2024 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.

BACKGROUND: The American Heart Association (AHA), in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, nutrition, sleep, and obesity) and health factors (cholesterol, blood pressure, glucose control, and metabolic syndrome) that contribute to cardiovascular health. The AHA Heart Disease and Stroke Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, brain health, complications of pregnancy, kidney disease, congenital heart disease, rhythm disorders, sudden cardiac arrest, subclinical atherosclerosis, coronary heart disease, cardiomyopathy, heart failure, valvular disease, venous thromboembolism, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The AHA, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States and globally to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2024 AHA Statistical Update is the product of a full year's worth of effort in 2023 by dedicated volunteer clinicians and scientists, committed government professionals, and AHA staff members. The AHA strives to further understand and help heal health problems inflicted by structural racism, a public health crisis that can significantly damage physical and mental health and perpetuate disparities in access to health care, education, income, housing, and several other factors vital to healthy lives. This year's edition includes additional global data, as well as data on the monitoring and benefits of cardiovascular health in the population, with an enhanced focus on health equity across several key domains. RESULTS: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Outcomes of latent rheumatic heart disease: External validation of a simplified score in patients with and without secondary prophylaxis.

BACKGROUND: Secondary antibiotic prophylaxis reduces progression of latent rheumatic heart disease (RHD) but not all children benefit. Improved risk stratification could refine recommendations following positive screening. We aimed to evaluate the performance of a previously developed echocardiographic risk score to predict mid-term outcomes among children with latent RHD. METHODS: We included children who completed the GOAL, a randomized trial of secondary antibiotic prophylaxis among children with latent RHD in Uganda. Outcomes were determined by a 4-member adjudication panel. We applied the point-based score, consisting of 5 variables (mitral valve (MV) anterior leaflet thickening (3 points), MV excessive leaflet tip motion (3 points), MV regurgitation jet length ≥ 2 cm (6 points), aortic valve focal thickening (4 points) and any aortic regurgitation (5 points)), to panel results. Unfavorable outcome was defined as progression of diagnostic category (borderline to definite, mild definite to moderate/severe definite), worsening valve involvement or remaining with mild definite RHD. RESULTS: 799 patients (625 borderline and 174 definite RHD) were included, with median follow-up of 24 months. At total 116 patients (14.5%) had unfavorable outcome per study criteria, 57.8% not under prophylaxis. The score was strongly associated with unfavorable outcome (HR = 1.26, 95% CI 1.16-1.37, p < 0.001). Unfavorable outcome rates in low (≤6 points), intermediate (7-9 points) and high-risk (≥10 points) children at follow-up were 11.8%, 30.4%, and 42.2%, (p < 0.001) respectively (C-statistic = 0.64 (95% CI 0.59-0.69)). CONCLUSIONS: The simple risk score provided an accurate prediction of RHD status at 2-years, showing a good performance in a population with milder RHD phenotypes.

Heart Disease and Stroke Statistics-2023 Update: A Report From the American Heart Association.

BACKGROUND: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The American Heart Association, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2023 Statistical Update is the product of a full year's worth of effort in 2022 by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. The American Heart Association strives to further understand and help heal health problems inflicted by structural racism, a public health crisis that can significantly damage physical and mental health and perpetuate disparities in access to health care, education, income, housing, and several other factors vital to healthy lives. This year's edition includes additional COVID-19 (coronavirus disease 2019) publications, as well as data on the monitoring and benefits of cardiovascular health in the population, with an enhanced focus on health equity across several key domains. RESULTS: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Reasons for disagreement between screening and standard echocardiography in primary care: data from the PROVAR + study : Disagreement between screening and standard echo.

