Explaining Ethnic Differentials in COVID-19 Mortality: A Cohort Study.

Ethnic inequalities in coronavirus disease 2019 (COVID-19) hospitalizations and mortality have been widely reported, but there is scant understanding of how they are embodied. The UK Biobank prospective cohort study comprises approximately half a million people who were aged 40-69 years at study induction, between 2006 and 2010, when information on ethnic background and potential explanatory factors was captured. Study members were prospectively linked to a national mortality registry. In an analytical sample of 448,664 individuals (248,820 women), 705 deaths were ascribed to COVID-19 between March 5, 2020, and January 24, 2021. In age- and sex-adjusted analyses, relative to White participants, Black study members experienced approximately 5 times the risk of COVID-19 mortality (odds ratio (OR) = 4.81, 95% confidence interval (CI): 3.28, 7.05), while there was a doubling in the South Asian group (OR = 2.05, 95% CI: 1.30, 3.25). Controlling for baseline comorbidities, social factors (including socioeconomic circumstances), and lifestyle indices attenuated this risk differential by 34% in Black study members (OR = 2.84, 95% CI: 1.91, 4.23) and 37% in South Asian individuals (OR = 1.57, 95% CI: 0.97, 2.55). The residual risk of COVID-19 deaths in ethnic minority groups may be ascribed to a range of unmeasured characteristics and requires further exploration.

Ethnic disparities in hospitalisation for COVID-19 in England: The role of socioeconomic factors, mental health, and inflammatory and pro-inflammatory factors in a community-based cohort study.

BACKGROUND: Differentials in COVID-19 hospitalisations and mortality according to ethnicity have been reported but their origin is uncertain. We examined the role of socioeconomic, mental health, and pro-inflammatory factors in a community-based sample. METHODS: We used data on 340,966 men and women (mean age 56.2 years) from the UK Biobank study, a prospective cohort study with linkage to hospitalisation for COVID-19. Logistic regression models were used to estimate associations between ethnicity and hospitalisation for COVID-19. RESULTS: There were 640 COVID-19 cases (571/324,306 White, 31/4,485 Black, 21/5,732 Asian, 17/5,803 Other). Compared to the White study members and after adjusting for age and sex, Black individuals had over a 4-fold increased risk of COVID-19 infection (odds ratio; 95% confidence interval: 4.32; 3.00-6.23), and there was a doubling of risk in the Asian group (2.12; 1.37, 3.28) and the 'other' non-white group (1.84; 1.13, 2.99). After controlling for potential explanatory factors which included neighbourhood deprivation, household crowding, smoking, body size, inflammation, glycated haemoglobin, and mental illness, these effect estimates were attenuated by 33% for Blacks, 52% for Asians and 43% for Other, but remained raised for Blacks (2.66; 1.82, 3.91), Asian (1.43; 0.91, 2.26) and other non-white groups (1.41; 0.87, 2.31). CONCLUSIONS: There were clear ethnic differences in risk of COVID-19 hospitalisation and these do not appear to be fully explained by measured factors. If replicated, our results have implications for health policy, including the targeting of prevention advice and vaccination coverage.

Degree of anemia, indirect markers of hemolysis, and vascular complications of sickle cell disease in Africa.

