. Future work is warranted to determine whether these results extend to individuals with established cardiovascular risk factors or cardiovascular disease. Support: NIH T32-DK007013, R01-114676, and CTSA grant UL1-TR002377. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Temporal trends in the contribution of modifiable cardiovascular risk factors to cardiovascular and all-cause mortality in patients undergoing myocardial perfusion imaging in a large city in Brazil

BackgroundMost cardiovascular (CV) events stem from modifiable, but it remains uncertain whether their impact on mortality has decreased in recent years as a result of treatment, particularly in low- and middle-income countries. We evaluated the temporal trends in the population attributable fraction (PAF) of modifiable risk factors to CV mortality in patients undergoing myocardial perfusion imaging (MPI) for suspected coronary artery disease in a large city in Brazil. MethodsThe cohort comprised 25,127 patients without established CV disease undergoing MPI in a referral center in Curitiba, Brazil, from 2010 to 2018. Baseline demographic, clinical and risk factors were prospectively collected. Modifiable risk factors encompassed hypertension, dyslipidemia, diabetes mellitus, sedentary lifestyle, obesity, and smoking. The primary outcome was CV death occurring up to 4 years of follow-up. The PAF of each risk factor was calculated for each triennium using multivariable Cox proportional regression models, adjusting for age, sex and family history of premature coronary disease. ResultsOver 9 years, there were 1438 deaths, 444 due to CV causes. In the first triennium, sedentary lifestyle exhibited the highest PAF (49%) for CV death, followed by hypertension (17%), diabetes mellitus (8%) and smoking habit (6%). The PAF for all risk factors combined remained relatively stable thorough the triennia (2010–2012: 57% vs 2013–2015: 64% vs 2016–2018: 47%, p = NS). ConclusionIn this large cohort of patients referred to MPI, the PAF of modifiable CV risk factors did not diminish in the last decade, with sedentary lifestyle having the largest contribution for CV mortality. Condensed abstractThis study examinated temporal trends in the impact of modifiable cardiovascular (CV) risk factors on CV and overall mortality in a cohort of 25,127 patients undergoing myocardial perfusion imaging from 2010 to 2018. Sedentary behavior consistently had the greatest impact on both CV and overall mortality, followed by hypertension and diabetes. Smoking had a lesser effect, while obesity showed no independent association with the outcomes. The contributions of these modifiable CV risk factors remained stable over the study period, suggesting that interventions promoting physical activity may be essential in mitigating the burden of CV disease.

Houston Methodist cardiovascular learning health system (CVD-LHS) registry: Methods for development and implementation of an automated electronic medical record-based registry using an informatics framework approach

ObjectivesTo investigate the potential value and feasibility of creating a listing system-wide registry of patients with at-risk and established Atherosclerotic Cardiovascular Disease (ASCVD) within a large healthcare system using automated data extraction methods to systematically identify burden, determinants, and the spectrum of at-risk patients to inform population health management. Additionally, the Houston Methodist Cardiovascular Disease Learning Health System (HM CVD-LHS) registry intends to create high-quality data-driven analytical insights to assess, track, and promote cardiovascular research and care. MethodsWe conducted a retrospective multi-center, cohort analysis of adult patients who were seen in the outpatient settings of a large healthcare system between June 2016 - December 2022 to create an EMR-based registry. A common framework was developed to automatically extract clinical data from the EMR and then integrate it with the social determinants of health information retrieved from external sources. Microsoft's SQL Server Management Studio was used for creating multiple Extract-Transform-Load scripts and stored procedures for collecting, cleaning, storing, monitoring, reviewing, auto-updating, validating, and reporting the data based on the registry goals. ResultsA real-time, programmatically deidentified, auto-updated EMR-based HM CVD-LHS registry was developed with ∼450 variables stored in multiple tables each containing information related to patient's demographics, encounters, diagnoses, vitals, labs, medication use, and comorbidities. Out of 1,171,768 adult individuals in the registry, 113,022 (9.6%) ASCVD patients were identified between June 2016 and December 2022 (mean age was 69.2 ± 12.2 years, with 55% Men and 15% Black individuals). Further, multi-level groupings of patients with laboratory test results and medication use have been analyzed for evaluating the outcomes of interest. ConclusionsHM CVD-LHS registry database was developed successfully providing the listing registry of patients with established ASCVD and those at risk. This approach empowers knowledge inference and provides support for efforts to move away from manual patient chart abstraction by suggesting that a common registry framework with a concurrent design of data collection tools and reporting rapidly extracting useful structured clinical data from EMRs for creating patient or specialty population registries.

A new indication for semaglutide (Wegovy).

The injectable glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide (Wegovy) has been approved by the FDA to reduce the risk of major adverse cardiovascular events (MACE) in adults with established cardiovascular disease (CVD) and either obesity or overweight.

