Primary Prevention Of Cardiovascular Disease Research Articles

Antihypertensive Medication Category Prescriptions and Blood Pressure Control in African Surinamese and Ghanaian Migrants with Hypertension in Amsterdam, The Netherlands: The HELIUS Study.

West African (WA) migrants in Europe have higher hypertension rates than the host populations. For African migrants, guidelines recommend diuretics and/or calcium channel blockers (CCB) for primary cardiovascular disease prevention, but data on antihypertensive medication (AHM) prescription patterns or related hypertension control rates are lacking. We assessed AHM prescription patterns and its relation to hypertension control among hypertensive WA migrants in the Netherlands compared to the host population. Cross-sectional data from WA or Dutch origin participants from the HELIUS study were used. Participants with treated hypertension and without diabetes, cardiovascular disease, or microalbuminuria were selected. We used logistic and linear regression analyses to assess the association between AHM categories and hypertension control rates (systolic blood pressure (BP) ≤ 140 mmHg and diastolic BP ≤ 90 mmHg) and the systolic BP levels. We compared 999 WA participants and 314 Dutch participants. Hypertension control rates were lower in the WA origin compared to Dutch origin participants (44.3% versus 58.0%, p < 0.001). For WA participants, prescription rates for any AHM category were: CCB (54.8%), diuretics (18.5%) beta-blocking agents (27.3%) and renin-angiotensin system blockers (52.6%). Prescription rates were higher for CCB and similar for diuretics compared to the Dutch participants. Neither CCB nor diuretics were associated with better control rates. Compared to Dutch participants, West African participants had similar diuretic prescriptions but significantly higher prescriptions for CCB. However, neither medications was associated with better hypertension control. Future research should explore physician and patient factors to improve hypertension control.

Cardiovascular disease risk reduction for all-cause mortality benefit in low-risk individuals

Background: Current recommendations for the primary prevention of cardiovascular disease (CVD) are based solely on 10-year CVD risk assessment. However, CVD mortality is not compared with all-cause mortality, which could provide insights into the potential benefits of CVD risk interventions on overall mortality. Methods: CVD risk for average American white and black males and females is calculated using the 2013 American Heart Association equations. CVD death risk is determined by combining CVD risk with the death rate following a CVD diagnosis. This CVD death risk is then compared with all-cause mortality data from National Vital Statistics Reports. A larger ratio indicates that most deaths are attributed to CVD, suggesting that intervention may be more beneficial. Results: The CVD mortality ratio is highest for white men and lowest for black men, indicating that white male likely to benefit most from CVD risk modification, while black males will benefit the least. Additionally, the ratio, and the potential benefit, decreases with age for all groups, especially after the age of 70. Conclusion: For the average U.S. population without a CVD diagnosis, the potential mortality benefit from interventions targeting CVD risk factors varies significantly based on patient characteristics such as race, age, and gender. The potential benefit is greatest for white males and decreases with age for all groups.

A survey of availability and affordability of polypills for primary and secondary prevention of cardiovascular diseases in selected countries

Abstract Background/Introduction The recent inclusion of polypills—fixed-dose combinations of two or more antihypertensive drugs and statin with or without aspirin—in the World Health Organization’s Essential Medicines List (EML) reiterates the potential of this approach to improve global treatment coverage for primary or secondary prevention of cardiovascular diseases (CVDs). Although there exists extensive evidence on efficacy, safety, and acceptability of polypills, there is no research to-date assessing the "real world" availability and affordability of polypills globally. Purpose We conducted a cross-sectional survey of public and private sector facilities in 13 countries from around the world to evaluate the availability and affordability of polypills. Methods In the surveyed countries, we first ascertained whether any polypill was authorized for marketing and/or included in the national EMLs and clinical guidelines. The facility survey employed a modified WHO/Health Action International methodology. In each country, we collected retail and price data for polypills from at least one public sector facility and three private pharmacies using convenience sampling. Polypills were considered unaffordable in a given country if the lowest paid worker spends more than a days’ wage to purchase monthly supply. Results Polypills were approved for marketing in four of the 13 surveyed countries: Spain, India, Mauritius, and Argentina. None of these countries included polypills in national guidelines, formularies, or EMLs. Further, none of the surveyed public pharmacies in any of the four countries stocked any polypills. Among the surveyed private sector facilities, availability ranged from 0% in India (out-of-stock on the survey day but listed for sale) to 100% in Argentina and Spain. In the private sector, we identified seven unique polypill combinations, marketed by eight different companies. Although not in stock, India had a wider range of various combinations (n=5). Many combinations (63%) found in this survey were affordable in the local context, but these were limited to India and Spain. A lowest paid government worker would spend between 0.2 (India)–2.8 (Mauritius) days’ wages to pay the price for one month’s supply of the polypills. Polypills were likely to be affordable in countries that locally manufactured them. Further, two-pill combinations (one antihypertensive and a statin) were stocked by private pharmacies in Argentina, Bangladesh, Cameroon, India, Nepal, and Spain, with affordability ranging from 0.2 (India)–7.1 (Cameroon) days’ wages. Conclusion Low availability and affordability of polypills in both public and private sectors suggest that the implementation and overall uptake of polypills remains poor globally. Context-specific multi-disciplinary health system research is required to understand factors affecting polypill implementation and to design and evaluate appropriate implementation strategies.