The hyperhemolysis paradigm that describes overlapping "hyperhemolytic-endothelial dysfunction" and "high hemoglobin-hyperviscous" subphenotypes of sickle cell disease (SCD) patients is based on North American studies. We performed a transversal study nested in the CADRE cohort to analyze the association between steady-state hemolysis and vascular complications of SCD among sub-Saharan African patients. In Mali, Cameroon, and Ivory Coast, 2407 SCD patients (1751 SS or sickle ß-zero-thalassemia [Sß0], 495 SC, and 161 sickle ß+-thalassemia [Sß+]), aged 3 years old and over, were included at steady state. Relative hemolytic intensity was estimated from a composite index derived from principal component analysis, which included bilirubin levels or clinical icterus, and lactate dehydrogenase levels. We assessed vascular complications (elevated tricuspid regurgitant jet velocity [TRV], microalbuminuria, leg ulcers, priapism, stroke, and osteonecrosis) by clinical examination, laboratory tests, and echocardiography. After adjustment for age, sex, country, and SCD phenotype, a low hemoglobin level was significantly associated with TRV and microalbuminuria in the whole population and with leg ulcers in SS-Sß0 adults. A high hemolysis index was associated with microalbuminuria in the whole population and with elevated TRV, microalbuminuria, and leg ulcers in SS-Sß0 adults, but these associations were no longer significant after adjustment for hemoglobin level. In conclusion, severe anemia at steady state in SCD patients living in West and Central Africa is associated with elevated TRV, microalbuminuria, and leg ulcers, but these vascular complications are not independently associated with indirect markers of increased hemolysis. Other mechanisms leading to anemia, including malnutrition and infectious diseases, may also play a role in the development of SCD vasculopathy.

Association of Cardiovascular Health Level in Older Age With Cognitive Decline and Incident Dementia.

Importance: Evidence is limited regarding the relation between cardiovascular health level and dementia risk. Objective: To investigate the association between cardiovascular health level, defined using the 7-item tool from the American Heart Association (AHA), and risk of dementia and cognitive decline in older persons. Design, Setting, and Participants: Population-based cohort study of persons aged 65 years or older from Bordeaux, Dijon, and Montpellier, France, without history of cardiovascular diseases or dementia at baseline who underwent repeated in-person neuropsychological testing (January 1999-July 2016) and systematic detection of incident dementia (date of final follow-up, July 26, 2016). Exposures: The number of the AHA's Life's Simple 7 metrics at recommended optimal level (nonsmoking, body mass index <25, regular physical activity, eating fish twice a week or more and fruits and vegetables at least 3 times a day, cholesterol <200 mg/dL [untreated], fasting glucose <100 mg/dL [untreated], and blood pressure <120/80 mm Hg [untreated]; score range, 0-7) and a global cardiovascular health score (range, 0-14; poor, intermediate, and optimal levels of each metric assigned a value of 0, 1, and 2, respectively). Main Outcomes and Measures: Incident dementia validated by an expert committee and change in a composite score of global cognition (in standard units, with values indicating distance from population means, 0 equal to the mean, and +1 and -1 equal to 1 SD above and below the mean). Results: Among 6626 participants (mean age, 73.7 years; 4200 women [63.4%]), 2412 (36.5%), 3781 (57.1%), and 433 (6.5%) had 0 to 2, 3 to 4, and 5 to 7 health metrics at optimal levels, respectively, at baseline. Over a mean follow-up duration of 8.5 (range, 0.6-16.6) years, 745 participants had incident adjudicated dementia. Compared with the incidence rate of dementia of 1.76 (95% CI, 1.38-2.15) per 100 person-years among those with 0 or 1 health metrics at optimal levels, the absolute differences in incident dementia rates for 2, 3, 4, 5, and 6 to 7 metrics were, respectively, -0.26 (95% CI, -0.48 to -0.04), -0.59 (95% CI, -0.80 to -0.38), -0.43 (95% CI, -0.65 to -0.21), -0.93 (95% CI, -1.18 to -0.68), and -0.96 (95% CI, -1.37 to -0.56) per 100 person-years. In multivariable models, the hazard ratios for dementia were 0.90 (95% CI, 0.84-0.97) per additional optimal metric and 0.92 (95% CI, 0.89-0.96) per additional point on the global score. Furthermore, the gain in global cognition associated with each additional optimal metric at baseline was 0.031 (95% CI, 0.009-0.053) standard units at inclusion, 0.068 (95% CI, 0.045-0.092) units at year 6, and 0.072 (95% CI, 0.042-0.102) units at year 12. Conclusions and Relevance: In this cohort of older adults, increased numbers of optimal cardiovascular health metrics and a higher cardiovascular health score were associated with a lower risk of dementia and lower rates of cognitive decline. These findings may support the promotion of cardiovascular health to prevent risk factors associated with cognitive decline and dementia.

