Social Risk Profile and Cardiovascular‐Kidney‐Metabolic Syndrome in US Adults

Khan S.S., Coresh J., Pencina M.J., Ndumele C.E., Rangaswami J., Chow S.L., Palaniappan L.P., Sperling L.S., Virani S.S., Ho J.E., Neeland I.J., Tuttle K.R., Rajgopal Singh R., Elkind M.S., Lloyd-Jones D.M.

Cardiovascular-kidney-metabolic (CKM) syndrome is a novel construct recently defined by the American Heart Association in response to the high prevalence of metabolic and kidney disease. Epidemiological data demonstrate higher absolute risk of both atherosclerotic cardiovascular disease (CVD) and heart failure as an individual progresses from CKM stage 0 to stage 3, but optimal strategies for risk assessment need to be refined. Absolute risk assessment with the goal to match type and intensity of interventions with predicted risk and expected treatment benefit remains the cornerstone of primary prevention. Given the growing number of therapies in our armamentarium that simultaneously address all 3 CKM axes, novel risk prediction equations are needed that incorporate predictors and outcomes relevant to the CKM context. This should also include social determinants of health, which are key upstream drivers of CVD, to more equitably estimate and address risk. This scientific statement summarizes the background, rationale, and clinical implications for the newly developed sex-specific, race-free risk equations: PREVENT (AHA Predicting Risk of CVD Events). The PREVENT equations enable 10- and 30-year risk estimates for total CVD (composite of atherosclerotic CVD and heart failure), include estimated glomerular filtration rate as a predictor, and adjust for competing risk of non-CVD death among adults 30 to 79 years of age. Additional models accommodate enhanced predictive utility with the addition of CKM factors when clinically indicated for measurement (urine albumin-to-creatinine ratio and hemoglobin A1c) or social determinants of health (social deprivation index) when available. Approaches to implement risk-based prevention using PREVENT across various settings are discussed.

Ndumele C.E., Neeland I.J., Tuttle K.R., Chow S.L., Mathew R.O., Khan S.S., Coresh J., Baker-Smith C.M., Carnethon M.R., Després J., Ho J.E., Joseph J.J., Kernan W.N., Khera A., Kosiborod M.N., et. al.

A growing appreciation of the pathophysiological interrelatedness of metabolic risk factors such as obesity and diabetes, chronic kidney disease, and cardiovascular disease has led to the conceptualization of cardiovascular-kidney-metabolic syndrome. The confluence of metabolic risk factors and chronic kidney disease within cardiovascular-kidney-metabolic syndrome is strongly linked to risk for adverse cardiovascular and kidney outcomes. In addition, there are unique management considerations for individuals with established cardiovascular disease and coexisting metabolic risk factors, chronic kidney disease, or both. An extensive body of literature supports our scientific understanding of, and approach to, prevention and management for individuals with cardiovascular-kidney-metabolic syndrome. However, there are critical gaps in knowledge related to cardiovascular-kidney-metabolic syndrome in terms of mechanisms of disease development, heterogeneity within clinical phenotypes, interplay between social determinants of health and biological risk factors, and accurate assessments of disease incidence in the context of competing risks. There are also key limitations in the data supporting the clinical care for cardiovascular-kidney-metabolic syndrome, particularly in terms of early-life prevention, screening for risk factors, interdisciplinary care models, optimal strategies for supporting lifestyle modification and weight loss, targeting of emerging cardioprotective and kidney-protective therapies, management of patients with both cardiovascular disease and chronic kidney disease, and the impact of systematically assessing and addressing social determinants of health. This scientific statement uses a crosswalk of major guidelines, in addition to a review of the scientific literature, to summarize the evidence and fundamental gaps related to the science, screening, prevention, and management of cardiovascular-kidney-metabolic syndrome.

Ndumele C.E., Rangaswami J., Chow S.L., Neeland I.J., Tuttle K.R., Khan S.S., Coresh J., Mathew R.O., Baker-Smith C.M., Carnethon M.R., Despres J., Ho J.E., Joseph J.J., Kernan W.N., Khera A., et. al.

