High Burden Of Cardiovascular Disease Research Articles

E012 Burden and risk factors for cardiovascular involvement in connective tissue disease

Abstract Background/Aims Connective tissue diseases (CTD) are associated with several cardiovascular manifestations. Cardiovascular diseases (CVD) are significant cause of morbidity and premature death. The pathogenesis of CVD in CTD patients is incompletely understood and likely multifactorial. Traditional risk factors for atherosclerosis are common among patients with CTD as well as metabolic syndrome. Furthermore, diabetes, dyslipidaemia, hypertension, and obesity may all be exacerbated by connective tissue disease itself or treatment with glucocorticoids. The aim of this study was to assess the burden of CVD and the risk factors for the development of cardiovascular disease in patients with CTD. Methods This was a retrospective study from a single centre. We reviewed clinical records of CTD patients as determined by treating rheumatologist. This CTD cohort included patients with systemic lupus erythematosus (SLE), myositis, systemic sclerosis, Sjogren’s syndrome, mixed and undifferentiated connective tissue diseases. Data on demographic, clinical, laboratory parameters, cardiac investigations, treatment and outcome were collected from electronic patient records. CVD and traditional risk factors were defined using standard criteria. Results A total of 298 patients with CTD were included in the analysis. Mean age of the cohort was 61±17.7 years and majority were females (n = 240, 80.5%). Of the 298 patients, 64 had CVD (21.5%). Most common CVD was ischaemic heart disease (17 patients) followed by hypertension (12), arrhythmia (9), pulmonary arterial hypertension (7), valvular diseases (5), pericardial disease (3), cardiomyopathy (3), myocarditis (2), thromboembolism (3), aortic dissection (2) and coronary spasm (1). Patient with CTD who had CVD were older (72.5±12.2 years) compared to CTD patients who did not develop CVD (non-CVD group, 57.7±17.6 years). The duration of CTD was shorter in patients with CVD (88.9±41.7 months), compared to 106±84.3 months in non-CVD group. The risk factors such as smoking, diabetes and dyslipidaemia was higher in the CVD group. Comparing CVD vs non-CVD patients respectively, systolic BP (147.1±23.0 vs 133.6±18.3mmHg), diastolic BP (83.2 ± 16.3 vs 78.2 ± 11.2mmHg) and serum uric acid (321.8±97.4 vs 292±83.9mg/dL) values were higher and statistically significant (p < 0.05) in CVD group. Patients with CVD had longer exposure to steroids (50%) compared to non-CVD patients (31.6%). They required high dose steroids (9.4% vs 5.6% in non-CVD patients). Current and previous DMARD use was also higher in patients who had CVD (51.6% vs 44.9%). Conclusion This study has demonstrated high burden of cardiovascular disease in CTD patients. Traditional risk factors were more prevalent in the CVD group. DMARD’s and steroid use was also higher in the CVD group. Screening for cardiovascular diseases and disease control in CTD patients is paramount for better outcomes. Further analysis will be carried out for risk factors and relevant outcomes. Disclosure K.K. Garg: None. S. Sampath: None. A. Erinjogunola: None. B. Ting: None. H. Noori: None. G.M. Koduri: None.

Long-term Effects of Kidney Transplantation Compared With Dialysis on Intima-media Thickness in Children-Results From the 4C-T Study.

Children requiring kidney replacement therapy experience high burden of cardiovascular (CV) disease leading to increased mortality. Intima-media thickness (IMT) indicating atherosclerosis is a validated surrogate marker for future CV events. We investigated the effect of different treatment modalities (dialysis, preemptive kidney transplantation (KTx), late KTx after dialysis) on IMT by multivariable linear mixed-effect modeling. Patients were enrolled in a prospective cohort study. A total of 261 analyzed children had a mean follow-up of 3 y. Children after preemptive and late KTx had lower levels of IMT when compared with dialysis. Using an interaction term, a significant progression of IMT over time was seen during dialysis (β = 0.0053 mm/y, P = 0.004). IMT before the start of therapy was the most influential determinant in all models. Low IMT was associated with maintenance steroid treatment after preemptive KTx. High IMT on dialysis was associated with higher systolic blood pressure, lower body mass index, lower serum albumin, and lower bicarbonate. IMT remained rather stable in children several years after KTx. In contrast, children on dialysis had higher IMT values, which increased over time. In these children, blood pressure control, calorie and protein intake, and acid-base homeostasis seem important. Taken together, children might profit from early transplantation to limit accumulation of CV risk.

Transnational inequities in cardiovascular diseases from 1990 to 2019: exploration based on the global burden of disease study 2019.