Development and validation of a lifetime prediction model for incident type 2 diabetes in patients with established cardiovascular disease: the CVD2DM model.

Identifying patients with established cardiovascular disease (CVD) who are at high risk of type 2 diabetes (T2D) may allow for early interventions, reducing the development of T2D and associated morbidity. The aim of this study was to develop and externally validate the CVD2DM model to estimate the 10-year and lifetime risks of T2D in patients with established CVD. Sex-specific, competing risk-adjusted Cox proportional hazard models were derived in 19 281 participants with established CVD and without diabetes at baseline from the UK Biobank. The core model's pre-specified predictors were age, current smoking, family history of diabetes mellitus, body mass index, systolic blood pressure, fasting plasma glucose, and HDL cholesterol. The extended model also included HbA1c. The model was externally validated in 3481 patients from the UCC-SMART study. During a median follow-up of 12.2 years (interquartile interval 11.3-13.1), 1628 participants with established CVD were diagnosed with T2D in the UK Biobank. External validation c-statistics were 0.79 [95% confidence interval (CI) 0.76-0.82] for the core model and 0.81 (95% CI 0.78-0.84) for the extended model. Calibration plots showed agreement between predicted and observed 10-year risk of T2D. The 10-year and lifetime risks of T2D can be estimated with the CVD2DM model in patients with established CVD, using readily available clinical predictors. The model would benefit from further validation across diverse ethnic groups to enhance its applicability. Informing patients about their T2D risk could motivate them further to adhere to a healthy lifestyle.

SGLT2 Inhibitors in the Cardiovascular Disease

Sodium glucose cotransporter 2 (SGLT2) inhibitors, initially designed for type 2 diabetes management, have exhibited consistent efficacy across the cardiovascular disease continuum. Their benefits are experienced by patients with cardiovascular risk factors, those with established atherosclerotic cardiovascular disease, and even individuals suffering from heart failure (HF). Notably, SGLT2 inhibitors have demonstrated remarkable effectiveness in preventing and managing HF, positioning them as essential primary therapies for HF patients irrespective of their diabetic status. They have emerged as a uniquely effective treatment for HF with preserved ejection fraction, filling a therapeutic gap that previously existed in this population. These cardiovascular benefits are not limited to diabetic patients, indicating a broader potential for SGLT2 inhibitors in cardiovascular care. Their expanded indications suggest a pivotal role in both the prevention and treatment of cardiovascular disease. However, while clinical outcomes with SGLT2 inhibitors are promising, the precise mechanism underlying their cardiovascular protection remains unclear. Further research is warranted to elucidate these mechanisms, potentially unveiling new therapeutic avenues and facilitating the development of novel drugs.

Fibrinogen to HDL-Cholesterol ratio as a predictor of mortality risk in patients with acute myocardial infarction

BackgroundAcute myocardial infarction (AMI) is characterized by inflammation, oxidative stress, and atherosclerosis, contributing to increased mortality risk. High-density lipoprotein (HDL) takes a crucial part in mitigating atherosclerosis and inflammation through its diverse functionalities. Conversely, fibrinogen is implicated in the development of atherosclerotic plaques. However, the mortality risk predictive capacity of fibrinogen to HDL-cholesterol ratio (FHR) in AMI patients remains unexplored. This research aimed to evaluate the effectiveness of FHR for mortality risk prediction in relation to AMI.MethodsA retrospective study involving 13,221 AMI patients from the Cardiorenal ImprovemeNt II cohort (NCT05050877) was conducted. Baseline FHR levels were used to categorize patients into quartiles. The assessment of survival disparities among various groups was conducted by employing Kaplan‒Meier diagram. Cox regression was performed for investigating the correlation between FHR and adverse clinical outcomes, while the Fine-Gray model was applied to evaluate the subdistribution hazard ratios for cardiovascular death.ResultsOver a median follow-up of 4.66 years, 2309 patients experienced all-cause death, with 1007 deaths attributed to cardiovascular disease (CVD). The hazard ratio (HR) and its 95% confidence interval (CI) for cardiac and all-cause death among individuals in the top quartile of FHR were 2.70 (1.99–3.65) and 1.48 (1.26–1.75), respectively, in comparison to ones in the first quartile, after covariate adjustment. Restricted cubic spline analysis revealed that FHR was linearly correlated with all-cause mortality, irrespective of whether models were adjusted or unadjusted (all P for nonlinearity > 0.05).ConclusionAMI patients with increased baseline FHR values had higher all-cause and cardiovascular mortality, regardless of established CVD risk factors. FHR holds promise as a valuable tool for evaluating mortality risk in AMI patients.Trial registrationThe Cardiorenal ImprovemeNt II registry NCT05050877.

Attainment of LDL-Cholesterol Goals in Patients with Previous Myocardial Infarction: A Real-World Cross-Sectional Analysis.