Ideal Cardiovascular Health and Subclinical Markers of Carotid Structure and Function: The Paris Prospective Study III.

OBJECTIVE: We hypothesized that subclinical markers of vascular structure and function, which are independent predictors of cardiovascular disease, would be less frequent in subjects with ideal than poor cardiovascular health (CVH) as defined by the American Heart Association (AHA). APPROACH AND RESULTS: Carotid parameters were measured using high-precision echotracking device in 9155 nonreferred participants attending a health checkup in a large health center in Paris (France) between 2008 and 2012. According to the AHA, participants with 0 to 2, 3 to 4, and 5 to 7 metrics (smoking, physical activity, body mass index, diet, blood glucose and total cholesterol, blood pressure) at the ideal level were categorized as having poor, intermediate, and ideal CVH. Carotid parameters were dichotomized according to their median value, and multivariable logistic regression analysis was performed. Mean age was 59.5 (SD 6.3) years; 39% were females, and ideal CVH was present in 10.11% of the study participants. After adjustment for age, sex, education, and living alone and compared with a poor CVH, an ideal CVH was associated with lower common carotid artery intima-media thickness (odds ratio=1.64; 95% confidence interval 1.40, 1.93), absence of carotid plaques (odds ratio=2.14; 95% confidence interval 1.60, 2.87), lower Young's elastic modulus (odds ratio=2.43; 95% confidence interval 2.07, 2.84), and higher carotid distensibility coefficient (odds ratio=2.90; 95% confidence interval 2.47, 3.41). CONCLUSIONS: In community subjects aged 50 to 75 years, ideal CVH was associated with substantially less arterial stiffness and thickness. These associations might contribute to the lower risk of cardiovascular diseases in subjects with ideal CVH.

High adherence to the French dietary guidelines decreases type 2 diabetes risk in females through pathways of obesity markers: Evidence from the E3N-EPIC prospective cohort study.

OBJECTIVE: Obesity and type 2 diabetes (T2D) have been associated with low adherence to the 2017 French food-based dietary guidelines, as assessed by the Programme National Nutrition Santé - guidelines score 2 (PNNS-GS2). Whether the association between T2D and PNNS-GS2 is direct or mediated by obesity has been little investigated. RESEARCH METHODS: The study included 71,450 women from the E3N-EPIC cohort, mean age of 52.9 y (SD 6.7). The simplified PNNS-GS2 was derived via food history questionnaire. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of T2D. Causal mediation analyses were used to decompose the total effect of sPNNS-GS2 on T2D into a direct effect and indirect effect mediated by body mass index (BMI) or the waist-hip ratio (WHR). RESULTS: During a mean follow-up of 19 y, 3679 incident T2D cases were identified and validated. There was a linear association between adherence to sPNNS-GS2 and T2D (P-nonlinearity = 0.92). In the fully adjusted model, each 1-SD increase in the sPNNS-GS2 was associated with a lower T2D risk [HR (95% CI), 0.92 (0.89, 0.95)]. The overall associations were mainly explained by sPNNS-GS2-associated excess weight, with BMI and WHR mediating 52% and 58% of the associations, respectively. CONCLUSIONS: Higher adherence to French food-based dietary guidelines was associated with a lower risk of T2D in women, and a significant portion of this effect could be attributed to excess weight measured by BMI or WHR. This finding helps better understand the mechanisms underlying the diet-T2D association.

Deep Diving Into the Cardiovascular Health Paradox: A Journey Towards Personalized Prevention.