The projected global burden of modifiable risk factors on cardiovascular disease from 2025 to 2100

Abstract Background Cardiovascular diseases (CVDs) are the primary cause of global mortality and morbidity. Controlling modifiable risk factors driving the CVD epidemic is a vital focus of primary prevention efforts worldwide. Understanding the epidemiological trends in these risk factors is therefore essential in designing effective countermeasures against CVDs for the years to come. Purpose This study aims to forecast the disability-adjusted life years (DALYs) associated with CVDs attributable to high systolic blood pressure (SBP), high body-mass index (BMI), high fasting plasma glucose (FPG), high low-density lipoprotein (LDL) and tobacco use from 2025 to 2100, stratified by GBD super-regions, sex, sociodemographic index (SDI), and age-groups. Methods Historical data on DALYs from 1990 to 2019 from the Global Burden of Disease (GBD) study was used to project DALYs associated with modifiable risk factors of CVDs from 2025 to 2100. Trends across GBD super-regions, sex, SDI, and age-groups were also examined. Results Between 2025 and 2100, age-standardised DALY rates (ASDR) per 100,000 population are forecasted to fall across all modifiable risk factors, with the greatest decline seen in tobacco use (-76.0%) and high LDL (-66.9%). Globally, high SBP and high BMI expect the greatest ASDR in 2100 (both 891 per 100,000 population), while tobacco use expects the least (213 per 100,000 population). High BMI is expected to rise 623.0% in South Asia and 221.5% in South-east Asia, East Asia and Oceania from 2025 to 2100, while high FPG is expected to rise 114.2% in North Africa and the Middle-east and 110.6% in South Asia. Females are expected to have lower overall and greater reductions in ASDR across all modifiable risk factors when compared to males from 2025 to 2100. Notably, males expect a 11.0% rise in high BMI worldwide across this period. The age-prevalence of modifiable risk factors is expected to be bimodal in 2100, highest in those aged 50-59 as well as 75-84 years old, possibly suggesting improvements in global screening efforts or the earlier development of metabolic dysfunction. All modifiable risk factors are predicted to fall in high and high-middle SDI regions from 2025 to 2100. In contrast, low, low-middle, and middle SDI regions expect a rise in high FPG and high BMI across this same time frame. The burden of modifiable CVD risk factors is expected to be highest in low-middle SDI regions in 2100, as compared to high-middle SDI regions in 2025. Conclusion While the global decline in ASDR of modifiable risk factors suggests overall improvements in the primary prevention of CVDs, regional spikes in high BMI and FPG calls for the implementation of timely, targeted interventions accounting for local trends in CVD. Moreover, the disproportionate metabolic burden expected in lower SDI regions in the coming decades requires concerted, international support to alleviate the global burden of CVDs.

Implications of five different risk models in primary prevention guidelines

Abstract Background A lack of consensus exists across guidelines as to which risk model should be used for the primary prevention of cardiovascular disease (CVD). Purpose The objective of this study was to determine potential improvements in the number needed to treat (NNT) with statins using different risk models in patients eligible for risk stratification. Methods A retrospective observational cohort was assembled from primary care patients in Ontario, Canada between January 1st, 2010, to December 31st, 2014 and followed for up to 5 years. Risk estimation was undertaken in patients 40-75 years of age, without CVD, diabetes, or chronic kidney disease using the Framingham Risk Score (FRS), Pooled Cohort Equations (PCEs), a recalibrated FRS (R-FRS), Systematic Coronary Risk Evaluation 2 (SCORE2), and the low-risk region recalibrated SCORE2 (LR-SCORE2). Results The cohort consisted of 47,399 patients (59% women, mean age 54). The NNT at 5 years with statins was lowest for SCORE2 at 40, followed by LR-SCORE2 at 41, R-FRS at 43, PCEs at 55, and FRS at 65. Models that selected for individuals with a lower NNT recommended statins to fewer, but higher risk patients. For instance, SCORE2 recommended statins to 7.9% of patients (5-year CVD incidence 5.92%). The FRS, however, recommended statins to 34.6% of patients (5-year CVD incidence 4.01%; Figure). Conclusions Newer models such as SCORE2 may improve statin allocation to higher risk groups with a lower NNT.Figure

Association of lipid target achievement and cardiovascular outcomes following statin initiation: a population-based cohort study

Abstract Introduction Non-high density lipoprotein cholesterol (non-HDL-C) is increasingly incorporated into clinical practice guidelines along with low density lipoprotein cholesterol (LDL-C) to guide lipid-lowering therapy decisions. We aimed to examine patterns of LDL-C and non-HDL-C levels after statin initiation for primary prevention of cardiovascular disease (CVD), and their association with incident CV events. Methods We conducted a population-based cohort study of Ontario, Canada residents age ≥66 years who initiated a statin for primary prevention between January 1, 2012 and December 31, 2019. For those surviving 1-year after statin initiation, we determined the proportion with a lipid panel in the 1-year period after a statin was started. For those with a lipid panel, we used the lipid panel closest to the end of the 1-year period to categorize individuals based on the LDL-C and non-HDL-C thresholds in the 2021 Canadian Cardiovascular Society dyslipidemia guidelines (Table 1). We stratified by diabetes/chronic kidney disease (CKD) status. We evaluated the association between LDL-C/non-HDL-C category and a composite of all-cause mortality or hospitalization for myocardial infarction, stroke or revascularization (primary outcome). We also investigated the association between each category and each component of the primary outcome. The index date was the 365 days after a statin was initiated and follow-up was until December 31, 2020. We used a cause-specific hazards model for analysis, adjusted for clinical and sociodemographic confounders. Results Our cohort comprised 173,127 people. In the 1-year period after statin initiation, 72% of people had a follow-up lipid panel performed. Median follow-up after that was 2.5 years. Compared with those meeting both LDL-C and non-HDL-C targets, being above both targets was associated with an increased rate of the primary outcome for people without diabetes/CKD (HR 1.10, 95% CI 1.05 to 1.15) and those with diabetes/CKD (HR 1.16, 95% CI 1.09 to 1.23). Being at LDL-C target but above non-HDL-C target was associated with an increased rate of the primary outcome for people with diabetes/CKD (HR 1.16, 95% CI 1.03 to 1.30) but not for those without diabetes/CKD (HR 1.05, 95% CI 0.93 to 1.17). Conclusions In this population-based cohort, having an LDL-C and non-HDL-C above guideline-recommended targets after statin initiation was associated with an increased rate of adverse outcomes. These findings support the residual risk associated with incompletely controlled LDL-C or non-HDL-C levels after initiating statin therapy for primary prevention.Primary outcome associationsComponents of primary outcome