We aimed to evaluate the reasons for disagreement between screening echocardiography (echo), acquired by nonexperts, and standard echo in the Brazilian primary care (PC). Over 20 months, 22 PC workers were trained on simplified handheld (GE VSCAN) echo protocols. Screening groups, consisting of patients aged 17-20, 35-40 and 60-65 years, and patients referred for clinical indications underwent focused echo. Studies were remotelyinterpreted in US and Brazil, and those diagnosed with major or severe HD were referred for standard echoperformed by an expert. Major HD was defined as moderate to severe valve disease, ventriculardysfunction/hypertrophy, pericardial effusion or wall-motion abnormalities. A random sample of exams wasselected for evaluation of variables accounting for disagreement. A sample of 768 patients was analyzed, 651(85%) in the referred group. Quality issues were reported in 5.8%, and the random Kappa for major HD between screening and standard echo was 0.51. The most frequent reasons for disagreement were: overestimation of mitral regurgitation (MR) (17.9%, N=138), left ventricular (LV) dysfunction (15.7%, N=121), aortic regurgitation (AR) (15.2%, N=117), LV hypertrophy (13.5%, N=104) and tricuspid regurgitation (12.7%, N=98). Misdiagnosis of mitral and aortic morphological abnormalities was observed in 12.4% and 3.0%, and underestimation of AR and MR occurred in 4.6% and 11.1%. Among 257 patients with suspected mild/moderate MR, 129 were reclassified to normal. In conclusion, although screening echo with task-shifting in PC is a promising tool in low-income areas, estimation of valve regurgitation and LV function and size account for considerable disagreement with standard exams.

Standardization of Epidemiological Surveillance of Acute Rheumatic Fever.

Acute rheumatic fever (ARF) is a multiorgan inflammatory disorder that results from the body's autoimmune response to pharyngitis or a skin infection caused by Streptococcus pyogenes (Strep A). Acute rheumatic fever mainly affects those in low- and middle-income nations, as well as in indigenous populations in wealthy nations, where initial Strep A infections may go undetected. A single episode of ARF puts a person at increased risk of developing long-term cardiac damage known as rheumatic heart disease. We present case definitions for both definite and possible ARF, including initial and recurrent episodes, according to the 2015 Jones Criteria, and we discuss current tests available to aid in the diagnosis. We outline the considerations specific to ARF surveillance methodology, including discussion on where and how to conduct active or passive surveillance (eg, early childhood centers/schools, households, primary healthcare, administrative database review), participant eligibility, and the surveillance population. Additional considerations for ARF surveillance, including implications for secondary prophylaxis and follow-up, ARF registers, community engagement, and the impact of surveillance, are addressed. Finally, the core elements of case report forms for ARF, monitoring and audit requirements, quality control and assurance, and the ethics of conducting surveillance are discussed.

Modelling study of the ability to diagnose acute rheumatic fever at different levels of the Ugandan healthcare system.

OBJECTIVE: To determine the ability to accurately diagnose acute rheumatic fever (ARF) given the resources available at three levels of the Ugandan healthcare system. METHODS: Using data obtained from a large epidemiological database on ARF conducted in three districts of Uganda, we selected variables that might positively or negatively predict rheumatic fever based on diagnostic capacity at three levels/tiers of the Ugandan healthcare system. Variables were put into three statistical models that were built sequentially. Multiple logistic regression was used to estimate ORs and 95% CI of predictors of ARF. Performance of the models was determined using Akaike information criterion, adjusted R2, concordance C statistic, Brier score and adequacy index. RESULTS: A model with clinical predictor variables available at a lower-level health centre (tier 1) predicted ARF with an optimism corrected area under the curve (AUC) (c-statistic) of 0.69. Adding tests available at the district level (tier 2, ECG, complete blood count and malaria testing) increased the AUC to 0.76. A model that additionally included diagnostic tests available at the national referral hospital (tier 3, echocardiography, anti-streptolysin O titres, erythrocyte sedimentation rate/C-reactive protein) had the best performance with an AUC of 0.91. CONCLUSIONS: Reducing the burden of rheumatic heart disease in low and middle-income countries requires overcoming challenges of ARF diagnosis. Ensuring that possible cases can be evaluated using electrocardiography and relatively simple blood tests will improve diagnostic accuracy somewhat, but access to echocardiography and tests to confirm recent streptococcal infection will have the greatest impact.

