Overall Burden Of Cardiovascular Disease Research Articles

Abstract 11767: Alarmingly Rising Trends in Cardiovascular Disease Risk Factors and Atrial Fibrillation in Young [18-44 Years] Asian Patients: A Nationwide Analysis Between 2016 and 2019

Background: Traditional cardiovascular disease (CVD) risk factors can increase the risk of Atrial Fibrillation (AF) even in young adults. With rising trends in CVD in the Asian population, we aimed to assess the prevalence and disparities of major modifiable risk factors for CVD and AF in the young Asians hospitalized in the US. Methods: The National Inpatient Sample (2016-2019) was used to estimate the temporal trends in modifiable CVD risk factors among young (18-44 years) Asian hospitalizations and evaluated disparities by sex. Also, we assessed the prevalence of AF in young Asians hospitalized with vs. without atleast one CVD risk factor. Results: From 2016 through 2019, a total of 1,324,259 young Asian admissions (Male 85%, age 18-44 years) were analyzed, the highest increase was noted for Obesity (1.8%) followed by Diabetes (1.3%). Males demonstrated the most prominent prevalence of Obesity (2.1%) and Hypertension (1.7%) as compared to the female population (1.7% and 0.4%), respectively. The incidence of AF in patients with at least one CVD risk factor increased by 0.4% (males 0.9% vs females 0.15%), (OR 2.80, 95%CI 2.44-3.21, p<0.001). Conclusion: The prevalence of modifiable risk factors for CVD are increasing at a steady pace in the young Asian population. There is a need for urgent preventive and curative strategies to decrease the overall burden of CVD in this population.

Abstract 013: Metabolomic Profiles And Ideal Cardiovascular Health: Insights From The Framingham Heart Study (fhs)

Introduction: The American Heart Association’s framework “ideal cardiovascular health” (CVH) focuses on modifiable risk factors to reduce the overall burden of cardiovascular disease (CVD). Metabolomics provide important pathobiological insights into risk factors and CVD development. Whether circulating metabolites relate to CVH status and mediate the relations of CVH score with atrial fibrillation (AF) and heart failure (HF) has not been explored. Hypothesis: We hypothesized: a) CVH score associates with metabolites; and b) metabolites mediate the relation of CVH score with incident AF and HF. Methods and Results: We analyzed 3056 adults (mean age 54 years; 54% women) in FHS Offspring Cohort (Exam 5); 2059 participants had metabolomics data. Each metabolite measurement was log transformed and standardized for data normalization. Using linear mixed models, CVH score was associated with 144 metabolites (false discovery rate, q-value < 0.05), adjusting for age, sex, estimated glomerular filtration rate (eGFR) and family structure. Of these 144 metabolites, 65 metabolites overlapped with key cardiometabolic components of the CVH score (body mass index, blood pressure, and fasting blood sugar). In mediation analyses (adjusting for age, sex, eGFR), no metabolites mediated the relation between CVH score and incident AF. However, 11 metabolites (C36:4 phosphatidylcholine, isocitrate, glycerol, ornithine, aminoadipate, 3-indolepropionic acid, cystathionine, asparagine, alpha-hydroxybutyrate, phosphorylated saccharides, and C52:5 triacylglycerol) partially mediated the association between CVH score and incident HF in multivariable-adjusted models. Conclusion: Multiple metabolites associate with the CVH score and many of the metabolites are specifically associated with the cardiometabolic components of the CVH score. Several metabolic signatures, particularly lipids and tricarboxylic acid cycle intermediates, partially mediated the relation between CVH score and incident HF. Our findings lend insight into the role of metabolites in the relations of modifiable cardiovascular risk factors with incident HF.

Differential Role of Circulating microRNAs to Track Progression and Pre-Symptomatic Stage of Chronic Heart Failure: A Pilot Study.

