Using Artificial Intelligence to Predict Heart Failure Risk from Single-lead Electrocardiographic Signals: A Multinational Assessment.

Importance: Despite the availability of disease-modifying therapies, scalable strategies for heart failure (HF) risk stratification remain elusive. Portable devices capable of recording single-lead electrocardiograms (ECGs) can enable large-scale community-based risk assessment. Objective: To evaluate an artificial intelligence (AI) algorithm to predict HF risk from noisy single-lead ECGs. Design: Multicohort study. Setting: Retrospective cohort of individuals with outpatient ECGs in the integrated Yale New Haven Health System (YNHHS) and prospective population-based cohorts of UK Biobank (UKB) and Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Participants: Individuals without HF at baseline. Exposures: AI-ECG-defined risk of left ventricular systolic dysfunction (LVSD). Main Outcomes and Measures: Among individuals with ECGs, we isolated lead I ECGs and deployed a noise-adapted AI-ECG model trained to identify LVSD. We evaluated the association of the model probability with new-onset HF, defined as the first HF hospitalization. We compared the discrimination of AI-ECG against the pooled cohort equations to prevent HF (PCP-HF) score for new-onset HF using Harrel's C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI). Results: There were 194,340 YNHHS patients (age 56 years [IQR, 41-69], 112,082 women [58%]), 42,741 UKB participants (65 years [59-71], 21,795 women [52%]), and 13,454 ELSA-Brasil participants (56 years [41-69], 7,348 women [55%]) with baseline ECGs. A total of 3,929 developed HF in YNHHS over 4.5 years (2.6-6.6), 46 in UKB over 3.1 years (2.1-4.5), and 31 in ELSA-Brasil over 4.2 years (3.7-4.5). A positive AI-ECG screen was associated with a 3- to 7-fold higher risk for HF, and each 0.1 increment in the model probability portended a 27-65% higher hazard across cohorts, independent of age, sex, comorbidities, and competing risk of death. AI-ECG's discrimination for new-onset HF was 0.725 in YNHHS, 0.792 in UKB, and 0.833 in ELSA-Brasil. Across cohorts, incorporating AI-ECG predictions in addition to PCP-HF resulted in improved Harrel's C-statistic (Δ=0.112-0.114), with an IDI of 0.078-0.238 and an NRI of 20.1%-48.8% for AI-ECG vs. PCP-HF. Conclusions and Relevance: Across multinational cohorts, a noise-adapted AI model with lead I ECGs as the sole input defined HF risk, representing a scalable portable and wearable device-based HF risk-stratification strategy. KEY POINTS: Question: Can single-lead electrocardiogram (ECG) tracings predict heart failure (HF) risk?Findings: We evaluated a noise-adapted artificial intelligence (AI) algorithm for single-lead ECGs as the sole input across multinational cohorts, spanning a diverse integrated US health system and large community-based cohorts in the UK and Brazil. A positive AI-ECG screen was associated with a 3- to 7-fold higher HF risk, independent of age, sex, and comorbidities. The AI model achieved incremental discrimination and improved reclassification for HF over the pooled cohort equations to prevent HF (PCP-HF).Meaning: A noise-adapted AI model for single-lead ECG predicted the risk of new-onset HF, representing a scalable HF risk-stratification strategy for portable and wearable devices.

Performance of contemporary cardiovascular risk stratification scores in Brazil: an evaluation in the ELSA-Brasil study.

AIMS: Despite notable population differences in high-income and low- and middle-income countries (LMICs), national guidelines in LMICs often recommend using US-based cardiovascular disease (CVD) risk scores for treatment decisions. We examined the performance of widely used international CVD risk scores within the largest Brazilian community-based cohort study (Brazilian Longitudinal Study of Adult Health, ELSA-Brasil). METHODS: All adults 40-75 years from ELSA-Brasil (2008-2013) without prior CVD who were followed for incident, adjudicated CVD events (fatal and non-fatal MI, stroke, or coronary heart disease death). We evaluated 5 scores-Framingham General Risk (FGR), Pooled Cohort Equations (PCEs), WHO CVD score, Globorisk-LAC and the Systematic Coronary Risk Evaluation 2 score (SCORE-2). We assessed their discrimination using the area under the receiver operating characteristic curve (AUC) and calibration with predicted-to-observed risk (P/O) ratios-overall and by sex/race groups. RESULTS: There were 12 155 individuals (53.0±8.2 years, 55.3% female) who suffered 149 incident CVD events. All scores had a model AUC>0.7 overall and for most age/sex groups, except for white women, where AUC was <0.6 for all scores, with higher overestimation in this subgroup. All risk scores overestimated CVD risk with 32%-170% overestimation across scores. PCE and FGR had the highest overestimation (P/O ratio: 2.74 (95% CI 2.42 to 3.06)) and 2.61 (95% CI 1.79 to 3.43)) and the recalibrated WHO score had the best calibration (P/O ratio: 1.32 (95% CI 1.12 to 1.48)). CONCLUSION: In a large prospective cohort from Brazil, we found that widely accepted CVD risk scores overestimate risk by over twofold, and have poor risk discrimination particularly among Brazilian women. Our work highlights the value of risk stratification strategies tailored to the unique populations and risks of LMICs.