To describe the burden and examine transnational inequities in overall cardiovascular disease (CVD) and ten specific CVDs across different levels of societal development. Estimates of disability-adjusted life-years (DALYs) for each disease and their 95% uncertainty intervals (UI) were extracted from the Global Burden of Diseases (GBD). Inequalities in the distribution of CVD burdens were quantified using two standard metrics recommended absolute and relative inequalities by the World Health Organization (WHO), including the Slope Index of Inequality (SII) and the relative concentration Index. Between 1990 and 2019, for overall CVD, the Slope Index of Inequality changed from 3760.40 (95% CI: 3758.26 to 3756.53) in 1990 to 3400.38 (95% CI: 3398.64 to 3402.13) in 2019. For ischemic heart disease, it shifted from 2833.18 (95% CI: 2831.67 to 2834.69) in 1990 to 1560.28 (95% CI: 1559.07 to 1561.48) in 2019. Regarding hypertensive heart disease, the figures changed from-82.07 (95% CI: -82.56 to-81.59) in 1990 to 108.99 (95% CI: 108.57 to 109.40) in 2019. Regarding cardiomyopathy and myocarditis, the data evolved from 273.05 (95% CI: 272.62 to 273.47) in 1990 to 250.76 (95% CI: 250.42 to 251.09) in 2019. Concerning aortic aneurysm, the index transitioned from 104.91 (95% CI: 104.65 to 105.17) in 1990 to 91.14 (95% CI: 90.94 to 91.35) in 2019. Pertaining to endocarditis, the figures shifted from-4.50 (95% CI: -4.64 to-4.36) in 1990 to 16.00 (95% CI: 15.88 to 16.12) in 2019. As for rheumatic heart disease, the data transitioned from-345.95 (95% CI: -346.47 to-345.42) in 1990 to-204.34 (95% CI: -204.67 to-204.01) in 2019. Moreover, the relative concentration Index for overall CVD and each specific type also varied from 1990 to 2019. There's significant heterogeneity in transnational health inequality for ten specific CVDs. Countries with higher levels of societal development may bear a relatively higher CVD burden except for rheumatic heart disease, with the extent of inequality changing over time.

Physical activity moderates the relationship between cardiovascular disease risk burden and cognition in older adults.

Introduction Older individuals with higher cardiovascular disease (CVD) burden have a higher risk for accelerated cognitive decline and dementia. Physical activity (PA) is an inexpensive and accessible preventive measure to CVD, cognitive impairment, and dementia. The current study examined (1) whether PA moderates the relationship between CVD burden and cognition and (2) whether the moderating effect of PA differs by race/ethnicity groups and by APOE-ɛ4 status. Methods Our cross-sectional study included participants from the Washington Heights-Inwood Columbia Aging Project (WHICAP), a multi-ethnic, community-based, longitudinal study on aging and dementia among individuals aged 65 years and older who reside in northern Manhattan. All participants underwent an interview and a neuropsychological assessment for global cognition, memory, language, visuospatial, and speed functioning. Results In 2122 older individuals without dementia, having higher CVD burden was associated with worse cognitive scores for global, language, speed, and visuospatial cognitive functions. PA mitigated the relationship between CVD burden and visuospatial function. Furthermore, PA mitigated the association of CVD burden with global cognition, language, and visuospatial functions in APOE-ɛ4 carriers, but not in non-carriers. Discussion/Conclusion Our study suggests that PA may mitigate the negative association between CVD and cognition, especially in APOE-ɛ4 carriers. The moderating effect of PA did not differ by race/ethnicity.

Associations between inflammatory and angiogenic proteomic biomarkers, and cardiovascular events and mortality in relation to kidney function

ABSTRACT Background The links between chronic kidney disease (CKD) and the high burden of cardiovascular disease remain unclear. We aimed to explore the association between selected inflammatory and angiogenic biomarkers, kidney function and long-term outcome in patients with an acute coronary syndrome (ACS) and to test the hypothesis that CKD status modifies this association. Methods A total of 1293 ACS patients hospitalized between 2008 and 2015 were followed until 31 December 2017. Plasma was collected on days 1–3 after admission. A total of 13 biomarkers were a priori identified and analysed with two proteomic methods, proximity extension assay or multiple reaction monitoring mass spectrometry. Boxplots and multiple linear regression models were used to study associations between biomarkers and kidney function and adjusted standardized Cox regression with an interaction term for CKD was used to assess whether CKD modified the association between biomarkers and major adverse cardiovascular events and death (MACE+). Results The concentrations of nine biomarkers—endothelial cell-specific molecule-1 (ESM-1), fibroblast growth factor 23 (FGF-23), fractalkine (CX3CL1), interleukin-1 receptor antagonist (IL-1RA), interleukin-18 (IL-18), monocyte chemotactic protein-1 (MCP-1), placenta growth factor (PlGF), transmembrane immunoglobulin 1 (TIM-1) and vascular endothelial growth factor A (VEGFA)—were inversely associated with kidney function. ESM-1, FGF-23 and TIM-1 showed associations with MACE+. Only FGF23 remained independently associated after adjustment for the other biomarkers (hazard ratio per standard deviation increase 1.34; 95% Bonferroni corrected confidence interval 1.19–1.50). None of the biomarkers showed an interaction with CKD. Conclusions The concentrations of 9 of the 13 prespecified inflammatory and angiogenic proteomic biomarkers increased when kidney function declined. Only FGF-23 demonstrated an independent association with MACE+, and this association was not modified by CKD status. These findings further support FGF-23 as an independent prognostic marker in ACS patients with and without CKD.