Objectives: The Life's Simple 7 score (LS7) promotes cardiovascular health (CVH). Despite this, some with optimal LS7 develop cardiovascular disease (CVD), while others with poor CVH do not, termed the "CVH paradox." This paper explores pathways explaining this paradox. Methods: We examined methodological aspects: 1) misclassification bias in self-reported lifestyle factors (smoking, physical activity, diet); 2) cumulative exposure to risk factors over a lifetime, impacting the CVH paradox. Punctual risk factor assessments are suboptimal for predicting outcomes. We proposed personalized prevention using "novel" elements to refine CVH assessment: 1) subclinical vascular disease markers, 2) metabolic biomarkers in blood and urine, 3) emerging risk factors, 4) polygenic risk scores (PRS), 5) epigenetics, and 6) the exposome. Results: Addressing the CVH paradox requires a multifaceted approach, reducing misclassification bias, considering cumulative risk exposure, and incorporating novel personalized prevention elements. Conclusion: A holistic, individualized approach to CVH assessment and CVD prevention can better reduce cardiovascular outcomes and improve population health. Collaboration among researchers, healthcare providers, policymakers, and communities is essential for effective implementation and realization of these strategies.

Predictive machine learning models for ascending aortic dilatation in patients with bicuspid and tricuspid aortic valves undergoing cardiothoracic surgery: a prospective, single-centre and observational study.

OBJECTIVES: The objective of this study was to develop clinical classifiers aiming to identify prevalent ascending aortic dilatation in patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV). DESIGN AND SETTING: A prospective, single-centre and observational cohort. PARTICIPANTS: The study involved 543 BAV and 491 TAV patients with aortic valve disease and/or ascending aortic dilatation, excluding those with coronary artery disease, undergoing cardiothoracic surgery at the Karolinska University Hospital (Sweden). MAIN OUTCOME MEASURES: Predictors of high risk of ascending aortic dilatation (defined as ascending aorta with a diameter above 40 mm) were identified through the application of machine learning algorithms and classic logistic regression models. EXPOSURES: Comprehensive multidimensional data, including valve morphology, clinical information, family history of cardiovascular diseases, prevalent diseases, demographic details, lifestyle factors, and medication. RESULTS: BAV patients, with an average age of 60.4±12.4 years, showed a higher frequency of aortic dilatation (45.3%) compared with TAV patients, who had an average age of 70.4±9.1 years (28.9% dilatation, p <0.001). Aneurysm prediction models for TAV patients exhibited mean area under the receiver-operating-characteristic curve (AUC) values above 0.8, with the absence of aortic stenosis being the primary predictor, followed by diabetes and high-sensitivity C reactive protein. Conversely, prediction models for BAV patients resulted in AUC values between 0.5 and 0.55, indicating low usefulness for predicting aortic dilatation. Classification results remained consistent across all machine learning algorithms and classic logistic regression models. CONCLUSION AND RECOMMENDATION: Cardiovascular risk profiles appear to be more predictive of aortopathy in TAV patients than in patients with BAV. This adds evidence to the fact that BAV-associated and TAV-associated aortopathy involves different pathways to aneurysm formation and highlights the need for specific aneurysm preventions in these patients. Further, our results highlight that machine learning approaches do not outperform classical prediction methods in addressing complex interactions and non-linear relations between variables.

Association between change in heart rate over years and life span in the Paris Prospective 1, the Whitehall 1, and Framingham studies.

Heart rate, a measure of the frequency of the cardiac cycle, reflects the health of the cardiovascular system, metabolic rate, and activity of the autonomic nervous system. Whether changes in resting heart rate are related to lifespan has not yet been explored to our best knowledge. In this study, we examined the association between resting heart rate and lifespan using linear regression in the Paris Prospective Study I, the Whitehall I Study, and the Framingham Heart Study. We used Cox proportional hazards regression to relate changes in heart rate over years to mortality risk. We observed a statistically significant association between increases in resting heart rate over a 5-year period and risk of mortality in the Paris Prospective Study I (HR mortality per 10 bpm increase over time: 1.20; 95% CI: 1.13 to 1.27) and over an 8-year period in the Framingham Heart Study (HR: 1.13; 95% CI: 1.07 to 1.19 for men and HR: 1.09; 95% CI: 1.04 to 1.15 for women), after adjusting for classical risk factors and resting heart rate. Our study shows that men and women who increase their resting heart rate over time increase their risk of mortality.