Investigation of the Familial Risk of Rheumatic Heart Disease with Systematic Echocardiographic Screening: Data from the PROVAR+ Family Study.

We aimed to use echocardiographic (echo) screening to evaluate the risk of Rheumatic Heart Disease (RHD) among the relatives of patients with advanced RHD, who were enrolled in the University Hospital's outpatient clinics from February 2020 to September 2021. Consenting first-degree relatives were invited for echo screening using handheld devices (GE VSCAN) by non-physicians, with remote interpretation. Matched controls (spouses, neighbors) living in the same household were enrolled in a 1:5 fashion. A standard echo (GE Vivid-IQ) was scheduled if abnormalities were observed. In 16 months, 226 relatives and 47 controls of 121 patients were screened, including 129 children, 77 siblings and 20 parents. The mean age was 40 ± 17 years, 67% of the patients were women, and 239 (88%) lived with the index case for >10 years. Echo findings suggestive of RHD were confirmed in zero controls and 14 (7.5%) relatives (p = 0.05): 11 patients had mild/moderate mitral regurgitation, and four were associated with mitral stenosis and abnormal morphology. Two patients had mild aortic regurgitation and abnormal morphology, which were associated with mild aortic and mitral stenosis, and two patients with advanced RHD had bioprostheses in the mitral (2) and aortic (1) positions. In conclusion, first-degree relatives of individuals with clinical RHD are at greater risk of having RHD, on top of socioeconomic conditions.

Penicillin Reactions in Patients With Severe Rheumatic Heart Disease: A Presidential Advisory From the American Heart Association.

Secondary antibiotic prophylaxis with regular intramuscular benzathine penicillin G (BPG) is the cornerstone of rheumatic heart disease management. However, there is a growing body of evidence that patients with rheumatic heart disease who have severe valvular heart disease with or without reduced ventricular function may be dying from cardiovascular compromise following BPG injections. This advisory responds to these concerns and is intended to: (1) raise awareness, (2) provide risk stratification, and (3) provide strategies for risk reduction. Based on available evidence and expert opinion, we have divided patients into low- and elevated-risk groups, based on symptoms and the severity of underlying heart disease. Patients with elevated risk include those with severe mitral stenosis, aortic stenosis, and aortic insuffiency; those with decreased left ventricular systolic dysfunction; and those with no symptoms. For these patients, we believe the risk of adverse reaction to BPG, specifically cardiovascular compromise, may outweigh its theoretical benefit. For patients with elevated risk, we newly advise that oral prophylaxis should be strongly considered. In addition, we advocate for a multifaceted strategy for vasovagal risk reduction in all patients with rheumatic heart disease receiving BPG. As current guidelines recommend, all low-risk patients without a history of penicillin allergy or anaphylaxis should continue to be prescribed BPG for secondary antibiotic prophylaxis. We publish this advisory in the hopes of saving lives and avoiding events that can have devastating effects on patient and clinician confidence in BPG.

Heart Disease and Stroke Statistics-2022 Update: A Report From the American Heart Association.

BACKGROUND: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2022 Statistical Update is the product of a full year's worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year's edition includes data on the monitoring and benefits of cardiovascular health in the population and an enhanced focus on social determinants of health, adverse pregnancy outcomes, vascular contributions to brain health, and the global burden of cardiovascular disease and healthy life expectancy. RESULTS: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Clinical Outcomes, Echocardiographic Findings, and Care Quality Metrics for People Living With Human Immunodeficiency Virus (HIV) and Rheumatic Heart Disease in Uganda.