Cardiovascular-kidney-metabolic health reflects the interplay among metabolic risk factors, chronic kidney disease, and the cardiovascular system and has profound impacts on morbidity and mortality. There are multisystem consequences of poor cardiovascular-kidney-metabolic health, with the most significant clinical impact being the high associated incidence of cardiovascular disease events and cardiovascular mortality. There is a high prevalence of poor cardiovascular-kidney-metabolic health in the population, with a disproportionate burden seen among those with adverse social determinants of health. However, there is also a growing number of therapeutic options that favorably affect metabolic risk factors, kidney function, or both that also have cardioprotective effects. To improve cardiovascular-kidney-metabolic health and related outcomes in the population, there is a critical need for (1) more clarity on the definition of cardiovascular-kidney-metabolic syndrome; (2) an approach to cardiovascular-kidney-metabolic staging that promotes prevention across the life course; (3) prediction algorithms that include the exposures and outcomes most relevant to cardiovascular-kidney-metabolic health; and (4) strategies for the prevention and management of cardiovascular disease in relation to cardiovascular-kidney-metabolic health that reflect harmonization across major subspecialty guidelines and emerging scientific evidence. It is also critical to incorporate considerations of social determinants of health into care models for cardiovascular-kidney-metabolic syndrome and to reduce care fragmentation by facilitating approaches for patient-centered interdisciplinary care. This presidential advisory provides guidance on the definition, staging, prediction paradigms, and holistic approaches to care for patients with cardiovascular-kidney-metabolic syndrome and details a multicomponent vision for effectively and equitably enhancing cardiovascular-kidney-metabolic health in the population.

Vanjani R., Reddy N., Giron N., Bai E., Martino S., Smith M., Harrington-Steppen S., Trimbur M.C.

Wang L., Zhang H., Yao H., Gong C., Zhong J., Liu D., Liang Z.

AbstractBackgroundSocial determinants of health (SDH) reflecting social deprivation have been developed for population health management. There is a paucity of data on the prevalence of SDH and its associations with prevalent hypertension in women compared with men.MethodsA total of 49 791 participants aged over 20 years from the 1999–2018 National Health and Nutrition Examination Surveys, were included. Information on the SDH, including race/ethnicity, education level, family income, housing, marriage status, employment, were collected. We calculated the prevalence ratio (PR) for each adverse SDH with prevalent hypertension and uncontrolled hypertension by using Cox regression with equal times of follow‐up assigned to all individuals with adjustment for age, diabetes, taking lipid‐lowering medication, and health behaviors. The population‐attributable fractions (PAF) of the SDH were also assessed.ResultsA lower proportion of low education attainment was observed in women than men (women: 16.8% vs. men: 17.9%, p = .003), but women had higher proportions of low family income (15.3% vs. 12.5%, p < .001), unmarried state (47.3% vs. 40.9%, p < .001), and unemployment (22.7% vs. 10.7%, p < .001). All the SDH was significantly associated with hypertension in women. There were significant dose–response associations between the numbers of adverse SDH with hypertension. The total PAF of SDH for prevalent hypertension was greater in women (22.2%) than in men (13.9%).ConclusionsThe widely influential SDH is associated with prevalent hypertension and uncontrolled hypertension. To improve hypertension management, health resources should prioritize socioeconomically disadvantaged groups considering gender differences.

Brandt E.J., Mozaffarian D., Leung C.W., Berkowitz S.A., Murthy V.L.

Poor nutrition is the leading cause of poor health, health care spending, and lost productivity in the United States and globally, which acts through cardiometabolic diseases as precursors to cardiovascular disease, cancer, and other conditions. There is great interest in how the social determinants of health (the conditions in which people are born, live, work, develop, and age) impact cardiometabolic disease. Food insecurity is an example of a powerful social determinant of health that impacts health outcomes. Nutrition insecurity, a distinct but related concept to food insecurity, is a direct determinant of health. In this article, we provide an overview of how diet in early life relates to cardiometabolic disease and then continue to focus on the concepts of food insecurity and nutrition insecurity. In the discussions herein we make important distinctions between the concepts of food insecurity and nutrition insecurity and provide a review of their concepts, histories, measurement and assessment devices, trends and prevalence, and links to health and health disparities. The discussions here set the stage for future research and practice to directly address the negative consequences of food and nutrition insecurity.