Cardiac Involvement in Neurosarcoidosis: A Single-Center Investigation

Sarcoidosis is a multisystem inflammatory granulomatous disease. Among systemic sarcoidosis manifestations, cardiac or nervous system involvement can result in significant morbidity and mortality. We describe the overlapping incidence of cardiac sarcoidosis (CS) within a neurosarcoidosis (NS) cohort and determine the frequency of other nonsarcoid cardiac diseases in these patients. We performed a retrospective chart review of patients evaluated at the University of Utah from 2010 to 2022. Patients were included if they had (1) at least one instance of a diagnostic code for sarcoidosis in their medical record-International Classification of Diseases (ICD) 9 code 135 or ICD 10 code D86; (2) at least one outpatient visit in the Neurology Department within the University of Utah electronic health record with a diagnosis of definite, probable, or possible NS based on 2018 consensus criteria; (3) at least one outpatient visit in the Cardiology Department within the University of Utah electronic health record; and (4) ECG available in their medical record for review. Of 64 definite, probable, or possible patients with NS in the University of Utah cohort, 52 met our inclusion criteria and were included in this study. Of 52 patients with NS who met our inclusion criteria, 65.38% were female, with an average age of 60.9 years (range 38-84). More than half (58%) were obese (BMI ≥ 30). CS was diagnosed in 6 patients with NS (12%). Symptoms suggestive of possible cardiac dysfunction included lower extremity edema (50%), palpitations (46%), chest pain (44%), and shortness of breath (27%). ECG abnormalities included nonspecific T-wave change (40%) and right bundle branch block (17%). Three patients experienced ventricular tachycardia: sustained in one patient and nonsustained in 2 patients. Cardiac MRI was performed in 17 patients (32.7%) and in 3 patients (17.6%), which revealed diffuse myocardial enhancement suggesting CS. In this cohort, 12% of patients with NS also had confirmed CS. In addition, these patients had a high burden of cardiovascular disease not directly attributed to sarcoidosis. Our data suggest that patients with NS require comprehensive cardiac evaluation. Future studies are needed to clarify the extent of the direct contribution of granulomatous inflammation on the cardiovascular system from the indirect contribution of treatments such as glucocorticoids that lead to increased risk of cardiovascular disease in sarcoidosis.

Correlates and consequences of atrial fibrillation in a prospective study of 25 000 participants in the China Kadoorie Biobank.

The prevalence of atrial fibrillation (AF) is positively correlated with prior cardiovascular diseases (CVD) and CVD risk factors but is lower in Chinese than Europeans despite their higher burden of CVD. We examined the prevalence and prognosis of AF and other electrocardiogram (ECG) abnormalities in the China Kadoorie Biobank. A random sample of 25 239 adults (mean age 59.5 years, 62% women) had a 12-lead ECG recorded and interpreted using a Mortara VERITAS™ algorithm in 2013-14. Participants were followed up for 5 years for incident stroke, ischaemic heart disease, heart failure (HF), and all CVD, overall and by CHA2DS2-VASc scores, age, sex, and area. Overall, 1.2% had AF, 13.6% had left ventricular hypertrophy (LVH), and 28.1% had ischaemia (two-thirds of AF cases also had ischaemia or LVH). The prevalence of AF increased with age, prior CVD, and levels of CHA₂DS₂-VASc scores (0.5%, 1.3%, 2.1%, 2.9%, and 4.4% for scores <2, 2, 3, 4, and ≥5, respectively). Atrial fibrillation was associated with two-fold higher hazard ratios (HR) for CVD (2.15; 95% CI, 1.71-2.69) and stroke (1.88; 1.44-2.47) and a four-fold higher HR for HF (3.79; 2.21-6.49). The 5-year cumulative incidence of CVD was comparable for AF, prior CVD, and CHA₂DS₂-VASc scores ≥ 2 (36.7% vs. 36.2% vs. 37.7%, respectively) but was two-fold greater than for ischaemia (19.4%), LVH (18.0%), or normal ECG (14.1%), respectively. The findings highlight the importance of screening for AF together with estimation of CHA₂DS₂-VASc scores for prevention of CVD in Chinese adults.

The burden of cardiovascular disease attributable to high dietary sodium intake in Australia between 1990 and 2019.