(1)Background: Chronic heart failure (CHF) contributes to the overall burden of cardiovascular disease. Early identification of at-risk individuals may facilitate the targeting of precision therapies. Plasma microRNAs are promising circulating biomarkers for their implications with cardiac pathologies. In this pilot study, we investigate the possible exploitability of circulating micro-RNAs (miRNAs) to track chronic heart failure (CHF) occurrence, and progression from NYHA class I to IV. (2)Methods: We screened 367 microRNAs using TaqMan microRNA Arrays in plasma samples from healthy controls (HC) and CHF NYHA-class I-to-IV patients (5/group). Validation was performed by singleplex assays on 10 HC and 61 CHF subjects. Differences in the expression of validated microRNAs were evaluated through analysis of covariance (ANCOVA). Associations between N-terminal pro-BNP (NT-proBNP), left ventricular end-diastolic volume (LVEDV) or peak oxygen uptake (VO2 peak) and plasma microRNA were assessed by multivariable linear regression analysis. (3)Results: Twelve microRNAs showed higher expression in CHF patients vs. HC. Seven microRNAs were associated with NT-proBNP concentration; of these, miR-423-5p was also an independent predictor of LVEDV. Moreover, miR-499-5p was a predictor of the VO2 peak. Finally, a cluster of 5 miRNAs discriminated New York Heart Association (NYHA) class-I from HC subjects. (4)Conclusions: Our data suggest that circulating miRNAs have the potential to serve as pathophysiology-based markers of HF status and progression, and as indicators of pre-symptomatic individuals.

High-Sensitivity Cardiac Troponin I Levels and Prediction of Heart Failure: Results From the BiomarCaRE Consortium

ObjectivesThe aims of this study were to characterize the association of high-sensitivity cardiac troponin I (hs-cTnI) with heart failure (HF), to determine its predictive value beyond classical cardiovascular risk factors (CVRFs) and N-terminal pro–B-type natriuretic peptide, and to derive a relevant cutoff for potential clinical application. BackgroundHF is an important contributor to the overall burden of cardiovascular disease. Early identification of individuals at risk could be beneficial for preventive therapies. MethodsBased on the Biomarker for Cardiovascular Risk Assessment in Europe consortium, we analyzed individual-level data from 4 prospective population-based cohort studies including 48,455 individuals. Participants with myocardial infarction, HF, and stroke at baseline were excluded. We investigated the value of adding hs-cTnI to CVRFs and N-terminal pro–B-type natriuretic peptide using Cox proportional hazards survival models and for prediction by calculating C-statistics and Brier score. ResultsThe median age of the study population was 51 years, and the median follow-up time for occurrence of HF was 6.61 years. Cox regression models adjusted for age, sex, and CVRFs revealed a significant association of hs-cTnI with incident HF (hazard ratio: 1.42 per log [ng/l] unit change [95% confidence interval: 1.31 to 1.53]). The best predictive value was achieved in the model with CVRFs (base model) and both biomarkers (C-index = 0.862; 95% confidence interval: 0.841 to 0.882). Optimal hs-cTnI cutoff values of 2.6 ng/l for women and 4.2 ng/l for men were derived for selecting individuals at risk. ConclusionsIn this large dataset from the general population, hs-cTnI could show its independence for the prognosis of HF.

P1642High-sensitivity cardiac troponin I and NT-proBNP and their relationship to heart failure in the European BiomarCaRE population

Abstract Aims Heart failure (HF) is an increasingly important contributor to the overall burden of cardiovascular disease in the population. We aimed to determine the distribution of the cardiac biomarkers high-sensitivity cardiac troponin I (hs-cTnI) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentrations across the European population to characterize the association with incident HF. Methods and results Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE)-project, we analysed data of 48,455 individuals from four prospective population-based cohort studies (DanMONICA, FINRISK, Moli-Sani, Northern Sweden MONICA study) across Europe with a maximum follow-up of 27 years. The median age of the participants was 50.7 years (25th percentile: 40.0 years, 75th percentile: 61.7 years) and 49.1% (25,146) were men. Considered endpoints were incident HF and all-cause mortality. The median follow-up time for occurrence of HF was 6.61 (6.55; 6.66) years. We found that cardiovascular risk factors (CVRFs), especially diabetes with HR of 2.11 (95% CI 1.8, 2.5) and smoking status with HR of 1.79 (95% CI 1.59, 2.1) (Figure 1) were associated with incident HF. Furthermore, beyond the CVRFs, elevated hs-cTnI and NT-proBNP concentrations contributed to risk of HF in the general population with HR of 1.49 (95% CI 1.21, 1.9) and HR of 2.37 (95% CI 1.97, 3.0) respectively. As a cut-off value to select individuals, who would benefit most from preventive strategies, a hs-cTnI concentration of 2.8 ng/L was calculated using the optimal cut-off methodology by Contal and O'Quigley in CSDA 1999. Hazard ratio for incident HF Conclusion In our large population-based cohort, hs-cTnI and NT-proBNP were independently associated with incident HF. Use of biomarkers for HF screening thus may help to select those individuals in the general population who would benefit most from preventive strategies. Based on the cut-off value future studies are needed to evaluate therapeutic options.