Scalable Risk Stratification for Heart Failure Using Artificial Intelligence applied to 12-lead Electrocardiographic Images: A Multinational Study.

Background: Current risk stratification strategies for heart failure (HF) risk require either specific blood-based biomarkers or comprehensive clinical evaluation. In this study, we evaluated the use of artificial intelligence (AI) applied to images of electrocardiograms (ECGs) to predict HF risk. Methods: Across multinational longitudinal cohorts in the integrated Yale New Haven Health System (YNHHS) and in population-based UK Biobank (UKB) and Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), we identified individuals without HF at baseline. Incident HF was defined based on the first occurrence of an HF hospitalization. We evaluated an AI-ECG model that defines the cross-sectional probability of left ventricular dysfunction from a single image of a 12-lead ECG and its association with incident HF. We accounted for the competing risk of death using the Fine-Gray subdistribution model and evaluated the discrimination using Harrel's c-statistic. The pooled cohort equations to prevent HF (PCP-HF) were used as a comparator for estimating incident HF risk. Results: Among 231,285 individuals at YNHHS, 4472 had a primary HF hospitalization over 4.5 years (IQR 2.5-6.6) of follow-up. In UKB and ELSA-Brasil, among 42,741 and 13,454 people, 46 and 31 developed HF over a follow-up of 3.1 (2.1-4.5) and 4.2 (3.7-4.5) years, respectively. A positive AI-ECG screen portended a 4-fold higher risk of incident HF among YNHHS patients (age-, sex-adjusted HR [aHR] 3.88 [95% CI, 3.63-4.14]). In UKB and ELSA-Brasil, a positive-screen ECG portended 13- and 24-fold higher hazard of incident HF, respectively (aHR: UKBB, 12.85 [6.87-24.02]; ELSA-Brasil, 23.50 [11.09-49.81]). The association was consistent after accounting for comorbidities and the competing risk of death. Higher model output probabilities were progressively associated with a higher risk for HF. The model's discrimination for incident HF was 0.718 in YNHHS, 0.769 in UKB, and 0.810 in ELSA-Brasil. Across cohorts, incorporating model probability with PCP-HF yielded a significant improvement in discrimination over PCP-HF alone. Conclusions: An AI model applied to images of 12-lead ECGs can identify those at elevated risk of HF across multinational cohorts. As a digital biomarker of HF risk that requires just an ECG image, this AI-ECG approach can enable scalable and efficient screening for HF risk.

Comparison of Cardiovascular Health Profiles Across Population Surveys From 5 High- to Low-Income Countries.

Background: To facilitate the shift from risk-factor management to primordial prevention of cardiovascular disease, the American Heart Association developed guidelines to score and track cardiovascular health (CVH). How the prevalence and trajectories of a high level of CVH across the life course compare among high- and lower-income countries is unknown. Methods: Nationally representative survey data with CVH variables (physical activity, cigarette smoking, body mass index, blood pressure, blood glucose, and total cholesterol levels) were identified in Ethiopia, Bangladesh, Brazil, England, and the US for adults (aged 18-69 years and not pregnant). Data were harmonized, and CVH metrics were scored using the American Heart Association guidelines, as high (2), moderate (1), or low (0), with the prevalence of high scores (better CVH) across the life course compared across countries. Results: Among 28,092 adults (Ethiopia n = 7686, 55.2% male; Bangladesh n = 6731, 48.4% male; Brazil n = 7241, 47.9% male; England n = 2691, 49.5% male, and the US n = 3743, 50.3% male), the prevalence of high CVH scores decreased as country income level increased. Declining CVH with age was universal across countries, but differences were already observable in those aged 18 years. Excess body weight appeared to be the main driver of poor CVH in higher-income countries, and the prevalence of current smoking was highest in Bangladesh. Conclusions: Our findings suggest that CVH decline with age may be universal. Interventions to promote and preserve CVH throughout the life course are needed in all populations, tailored to country-specific time courses of the decline. In countries where the level of CVH remains relatively high, protection of whole societies from risk-factor epidemics may still be feasible.