Diets high in sodium are associated with adverse cardiovascular outcomes. We aimed to quantify the burden of cardiovascular disease (CVD) attributable to high dietary sodium consumption in the Australian population. Using data from the Global Burden of Disease (GBD) 2019, we estimated the age-standardised rates (per 100 000 population) and the total numbers of years lived with a disability (YLDs), years of life lost (YLLs), disability-adjusted life years (DALYs), and deaths for CVD attributable to high sodium (≥1000 mg/day) consumption in the Australian population, by sex and age groups (≥25 years) between 1990 and 2019. The study compared Australian estimates with similar high-income countries (Group of 20 [G20] members). From 1990 to 2019, the age-standardized rates of CVD deaths, DALYs, YLDs, and YLLs per 100 000 population in Australia attributable to high sodium decreased. However, between 2013 and 2019, the total number of CVD deaths increased, and the number of CVD YLDs increased exponentially for both sexes for the whole period between 1990 and 2019. Men had a two-fold higher rate for high sodium CVD burden, compared to females between 1990 to 2019. Individuals aged between 80 and 84 years had the highest rates of CVD burden during the same period; however, older age groups reported the greatest decline in CVD burden compared to young and middle-aged adults in Australia. The age-standardised rates for high sodium attributable CVD consistently contributed more towards DALYs than YLDs in 2019 for both sexes. When compared to G20 countries, Australians displayed the lowest age-standardized rates for CVD deaths, DALYs, YLDs, and YLLs alongside Turkey, France, and the United Kingdom in 2019. While age-standardized CVD burden attributable to high sodium consumption decreased for both sexes over the past 30 years, the total number of CVD deaths showed an increase between 2013 and 2019. This study underscores the need for sustained efforts to address the rising absolute number of CVD deaths, especially among men and older people, and emphasizes the importance of continued vigilance in monitoring and implementing strategies to reduce the impact of high sodium consumption on cardiovascular health in Australia.

Prevalence of Cardiovascular Disease and Risk Factors in Ghana: A Systematic Review and Meta-analysis.

The increasing cardiovascular disease (CVD) burden threatens the global population as the major cause of disability and premature death. Data are scarce on the magnitude of CVD among the population in West Africa, particularly in Ghana. This study examined the available scientific evidence to determine the pooled prevalence (PP) of CVD and risk factors in Ghana. We searched electronic databases such as PubMed, Google Scholar, the Cochrane Library, Science Direct and Africa Journal Online databases to identify literature published from the start of the indexing of the database to 10th February 2023. All articles published in the English language that assessed the prevalence of CVD or reported on CVD in Ghana were included. Two authors independently performed the study selection, assessed the risk of bias, extracted the data and checked by the third author. The effect sizes and pooled odds ratio (POR) were determined using the random-effects DerSimonian-Laird (DL) model. Sixteen studies with 58912 participants from 1954 to 2022 were included in the meta-analysis. Six studies out of 16 reported more than one prevalence of CVD, giving a total of 59 estimates for PP. The PP of CVD in the general population in Ghana was 10.34% (95% Cl: [8.48, 12.20]; l2 99.54%, p < 0.001). Based on the subgroup analysis, the prevalence of CVD was higher in hospital-based settings at 10.74% (95%, confidence interval [Cl]: 8.69, 12.79) than in community-based settings at 5.04% (95% Cl: 2.54, 7.53). The risk factors were male gender (pooled odds ratio [POR]: 1.66; 95% CI: 1.02, 2.70), old age (POR: 1.32; 95% CI: 1.21, 1.45), unemployment (POR: 2.62; 95% CI: 1.33, 5.16), diabetes (POR: 2.79; 95% CI: 1.62, 4.81) and hypertension (POR: 3.41; 95% CI: 1.75, 6.66). The prevalence of CVD was high in Ghana. Urgent interventions are needed for the prevention and management of the high burden of CVD and its risk factors.

Risk and Incidence of Cardiovascular Disease Associated with Polycystic Ovary Syndrome.

We aimed to evaluate the risk of cardiovascular disease (CVD) in women with polycystic ovary syndrome (PCOS) and estimate the global incidence of PCOS-associated CVD. We conducted a meta-analysis across five databases to evaluate the risk of CVD among women with PCOS. Global incidence of PCOS-associated CVD was calculated by a population attributable fraction (PAF) modelling using the pooled RR, PCOS prevalence, CVD incidence number and age-standardized rate (ASIR), from the Global Burden of Diseases 2019. An estimated annual percentage change (EAPC) was used to assess the temporal trend of PCOS-associated CVD. The risk of CVD was significantly increased in the women with PCOS for all-age group (pooled RR 1.51, 95% CI 1.36-1.69), and 10- to 54-year-old (1.37, 1.17-1.59). Globally, from 1990 to 2019, the PCOS associated CVD cases in women across all-age group has rised from 102 530 to 235 560. The most affected regions were East Asia & Pacific (108 430, 66 090-166 150) in 2019. The South Asia has the highest increase trend of PCOS-associated CVD ASIRs (EAPC 2.61%, 2.49-2.73). The annual increase ASIR in PCOS-CVD incidence for the 10-54 age group (EAPC 0.49%; 0.41-0.56) is faster than that of the all-age group (0.34; 0.27-0.42). The middle- or low-middle sociodemographic index countries, experienced higher increase trend of CVD due to PCOS in the past thirty years. Women with PCOS have a significantly increased risk of CVD. Efficient measures to enhance its prevention and treatment are important for regions with high PCOS-associated CVD burden, especially premature CVD in women under 55 years.