Baccarelli A.A., Ordovás J.

Epigenetics has transformed our understanding of the molecular basis of complex diseases, including cardiovascular and metabolic disorders. This review offers a comprehensive overview of the current state of knowledge on epigenetic processes implicated in cardiovascular and metabolic diseases, highlighting the potential of DNA methylation as a precision medicine biomarker and examining the impact of social determinants of health, gut bacterial epigenomics, noncoding RNA, and epitranscriptomics on disease development and progression. We discuss challenges and barriers to advancing cardiometabolic epigenetics research, along with the opportunities for novel preventive strategies, targeted therapies, and personalized medicine approaches that may arise from a better understanding of epigenetic processes. Emerging technologies, such as single-cell sequencing and epigenetic editing, hold the potential to further enhance our ability to dissect the complex interplay between genetic, environmental, and lifestyle factors. To translate research findings into clinical practice, interdisciplinary collaborations, technical and ethical considerations, and accessibility of resources and knowledge are crucial. Ultimately, the field of epigenetics has the potential to revolutionize the way we approach cardiovascular and metabolic diseases, paving the way for precision medicine and personalized health care, and improving the lives of millions of individuals worldwide affected by these conditions.

Bundy J.D., Mills K.T., He H., LaVeist T.A., Ferdinand K.C., Chen J., He J.

BackgroundRacial and ethnic disparities in mortality persist in the US population. We studied the contribution of social determinants of health (SDoH) to racial and ethnic disparities in premature death.MethodsA nationally representative sample of individuals aged 20–74 years who participated in the US National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018 were included. Self-reported SDoH (employment, family income, food security, education, access to health care, health insurance, housing instability, and being married or living with a partner) were collected in each survey cycle. Participants were categorised into four groups of race and ethnicity: Black, Hispanic, White, and other. Deaths were ascertained from linkage to the National Death Index with follow-up until 2019. Multiple mediation analysis was used to assess simultaneous contributions of each individual SDoH to racial disparities in premature all-cause mortality.FindingsWe included 48 170 NHANES participants in our analyses, consisting of 10 543 (21·9%) Black participants, 13 211 (27·4%) Hispanic participants, 19 629 (40·7%) White participants, and 4787 (9·9%) participants of other racial and ethnic groups. Mean survey-weighted age was 44·3 years (95% CI 44·0–44·6), 51·3% (50·9–51·8) of participants were women, and 48·7% (48·2–49·1) were men. 3194 deaths before age 75 years were recorded (930 Black participants, 662 Hispanic participants, 1453 White participants, and 149 other participants). Black adults had significantly higher premature mortality than other racial and ethnic groups (p

Khan N., Javed Z., Acquah I., Hagan K., Khan M., Valero-Elizondo J., Chang R., Javed U., Taha M.B., Blaha M.J., Virani S.S., Sharma G., Blankstein R., Gulati M., Mossialos E., et. al.

Abstract Introduction Educational attainment is an important social determinant of health (SDOH) for cardiovascular disease (CVD). However, the association between educational attainment and all-cause and CVD mortality has not been longitudinally evaluated on a population-level in the US, especially in individuals with atherosclerotic cardiovascular disease (ASCVD). In this nationally representative study, we assessed the association between educational attainment and the risk of all-cause and cardiovascular (CVD) mortality in the general adult population and in adults with ASCVD in the US. Methods We used data from the 2006–2014 National Death Index-linked National Health Interview Survey for adults ≥ 18 years. We generated age-adjusted mortality rates (AAMR) by levels of educational attainment (< high school (HS), HS/General Education Development (GED), some college, and ≥ College) in the overall population and in adults with ASCVD. Cox proportional hazards models were used to examine the multivariable-adjusted associations between educational attainment and all-cause and CVD mortality. Results The sample comprised 210,853 participants (mean age 46.3), representing ~ 189 million adults annually, of which 8% had ASCVD. Overall, 14.7%, 27%, 20.3%, and 38% of the population had educational attainment < HS, HS/GED, Some College, and ≥ College, respectively. During a median follow-up of 4.5 years, all-cause age-adjusted mortality rates were 400.6 vs. 208.6 and 1446.7 vs. 984.0 for the total and ASCVD populations for < HS vs ≥ College education, respectively. CVD age adjusted mortality rates were 82.1 vs. 38.7 and 456.4 vs 279.5 for the total and ASCVD populations for < HS vs ≥ College education, respectively. In models adjusting for demographics and SDOH, < HS (reference =  ≥ College) was associated with 40–50% increased risk of mortality in the total population and 20–40% increased risk of mortality in the ASCVD population, for both all-cause and CVD mortality. Further adjustment for traditional risk factors attenuated the associations but remained statistically significant for < HS in the overall population. Similar trends were seen across sociodemographic subgroups including age, sex, race/ethnicity, income, and insurance status. Conclusions Lower educational attainment is independently associated with increased risk of all-cause and CVD mortality in both the total and ASCVD populations, with the highest risk observed for individuals with < HS education. Future efforts to understand persistent disparities in CVD and all-cause mortality should pay close attention to the role of education, and include educational attainment as an independent predictor in mortality risk prediction algorithms.