Contexte: Afin de faciliter la transition de la prise en charge des facteurs de risque vers la prévention primordiale des maladies cardiovasculaires, l'American Heart Association a élaboré des lignes directrices en vue de mesurer la santé cardiovasculaire (SCV) et d'en faire le suivi. On ignore dans quelle mesure la prévalence et la trajectoire d'un niveau élevé de SCV au cours d'une vie se comparent entre les pays à revenu élevé et les pays à plus faible revenu. Méthodologie: Des résultats de sondages représentatifs des pays concernant les variables de la SCV (activité physique, tabagisme, indice de masse corporelle, pression artérielle, glycémie et taux de cholestérol total) ont été obtenus de l'Éthiopie, du Bangladesh, du Brésil, de l'Angleterre et des États-Unis, pour des adultes âgés de 18 à 69 ans, excluant les femmes enceintes. Les données ont été harmonisées, et la SCV a été mesurée conformément aux lignes directrices de l'American Heart Association, et notée en fonction des scores suivants : élevée (2), modérée (1) ou faible (0). La prévalence de scores élevés, soit une meilleure SCV tout au long de la vie, a été comparée entre les pays. Résultats: Parmi 28 092 adultes (Éthiopie, n = 7 686, 55,2 % de sexe masculin; Bangladesh, n = 6 731, 48,4 % de sexe masculin; Brésil, n = 7 241, 47,9 % de sexe masculin; Angleterre, n = 2 691, 49,5 % de sexe masculin, et États-Unis, n = 3 743, 50,3 % de sexe masculin), la prévalence de scores correspondant à une SCV élevée diminuait à mesure que le niveau de revenu du pays augmentait. La diminution de la SCV avec l'âge était universelle dans tous les pays, mais des différences étaient déjà observables chez les personnes âgées de 18 ans. Un surplus de poids corporel semblait être le principal facteur d'une faible SCV dans les pays à revenu plus élevé; la prévalence d'un tabagisme actuel était la plus élevée au Bangladesh. Conclusions: Nos observations laissent croire que le déclin de la SCV avec l'âge pourrait être universel. Il est nécessaire de mener des interventions adaptées à la progression du déclin dans chacun des pays en vue de favoriser et de préserver la SCV tout au long de la vie, et ce, dans toutes les populations. Dans les pays où le niveau de SCV demeure relativement élevé, il pourrait être encore possible de protéger des sociétés entières contre des épidémies liées aux facteurs de risque.

Higher Arterial Stiffness Predicts Chronic Kidney Disease in Adults: The ELSA-Brasil Cohort Study. / Maior Rigidez Arterial Prediz Doença Renal Crônica no Estudo de Coorte ELSA-Brasil.

BACKGROUND: Central Illustration : Higher Arterial Stiffness Predicts Chronic Kidney Disease in Adults: The ELSA-Brasil Cohort Study. BACKGROUND: Arterial stiffening can directly affect the kidneys, which are passively perfused by a high flow. However, whether the relation between arterial stiffness and renal function depends on diabetes and hypertension conditions, is a matter of debate. OBJECTIVE: To investigate the relationship between arterial stiffening by carotid-to-femoral pulse wave velocity (cfPWV) and chronic kidney disease (CKD) incidence in individuals and verify whether this association is present in individuals without hypertension and diabetes. METHODS: A longitudinal study of 11,647 participants of the ELSA-Brasil followed up for four years (2008/10-2012/14). Baseline cfPWV was grouped per quartile, according to sex-specific cut-offs. Presence of CKD was ascertained by glomerular filtration rate (eGFR-CKD-EPI) < 60 ml/min/1.73 m2 and/or albumin-to-creatinine ratio ≥ 30 mg/g. Logistic regression models were run for the whole cohort and a subsample free from hypertension and diabetes at baseline, after adjustment for age, sex, race, schooling, smoking, cholesterol/HDL ratio, body mass index, diabetes, use of antihypertensive, systolic blood pressure, heart rate, and cardiovascular disease. Statistical significance was set at 5%. RESULTS: The chance of CKD was 42% (CI 95%: 1.05;1.92) greater among individuals in the upper quartile of cfPWV. Among normotensive, non-diabetic participants, individuals in the 2nd, 3rd, and 4th quartiles of cfPWV presented greater chances of developing CKD, as compared to those in the lower quartile, and the magnitude of this association was the greatest for those in the upper quartile (OR: 1.81 CI 95%: 1.14;2.86). CONCLUSION: Higher cfPWV increased the chances of CKD and suggests that this effect is even greater in individuals without diabetes and hypertension.