BACKGROUND: Rheumatic heart disease (RHD) affects 41 million people worldwide, mostly in low- and middle-income countries, where it is co-endemic with human immunodeficiency virus (HIV). HIV is also a chronic inflammatory disorder associated with cardiovascular complications, yet the epidemiology of patients affected by both diseases is poorly understood. METHODS: Utilizing the Uganda National RHD Registry, we described the echocardiographic findings, clinical characteristics, medication prescription rates, and outcomes of all 73 people carrying concurrent diagnoses of HIV and RHD between 2009 and 2018. These individuals were compared to an age- and sex-matched cohort of 365 subjects with RHD only. RESULTS: The median age of the HIV-RHD group was 36 years (interquartile range [IQR] 15), and 86% were women. The HIV-RHD cohort had higher rates of prior stroke/transient ischemic attack (12% vs 5%, P = .02) than the RHD-only group, with this association persisting following multivariable adjustment (odds ratio [OR] 3.08, P = .03). Prevalence of other comorbidities, echocardiographic findings, prophylactic penicillin prescription rates, retention in clinical care, and mortality were similar between the 2 groups. CONCLUSIONS: Patients living with RHD and HIV in Uganda are a relatively young, predominantly female group. Although RHD-HIV comorbid individuals have higher rates of stroke, their similar all-cause mortality and RHD care quality metrics (such as retention in care) compared to those with RHD alone suggest rheumatic heart disease defines their clinical outcome more than HIV does. We believe this study to be one of the first reports of the epidemiologic profile and longitudinal outcomes of patients who carry diagnoses of both conditions.

The Global Impact of Rheumatic Heart Disease.

PURPOSE OF REVIEW: Rheumatic heart disease (RHD) is a neglected disease of poverty, which presents challenges for patients, communities, and health systems. These effects are magnified in low resource countries, which bear the highest disease burden. When considering the impact of RHD, it is imperative that we widen our lens in order to better understand how RHD impacts the over 40 million people currently living with this preventable condition and their communities. We aimed to perform an updated literature review on the global impact of RHD, examining a broad range of aspects from disease burden to impact on healthcare system to socioeconomic implications. RECENT FINDINGS: RHD accounts for 1.6% of all cardiovascular deaths, resulting in 306,000 deaths yearly, with a much higher contribution in low- and middle-income countries, where 82% of the deaths occurred in 2015. RHD can result in severe health adverse outcomes, markedly heart failure, arrhythmias, stroke and embolisms, and ultimately premature death. Thus, preventive, diagnostic and therapeutic interventions are required, although insufficiently available in undersourced settings. As examples, anticoagulation management is poor in endemic regions - and novel oral anticoagulants cannot be recommended - and less than 15% of those in need have access to interventional procedures and valve replacement in Africa. RHD global impact remains high and unequally distributed, with a marked impact on lower resourced populations. This preventable disease negatively affects not only patients, but also the societies and health systems within which they live, presenting broad challenges and high costs along the pathway of prevention, diagnosis, and management.

Outcomes of Echocardiography-Detected Rheumatic Heart Disease: Validating a Simplified Score in Cohorts From Different Countries.

Background The natural history of latent rheumatic heart disease (RHD) detected by echocardiography remains unclear. We aimed to assess the accuracy of a simplified score based on the 2012 World Heart Federation criteria in predicting mid-term RHD echocardiography outcomes in children from 4 different countries. Methods and Results Patient-level baseline and follow-up data of children with latent RHD from 4 countries (Australia, n=62; Brazil, n=197; Malawi, n=40; New Zealand, n=94) were combined. A simplified echocardiographic scoring system previously developed from Brazilian and Ugandan cohorts, consisting of 5 point-based variables with respective weights, was applied: mitral valveanterior leaflet thickening (weight=3), excessive leaflettip motion (3), regurgitation jet length ≥2 cm (6), aortic valvefocal thickening (4), and any regurgitation (5). Unfavorable outcome was defined as worsening diagnostic category, persistent definite RHD or development/worsening of valve regurgitation/stenosis. The score model was updated using methods for recalibration. 393 patients (314 borderline, 79 definite RHD) with median follow-up of 36 (interquartile range, 25-48) months were included. Median age was 14 (interquartile range, 11-16) years and secondary prophylaxis was prescribed to 16%. The echocardiographic score model applied to this external population showed significant association with unfavorable outcome (hazard ratio, 1.10; 95% CI, 1.04-1.16; P=0.001). Unfavorable outcome rates in low (≤5 points), intermediate (6-9), and high-risk (≥10) children at 3-year follow-up were 14.3%, 20.8%, and 38.5% respectively (P<0.001). The updated score model showed good performance in predicting unfavorable outcome. Conclusions The echocardiographic score model for predicting RHD outcome was updated and validated for different latent RHD populations. It has potential utility in the clinical and screening setting for risk stratification of latent RHD.