Baez A.S., Ortiz-Whittingham L.R., Tarfa H., Baah F.O., Thompson K., Baumer Y., Powell-Wiley T.M.

Social determinants of health (SDoH), or the socioeconomic, environmental, and psychosocial conditions in which individuals spend their daily lives, substantially influence obesity as a cardiovascular disease (CVD) risk factor. The coronavirus disease 2019 (COVID-19) pandemic highlighted the converging epidemics of obesity, CVD, and social inequities globally. Obesity and CVD serve as independent risk factors for COVID-19 severity and lower-resourced populations most impacted by adverse SDoH have the highest COVID-19 mortality rates. Better understanding the interplay between social and biologic factors that contribute to obesity-related CVD disparities are important to equitably address obesity across populations. Despite efforts to investigate SDoH and their biologic effects as drivers of health disparities, the connections between SDoH and obesity remain incompletely understood. This review aims to highlight the relationships between socioeconomic, environmental, and psychosocial factors and obesity. We also present potential biologic factors that may play a role in the biology of adversity, or link SDoH to adiposity and poor adipo-cardiology outcomes. Finally, we provide evidence for multi-level obesity interventions targeting multiple aspects of SDoH. Throughout, we emphasize areas for future research to tailor health equity-promoting interventions across populations to reduce obesity and obesity-related CVD disparities.

Brandt E.J., Chang T., Leung C., Ayanian J.Z., Nallamothu B.K.

ImportanceFood insecurity is a risk factor for poor cardiovascular outcomes that occur disproportionately among individuals from racial and ethnic minority backgrounds who have cardiovascular disease (CVD) or cardiometabolic risk factors.ObjectiveTo assess long-term prevalence of food insecurity among those with CVD or cardiometabolic risk factors in the United States.Design, Setting, and ParticipantsThis serial cross-sectional study includes data for noninstitutionalized US adults from the National Health and Nutrition Examination Survey (1999-2018).Main Outcomes and MeasuresFood insecurity was assessed using the US Department of Agriculture Adult Food Security Survey Module. We estimated prevalence of food insecurity among adults with prior CVD (myocardial infarction, stroke, heart failure) and cardiometabolic risk factors (hypertension, diabetes, obesity, hyperlipidemia) across racial and ethnic groups and prevalence of Supplemental Nutrition Assistance Program (SNAP) participation among those reporting food insecurity.ResultsIn the analytic sample of 57 517 adults, 6770 individuals (11.8%) reported food insecurity, which was more prevalent among Hispanic (1938 [24.0%]) and non-Hispanic Black (1202 [18.2%]) than non-Hispanic Asian (100 [8.0%]) and non-Hispanic White adults (3221 [8.5%]). Among 57 517 adults, 4527 (7.9%) had any CVD, 2933 (5.1%) coronary artery disease, 1536 (2.7%) stroke, 1363 (2.4%) heart failure, 28 528 (49.6%) hypertension, 17 979 (33.2%) obesity, 6418 (11.2%) diabetes, and 19 178 (30.8%) dyslipidemia. All CVD and cardiometabolic diseases except coronary artery disease were more prevalent among those with food insecurity. Food insecurity increased over time and was more frequent for patients with CVD but not for cardiometabolic risk factors. From 2011 to 2018, non-Hispanic Black adults with CVD had a decrease in food insecurity prevalence (36.6%; 95% CI, 23.9%-49.4%, to 25.4%; 95% CI, 21.4%-29.3%; P = .04 for trend), whereas adults of other races and ethnicities or data based on cardiometabolic risk factors had no significant change. For individuals who had food insecurity, SNAP participation was higher among those with CVD vs without CVD (54.2%; 95% CI, 46.6%-61.8%, vs 44.3%; 95% CI, 40.5%-48.1%; P = .01).Conclusions and RelevanceThe prevalence of food insecurity among patients with CVD increased over time. Although members of non-Hispanic Black and Hispanic groups had the highest food insecurity, non-Hispanic Black individuals with CVD were the only group to have a significant decrease in food insecurity since 2011. Increased recognition of food insecurity and resources for treating it are needed to address the negative consequences of food insecurity on CVD outcomes.