The role of coronary artery calcium score and european score2 in primary prevention of cardiovascular disease

Abstract Background There is limited evidence about the role of using coronary artery calcium (CAC) score in conjunction with the European SCORE2 (systematic coronary risk evaluation) for the identification of individuals at higher risk of cardiovascular disease. Purpose To evaluate the relationship between CAC score and the European SCORE2 for cardiovascular risk stratification in an asymptomatic population in primary prevention. Methods This is a preliminary analysis from a single-centre, prospective, randomised 1:1, controlled trial assessing the use of CAC score vs standard preventive strategies in asymptomatic individuals undergoing primary cardiovascular prevention. The 10-year risk of cardiovascular events was assessed with either SCORE2 (ages 45-69) or SCORE2-OP (ages 70-89). Subjects were classified as 1) low to moderate risk, 2) high risk, and 3) very high risk according to SCORE2/SCORE2-OP. CAC score was assessed by ECG gated low-dose computed tomography with no contrast administration. A CAC score of zero was considered to reclassify risk one level downward in high or very-high risk patients. CAC score ≥ 100 was used to reclassify risk one level upward in patients with low to moderate risk and a CAC score &amp;gt; 1000 to reclassify risk upward in subjects with high risk. Results A total of 1,252 participants: 627 in the CAC group and 625 in the control group, median age 55 yrs, 25th-75th 50-61 yrs, with availability of SCORE2 and SCORE2-OP were included in this analysis. SCORE2/SCORE 2-OP was similar in the CAC and control groups. Among the subjects in the CAC group, there was a highly significant difference in SCORE2/SCORE 2-OP between participants with CAC score = zero and those with CAC &amp;gt; zero (median 5.6, 25th-75th 3.6-8.55 vs 2.9, 1.8-4.6, p&amp;lt; 0.001) as well as between those with CAC ≥ 100 and those with CAC score &amp;lt; 100 [median 6.8, 25th-75th (10.3-4.5) vs 3.3 (2.0-5.3), p&amp;lt;0.001]. The prevalence of CAC score = zero was 75% in the low to moderate risk group, 47% in the high risk, and 20% in the very high risk, p&amp;lt;0.001. By contrast the prevalence of CAC score ≥ 100 was 7% in the low to moderate risk group, 24% in the high risk, and 45% in the very high risk, p&amp;lt; 0.001. The proportion of patients classified as low to moderate risk group was 72% with CAC score vs 59% without CAC score, high risk 23% with CAC score vs 35% without CAC score, very high risk 5% vs 6% respectively, p&amp;lt;0.001. Using CAC score risk reclassification occurred in 48% downward and 2% upward in originally classified high risk subjects, 7% upward in originally classified low to moderate risk, and 20% downward in originally classified very high risk subjects. Conclusions CAC score may lead to risk reclassification in a substantial proportion of individuals, in particular among those originally classified as high risk by the SCORE2/SCORE2-OP. The cardiovascular risk prediction accuracy of adding CAC score to SCORE2/SCORE2-OP awaits validation at long-term follow-up.

A sex-related analysis on the influence of lipoprotein(a) on primary cardiovascular disease prevention and its interplay with traditional lipid markers: results from a 20-year cohort study

Abstract Introduction Elevated lipoprotein(a) [Lp(a)] levels is an established risk factor mediating cardiovascular disease. Purpose The relationship between Lp(a) and the first fatal/non-fatal CVD incident over a 20-year period in males and females without CVD was assessed. Methods A longitudinal prospective study was conducted during 2002–2022. In 2002, a total of 3,042 CVD-free adults (1,514 males and 1,528 females) were enrolled. A follow-up was carried out after 20 years, in 2022, which included 2,169 participants. Out of these, 1,988 had comprehensive data for the occurrence of CVD. The recommended threshold of 50mg/dL was used to define abnormal Lp(a) status (≥50mg/dL). Results During the 2002-2022 period, 718 (i.e. 36%) of participants had a fatal or non-fatal CVD event. Twenty-year CVD-event rate was 35.8% and 40.0% in participants with normal and abnormal Lp(a) levels, respectively. For every mg/dL increase in Lp(a), the odds of having a CVD event within 20 years increases by approximately 0.36% (Hazard ratio (HR) = 1.0036, 95% confidence interval (CI) 1.001,1.007, p=0.048). When stratified by sex the relationship remained significant only in females (HR= 1.006, 95% confidence interval (CI) 1.001,1.011, p=0.023). In the multivariate analysis, significance was lost after adjusting for low- and high-density lipoprotein (LDL-C, HDL-C) and triglycerides (HR= 1.0017, 95% confidence interval (CI) 0.998,1.005, p=0.348). Conclusion Elevated Lp(a) levels are linked to higher CVD risk, particularly in females. Despite growing efforts to clarify Lp(a) as a risk-predicting marker in CVD, clinical guidelines still require definitive evidence, particularly from a sex-focused perspective.