Advancing the Cardiovascular Workforce in Africa to Tackle the Epidemic of Cardiovascular Disease: The Time is Now.

The African region is experiencing an epidemic of cardiovascular disease with dire consequences of increasing morbidity and mortality. Compared with high-income countries where older populations are most affected, the burden of CVD in Africa is higher in the younger populations, which hampers regional socioeconomic development. Strategies to increase and advance the cardiovascular workforce are urgently needed to help address this problem. This commentary highlights the critical lack of skilled cardiovascular healthcare professionals, including cardiologists, cardiac surgeons, and cardiovascular nurses in the African region. Multilevel viable solutions to advance the cardiovascular workforce in Africa based on successful models in Africa are also presented.

Association of Life's Simple 7 and ideal cardiovascular health in American Indians/Alaska Natives.

OBJECTIVE: American Indians and Alaska Natives (AI/ANs) are an understudied population at high risk for cardiovascular diseases (CVDs); little is known about contextual factors contributing to CVDs in AI/ANs. This study examined the association of Life's Simple 7 (LS7) factors and social determinants of health (SDH) with CVD outcomes in a nationally representative sample of AI/ANs. METHODS: We conducted a cross-sectional study of 8497 AI/ANs using 2017 Behavioural Risk Factor Surveillance Survey data. Individual LS7 factors were summarised as ideal and poor levels. Coronary heart disease, myocardial infarction and stroke were defined as CVD outcomes. Healthcare access measures represented SDH. Logistic regression analyses examined associations of LS7 factors and SDH with CVD outcomes. Population attributable fractions (PAFs) quantified individual contributions of LS7 factors to CVD outcomes. RESULTS: N=1,297 (15%) participants with CVD outcomes were identified. Smoking, physical inactivity, diabetes, hypertension and hyperlipidaemia were LS7 factors associated with CVD outcomes. Hypertension was the largest contributor to CVD (aPAF 42%; 95% CI 37% to 51%), followed by hyperlipidaemia (aPAF 27%; 95% CI 17% to 36%) and diabetes (aPAF 18%; 95% CI 7% to 23%). Compared with individuals with poor LS7 levels, participants with ideal levels showed 80% lower odds of CVD outcomes (aOR 0.20; 95% CI 0.16 to 0.25). Access to health insurance (aOR 1.43, 95% CI 1.08 to 1.89) and a regular care provider (aOR 1.47, 95% CI 1.24 to 1.76) were associated with CVD outcomes. CONCLUSIONS: Effective interventions are needed to address SDH and attain ideal LS7 factors to improve cardiovascular health among AI/ANs.

Cardiovascular health metrics and risk of heart failure in a Finnish population: a prospective cohort study.

AIMS: This study aimed to examine the association between cardiovascular health (CVH) metrics and the risk of heart failure (HF) in a Finnish population. METHODS AND RESULTS: We used the prospective population-based Kuopio Ischaemic Heart Disease cohort study comprising men aged 42-60 years at baseline (1984-89) and women aged 53-73 years at baseline (1998-2001). The CVH scores were computed from American Heart Association's CVH metrics for 2385 men and 825 women without a history of HF at baseline. The CVH scores, ranging from 0 to 14, were categorized into three: inadequate, average, and optimal groups. Multivariable Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for HF. During a median follow-up period of 27 years for men, and 18 years for women, 465 and 124 HF events were recorded, respectively. The mean ages for men and women were 53 and 63 years, respectively. One hundred and thirty-three men (5.6%) and 73 women (8.8%) had five or more ideal CVH metrics. Participants with optimal CVH scores had a 64% and 48% lower risk of HF when compared with those with inadequate CVH scores among men and women, respectively (HR, 95% CI: men = 0.36, 0.26-0.49, P < 0.01; women = 0.52, 0.31-0.89, P = 0.02). CONCLUSIONS: Optimal CVH metrics is associated with a lower risk of HF among an ageing Finnish population. Optimal CVH score should be targeted among the general population to reduce the risk of HF.