Hundemer G.L., Ravani P., Sood M.M., Zimmerman D., Molnar A.O., Moorman D., Oliver M.J., White C., Hiremath S., Akbari A.

ABSTRACT Background The transition from chronic kidney disease (CKD) to kidney failure is a vulnerable time for patients, with suboptimal transitions associated with increased morbidity and mortality. Whether social determinants of health are associated with suboptimal transitions is not well understood. Methods This retrospective cohort study included 1070 patients with advanced CKD who were referred to the Ottawa Hospital Multi-Care Kidney Clinic and developed kidney failure (dialysis or kidney transplantation) between 2010 and 2021. Social determinant information, including education level, employment status and marital status, was collected under routine clinic protocol. Outcomes surrounding suboptimal transition included inpatient (versus outpatient) dialysis starts, pre-emptive (versus delayed) access creation and pre-emptive kidney transplantation. We examined the association between social determinants of health and suboptimal transition outcomes using multivariable logistic regression. Results The mean age and estimated glomerular filtration rate were 63 years and 18 ml/min/1.73 m2, respectively. Not having a high school degree was associated with higher odds for an inpatient dialysis start compared with having a college degree {odds ratio [OR] 1.71 [95% confidence interval (CI) 1.09–2.69]}. Unemployment was associated with higher odds for an inpatient dialysis start [OR 1.85 (95% CI 1.18–2.92)], lower odds for pre-emptive access creation [OR 0.53 (95% CI 0.34–0.82)] and lower odds for pre-emptive kidney transplantation [OR 0.48 (95% CI 0.24–0.96)] compared with active employment. Being single was associated with higher odds for an inpatient dialysis start [OR 1.44 (95% CI 1.07–1.93)] and lower odds for pre-emptive access creation [OR 0.67 (95% CI 0.50–0.89)] compared with being married. Conclusions Social determinants of health, including education, employment and marital status, are associated with suboptimal transitions from CKD to kidney failure.

Cogley C., Carswell C., Bramham K., Chilcot J.

Winitzki D., Zacharias H.U., Nadal J., Baid-Agrawal S., Schaeffner E., Schmid M., Busch M., Bergmann M.M., Schultheiss U., Kotsis F., Stockmann H., Meiselbach H., Wolf G., Krane V., Sommerer C., et. al.

Prospective data on impact of educational attainment on prognosis in patients with chronic kidney disease (CKD) are scarce. We investigated the association between educational attainment and all-cause mortality, major adverse cardiovascular (CV) events (MACEs), kidney failure requiring dialysis, and CKD etiology.Participants (N = 5095, aged 18-74 years) of the ongoing multicenter German Chronic Kidney Disease (GCKD) cohort, enrolled on the basis of an estimated glomerular filtration rate (eGFR) of 30 to 60 ml/min (stages G3, A1-A3) or overt proteinuria (stages G1-G2, A3), were divided into 3 categories according to their educational attainment and were followed for 6.5 years.Participants with low educational attainment (vs. high) had a higher risk for mortality (hazard ratio [HR] 1.48, 95% CI: 1.16-1.90), MACE (HR 1.37, 95% CI: 1.02-1.83), and kidney failure (HR 1.54, 95% CI: 1.15-2.05). Mediators between low educational attainment and mortality were smoking, CV disease (CVD) at baseline, low income, higher body mass index, and higher serum levels of CRP, high-density lipoprotein cholesterol, uric acid, NGAL, BAP, NT-proBNP, OPN, H-FABP, and urea. Low educational attainment was positively associated with diabetic nephropathy (odds ratio [OR] 1.65, 95% CI: 1.36-2.0) and CKD subsequent to acute kidney injury (OR 1.56, 95% CI: 1.03-2.35), but negatively associated with IgA nephropathy (OR 0.68, 95% CI: 0.52-0.90).Low educational attainment is associated with adverse outcomes and CKD etiology. Lifestyle habits and biomarkers mediate associations between low educational attainment and mortality. Recognition of the role of educational attainment and the associated health-relevant risk factors is important to optimize the care of patients with CKD and improve prognosis.