Hypertension care cascades and reducing inequities in cardiovascular disease in low- and middle-income countries.

Improving hypertension control in low- and middle-income countries has uncertain implications across socioeconomic groups. In this study, we simulated improvements in the hypertension care cascade and evaluated the distributional benefits across wealth quintiles in 44 low- and middle-income countries using individual-level data from nationally representative, cross-sectional surveys. We raised diagnosis (diagnosis scenario) and treatment (treatment scenario) levels for all wealth quintiles to match the best-performing country quintile and estimated the change in 10-year cardiovascular disease (CVD) risk of individuals initiated on treatment. We observed greater health benefits among bottom wealth quintiles in middle-income countries and in countries with larger baseline disparities in hypertension management. Lower-middle-income countries would see the greatest absolute benefits among the bottom quintiles under the treatment scenario (29.1 CVD cases averted per 1,000 people living with hypertension in the bottom quintile (Q1) versus 17.2 in the top quintile (Q5)), and the proportion of total CVD cases averted would be largest among the lowest quintiles in upper-middle-income countries under both diagnosis (32.0% of averted cases in Q1 versus 11.9% in Q5) and treatment (29.7% of averted cases in Q1 versus 14.0% in Q5) scenarios. Targeted improvements in hypertension diagnosis and treatment could substantially reduce socioeconomic-based inequalities in CVD burden in low- and middle-income countries.

Advancing Cardiovascular Health Equity Globally Through Digital Technologies.

Cardiovascular diseases (CVDs) remain the leading cause of death and disability worldwide. Digital health technologies are important public health interventions for addressing the burden of cardiovascular disease. In this article, we discuss the importance of translating digital innovations in research-funded projects to low-resource settings globally to advance global cardiovascular health equity. We also discuss current global cardiovascular health inequities and the digital health divide within and between countries. We present various considerations for translating digital innovations across different settings across the globe, including reciprocal innovation, a "bidirectional, co-constituted, and iterative exchange of ideas, resources, and innovations to address shared health challenges across diverse global settings." In this case, afferent reciprocal innovations may flow from high-income countries toward low- and middle-income countries, and efferent reciprocal innovations may be exported to high-income countries from low- and middle-income countries with adaptation. Finally, we discuss opportunities for bidirectional learning between local and global institutions and highlight examples of projects funded through the American Heart Association Health and Innovation Strategically Funded Research Network that have been adapted to lower-resource settings or have the potential to be adapted to lower-resource settings.

Use of Antihypertensive Drugs and Arterial Stiffness in the Longitudinal Study of Adult Health (ELSA-Brasil).

OBJECTIVE: Evaluate the longitudinal association between BP control and the use of antihypertensive classes with arterial stiffness (AS) in Brazilian adults. METHODS: This study included 1830 participants with arterial hypertension (1092 participants with controlled BP and 738 participants with uncontrolled BP) from the Longitudinal Study of Adult Health (ELSA-Brasil). AS was assessed by pulse wave velocity (PWV) and pulse pressure (PP) at baseline and repeated after approximately 9 years. Associations between AS and BP control and the use of antihypertensives, diuretics, angiotensin-converting enzyme inhibitors (ACEI), AT1 receptor blockers (ARB), calcium channel blockers (CCB), and beta blockers (in the population with controlled BP), at baseline were investigated using linear mixed-effects models. RESULTS: Uncontrolled BP was associated with worse PWV and PP trajectory, respectively (ß = 0.026 [0.008 to 0.036] / ß = 0.273 [0.216 to 0.330]). Among the participants with controlled BP, using CCB (ß = 0.031 [0.011 to 0.051]) was associated with a worse PWV trajectory, compared to not using this class and this combination, respectively. CONCLUSION: BP control, regardless of the class of antihypertensive used is associated with a better AS trajectory, as assessed by PWV and PP. Among participants with controlled BP, the use of BCC, compared to not using this class, seems to be worse for the trajectory of PWV in individuals with arterial hypertension without cardiovascular disease. Further studies are needed to assess whether this effect results in a better prognosis for patients with arterial hypertension.