The European Society of Cardiology guidelines recommend an LDL-cholesterol (LDL-C) < 55 mg/dL for patients with established cardiovascular disease. While the Friedewald equation to estimate LDL-C is still widely used, the newer Martin-Hopkins equation has shown greater accuracy. We aimed to assess: A) the proportion of patients reaching LDL-C goal and the therapies used in a tertiary center; B) the impact of using the Martin-Hopkins method instead of Friedewald's on the proportion of controlled patients. A single-center cross-sectional study including consecutive post-myocardial infarction patients followed by 20 cardiologists in a tertiary hospital. Data was collected retrospectively from clinical appointments that took place after April 2022. For each patient, the LDL-C levels and attainment of goals were estimated from an ambulatory lipid profile using both Friedewald and Martin-Hopkins equations. A two-tailed p-value of < 0.05 was considered statistically significant for all tests. Overall, 400 patients were included (aged 67 ± 13 years, 77% male). Using Friedewald's equation, the median LDL-C under therapy was 64 (50-81) mg/dL, and 31% had LDL-C within goals. High-intensity statins were used in 64% of patients, 37% were on ezetimibe, and 0.5% were under PCSK9 inhibitors. Combination therapy of high-intensity statin + ezetimibe was used in 102 patients (26%). Applying the Martin-Hopkins method would reclassify a total of 31 patients (7.8%). Among those deemed controlled by Friedewald's equation, 27 (21.6%) would have a Martin-Hopkins' LDL-C above goals. Less than one-third of post-myocardial infarction patients had LDL-C within the goal. Applying the Martin-Hopkins equation would reclassify one-fifth of presumably controlled patients into the non-controlled group.

Vaccines in cardiology, an underutilized strategy to reduce the residual cardiovascular risk.

Cardiovascular diseases stand as the leading cause of mortality among adults globally. For decades, comprehensive evidence has underscored the correlation between infections, particularly those involving the respiratory system, and an elevated risk of cardiovascular and cerebrovascular events, as well as all-cause mortality. The mechanisms through which infections heighten cardiovascular events are intricate, encompassing immune system activation, systemic inflammation, hypercoagulable states, sympathetic system activation, and increased myocardial oxygen demand. Respiratory infections further contribute hypoxemia to this complex interplay. These mechanisms intertwine, giving rise to endothelial dysfunction, plaque ruptures, myocardial depression, and heart failure. They can either instigate de novo cardiovascular events or exacerbate pre-existing conditions. Compelling evidence supports the safety of influenza, pneumococcal, herpes zoster, COVID-19 and respiratory syncytial virus vaccines in individuals with cardiovascular risk factors or established cardiovascular disease. Notably, the influenza vaccine has demonstrated safety even when administered during the acute phase of a myocardial infarction in individuals undergoing angioplasty. Beyond safety, these vaccinations significantly reduce the incidence of cardiovascular events in individuals with an augmented cardiovascular risk. Nevertheless, vaccination rates remain markedly suboptimal. This manuscript delves into the intricate relationship between infections and cardiovascular events. Additionally, we highlight the role of vaccinations as a tool to mitigate these occurrences and reduce residual cardiovascular risk. Finally, we emphasize the imperative need to optimize vaccination rates among individuals with heart diseases.

Pregnancy History at 40 Years of Age as a Marker of Cardiovascular Risk.

Individual pregnancy complications are associated with increased maternal risk of cardiovascular disease. We assessed the link between a woman's total pregnancy history at 40 years of age and her relative risk of dying from atherosclerotic cardiovascular disease (ASCVD). This population-based prospective study combined several Norwegian registries covering the period 1967 to 2020. We identified 854 442 women born after 1944 or registered with a pregnancy in 1967 or later, and surviving to 40 years of age. The main outcome was the time to ASCVD mortality through age 69 years. The exposure was a woman's number of recorded pregnancies (0, 1, 2, 3, or 4) and the number of those with complications (preterm delivery <35 gestational weeks, preeclampsia, placental abruption, perinatal death, and term or near-term birth weight <2700 g). Cox models provided estimates of hazard ratios across exposure categories. The group with the lowest ASCVD mortality was that with 3 pregnancies and no complications, which served as the reference group. Among women reaching 40 years of age, risk of ASCVD mortality through 69 years of age increased with the number of complicated pregnancies in a strong dose-response fashion, reaching 23-fold increased risk (95% CI, 10-51) for women with 4 complicated pregnancies. Based on pregnancy history alone, 19% of women at 40 years of age (including nulliparous women) had an increased ASCVD mortality risk in the range of 2.5- to 5-fold. Pregnancy history at 40 years of age is strongly associated with ASCVD mortality. Further research should explore how much pregnancy history at 40 years of age adds to established cardiovascular disease risk factors in predicting cardiovascular disease mortality.