Scaling up joint efforts to tackle cardiovascular diseases and diabetes in Europe

Abstract JACARDI, a Joint Action on cardiovascular diseases (CVD) and diabetes (DM), aims to support EU countries in reducing the burden of CVD and DM and related risk factors, both at individual and societal levels, while ensuring health systems sustainability and equity. In particular, JACARDI aims to implement best practices and pilot testing of innovative practices throughout the entire patient journey. Commencing by improving health literacy and raising awareness among general and target populations, moving through primary prevention and screening of CVD and DM among high-risk populations, and then address people living with CVD and DM and their health service providers, through the improvement of service paths and (self) management, including through digital tools, and completing the path by supporting and encouraging the labour participation of people living with these diseases. With 21 European countries and 76 partners engaged, JACARDI undertakes 142 pilot projects, promising to advance CVD and DM care for millions across Europe. In particular, through an innovative Work Package on methodology, JACARDI will develop and implement a methodological framework to guide all the pilot projects in the design, preparation, implementation, monitoring, reporting, and assessment processes. This framework will encompass transversal and intersectional aspects, ensuring a harmonized and efficient approach for all JA activities. Through rigorous and multidimensional evaluation, JACARDI aims to uncover new approaches to enhance healthcare systems, grounded in evidence-based practices and current needs, while adopting the lens of equity and sustainability throughout the entire methodological and implementation process.

Effect of a cardiovascular post discharge sms support program on healthcare utilisation - the hearthealth program

Abstract Background Cardiovascular disease (CVD) is a leading cause of mortality worldwide[1]. Targeting modifiable risk factors is key to primary and secondary prevention of CVD but many barriers to good risk factor control exist[2]. SMS message programs have shown to be an efficient modality to deliver information to improve knowledge and risk factor profiles for CVD patients[3]; however, their impact on healthcare utilisation has not been thoroughly examined. The HeartHealth program is a text message post-discharge support program delivered to CVD patients. It comprised regular semi-personalised text messages providing CVD information, advice, and support to patients over a 6-month period. Purpose This study aimed to examine the impact of the Heart Health program on healthcare service utilisation. Methods Patients ≥18 years old who recently attended cardiology clinics or were discharged from a cardiology unit, between April 2020 and April 2022 were invited to the program. We compared healthcare utilisation rates in patients who enrolled into the HeartHealth text program (intervention group) to contemporaneous patients who did not enrol in the program (control group). The primary outcome was the incidence rate of all-cause healthcare utilisation events (composite of ED presentations and/or hospital admissions for any medical cause) in the 6 months post-discharge. The secondary outcomes were incidence rates of CVD events and unplanned CVD events. All analyses were adjusted for demographic and co-morbidity variables. Results 11542 patients were included in analysis (intervention: 4324, control: 7218), mean age 58.8 years, 60.7% were male, and 78.3% with English as their preferred language. HeartHealth Intervention participants had lower rates of the primary outcome of healthcare service events compared to control participants (mean number of events 0.43 intervention vs 0.52 control, adjusted rate ratio [RR], 0.91 [95% CI, 0.83-0.99], p=0.033, Table 1). The intervention was significantly more effective in older patients compared to younger patients (RR, 0.82, [95% CI, 0.72-0.93] in patients aged ≥65 years, compared to patients &amp;lt;65 years, RR, 0.98, [95% CI, 0.87-1.10]; p-value for interaction =0.043, Figure 1). The subset of CVD events and unplanned CVD events were numerically lowering in the intervention group compared to the control, but the risk ratio not statistically significantly different in adjusted models (Table 1). Conclusion This analysis demonstrates that a text message post-discharge support program for CVD patients decreased the need for healthcare service utilisation for all medical causes. Future randomised controlled trials are required to further support these findings.Figure 1:Adjusted interaction analysisTable 1:Adjusted Incidence of events