Maior Rigidez Arterial Prediz Doença Renal Crônica no Estudo de Coorte ELSA-Brasil / Higher Arterial Stiffness Predicts Chronic Kidney Disease in Adults: The ELSA-Brasil Cohort Study

Resumo Fundamento A rigidez arterial pode afetar diretamente os rins, que são perfundidos passivamente por alto fluxo. No entanto, determinar se a relação entre rigidez arterial e função renal depende das condições de diabetes e hipertensão é uma questão controversa. Objetivo Investigar a relação entre a rigidez arterial, por velocidade da onda de pulso carotídea-femoral (VOPcf), e a incidência de doença renal crônica (DRC) em indivíduos e verificar se essa associação está presente em indivíduos sem hipertensão e diabetes. Métodos Estudo longitudinal com 11.647 participantes do ELSA-Brasil acompanhados por quatro anos (2008/10-2012/14). A VOPcf basal foi agrupada por quartil, de acordo com pontos de corte específicos com relação a sexo. A presença de DRC foi verificada pela taxa de filtração glomerular (TFGe-CKD-EPI) < 60 ml/min/1,73 m2 e/ou relação albumina/creatinina ≥ 30 mg/g. Modelos de regressão logística foram executados para toda a coorte e uma subamostra livre de hipertensão e diabetes no início do estudo, após ajuste para idade, sexo, raça, escolaridade, tabagismo, relação colesterol/HDL, índice de massa corporal, diabetes, uso de anti-hipertensivos, pressão arterial sistólica, frequência cardíaca e doenças cardiovasculares. A significância estatística foi fixada em 5%. Resultados A chance de DRC foi de 42% (IC de 95%: 1,05;1,92) maior entre indivíduos no quartil superior da VOPcf. Entre os participantes normotensos e não diabéticos, os indivíduos do 2º, 3º e 4º quartis da VOPcf apresentaram maiores chances de desenvolver DRC, quando comparados aos do quartil inferior, sendo a magnitude dessa associação maior para aqueles do quartil superior (OR: 1,81 IC de 95%: 1,14;2,86). Conclusão A maior VOPcf aumentou as chances de DRC, e sugere que esse efeito é ainda maior em indivíduos sem diabetes e hipertensão.

Abstract Background Arterial stiffening can directly affect the kidneys, which are passively perfused by a high flow. However, whether the relation between arterial stiffness and renal function depends on diabetes and hypertension conditions, is a matter of debate. Objective To investigate the relationship between arterial stiffening by carotid-to-femoral pulse wave velocity (cfPWV) and chronic kidney disease (CKD) incidence in individuals and verify whether this association is present in individuals without hypertension and diabetes. Methods A longitudinal study of 11,647 participants of the ELSA-Brasil followed up for four years (2008/10-2012/14). Baseline cfPWV was grouped per quartile, according to sex-specific cut-offs. Presence of CKD was ascertained by glomerular filtration rate (eGFR-CKD-EPI) < 60 ml/min/1.73 m2 and/or albumin-to-creatinine ratio ≥ 30 mg/g. Logistic regression models were run for the whole cohort and a subsample free from hypertension and diabetes at baseline, after adjustment for age, sex, race, schooling, smoking, cholesterol/HDL ratio, body mass index, diabetes, use of antihypertensive, systolic blood pressure, heart rate, and cardiovascular disease. Statistical significance was set at 5%. Results The chance of CKD was 42% (CI 95%: 1.05;1.92) greater among individuals in the upper quartile of cfPWV. Among normotensive, non-diabetic participants, individuals in the 2nd, 3rd, and 4th quartiles of cfPWV presented greater chances of developing CKD, as compared to those in the lower quartile, and the magnitude of this association was the greatest for those in the upper quartile (OR: 1.81 CI 95%: 1.14;2.86). Conclusion Higher cfPWV increased the chances of CKD and suggests that this effect is even greater in individuals without diabetes and hypertension.

Lifting all boats: strategies to promote equitable bidirectional research training opportunities to enhance global health reciprocal innovation.