The two different profiles in heart failure with preserved ejection fraction and type 2 diabetes mellitus: ischemic and diabetic

Objective Two profiles of patients with heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes mellitus (T2DM) can be discerned: those with ischemic and those with diabetic cardiomyopathy (DMC). We aim to analyze clinical differences and prognosis between patients of these two profiles. Material and methods This cohort study analyzes data from the Spanish Heart Failure Registry, a multicenter, prospective registry that enrolled patients admitted for decompensated heart failure and followed them for one year. Three groups were created according to the presence of T2DM and heart disease depending on the etiology (ischemic when coronary artery disease was present, or DMC when no coronary, valvular, or congenital heart disease; no hypertension; nor infiltrative cardiovascular disease observed on an endomyocardial biopsy). The groups and outcomes were compared. Results A total of 466 patients were analyzed. Group 1 (n = 210) included patients with ischemic etiology and T2DM. Group 2 (n = 112) included patients with DMC etiology and T2DM. Group 3 (n = 144), a control group, included patients with ischemic etiology and without T2DM. Group 1 had more hypertension and dyslipidemia; group 2 had more atrial fibrillation (AF) and higher body mass index; group 3 had more chronic kidney disease and were older. In the regression analysis, group 3 had a better prognosis than group 1 (reference group) for cardiovascular mortality and HF readmissions (HR 0.44;95%CI 0.2–1; p = .049). Conclusions Patients with T2DM and HFpEF, who had the poorest prognosis, were of two different profiles: either ischemic or DMC etiology. The first had a higher burden of cardiovascular disease and inflammation whereas the second had a higher prevalence of obesity and AF. The first had a slightly poorer prognosis than the second, though this finding was not significant.

Examining disparities in cardiovascular disease prevention strategies and incidence rates between urban and rural populations: insights from Kazakhstan

Kazakhstan is experiencing a high burden of cardiovascular disease (CVD), and the country has implemented a range of strategies aimed at controlling CVD. The study aims to conduct a content analysis of the policies implemented in the country and augment it with an analysis of official statistics over a 15-year period, from 2006 to 2020. The study also includes comparisons of incidence rates between urban and rural areas. A comprehensive search was conducted to identify policy documents that regulate the provision of primary, secondary, and tertiary prevention of cardiovascular diseases. Additionally, official data on the incidence of arterial hypertension, ischemic heart disease, acute myocardial infarction, and cerebrovascular disease were extracted from official statistics, disaggregated by urban and rural areas. Forecast modeling was utilized to project disease incidences up to 2030. The study reveals that Kazakhstan primarily focuses on tertiary prevention of cardiovascular diseases, with less attention given to secondary prevention, and primary prevention is virtually non-existent. In general, screening for arterial hypertension appears to be more successful than for ischemic heart disease. The incidence of arterial hypertension has increased threefold for urban residents and 1.7-fold for rural residents. In urban areas, residents saw a twofold increase in ischemic heart disease incidence, while it remained the same in rural areas. The findings of this study have practical implications for decision-makers, who can use the results to enhance the effectiveness of existing CVD prevention strategies.

The burden of cardiovascular disease in South Asia: the need for effective treatment

Dear Ma'am, Cardiovascular disease (CVD) is rapidly becoming the leading cause of death worldwide (1). According to global health projections, it will remain the number one cause of death in 2030. The Asian region has been shown to have a higher cardiovascular disease burden than Western countries, and most of this burden is borne by economically disadvantaged people mainly located in South Asian regions such as Pakistan. (1). A large-scale survey conducted in 53 cities in Punjab, Pakistan, found that 17.5% of the population suffered from cardiovascular disease (2). Mechanical thrombectomy is a minimally-invasive procedure where a specialized interventional radiologist utilizes specific equipment to remove a blood clot from an artery in a patient's body. This procedure treats arterial blockages caused by blood clots such as Deep Vein Thrombosis (DVT), Ischemic Stroke, etc (3). MegaVac, a part of mechanical thrombectomy, is the newest technique for the removal of blood clots from arteries. It is an invasive procedure that ensures the complete removal of clots from the occluded artery. The biggest advantage of this technique over typical clot removal is that it prevents embolus formation, which can occlude smaller arteries. The MegaVac Thrombectomy System is an intravascular mechanical thrombectomy and aspiration device with a single use that includes a thrombowire with an embolectomy component. A distal silicone-coated nitinol braid used in the SafeSealTM technology of the MegaVac Catheter swells to momentarily obstruct antegrade blood flow. The braid is expanded by the inner and outer coaxial shafts of the catheter body, briefly occluding the channel and enabling aspiration. SafeSeal funnel is activated by the assembly of the proximal handle. A nitinol embolectomy component that is part of the thrombowire can be used to draw material in the direction of the MegaVac catheter when it is inflated by the proximal actuation handle (4). Thrombectomy is a common and effective procedure for clot removal but in Pakistan thrombectomy is not as common compared to developed countries, primarily due to two reasons. First, Mechanical thrombectomy is exclusively available in four hospitals nationwide, with only one public hospital in Lahore providing this procedure (5). Second, it is an expensive procedure that ranges from 1700$ to 5000$ depending on the severity of the patient and the complexity of the procedure. Health Departments of Pakistan should provide this facility in more public hospitals so it becomes accessible to more people.