Pharmacogenomics of CRP response to statins: a GIST consortium study

Abstract Introduction Statins are first line treatments in the primary and secondary prevention of cardiovascular disease. Prior clinical studies have shown that statins act independently of lipid lowering mechanisms to decrease C-reactive protein (CRP), a marker of inflammation. Purpose To elucidate genetic loci associated with CRP response to statins. Methods CRP response was specified as the change from baseline in log CRP after at least 4 weeks of statin therapy. Cohort level Genome-wide Association Studies (GWAS) of this CRP response was performed by linear regression analysis adjusted for baseline CRP, age, sex and BMI covariates using genetic data imputed to 1000 Genomes, testing ~10 million single nucleotide polymorphisms (SNPs) of minor allele frequency (MAF) &amp;gt;2%. Following quality control with EasyQC, a meta-analysis was conducted with METAL to combine GWAS results from six different cohorts of European ancestry (CARDS, FHS, JUPITER, MESA, PARC, PROSPER) within the GIST consortium. 1Mb loci regions were defined, centred +/-500kb around the lead SNP. Conditional analysis was performed using GCTA. Results There were 11,075 statin-treated individuals. The meta-analysis results revealed two loci achieving genome wide significance (P&amp;lt;5e-8): APOE (chr 19) and HNF1A (chr 12) (Figure 1). A signal at the CRP locus was highly suggestive (P=2.3e-7). All three loci are known to be associated with CRP levels in the absence of statin. Conditional analysis did not reveal secondary signals. The most associated variant at the APOE locus was the missense SNP rs429358, which contributes to the APOE E4 haplotype and is a risk locus for both dyslipidaemia and Alzheimer’s dementia. It is a C&amp;gt;T missense variant of MAF 0.12 leading to a R/C amino acid change, more common in African ancestry populations (MAF 0.27), and least common in Asian populations (MAF 0.09). A nominally significant association (P=0.09) for interaction with randomized allocation to statin v. placebo within samples derived from clinical trials supports this pharmacogenetic effect at APOE beyond genetic effects on baseline CRP levels. The most associated variant at the HNF1A locus was the intronic SNP rs11065384, which is in strong LD with the HNF1A missense SNP (rs1169288). The HNF1A locus is associated with diabetes, cholesterol levels, and coronary artery disease. There was no between-study heterogeneity at the top three loci (P&amp;gt;0.1), and forest plots show contribution to these signals from all 6 studies within the meta-analysis (Figure 2 A,B,C). Conclusions APOE and HNF1A are associated with CRP response to statins at the level of genome-wide significance. TheAPOE E4 signal is also known to be associated with LDL-Cholesterol response to statins, whereas the HNF1A locus is identified here for the first time as a pharmacogenetic determinant of statin response. The effect of this interindividual variability in CRP response on non-cardiovascular clinical outcomes should be elucidated.Figure 1Figure 2 A,B,C

Cardioprotective potential of oleuropein, hydroxytyrosol, oleocanthal and their combination: unravelling complementary effects on acute myocardial infarction and metabolic syndrome

Abstract Background/Introduction Clinical studies have established the role of olive products in primary and secondary prevention of cardiovascular (CV) disease, but the single compounds or compound combinations responsible for the protective effects are still under investigation. Purpose We sought to explore and compare the cardioprotective potential of Oleuropein (OL), Hydroxytyrosol (HT), Oleocanthal (OC) and Oleanolic Acid (OA) and three combinational treatments after chronic oral administration in mice subjected to Ischemia/Reperfusion Injury (IRI) in the presence of metabolic syndrome (MS) and verify the effect of combination in a proof-of-concept clinical study in Chronic Coronary Artery Syndrome (CCAS) patients. Methods First, we explored the IRI-limiting potential of 6-weeks daily oral treatment with OL (20.6 mg/kg), HT (5.9 mg/kg), OC (11.6 mg/kg), OA (17.4 mg/kg) or vehicle (DMSO 5%) in healthy C57Bl6 mice. At week 6, myocardial ischemia/reperfusion (30 minutes/2 hours) was induced and infarct size was measured. Next, MS was established by 14 weeks of Western diet and the isolated compounds were administered for the last 6 weeks. At week 14, IRI was surgically induced, and infarct size was determined. Basic MS parameters (fasting blood glucose, plasma cholesterol, body weight and blood pressure) were recorded at baseline, weeks 8 and 14. According to the exerted benefits, three combinational treatments were designed and tested on the MS model of IRI. The underlying cardioprotective mechanism was investigated on the mixture with preponderant CV benefits (OL-HT-OC, Combo 2). ApoE-/- mice fed with Western diet for 12 weeks were treated with Combo 2 orally for the last 4 weeks and aortic atherosclerotic lesion extent was determined to detect possible antiatherosclerotic effects. After multi-organ toxicity evaluation, a Combo 2-based supplement was administered in CCAS patients for evaluation of cardiac function, inflammation and oxidative stress biomarkers. Results OL, OC and OA, but not HT, significantly reduced infarct size in vivo both in healthy and MS mice. OL was the only compound to reduce hyperglycemia, while OA significantly reduced plasma cholesterol. All mixtures (Combo 1: OL-HT-OA, Combo 2: OL-HT-OC, Combo 3: OL-HT-OC-OA) were cardioprotective, but only Combo 2 prevented MS progression by limiting hyperglycemia. Combo 2 protection against IRI was attributed to apoptosis suppression (reduced Bax/BcL-xL ratio) and increased expression of the antioxidant enzymes Superoxide Dismutase and Catalase in the ischemic myocardium. Combo 2 treatment also reduced atherosclerotic lesion extent. In our proof-of-concept clinical study, Combo 2 treatment ameliorated cardiac, vascular and endothelial function in CCAS patients. Conclusions Combinational treatment with OL-HT-OC exerts potent cardioprotective, antihyperglycemic and antiatherosclerotic properties in vivo, with remarkable and clinically translatable CV benefits in high-risk patients.

Synergies between diabetes and hyperhomocysteinaemia: New insights to predict and prevent adverse cardiovascular effects.