Inequities in global health research are well documented. For example, training opportunities for US investigators to conduct research in low-income and middle-income countries (LMIC) have exceeded opportunities for LMIC investigators to train and conduct research in high-income countries. Reciprocal innovation addresses these inequities through collaborative research across diverse global settings.The Fogarty International Center of the US National Institutes of Health (NIH) promotes research capacity building in LMICs. Fogarty K-grants for mentored career development in global health are available for both US and LMIC investigators, whereas the D43 is the standard grant to support institutional training programmes in LMIC. Other NIH institutes fund T32 training grants to support biomedical research training in the USA, but very few have any global health component. Most global health training partnerships have historically focused on research conducted solely in LMIC, with few examples of bidirectional training partnerships. Opportunities may exist to promote global health reciprocal innovation (GHRI) research by twinning K-awardees in the USA with those from LMIC or by intentionally creating partnerships between T32 and D43 training programmes.To sustain independent careers in GHRI research, trainees must be supported through the path to independence known as the K (mentored grantee)-to-R (independent grantee) transition. Opportunities to support this transition include comentorship, research training at both LMIC and US institutions and protected time and resources for research. Other opportunities for sustainability include postdoctoral training before and after the K-award period, absorption of trained researchers into home institutions, South-South training initiatives and innovations to mitigate brain drain.

Percentiles of predicted 10-year cardiovascular disease risk by sex and age in Brazil and their association with estimated risk of long-term atherosclerotic events.

OBJECTIVE: Expressing the cardiovascular disease (CVD) risk in relation to peers may complement the estimation of absolute CVD risk. We aimed to determine 10-year CVD risk percentiles by sex and age in the Brazilian population and evaluate their association with estimated long-term atherosclerotic CVD (ASCVD) risk. METHODS: A cross-sectional analysis of baseline data from the ELSA-Brasil study was conducted in individuals aged 40-74 years without prior ASCVD. Ten-year CVD risk and long-term ASCVD risk were estimated by the WHO risk score and the Multinational Cardiovascular Risk Consortium tool, respectively. Ten-year risk percentiles were determined by ranking the calculated risks within each sex and age group. RESULTS: Ten-year CVD risk versus percentile plots were constructed for each sex and age group using data from 13,364 participants (55% females; median age, 52 [IQR, 46-59] years). Long-term ASCVD risk was calculated in 12,973 (97.1%) participants. Compared to individuals at the <25th risk percentile, those at the ≥75th percentile had a greater risk of being in the highest quartile of long-term risk (ORs [95% CIs] 6.57 [5.18-8.30] in females and 11.59 [8.42-15.96] in males) in regression models adjusted for age, race, education, and 10-year CVD risk. In both sexes, the association between risk percentile and long-term risk weakened after age 50. A tool for calculating 10-year CVD risk and the corresponding percentile is available at https://bit.ly/3CzPUi6. CONCLUSIONS: We established percentiles of predicted 10-year CVD risk by sex and age in the Brazilian population, which independently reflect the estimated long-term ASCVD risk in younger individuals.

Prevalence and factors associated with possible cases of familial hypercholesterolemia in Brazilian adults: a cross-sectional study.

This study aimed to estimate the prevalence of possible cases of FH and analyze associated factors in the adult Brazilian population. Cross-sectional study with laboratory data from the Brazilian National Health Survey, with 8521 participants. Possible cases of FH were defined according to the Dutch Lipid Clinic Network criteria. The prevalence and 95% confidence intervals (95% CI) of possible cases of FH were estimated according to sociodemographic variables, lifestyle, diabetes, hypertension, altered tests, treatment and self-rated health. Logistic regression was used to analyze the associations. The prevalence of possible cases of FH was 0.96%, higher in women, between 45 and 59 years, white race/skin color and others, less education, people with diabetes, hypertension and total cholesterol ≥ 310 mg/dL. The presence of FH was positively associated with regular self-rated health (OR 1.96; 95% CI 0.99-3.84), poor/very poor (OR 3.02; 95% CI 1.30-7.03) and negatively with black race/skin color (OR 0.10; 95% CI 0.02-0.46) and complete elementary school, incomplete high school (OR 0.47; 95% CI 0.23-0.98) and complete high school and more (OR 0.45; 95% CI 0.21-0.95). FH affects 1:104 Brazilian adults, these findings contribute to understanding the burden of disease in Brazil. Due to the scarcity of studies on FH in low- and middle-income countries, further studies are desirable.

Consumption of ultra-processed foods and eight-year risk of death from all causes and noncommunicable diseases in the ELSA-Brasil cohort.