Time trends in infectious and chronic disease consultations in Dakar, Senegal: Impact of COVID-19 sanitary measures.

Background: The impact of COVID-19 sanitary measures on the time trends in infectious and chronic disease consultations in Sub-Saharan Africa remains unknown. Methods: We conducted a cohort study on all emergency medical consultations from January 2016 to July 2020, from SOS Medecins in Dakar, Senegal. The consultation records provided basic demographic information such as age, ethnicity (Senegalese or Caucasian), and sex as well as the principal diagnosis using an ICD-10 classification ("infectious", "chronic", and "other"). We first investigated how the pattern in emergency consultation differed from March to July 2020 compared to previous years. Then, we examined any potential racial/ethnic disparities in COVID-19 consultation. Results: We obtained data on emergency medical consultations from 53 583 patients of all ethnic origins. The mean age of patients was 37.0 (standard deviation (SD) = 25.2) and 30.3 (SD = 21.7) in 2016-2019 and 45.5 (SD = 24.7) and 39.5 (SD = 23.3) in 2020 for Senegalese and Caucasian patients, respectively. The type of consultations between January and July were similar from 2016 to 2019; however, in 2020, there was a drop in the number of infectious disease consultations, particularly from April to May 2020, when sanitary measures for COVID-19 were applied (average of 366.5 and 358.2 in 2016-1019 and 133.0 and 125.0 in 2020). The prevalence of chronic conditions remained steady during the same period (average of 381.0 and 394.7 in 2016-2019 and 373.0 and 367.0 in 2020). In a multivariate analysis adjusted for age and sex, infectious disease consultations were significantly more likely to occur in 2016-2019 compared to 2020 (2016 odds ratio (OR) = 2.39, 2017 OR = 2.74, 2018 OR = 2.39, 2019 OR = 2.01). Furthermore, the trend in the number of infectious and chronic consultations was similar among Senegalese and Caucasian groups, indicating no disparities among those seeking treatment. Conclusions: During the implementation of COVID-19 sanitary measures, infectious disease rates dropped as chronic disease rates remained stagnant in Dakar. We observed no racial/ethnic disparities among the infectious and chronic consultations.

Sociodemographic determinants of change in cardiovascular health in middle adulthood in a bi-racial cohort.