To explore the association of hyperhomocysteinaemia (HHcy) and diabetes synergies with cardiovascular events in the adult population of northern China. Data were collected from the Asymptomatic Polyvascular Abnomalities Community study for 2010 to 2019. Serum homocysteine (Hcy) levels were determined by enzyme-linked immunosorbent assay. The participants were categorized into four groups based on their Hcy levels and diabetes status: non-diabetes/non-HHcy, non-diabetes/HHcy, diabetes/non-HHcy and diabetes/HHcy. The composite endpoint consisted of the occurrence of first-ever stroke, myocardial infraction (MI) or all-cause mortality. Cox regression analyses were performed to evaluate the associations of diabetes and HHcy with cardiovascular disease (CVD) events. In total, 5278 participants were eligible (average age 55.1 years, 60% male). Over a follow-up of 9.1 years, 618 events were identified, 202 stroke, 52 MI and 406 all-cause deaths. Compared with the non-diabetes/non-HHcy group, hazard ratios with 95% confidence intervals in the diabetes/HHcy group for stroke, MI, major adverse cardiovascular event (MACE), all-cause death and composite endpoint were 1.85 (1.12-3.04), 1.33 (0.42-4.23), 1.78 (1.13-2.80), 2.24 (1.56-3.23) and 1.97 (1.47-2.65), respectively. Significant interactions between HHcy and diabetes status were found for stroke, MI and MACE (P for interaction = .002, .027 and .044, respectively). In addition, the association of diabetes/HHcy with stroke was modified by age (< 60 and ≥ 60 years; P for interaction = .016). The findings highlight the synergistic impact of diabetes and HHcy on CVD. Joint assessments of diabetes and Hcy levels should be emphasized for risk stratification and primary prevention of CVD.

Optimal risk thresholds for prescribing statins as primary prevention of cardiovascular disease in Iranian general population: a benefit-harm modelling study

PurposeThe use of statins for the primary prevention of cardiovascular diseases (CVD) is associated with various beneficial outcomes, alongside certain undesirable effects. This study aims to determine optimal risk thresholds above which statin therapy yields a net benefit, considering both the positive effects and potential adverse effects, as well as their probabilities and patient preferences.MethodsQuantitative benefit-harm balance modeling was applied to the Iranian general population aged 40 to 75 years with no history of CVD. The analysis utilized data from prior studies, including statin effect estimates for different outcomes from a meta-analysis, patient preferences obtained from an Iranian survey, and baseline incidence rates of adverse outcomes sourced from the Global Burden of Disease study for Iran. Outcomes were defined as angina, myocardial infarction, fatal coronary heart disease, fatal or non-fatal stroke, and heart failure. Benefit-harm balance indices were calculated for various combinations of age, sex, and 10-year CVD risk.ResultsStatin therapy was found to be advantageous at a lower 10-year CVD risk threshold in men (18–23%) compared to women (24–28%). Furthermore, individuals aged 40–45 years exhibited a lower risk threshold (18% in men, 24% in women) than those aged 70–75 years (23% in men, 28% in women).ConclusionThe desirable 10-year risk thresholds for statin prescription in the primary prevention of CVD vary by age and gender, ranging from 18 to 28%, encompassing a spectrum of outcomes from angina to CVD mortality. These results suggest hard-CVD risk thresholds of 7.5% to 10% for both sexes.

A Saudi Heart Association Position Statement on Obesity and Cardiovascular Disease.

The obesity pandemic is a major public health concern in Saudi Arabia, with significant impact on cardiovascular disease (CVD). This position statement aims to provide an overview of available evidence as well as the recommendations of the Saudi Heart Association on the management of obesity associated with CVD. Under the auspices of the Saudi Heart Association, a multidisciplinary expert panel comprised of cardiologists and endocrinologists discussed available evidence and provided recommendations on the management of obesity in CVD. The expert panel discussions occurred between September of 2023 and May of 2024 and also took into consideration local expertise in addition to published data in the management of obesity and CVD in the Kingdom of Saudi Arabia. The expert panel explored studies on obesity and its implication on CVD assessment modalities, while also examining the efficacy and cardiovascular safety of available interventions for weight reduction. The association between obesity and CVD is undeniable. The treatment of obesity, be it through lifestyle changes, pharmacological therapy or surgery, is an effective strategy for both weight loss as well as the primary and secondary prevention of CVD. The Saudi Heart Association position statement thus provides guidance and recommendations for the management of obesity/overweight and CVD in Saudi Arabia. This position statement is expected to contribute towards obesity and CVD prevention efforts in Saudi Arabia by promoting adequate and time-appropriate treatment of these conditions.

Association between colchicine use and adverse cardiovascular events in patients with gout: a nationwide nested case-control study.

The association between colchicine use and the primary prevention of atherosclerotic cardiovascular disease (ASCVD) remains unknown. This study aimed to explore the association between colchicine use and new development of ASCVD and ASCVD-related mortality in patients with incident gout. This nested case-control study utilized the nation-wide claims database of the Korean National Health Insurance System. Patients without a history of ASCVD who developed incident gout and were newly started on allopurinol as first-line therapy between 2011 and 2016 were initially screened. Individuals who experienced ASCVD event or ASCVD-related mortality during the follow-up period were matched with four controls for age, sex, income, residential area, co-morbidities, and medications. The main exposure was colchicine use, assessed by 1) the cumulative defined daily doses (cDDDs) and 2) the cumulative duration. For secondary analyses, the risk of ASCVD events and ASCVD-related mortality were examined, separately. Overall, 9,346 patients with ASCVD event or ASCVD-related mortality were matched with 35 070 controls. The patient population was predominantly male. Compared with non-users, a curvilinear relationship between higher cDDDs of colchicine and the odds of ASCVD event was observed; the odds ratios (95% confidence interval) were were 1.09 (1.04-1.15) for <90 cDDDs, 1.20 (1.07-1.33) for 80-179 cDDDs, and 1.21 (1.09-1.35) for ≥180 cDDDs. This association was similarly observed for ASCVD events and ASCVD-related mortality, respectively. Colchicine use was associated with an increased risk of ASCVD in patients with newly diagnosed gout who did not have a prior history of ASCVD.