Powell-Wiley T.M., Baumer Y., Baah F.O., Baez A.S., Farmer N., Mahlobo C.T., Pita M.A., Potharaju K.A., Tamura K., Wallen G.R.

Social determinants of health (SDoH), which encompass the economic, social, environmental, and psychosocial factors that influence health, play a significant role in the development of cardiovascular disease (CVD) risk factors as well as CVD morbidity and mortality. The COVID-19 pandemic and the current social justice movement sparked by the death of George Floyd have laid bare long-existing health inequities in our society driven by SDoH. Despite a recent focus on these structural drivers of health disparities, the impact of SDoH on cardiovascular health and CVD outcomes remains understudied and incompletely understood. To further investigate the mechanisms connecting SDoH and CVD, and ultimately design targeted and effective interventions, it is important to foster interdisciplinary efforts that incorporate translational, epidemiological, and clinical research in examining SDoH-CVD relationships. This review aims to facilitate research coordination and intervention development by providing an evidence-based framework for SDoH rooted in the lived experiences of marginalized populations. Our framework highlights critical structural/socioeconomic, environmental, and psychosocial factors most strongly associated with CVD and explores several of the underlying biologic mechanisms connecting SDoH to CVD pathogenesis, including excess stress hormones, inflammation, immune cell function, and cellular aging. We present landmark studies and recent findings about SDoH in our framework, with careful consideration of the constructs and measures utilized. Finally, we provide a roadmap for future SDoH research focused on individual, clinical, and policy approaches directed towards developing multilevel community-engaged interventions to promote cardiovascular health.

Tang H., Zhang X., Luo N., Huang J., Yang Q., Lin H., Lin M., Wu S., Wen J., Hong J., Chen P., Jiang L., Chen Y., Tan X.

Zhu R., Wang R., He J., Wang L., Chen H., Wang Y., An P., Li K., Ren F., Xu W., Martinez J.A., Raben A., Guo J.

Wu S., Zhu J., Lyu S., Wang J., Shao X., Zhang H., Zhong Z., Liu H., Zheng L., Chen Y.

Background The association between DNA methylation age acceleration (DNAmAA) and cardiovascular‐kidney‐metabolic (CKM) syndrome stages and long‐term mortality in the population with CKM syndrome remains unclear. Methods and Results This cohort study included 1889 participants from the National Health and Nutrition Examination Survey (1999–2002) with CKM stages and DNA methylation age data. DNAmAA was calculated as residuals from the regression of DNA methylation age on chronological age. The primary outcome was all‐cause mortality, with cardiovascular and noncardiovascular mortality as secondary outcomes. Proportional odds models assessed the associations between DNAmAAs and CKM stages, and Cox proportional hazards regression models estimated the associations between DNAmAAs and mortality. Significant associations were found between DNAmAAs and advanced CKM stages, particularly for GrimAge2Mort acceleration (GrimAA) (odds ratio [OR], 1.547 [95% CI, 1.316–1.819]). Over an average follow‐up of 14 years, 1015 deaths occurred. Each 5‐unit increase in GrimAA was associated with a 50% increase in all‐cause mortality (95% CI, 1.39–1.63), a 77% increase in cardiovascular mortality (95% CI, 1.46–2.15), and a 42% increase in noncardiovascular mortality (95% CI, 1.27–1.59). With the lowest GrimAA tertile as a reference, the highest GrimAA tertile showed hazard ratios of 1.95 (95% CI, 1.56–2.45) for all‐cause mortality, 3.06 (95% CI, 2.13–4.40) for cardiovascular mortality, and 1.65 (95% CI, 1.20–2.29) for noncardiovascular mortality. Mediation analysis indicated that GrimAA mediates the association between various exposures (including physical activity, Healthy Eating Index‐2015 score, hemoglobin A1c, etc.) and mortality. Conclusions GrimAA may serve as a valuable biomarker for assessing CKM stages and mortality risk in individuals with CKM syndrome, thereby informing personalized management strategies.