Increased consumption of ultra-processed foods (UPF) is associated with higher incidences of many noncommunicable diseases (NCDs) and death from all causes. However, the association between UPF and cardiovascular disease (CVD) mortality remains controversial. Our study investigated whether UPF consumption is associated with a higher risk of death from all causes, NCDs, and CVD. This study includes 14,747 participants from the ELSA-Brasil cohort followed up over an eight-year period. The NOVA classification was used to estimate the proportion of UPF (grams/day) in one's diet. Cox regression was also applied. After adjustment for sociodemographic, health, and behavioural factors, a 10% increase in UPF in participants' diets raised the risk of death from all causes and NCDs by 10% (95%CI: 1.01-1.19) and 11% (95%CI:1.02-1.21), respectively. However, UPF consumption was not associated with CVD mortality. The findings support public policies aimed at reducing UPF consumption in an attempt to reduce the NCD burden.

Use of Human-Centered Design Methodology to Develop a Digital Toolkit to Optimize Heart Failure Guideline-Directed Medical Therapy.

BACKGROUND: Guideline-directed medical therapies (GDMTs) improve quality of life and health outcomes for patients with heart failure (HF). However, GDMT utilization is suboptimal among patients with HF. OBJECTIVE: The aims of this study were to engage key stakeholders in semistructured, virtual human-centered design sessions to identify challenges in GDMT optimization posthospitalization and inform the development of a digital toolkit aimed at optimizing HF GDMTs. METHODS: For the human-centered design sessions, we recruited (a) clinicians who care for patients with HF across 3 hospital systems, (b) patients with HF with reduced ejection fraction (ejection fraction ≤ 40%) discharged from the hospital within 30 days of enrollment, and (c) caregivers. All participants were 18 years or older, English speaking, with Internet access. RESULTS: A total of 10 clinicians (median age, 37 years [interquartile range, 35-41], 12 years [interquartile range, 10-14] of experience caring for patients with HF, 80% women, 50% White, 50% nurse practitioners) and three patients and one caregiver (median age 57 years [IQR: 53-60], 75% men, 50% Black, 75% married) were included. Five themes emerged from the clinician sessions on challenges to GDMT optimization (eg, barriers to patient buy-in). Six themes on challenges (eg, managing medications), 4 themes on motivators (eg, regaining independence), and 3 themes on facilitators (eg, social support) to HF management arose from the patient and caregiver sessions. CONCLUSIONS: The clinician, patient, and caregiver insights identified through human-centered design will inform a digital toolkit aimed at optimizing HF GDMTs, including a patient-facing smartphone application and clinician dashboard. This digital toolkit will be evaluated in a multicenter, clinical trial.

Aspirin for Secondary Prevention of Cardiovascular Disease in 51 Low-, Middle-, and High-Income Countries.

Importance: Aspirin is an effective and low-cost option for reducing atherosclerotic cardiovascular disease (CVD) events and improving mortality rates among individuals with established CVD. To guide efforts to mitigate the global CVD burden, there is a need to understand current levels of aspirin use for secondary prevention of CVD. Objective: To report and evaluate aspirin use for secondary prevention of CVD across low-, middle-, and high-income countries. Design, Setting, and Participants: Cross-sectional analysis using pooled, individual participant data from nationally representative health surveys conducted between 2013 and 2020 in 51 low-, middle-, and high-income countries. Included surveys contained data on self-reported history of CVD and aspirin use. The sample of participants included nonpregnant adults aged 40 to 69 years. Exposures: Countries' per capita income levels and world region; individuals' socioeconomic demographics. Main Outcomes and Measures: Self-reported use of aspirin for secondary prevention of CVD. Results: The overall pooled sample included 124 505 individuals. The median age was 52 (IQR, 45-59) years, and 50.5% (95% CI, 49.9%-51.1%) were women. A total of 10 589 individuals had a self-reported history of CVD (8.1% [95% CI, 7.6%-8.6%]). Among individuals with a history of CVD, aspirin use for secondary prevention in the overall pooled sample was 40.3% (95% CI, 37.6%-43.0%). By income group, estimates were 16.6% (95% CI, 12.4%-21.9%) in low-income countries, 24.5% (95% CI, 20.8%-28.6%) in lower-middle-income countries, 51.1% (95% CI, 48.2%-54.0%) in upper-middle-income countries, and 65.0% (95% CI, 59.1%-70.4%) in high-income countries. Conclusion and Relevance: Worldwide, aspirin is underused in secondary prevention, particularly in low-income countries. National health policies and health systems must develop, implement, and evaluate strategies to promote aspirin therapy.

Diagnostic testing for hypertension, diabetes, and hypercholesterolaemia in low-income and middle-income countries: a cross-sectional study of data for 994 185 individuals from 57 nationally representative surveys.