8746 Primary Prevention and Early Intervention for Cardiovascular Disease in Polyglandular Autoimmune Syndrome Type 2

Abstract Disclosure: V.N. Flores-Robles: None. Y. Fuentes-Rosa: None. M. Sanchez-Cordero: None. D.A. Lopez: None. M. Carrero-Quinones: None. Introduction: Polyglandular autoimmune syndrome type 2 (PAS-2) is an autoimmune syndrome that is known for lymphocytic infiltration causing organ-specific damage. It can include primary adrenal insufficiency (Addison's disease), type 1 diabetes mellitus (T1DM), autoimmune thyroid disease-causing Grave’s disease, or hypothyroidism, and can be diagnosed when two out of these three pathologies are present. Carpenter syndrome, a type of PAS-2, is described as the triad of Addison's disease, autoimmune thyroid disease, and T1DM. Its initial manifestation can be associated with non-endocrine and endocrine disorders as in autoimmune thyroid disease, T1DM, primary hypogonadism, and diabetes insipidus. It is well documented that uncontrolled diabetes mellitus can accelerate the progression of cardiovascular disease of co-existing coronary artery disease, but documentation that Addison’s disease may accelerate the progression is scant with only ten cases documented. On the other hand, there are no documented cases of the presence of coronary artery disease in patients with PAS-2. Case report: This case involves a 66-year-old Hispanic male with a past medical history of hypertension, and PAS-2, presenting with Addison’s disease, type 1 diabetes mellitus, and hypothyroidism. The initial presentation at the hospital was that of a complete atrioventricular block that required pacemaker placement. Cardiology services were consulted as the patient also had a positive stress test and eventually cardiac catheterization was done as further workup. Cardiac catheterization showed obstruction of the left main coronary artery of 80% and left circumflex with mild disease, that required coronary artery bypass (CABG). A 2D ECHO was done for further evaluation of cardiac function and findings were pertinent for an ejection fraction of 65-70%, mild concentric hypertrophy of the left ventricular wall, and left ventricular diastolic function with impaired relaxation pattern. The patient underwent the CABG procedure without any complications. He has been followed up outpatient and remains without any symptoms or pertinent presentation. Early intervention in this patient with PAS-2 prevented any further cardiovascular complications. Conclusion: Patients with PAS-2 may have a predisposition to developing coronary artery disease due to concomitant endocrinopathies that independently increase the risk of cardiovascular disease. This promotes further investigation into the primary prevention of cardiovascular disease in patients presenting with PAS-2. Taking into consideration the increased risk and/or progression of cardiovascular disease in these patients, early intervention and evaluation by cardiology services should be suggested as it may decrease their morbidity or mortality. Presentation: 6/2/2024

12369 Clinical Experience With Inclisiran At An Academic Center

Abstract Disclosure: L. Chavez Marin: None. M. Gonzalez: None. M.F. Linton: None. B.G. Carranza Leon: None. Background: Inclisiran, a small interfering RNA (siRNA) molecule designed to inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9), is the only siRNA approved for management of elevated low-density lipoprotein cholesterol (LDL-C) in both primary (for patients with familial hypercholesterolemia) and secondary prevention of cardiovascular disease. In clinical trials, Inclisiran has been shown to reduce LDL-C by more than 50% in populations at high cardiovascular risk. However, real world data about its tolerability and efficacy is still limited. Methods: We conducted an electronic medical record search to identify subjects who were prescribed Inclisiran at a lipid clinic within Vanderbilt University Medical Center (Nashville, USA). Subjects were included if they received at least one dose of Inclisiran and had pre- and post- LDL-C levels. Subjects taking other LDL-C lowering medications like statins, ezetimibe, bempedoic acid, and PCSK-9 inhibitors were included. Pre- and post- LDL-C averages were calculated and analyzed with 95% confidence intervals. The reasons for medication discontinuation were also examined. Results: Out of 69 subjects identified, only 19 met criteria for inclusion, while 32 never received a dose due to cost burden and insurance denial. The other 18 subjects were not included due to inadequate lab results at the time of data collection. In subjects who received at least one dose of Inclisiran, average pre-LDL-C was 142 mg/dL [CI: 34.7] while post-LDL-C was 77 mg/dL [CI: 24.0], notable for a 46% decrease in LDL-C levels. These subjects were also receiving another lipid lowering agent, like a statin, or had previously used a monoclonal antibody-PCSK-9 inhibitor. Those without prior use of PCSK-9 inhibitors were also analyzed. Average pre-LDL-C was 109.5 mg/dL [CI: 15.8] while post-LDL-C was 39.8 mg/dL [CI: 17.2], which revealed a 64% decrease in LDL-C levels. The main reason for discontinuation of Inclisiran was insurance denial followed by individual preference. Only one subject discontinued Inclisiran due to experiencing a generalized rash. Conclusions: Inclisiran is an effective and overall well-tolerated medication indicated for the management of elevated LDL cholesterol. Our study revealed that for individuals with above goal LDL-C, despite maximum tolerated therapy with a statin, additional LDL-C lowering benefits can be seen with Inclisiran use. However, insurance approval and cost burden seem to be the main barriers for access. Presentation: 6/3/2024