Exploring the Evolution of Statin Pricing in Australia: Observations of Price Disclosure Effects on Pharmaceutical Benefits Scheme Expenditure

ObjectivesThe high cardiovascular disease burden globally and in Australia necessitates attention on statin expenditure, the primary pharmacological intervention for cardiovascular disease risk factors. The Pharmaceutical Benefits Scheme (PBS) subsidies approved statins for Australians. Managing PBS government expenditure occurs through price control strategies of statutory price decreases upon first generic entry and price disclosure. This study investigates the impact price control measures had on statin price evolution and government expenditure between 2010 and 2022. MethodsPrescription and pricing data were obtained from Services Australia Medicare Statistics, and price reduction strategies from the PBS. Summary statistics compared and described statin price, prescription, number of brands, market share, and government expenditure to atorvastatin, fluvastatin, pravastatin, rosuvastatin, and simvastatin price control timelines. ResultsStatin prices exposed to price control measures decreased irrespective of dosage and correlated with reductions in government expenditure, with a comparison of 2010 and 2022 showing annual statin expenditure declined by AU$833.5 million (83.25%) whereas prescriptions reduced by 3.0 million (15.7%). Effects of price disclosure on atorvastatin and rosuvastatin market share suggest industry-prompted price reductions may arise from market share loss, whereas reasons external to pricing prompted rosuvastatin to gain market share. ConclusionsLimited publications on contemporary effects of statin price control measures exist. This investigation found these measures reduced government expenditure for statins by AU$949.1 million, with the price reduction correlating with price control measures. In addition to affirming price control mechanisms remain effective in contemporary times, this investigation provides data for key insights into the Australian statin industry.

Association of proteomic signatures and immunophenotyping profiles with subclinical cardiovascular disease characterised by multimodal imaging in South African systemic lupus erythematosus patients

Abstract Background Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease associated with autoantibodies (aAb). Cardiovascular disease (CVD) is a leading cause of mortality later in the disease course. Protein signatures may have utility in predicting SLE patients at risk of CVD. Purpose To determine the association of aAb protein signatures and plasma markers of immune activation with subclinical CVD in South African SLE patients characterised by multimodal imaging. Methods SLE patients, without known CVD, were recruited from rheumatology clinics. Early cardiovascular (CV) involvement was characterised using carotid ultrasound, echocardiography and cardiovascular magnetic resonance (CMR). Commercially available ELISA and Luminex multibead platforms profiled plasma immunophenotyping and CV biomarkers including IL1B, IL6, TNFa, IFNg, MMP9, TIMP1, ICAM1, VCAM1, adiponectin, galectin3, ST2, NTproBNP, hsTropT and hsCRP. We investigated IgG and IgA aAb responses on 2 protein microarrays, first analysing pooled samples on the i-Ome array of over 1600 proteins and second, individual patient samples were analysed on an autoimmune disease array of 50 autoantigens. Raw data were imported and analysed using R. First, loess normalisation of proteomic data was conducted to remove any systematic experimental variation, followed by exploratory analyses on normalised data, then permutational multivariate analysis of variance (PERMANOVA) assessed which imaging variables were most influential on aAb profiles and these results were then further analysed using linear modelling. Results 18 SLE patients and 6 controls were included in this exploratory analysis. Mean age was 34±9 years, 89% were women and the most frequent CV risk factors were hypertension, smoking, and dyslipidaemia in 28%, 28% and 17%, respectively. On CMR, 72% of SLE patients were found to have subclinical CVD, predominantly myocardial (72%) and pericardial (22%) involvement. Compared to controls, SLE patients had significantly increased TNFa (p=0.046), VCAM1 (p=0.006), adiponectin (p=0.046) and NTproBNP (p=0.04). On IgG assay proteomic analyses, PERMANOVA results showed that impaired peak longitudinal strain (p=0.03) and the presence of any regional myocardial oedema (T2 ratio &amp;gt;1,9) (p=0.025) were the most influential variables related to peptide aAb profiles, and late gadolinium enhancement (LGE) was the most influential variable related to protein aAb profiles (p=0.075). Linear modelling considering peak longitudinal strain, T2 ratio (Figure 1) and LGE identified a list of 5, 9 and 13 candidate biomarkers respectively for these CMR parameters. Conclusions In South African SLE patients with a high burden of subclinical CVD associated with elevated immunophenotyping markers, we identified imaging parameters that were influential on protein signatures. Linear modelling identified a list of candidate biomarkers associated with CMR indicators of myocardial strain, oedema and fibrosis.Candidate biomarkers

Abstract 13692: Incidence, Recurrence, and Ethnicity Specific Risk Factors for Premature Coronary Artery Disease in South Asians and Europeans