Household Economic Consequences of Rheumatic Heart Disease in Uganda.

Background: Rheumatic heart disease (RHD) has declined dramatically in wealthier countries in the past three decades, but it remains endemic in many lower-resourced regions and can have significant costs to households. The objective of this study was to quantify the economic burden of RHD among Ugandans affected by RHD. Methods: This was a cross-sectional cost-of-illness study that randomly sampled 87 participants and their households from the Uganda National RHD registry between December 2018 and February 2020. Using a standardized survey instrument, we asked participants and household members about outpatient and inpatient RHD costs and financial coping mechanisms incurred over the past 12 months. We used descriptive statistics to analyze levels and distributions of costs and the frequency of coping strategies. Multivariate Poisson regression models were used to assess relationships between socioeconomic characteristics and utilization of financial coping mechanisms. Results: Most participants were young or women, demonstrating a wide variation in socioeconomic status. Outpatient and inpatient costs were primarily driven by transportation, medications, and laboratory tests, with overall RHD direct and indirect costs of $78 per person-year. Between 20 and 35 percent of households experienced catastrophic healthcare expenditure, with participants in the Northern and Western Regions 5-10 times more likely to experience such hardship and utilize financial coping mechanisms than counterparts in the Central Region, a wealthier area. Increases in total RHD costs were positively correlated with increasing use of coping behaviors. Conclusion: Ugandan households affected by RHD, particularly in lower-income areas, incur out-of-pocket costs that are very high relative to income, exacerbating the poverty trap. Universal health coverage policy reforms in Uganda should include mechanisms to reduce or eliminate out-of-pocket expenditures for RHD and other chronic diseases.

Diagnosing rheumatic heart disease: where are we now and what are the challenges?

INTRODUCTION: Rheumatic heart disease (RHD), a sequela of acute rheumatic fever (ARF), affects 40.5 million people worldwide. The burden of disease disproportionately falls on low- and middle-income countries (LMIC) and sub-populations within high-income countries (HIC). Advances have been made in earlier detection of RHD, though several barriers to ideal management persist. AREAS COVERED: This article reviews the current burden of RHD, highlighting the disparate impact of disease. It also reviews the clinical and echocardiographic presentation of RHD, as some may present in late stages of disease with associated complications. Finally, we review the advances which have been made in echocardiographic screening to detect latent RHD, highlighting the challenges which remain regarding secondary prophylaxis management and uncertainty of best practices for treatment of latent RHD. EXPERT OPINION: Advances in technology and validation of portable echocardiography have made screening and identifying latent RHD feasible in the most burdened regions. However, uncertainty remains around best management of those with latent RHD and best methods to ensure ideal secondary prophylaxis for RHD. Research regarding latent RHD management, as well as continued work on innovative solutions (such as group A streptococcal vaccine), are promising as efforts to improve outcomes of this preventable disease persist.

Towards automatic diagnosis of rheumatic heart disease on echocardiographic exams through video-based deep learning.