6550 National Statin Prescription Trends in Patients With Breast Cancer and Diabetes for Primary Cardiovascular Disease Prevention

Abstract Disclosure: A.B. Yang: None. G. Mhango: None. C. Kong: None. J.J. Lin: None. J.P. Wisnivesky: Consulting Fee; Self; Sanofi, Banook, PPD. Grant Recipient; Self; Sanofi, Regeneron Pharmaceuticals, Axella, Arnold Consultants. A. Leiter: None. Background: Cardiovascular disease (CVD) is the leading cause of death in older early-stage breast cancer (BC) survivors. Due to cardiotoxic BC treatments such as chemotherapy and radiation, patients with BC and diabetes (DM) are at increased risk of CVD. In patients with BC and DM, statins decrease CVD mortality. Since 2013, many clinical guidelines broadened statin indications for primary CVD prevention in patients with DM, making &amp;gt;85% of patients eligible. Little is known about statin prescription (Rx) patterns in older BC survivors with DM, a group at high risk of CVD. Hypothesis: We hypothesized that statin Rxs increased over time, but were less likely in BC survivors with more advanced locoregional BC and lower comorbidity burden. Methods: A population-based, retrospective cohort study was conducted using Surveillance, Epidemiology and End Results (SEER) cancer registry data linked to Medicare claims. We identified women with preexisting DM who were diagnosed with stage 0-III primary BC between 2008-17. We excluded patients with prior CVD who died &amp;lt;1 year after BC diagnosis. Statin Rx (atorvastatin, pravastatin, rosuvastatin, simvastatin, fluvastatin, lovastatin) was defined as ≥1 statin pharmacy claim &amp;lt;1 year after BC diagnosis. Comorbidity burden was assessed with a modified Charlson Comorbidity Index (CCI). We compared patient demographic and clinical characteristics by statin Rx status using the chi-square test. Using a multivariate logistic regression adjusting for age, race, CCI, BC stage, and diagnosis year, independent predictors of statin Rx were identified. Results: Of 8,423 BC patients with pre-existing DM, 5,698 (68%) had a statin Rx. Statin Rx increased over time (BC diagnosis year 2008-10: 66%, 2011-13: 66%, 2014-15: 69%, 2016-17: 70%; p=0.01) and differed by age (66-69: 66%, 70-74: 70%, 75-79: 69%, ≥80: 65%; p&amp;lt;0.01) and race (White: 68%, Black: 62%, Latinx: 66%, Other: 72%; p&amp;lt;0.01). Statin Rx did not differ by comorbidity burden (CCI 0: 68%, 1-2: 67%, ≥3: 67%; p=0.87) and declined with higher BC stage (0: 73%, I: 70%, II: 65%, III: 63%; p&amp;lt;0.01). In adjusted analyses, more recent BC diagnosis (2016-17 vs. 2008-10: odds ratio [OR]: 1.19, 95% confidence interval [CI]: 1.04-1.38), age group (70-74 vs. 66-69: OR: 1.24, 95% CI: 1.09-1.41), race (Black vs. White: OR 0.77, 95% CI: 0.66-0.89) and higher BC stages (II vs. 0: OR: 0.76, 95% CI: 0.58-1.00; III vs. 0: OR: 0.72, 95% CI: 0.54-0.97) remained predictors of statin Rx. Conclusions: In a nationally representative cohort analysis of older early-stage BC patients, statin Rx increased between 2008-17 and varied by age, race, and BC stage. Elucidating gaps in statin Rx can potentially improve guideline-concordant Rx in a group at high risk for CVD and reduce disparities. Presentation: 6/2/2024

Predicting the risk of coronary artery calcium progression in the general population: insights from the MESA and CARDIA studies

AIMCoronary artery calcium (CAC) progression is a strong predictor of cardiovascular disease. This study aims to develop and validate a practical tool for predicting individual CAC progression in the general population. METHODSData were utilized from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, comprising 5486 participants (47.3% male, mean ± SD age: 61.9 ± 10.2 years), who were randomly assigned to either a training set or an internal validation set at a 7:3 ratio. Additionally, a separate cohort of 2447 participants (44.6% male, mean ± SD age: 40.4 ± 3.5 years) from the Coronary Artery Risk Development in Young Adults (CARDIA) study served as the external validation set. A nomogram was developed based on a Cox regression model incorporating 10 variables selected by the least absolute shrinkage and selection operator (LASSO) method to predict CAC progression. RESULTSFrom the 61 features considered, 10 key variables were identified: age, male sex, smoking status, waist circumference, systolic blood pressure, fasting glucose, lipid abnormalities, and the use of antihypertensive, glucose-lowering, and lipid-lowering medications. The nomogram demonstrated good discrimination, with a C-statistic of 0.682 (95% CI, 0.665–0.699) in the training set and 0.750 (95% CI, 0.729–0.771) in the external validation set. Decision curve analysis further confirmed the nomogram’s clinical utility in predicting the risk of CAC progression. CONCLUSIONOur nomogram offers a practical tool for individualized prediction of CAC progression, potentially aiding in the primary prevention of cardiovascular disease in clinical practice. Registration URLhttps://www.clinicaltrials.gov; Unique identifier: NCT00005130 (CARDIA), NCT00005487 (MESA)