Introduction: Premature coronary artery disease (CAD) incidence is increasing globally. South Asians (SA) have a disproportionately high burden of atherosclerotic cardiovascular disease (ASCVD). However, the effect of SA ethnicity on the risk of recurrent events in patients with premature CAD has not been prospectively evaluated. Methods: Patients in the SAVEBC and UK biobank (UKB) registries were enrolled and stratified by ethnicity and presence of premature CAD. The co-primary outcomes were to compare proportion of premature CAD and the incidence of recurrent ASVCD events. Secondary exploratory outcomes included describing demographic, physical, biochemical variables between cohorts. Results: 11,136 patients were included, 1,129 (143 SA; 21%) were from SAVEBC and 10,007 (400 SA; 4.0%) from UKB. There was a higher proportion of premature CAD in SA compared to Caucasians in UKB (5.2% vs. 2.0%, p &lt; 0.001). Similarly, SA were overrepresented in SAVEBC (21% of cohort vs. 7.9% of British Columbia population). SA compared to Caucasians with premature CAD had increased prevalence of diabetes (SAVEBC: 20.1% vs 13.8%, p=0.08; UKB: 37.5% vs 18.0%, p&lt;0.001), and lower mean HDL cholesterol (SAVEBC: 1.4±0.4 vs 1.5±0.4, p=0.21; UKB: 1.1±0.3 vs 1.2±0.3, p&lt;0.001). SA had more diffuse disease reflected by more coronary segments affected (4.9±3.0 vs. 4.1±2.6, p=0.05), and a trend towards more affected coronary vessels compared to Caucasians (1.31±1.4 vs. 0.61±0.91, p=0.14). SA had greater incidence of recurrent ASCVD vs. Caucasians (4.19 vs. 3.08 events per 100 P-Y; incidence rate ratio p-value &lt; 0.001). SA had higher risk of recurrent ASCVD events (HR 1.35, 95% CI 1.13,1.61, p&lt;0.001). SA ethnicity remained a predictor of recurrent events on adjusted COX regression (HR 1.24, 95% CI 1.03,1.48, p=0.02). Conclusion: Using two prospective registries, SA had a higher proportion of premature CAD and recurrent cardiovascular events with shorter time to recurrent events. Some risk may be explained by adverse cardiometabolic profiles, however significant risk mechanisms are yet to be elucidated. Understanding the unique mechanisms of cardiovascular risk in SA is critical to appropriately identify high-risk individuals and initiate contemporary preventative therapies.

Medicaid Expansion And Outpatient Cardiovascular Care Use Among Low-Income Nonelderly Adults, 2012-15.

Adults with lower socioeconomic status have a disproportionately higher burden of cardiovascular disease. Medicaid expansion under the Affordable Care Act, which went into effect January 1, 2014, in adopting states, led to an expansion of health insurance coverage for low-income adults. To understand whether Medicaid expansion was associated with increased access to outpatient cardiovascular care in expansion states, we examined Medicaid Analytic eXtract administrative claims data for nonelderly adult beneficiaries from the period 2012-15 for two states that expanded Medicaid eligibility (New Jersey and Minnesota) and two states that did not (Georgia and Tennessee) and calculated population-level rates of cardiovascular care use. There was a 38.1percent greater increase in expansion states in the rate of beneficiaries with outpatient visits for cardiovascular disease management associated with Medicaid expansion relative to nonexpansion states. This was accompanied by a 42.9percent greater increase in the prescription rate for cardiovascular disease management agents. These results suggest that expansion of Medicaid eligibility was associated with an increase in cardiovascular care use among low-income nonelderly adults in expansion states.

39 Relationships among Cardiovascular Risk Factors, White Matter Hyperintensities, and Depressive Symptoms in Black and White Older Adults

Objective:The vascular depression hypothesis posits that there is a relationship between vascular disease and geriatric depressive symptoms. Black Americans are at higher risk for cardiovascular disease (CVD) than their White counterparts. However, it is not fully understood whether risk for CVD or potentially related neurovascular changes have a differential relationship in Black and White Americans. We investigated differences in the relationships between white matter hyperintensities, risk for CVD, and depressive symptoms in Black and White older adults.Participants and Methods:Participants were derived from the National Alzheimer Coordinating Center database. Black (N = 120) and White (N = 120) participants were matched on age, sex, and education. White matter hyperintensity (WMH) and CVD burden data (sum of vascular conditions) on 320 individuals were analyzed (mean age = 75.9; 69.4% female). Age, sex, race, and education were included as covariates in separate regression models in which WMH and CVD burden predicted scores on the 15-item Geriatric Depression Scale (GDS-15). Follow-up stratified analyses were conducted to explore the relationship between WMH and CVD burden on GDS scores in the Black and White samples.Results:Lower WMH volume and higher CVD burden were associated with higher GDS scores in the total sample. Analyses stratified by race showed a positive effect of CVD burden on GDS scores only for the Black sample and a trend effect of WMH on GDS scores only for the White sample, with higher WMH volume associated with lower rather than higher GDS scores.Conclusions:These findings are consistent with previous research showing that WMH and CVD burden are related to depression in older adults. Contrary to expectation, WMH had a negative trend association with GDS scores in the White sample. Findings also suggest that different etiologies may play a role in the clinical presentation of depression in Black and White Americans. Additional research is needed to further explore the relationships among CVD, its neural correlates, and depressive symptoms in diverse samples.