OBJECTIVE: Rheumatic heart disease (RHD) affects an estimated 39 million people worldwide and is the most common acquired heart disease in children and young adults. Echocardiograms are the gold standard for diagnosis of RHD, but there is a shortage of skilled experts to allow widespread screenings for early detection and prevention of the disease progress. We propose an automated RHD diagnosis system that can help bridge this gap. MATERIALS AND METHODS: Experiments were conducted on a dataset with 11 646 echocardiography videos from 912 exams, obtained during screenings in underdeveloped areas of Brazil and Uganda. We address the challenges of RHD identification with a 3D convolutional neural network (C3D), comparing its performance with a 2D convolutional neural network (VGG16) that is commonly used in the echocardiogram literature. We also propose a supervised aggregation technique to combine video predictions into a single exam diagnosis. RESULTS: The proposed approach obtained an accuracy of 72.77% for exam diagnosis. The results for the C3D were significantly better than the ones obtained by the VGG16 network for videos, showing the importance of considering the temporal information during the diagnostic. The proposed aggregation model showed significantly better accuracy than the majority voting strategy and also appears to be capable of capturing underlying biases in the neural network output distribution, balancing them for a more correct diagnosis. CONCLUSION: Automatic diagnosis of echo-detected RHD is feasible and, with further research, has the potential to reduce the workload of experts, enabling the implementation of more widespread screening programs worldwide.

Rheumatic Fever and Rheumatic Heart Disease in the United States.

During the 1920s, acute rheumatic fever (ARF) was the leading cause of mortality in children in the United States. By the 1980s, many felt ARF had all but disappeared from the US. However, although ARF and rheumatic heart disease (RHD) rates remain low in the US today, disease burden is unequal and tracks along other disparities of cardiovascular health. It is estimated that 1% to 3% of patients with untreated group A streptococcus (GAS) infection, most typically GAS pharyngitis, will develop ARF, and of these, up to 60% of cases will result in chronic RHD. This article reviews the epidemiology, pathogenesis, diagnosis, and management of ARF/RHD to increase awareness of ARF/RHD for clinicians based in the US. [Pediatr Ann. 2021;50(3):e98-e104.].

Cytokine gene functional polymorphisms and phenotypic expression as predictors of evolution from latent to clinical rheumatic heart disease.

INTRODUCTION: Inflammation associated with rheumatic heart disease (RHD) is influenced by gene polymorphisms and inflammatory cytokines. There are currently no immunologic and genetic markers to discriminate latent versus clinical patients, critical to predict disease evolution. Employing machine-learning, we searched for predictors that could discriminate latent versus clinical RHD, and eventually identify latent patients that may progress to clinical disease. METHODS: A total of 212 individuals were included, 77 with latent, 100 with clinical RHD, and 35 healthy controls. Circulating levels of 27 soluble factors were evaluated using Bio-Plex ProTM® Human Cytokine Standard 27-plex assay. Gene polymorphism analyses were performed using RT-PCR for the following genes: IL2, IL4, IL6, IL10, IL17A, TNF and IL23. RESULTS: Serum levels of all cytokines were higher in clinical as compared to latent RHD patients, and in those groups than in controls. IL-4, IL-8, IL-1RA, IL-9, CCL5 and PDGF emerged in the final multivariate model as predictive factors for clinical, compared with latent RHD. IL-4, IL-8 and IL1RA had the greater power to predict clinical RHD. In univariate analysis, polymorphisms in IL2 and IL4 were associated with clinical RHD and in the logistic analysis, IL6 (GG + CG), IL10 (CT + TT), IL2 (CA + AA) and IL4 (CC) genotypes were associated with RHD. CONCLUSION: Despite higher levels of all cytokines in clinical RHD patients, IL-4, IL-8 and IL-1RA were the best predictors of clinical disease. An association of polymorphisms in IL2, IL4, IL6 and IL10 genes and clinical RHD was observed. Gene polymorphism and phenotypic expression of IL-4 accurately discriminate latent versus clinical RHD, potentially instructing clinical management.