BACKGROUND: Testing for the risk factors of cardiovascular disease, which include hypertension, diabetes, and hypercholesterolaemia, is important for timely and effective risk management. Yet few studies have quantified and analysed testing of cardiovascular risk factors in low-income and middle-income countries (LMICs) with respect to sociodemographic inequalities. We aimed to address this knowledge gap. METHODS: In this cross-sectional analysis, we pooled individual-level data for non-pregnant adults aged 18 years or older from nationally representative surveys done between Jan 1, 2010, and Dec 31, 2019 in LMICs that included a question about whether respondents had ever had their blood pressure, glucose, or cholesterol measured. We analysed diagnostic testing performance by quantifying the overall proportion of people who had ever been tested for these cardiovascular risk factors and the proportion of individuals who met the diagnostic testing criteria in the WHO package of essential noncommunicable disease interventions for primary care (PEN) guidelines (ie, a BMI >30 kg/m2 or a BMI >25 kg/m2 among people aged 40 years or older). We disaggregated and compared diagnostic testing performance by sex, wealth quintile, and education using two-sided t tests and multivariable logistic regression models. FINDINGS: Our sample included data for 994 185 people from 57 surveys. 19·1% (95% CI 18·5-19·8) of the 943 259 people in the hypertension sample met the WHO PEN criteria for diagnostic testing, of whom 78·6% (77·8-79·2) were tested. 23·8% (23·4-24·3) of the 225 707 people in the diabetes sample met the WHO PEN criteria for diagnostic testing, of whom 44·9% (43·7-46·2) were tested. Finally, 27·4% (26·3-28·6) of the 250 573 people in the hypercholesterolaemia sample met the WHO PEN criteria for diagnostic testing, of whom 39·7% (37·1-2·4) were tested. Women were more likely than men to be tested for hypertension and diabetes, and people in higher wealth quintiles compared with those in the lowest wealth quintile were more likely to be tested for all three risk factors, as were people with at least secondary education compared with those with less than primary education. INTERPRETATION: Our study shows opportunities for health systems in LMICs to improve the targeting of diagnostic testing for cardiovascular risk factors and adherence to diagnostic testing guidelines. Risk-factor-based testing recommendations rather than sociodemographic characteristics should determine which individuals are tested. FUNDING: Harvard McLennan Family Fund, the Alexander von Humboldt Foundation, and the National Heart, Lung, and Blood Institute of the US National Institutes of Health.

Comparison of cardiovascular health profiles across population surveys from five high- to low-income countries.

Aims: With the greatest burden of cardiovascular disease morbidity and mortality increasingly observed in lower-income countries least prepared for this epidemic, focus is widening from risk factor management alone to primordial prevention to maintain high levels of cardiovascular health (CVH) across the life course. To facilitate this, the American Heart Association (AHA) developed CVH scoring guidelines to evaluate and track CVH. We aimed to compare the prevalence and trajectories of high CVH across the life course using nationally representative adult CVH data from five diverse high- to low-income countries. Methods: Surveys with CVH variables (physical activity, cigarette smoking, body mass, blood pressure, blood glucose, and total cholesterol levels) were identified in Ethiopia, Bangladesh, Brazil, England, and the United States (US). Participants were included if they were 18-69y, not pregnant, and had data for these CVH metrics. Comparable data were harmonized and each of the CVH metrics was scored using AHA guidelines as high (2), moderate (1), or low (0) to create total CVH scores with higher scores representing better CVH. High CVH prevalence by age was compared creating country CVH trajectories. Results: The analysis included 28,092 adults (Ethiopia n=7686, 55.2% male; Bangladesh n=6731, 48.4% male; Brazil n=7241, 47.9 % male; England n=2691, 49.5% male, and the US n=3743, 50.3% male). As country income level increased, prevalence of high CVH decreased (>90% in Ethiopia, >68% in Bangladesh and under 65% in the remaining countries). This pattern remained using either five or all six CVH metrics and following exclusion of underweight participants. While a decline in CVH with age was observed for all countries, higher income countries showed lower prevalence of high CVH already by age 18y. Excess body weight appeared the main driver of poor CVH in higher income countries, while current smoking was highest in Bangladesh. Conclusion: Harmonization of nationally representative survey data on CVH trajectories with age in 5 highly diverse countries supports our hypothesis that CVH decline with age may be universal. Interventions to promote and preserve high CVH throughout the life course are needed in all populations, tailored to country-specific time courses of the decline. In countries where CVH remains relatively high, protection of whole societies from risk factor epidemics may still be feasible.