Haeme oxygenase signalling pathway: implications for cardiovascular disease.

Evidence now points to the haeme oxygenase (HO) pathway as a possible actor in modulating risk for cardiovascular disease (CVD). In particular, the HO pathway may represent a key endogenous modulator of oxidative, inflammatory, and cytotoxic stress while also exhibiting vasoregulatory properties. In this review, we summarize the accumulating experimental and emerging clinical data indicating how activity of the HO pathway and its products may play a role in mechanisms underlying the development of CVD. We also identify gaps in the literature to date and suggest future directions for investigation. Because HO pathway activity can be influenced not only by genetic traits and environmental stimuli but also by a variety of existing pharmacologic interventions, the pathway could serve as a prime target for reducing the overall burden of CVD. Further work is needed to determine the role of HO pathway products as possible prognostic markers of risk for clinical CVD events and the extent to which therapeutic augmentation or inhibition of HO pathway activity could serve to modify CVD risk.

Changing the Conversation Regarding Pediatric Cholesterol Screening

Changing the Conversation Regarding Pediatric Cholesterol Screening

Primary Prevention of Cardiovascular Disease

IN THE 1980S, ROSE COINED THE TERM PREVENTION PARAdox to describe the fact that a large proportion of cardiovascular disease (CVD) events occur among the many individuals with average risk factor values. He distinguished between 2 approaches to CVD prevention. The highrisk strategy, which aims to truncate the upper tail of the normal distribution of risk factors, focuses on individuals who are most likely to benefit personally from preventive treatment. By contrast, the population-based strategy aims to shift the entire risk distribution. At the time, the available lipid-lowering therapies were limited, none was well tolerated, and the risk-benefit profile for clofibrate, for instance, argued against its widespread use. Soon, the high-risk approach came to be synonymous with the use of drugs, and the population approach was identified with efforts to shift norms about diet, physical activity, or smoking. Modest lifestyle changes could be recommended to the population at large because evolutionarily sensible interventions such as a low-salt diet may be “presumed to be safe.” The real-world effects of such recommendations have been limited. Targeting high-risk individuals with preventive drug therapies optimizes the benefits for the individuals concerned but does little to reduce the overall burden of CVD in the population. In the 1990s, evidence emerged documenting the efficacy of a new class of potent low-density lipoprotein (LDL)–cholesterol-lowering agents, the 3-hydroxy-3methylglutaryl coenzyme A reductase inhibitors (statins), first in patients with coronary disease and subsequently in primary prevention. Meta-analyses of large statin trials have demonstrated an approximately 25% relative reduction in risk of CVD events in both primary and secondary prevention populations and in patients with a varying risk factor profile. For this reason, the number needed to treat to prevent 1 CVD event depends largely on the baseline absolute risk. When evidence of the benefits of statins first emerged and the potential for high-volume use was recognized, a strategy was necessary to maximize benefit and to limit any potential harm because of the high initial cost of these agents and the uncertainty about their long-term safety. In the United States, individuals considered for statin therapy were originally identified according to an agreed LDL cholesterol threshold. Because LDL cholesterol does not perform well as a CVD screening test, a threshold based on absolute risk was adopted in the United Kingdom. This absolute risk– based approach reduces the number needed to treat to prevent 1 event and maximizes the health benefits for a given cost. In the United Kingdom, it is now routine for family practitioners to use tables or computer programs based on validated risk equations to estimate individual risk at the point of care. The widely used risk models accurately assign individuals to different categories of risk in such a way that the observed event rates for the risk groups are close to the predicted rates. It is not widely appreciated, however, that risk models fail to efficiently distinguish or discriminate between patients who will or will not experience events. Recent research efforts have therefore focused on new biomarkers and vascular imaging tools to improve discrimination and risk stratification. Of these, C-reactive protein (CRP) has been associated with risk of CVD events, and a US consensus statement suggests a CRP cut point of 3 mg/L may aid the identification of high-risk patients. The fact that mendelian randomization studies suggest that CRP is not a cause of vascular disease is not important for the purpose of prediction. Nevertheless, when assessed with appropriate metrics of predictive performance, a CRP measurement, like LDL cholesterol alone, is a poor discriminator of future CVD events and only marginally enhances risk stratification using established risk factors. Vascular imaging techniques are costly and some involve radiation exposure, which may limit their applicability for primary prevention. New metrics for assessing predictive performance have been advocated based on reclassification. These assess the extent to which the addition of a new marker to an estab-