2 Contributions of Cardiovascular Disease Burden and Concussion History on Cognitive Function in Older Former National Football League Players.

Objective:Traumatic brain injury and cardiovascular disease (CVD) are modifiable risk factors for cognitive decline and dementia. Greater concussion history can potentially increase risk for cerebrovascular changes associated with cognitive decline and may compound effects of CVD. We investigated the independent and dynamic effects of CVD/risk factor burden and concussion history on cognitive function and odds of mild cognitive impairment (MCI) diagnoses in older former National Football League (NFL) players.Participants and Methods:Former NFL players, ages 50-70 (N=289; mean age=61.02±5.33 years), reported medical history and completed the Brief Test of Adult Cognition by Telephone (BTACT). CVD/risk factor burden was characterized as ordinal (0-3+) based on the sum of the following conditions: coronary artery disease/myocardial infarction, chronic obstructive pulmonary disease, hypertension, hyperlipidemia, sleep apnea, type-I and II diabetes. Cognitive outcomes included BTACT Executive Function and Episodic Memory Composite Z-scores (standardized on age- and education-based normative data), and the presence of physician diagnosed (self-reported) MCI. Concussion history was discretized into five groups: 0, 1-2, 3-5, 6-9, 10+. Linear and logistic regression models were fit to test independent and joint effects of concussion history and CVD burden on cognitive outcomes and odds of MCI. Race (dichotomized as White and Non-white due to sample distribution) was included in models as a covariate.Results:Greater CVD burden (unstandardized beta [standard error]; B=-0.10[0.42], p=.013, and race (B=0.622[0.09], p&lt;.001), were associated with lower executive functioning. Compared to those with 0 prior concussions, no significant differences were observed for those with 1-2, 3-5, 6-9, or 10+ prior concussions (ps &gt;.05). Race (B=0.61[.13], p&lt;.001), but not concussion history or CVD burden, was associated with episodic memory. There was a trend for lower episodic memory scores among those with 10+ prior concussion compared to those with no prior concussions (B=-0.49[.25], p=.052). There were no significant differences in episodic memory among those with 1-2, 3-5, or 6-9 prior concussions compared to those with 0 prior concussions (ps&gt;.05). CVD burden (B=0.35[.13], p=.008), race (greater odds in Non-white group; B=0.82[.29], p=.005), and greater concussion history (higher odds of diagnosis in 10+ group compared to those with 0 prior concussions; B=2.19[0.78], p&lt;.005) were associated with higher odds of MCI diagnosis. Significant interaction effects between concussion history and CVD burden were not observed for any outcome (ps &gt;.05).Conclusions:Lower executive functioning and higher odds of MCI diagnosis were associated with higher CVD burden and race. Very high concussion history (10+) was selectively associated with higher odds of MCI diagnosis. Reduction of these modifiable factors may mitigate adverse outcomes in older contact sport athletes. In former athletes, consideration of CVD burden is particularly pertinent when assessing executive dysfunction, considered to be a common cognitive feature of traumatic encephalopathy syndrome, as designated by the recent diagnostic criteria. Further research should investigate the social and structural determinants contributing to racial disparities in long-term health outcomes within former NFL players.

Non-steroidal mineralocorticoid receptor antagonists in patients with chronic kidney disease and type 2 diabetes.

Chronic kidney disease (CKD) in patients with type 2 diabetes (T2D) is a major health challenge associated with a disproportionately high burden of end-stage renal disease, cardiovascular disease and death. This review summarizes the rationale, clinical evidence and practical implementation for non-steroidal mineralocorticoid receptor antagonists (nsMRAs), a drug class now approved and recommended for patients with T2D and CKD at risk of cardiorenal disease progression. Three nsMRAs (finerenone, esaxerenone and apararenone) have been evaluated but finerenone is currently the only approved nsMRA for this indication. Two large-scale, placebo-controlled, Phase 3 studies evaluated finerenone added to a maximally tolerated dose of an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker. Over >2 years of treatment, finerenone was associated with a significant reduction in composite endpoints of renal and cardiovascular outcomes versus placebo. Esaxerenone or apararenone have both shown significant improvements in albuminuria versus placebo. In general, nsMRAs were well tolerated. Hyperkalaemia was the most notable treatment-related adverse event and could generally be managed through serum potassium monitoring and dose adjustments. The nsMRAs are now an important component of recommended treatment for CKD associated with T2D, providing a significant reduction in the risk of cardiorenal progression beyond what can be achieved with glucose and blood pressure control.