BACKGROUND AND AIMS: Cardiovascular health (CVH), as many other aspects of health, is socially patterned. However, little is known about the socioeconomic determinants of following a more or less favourable pattern of CVH change at midlife. METHODS: We used data on 11,049 participants in the Atherosclerosis Risk in Communities (ARIC) study, a prospective, population-based, bi-racial cohort that included participants aged 44-66 years in 1987-1989, who attended a second visit 6 years later. At both visits, CVH was assessed with the American Heart Association's Life's Simple 7 (LS7) score ranging 0-14, based on 7 metrics: cholesterol, blood glucose, blood pressure, smoking, body mass index, physical activity, and diet. An LS7 score ≥8 was considered ideal, <8 was considered poor. Multivariable logistic regression models were used. In a first sample (N = 4416) of participants who started with a poor CVH, we modelled odds of improvement (Poor-Ideal vs. Poor-Poor). In a second sample (N = 6633) with baseline ideal CVH, we modelled odds of deterioration (Ideal-Poor vs. Ideal-Ideal). The determinants considered were baseline age, sex, race, educational level, income and working status. RESULTS: The majority (8,347, 75.5%) of participants remained in the same CVH category at both waves: 28.7% poor-poor, and 46.8% ideal-ideal. The remaining 24.5% were evenly split between improving (11.2%) and deteriorating (13.2%). Compared to poor-poor CVH, older participants displayed higher odds of improving to ideal CVH (OR>58yvs < 50y = 1.41; 95% CI:1.17, 1.69), whereas Black race (vs White, OR = 0.68; 0.57, 0.80), low education (vs high, OR = 0.65; 0.53, 0.79) and low income (vs high, OR = 0.71; 0.57, 0.87)) were associated with lower odds of improvement. Compared to ideal-ideal CVH, Black participants (OR = 1.59; 1.33, 1.89), with low education (OR = 1.98; 1.64, 2.39), low income (OR = 1.57; 1.30, 1.88), and non-working (vs currently working, OR = 1.27; 1.06, 1.51) had greater odds of deterioration to poor CVH. CONCLUSIONS: We identified vulnerable groups at higher risk of worsening their CVH over time: Black people, with low income, low education, and who are unemployed. Efforts to reduce income and educational gaps and address structural racism, which shapes the distribution of health-promoting and health-harming resources, are paramount to reduce inequities in CVH.

Notable paradoxical phenomena in associations between cardiovascular health score, subclinical and clinical cardiovascular disease in the community: The Framingham Heart Study.

IMPORTANCE: Cardiovascular Health (CVH) scores are inversely associated with prevalent subclinical (SubDz) and incident cardiovascular disease (CVD). However, the majority of people who develop CVD have intermediate or ideal CVH scores, while many with poor CVH profiles escape CVD development. OBJECTIVE: To describe the prevalence of paradoxical relations among CVH, SubDz, and CVD. DESIGN: Cohort study, Framingham Study data collected prospectively (1995-2016). SETTING: Population-based. PARTICIPANTS: 7,627 participants (mean age 49 years, 53% women) attending Offspring examinations 6/7 and Third Generation examinations 1/2. EXPOSURES: CVH score (range 0-14) constructed from poor, intermediate, or ideal status for each metric (smoking, diet, physical activity, blood pressure, body mass index, fasting glucose, total cholesterol); and prevalent SubDz (≥1 of: increased carotid intimal media thickness, CIMT; left ventricular hypertrophy, LVH; microalbuminuria, MA; elevated ankle brachial index, ABI; coronary artery calcium score ≥100,CAC). MAIN OUTCOME(S) AND MEASURE(S): Ideal CVH (scores 12-14), intermediate CVH (scores 8-11), and poor CVH (0-7). We described three distinct paradoxical phenomena, involving combinations of CVH, SubDz, and CVD, and generated CVD incidence rates and predicted CVD probabilities for all combinations. RESULTS: We observed 842 CVD events (median follow-up 13.7 years); 1,663 participants had SubDz. Most individuals with poor CVH (78%) or SubDz (57% for CIMT to 77% for LVH) did not develop CVD on follow-up. Among participants with incident CVD, the majority had intermediate or ideal CVH (68%) or absent SubDz (46% for CAC to 96% for ABI) at baseline. We observed similar paradoxical results in relations between CVH and prevalent SubDz. Poor CVH and prevalent SubDz were each associated with higher CVD incidence rates compared to intermediate or ideal CVH and absent SubDz, respectively. The predicted CVD probability was nearly three-times greater among participants with poor (22%) versus intermediate or ideal CVH (8%). Mean CVD predicted probabilities were nearly three (26% vs. 10% for MA) to six-times (29% vs. 5% for CAC) greater among participants with SubDz versus without SubDz. Findings were consistent within age and sex strata. CONCLUSIONS AND RELEVANCE: Although poor CVH and SubDz presence are associated with CVD incidence, paradoxical phenomena involving CVH, SubDz, and CVD are frequently prevalent in the community. Further studies to elucidate biological mechanisms underlying these phenomena are warranted.