Upcoming Challenges for Training in Cardiology

The prevalence of cardiovascular disease (CVD) is increasing in industrialised societies and is dramatically progressing in developing countries. The overall burden of CVD results in reduced availability of suitable healthcare facilities. Among the multiple emergencies generated by CVD, there is certainly the threat of a significant shortage of cardiologists. Furthermore, the field of cardiology is adapting to such changes by attempting to provide more specialists and more ‘hyper-specialised’ physicians to face the growing complexity of the clinical management of CVD. Two separate educational plans for specialty schools of cardiology are proposed. The first plan is for trainees who wish to undertake general clinical cardiology, which includes specific educational pathways for clinical, intensivist and preventive cardiology. The second plan is devoted to those willing to specialise in a specific area of the field, including diagnostic and interventional cardiology, or areas that require specific skills. It is fundamental to focus on new training programmes for people willing to get involved in cardiology, paying constant attention to the evolving needs of society in terms of high-quality and cost-effective cardiovascular care. In the future, the challenge for cardiologists will be to assign more patients to a specific and integrated plan of medical care including general management and high-level diagnostics and therapy. This could result in a better and more effective management of the overall burden of CVD, especially through the formation of more skilled healthcare providers.

Diabetes and the metabolic syndrome—When is it best to intervene to prevent?

In addition to microvascular complications, patients with type 2 diabetes are at increased risk of cardiovascular disease (CVD) and mortality. An important initial step in reducing the overall burden of CVD, as well as other diabetes complications, is to prevent progression to diabetes in individuals at risk. A number of studies have indicated the increased presence of both established and emerging cardiovascular risk factors associated with the metabolic syndrome in individuals before the onset of diabetes. First-line therapy in the treatment of the metabolic syndrome risk factors is lifestyle intervention, which can be highly successful in preventing or delaying progression to overt diabetes, but on its own may not achieve and/or maintain adequate risk reduction. In this case, individuals need to be identified and treated with appropriate pharmacological interventions. The data are unequivocal in the importance of the timely identification of at-risk subjects, and implementation of effective treatment strategies, which could potentially reduce diabetes- and CVD-related morbidity and mortality.

Lipoprotein-associated phospholipase A2: a novel marker of cardiovascular risk and potential therapeutic target

Although the clinical benefit of statins is well established, these agents reduce the risk of cardiovascular events by only 20 – 40%, and the residual risk for high-risk patients is considerable. The recognition of atherosclerosis as an inflammatory disease has opened the door to numerous complementary therapeutic approaches to further reduce risk and the overall burden of cardiovascular disease. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a novel inflammatory marker of cardiovascular risk that is being evaluated as a potential therapeutic target. The biological function of this enzyme in atherosclerosis has been controversial but recent evidence supports its pro-atherogenic role. The enzyme is predominantly bound to low-density lipoprotein cholesterol particles in humans, and its activity produces bioactive lipid mediators that promote inflammatory processes present at every stage of atherogenesis, from atheroma initiation to plaque destabilisation and rupture. Initial clinical studies suggest that the inhibitors of Lp-PLA2 can block enzyme activity in plasma and within atherosclerotic plaques. However, more studies are needed to determine the potential clinical benefits of inhibiting Lp-PLA2.

Hypertension curriculum review: epidemiology and the prevention of hypertension.

Hypertension curriculum review: epidemiology and the prevention of hypertension.

Managing dyslipidaemia ? multiple patients and multiple approaches: metabolic syndrome, familial hypercholesterolaemia and hypertension

High risk of coronary heart disease (CHD) events is present in a number of patient populations in addition to those with pre-existing CHD, other atherosclerotic disease or diabetes. Patients with the metabolic syndrome are at increased CHD risk and require attention to low-density lipoprotein cholesterol (LDL-C) lowering in addition to management of hypertriglyceridaemia, low high-density lipoprotein cholesterol and non-lipid risk factors. Patients with hypertension in addition to other cardiovascular risk factors are at increased risk of CHD and have recently been shown to derive marked benefit from statin treatment. Patients with heterozygous familial hypercholesterolaemia, characterised by dramatically raised LDL-C and high risk for early CHD, require large reductions in LDL-C to meet recommended target levels, and newer statins possess the LDL-C-lowering efficacy to bring many of these patients to such goals. Identification of high-risk patients and prompt institution of appropriate management strategies can serve to reduce the overall burden of cardiovascular disease.