Zhang H., Hu Z., Li X., Li Y., Wang X., Jin L., Jiang S., Li X., Hao M.

AbstractCardiovascular-kidney-metabolic (CKM) syndrome, characterized by pathophysiological interactions among metabolic risk factors, chronic kidney disease and the cardiovascular system, is a significant global health concern, particularly in populations with adverse social determinants of health (SDOH). However, the influence of CKM syndrome and the joint effects of SDOH on the risk of developing incident dementia has not been fully elucidated. Here, we examined these associations among 382569 individuals from the UK Biobank. We found that unfavorable SDOH and advanced CKM syndrome (stage 3-4) are independently associated with increased risks of incident all-cause dementia, Alzheimer’s disease and vascular dementia. Additionally, joint associations of CKM syndrome stages and SODH with incident dementia were observed. Individuals with ≥3 unfavorable SDOH and in CKM syndrome stage 4 exhibited the highest dementia risk, even after adjusting for APOE ε4 status. Our findings highlighted the importance of maintaining optimal CKM health and addressing unfavorable SODH in cognitive aging.

Kim J., Joo J., Kuku K.O., Downie C., Hashemian M., Powell-Wiley T.M., Shearer J.J., Roger V.L.

Tang J., Xu Z., Ren L., Xu J., Chen X., Jin Y., Liang R., Zhang H.

Cardiovascular-kidney-metabolic (CKM) syndrome is characterized as a systemic disease resulting from the pathophysiological interplay among metabolic risk factors, chronic kidney disease (CKD), and cardiovascular disease (CVD). The Klotho protein may serve as a novel biomarker. However, the utility of serum Klotho levels as an indicator of severity and mortality risk in CKM syndrome remains uncertain. This study involved 9,871 participants from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2016. Serum Klotho levels were measured using an enzyme-linked immunosorbent assay kit. The optimal cutoff value was established through the maximum Youden’s index. Multivariable weighted regression models were employed to calculate the odds ratio and hazard ratio, along with the 95% confidence interval, to evaluate the association between serum Klotho levels and the severity of CKM syndrome, as well as all-cause and cardiovascular mortality. Additionally, the receiver operating characteristic curve and restricted cubic spline curves were utilized to assess predictive efficacy and to explore nonlinear relationships. After adjusting for potential confounding factors, a non-linear relationship was seen between the Klotho protein, and CKM syndrome. In the multivariable, piecewise logistic regression, when the Serum klotho was less than 801, the risk of CKM syndrome decreased with the increase in Serum klotho (OR = 0.82, 95%CI 0.70, 0.96; p < 0.001). Furthermore, we observed the association when the Serum klotho was greater than 801 (OR = 0.94, 95%CI 0.89, 0.99; p = 0.035). The relationship between serum Klotho levels and all-cause mortality was U-shaped, while the relationship with cardiovascular mortality was L-shaped. Specifically, low serum Klotho levels were associated with an increase in all-cause mortality by 21% and cardiovascular mortality by 76% among patients with CKM syndrome. Furthermore, serum Klotho levels demonstrated excellent predictive efficacy for both the severity and mortality associated with CKM syndrome. This study indicates that low serum Klotho levels serve as reliable indicators of both the severity of CKM syndrome and the associated risk of mortality.

Trimarco V., Izzo R., Pacella D., Virginia Manzi M., Trama U., Lembo M., Piccinocchi R., Gallo P., Esposito G., Morisco C., Rozza F., Mone P., Jankauskas S.S., Piccinocchi G., Santulli G., et. al.

Johnson A.E., Magnani J.W.

April‐Sanders A.K.