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Circulation Nov 2023A growing appreciation of the pathophysiological interrelatedness of metabolic risk factors such as obesity and diabetes, chronic kidney disease, and cardiovascular... (Review)
Review
A Synopsis of the Evidence for the Science and Clinical Management of Cardiovascular-Kidney-Metabolic (CKM) Syndrome: A Scientific Statement From the American Heart Association.
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.
Topics: United States; Humans; Cardiovascular Diseases; Metabolic Syndrome; American Heart Association; Risk Factors; Kidney; Renal Insufficiency, Chronic
PubMed: 37807920
DOI: 10.1161/CIR.0000000000001186 -
Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the American Heart Association.Circulation Nov 2023Cardiovascular-kidney-metabolic health reflects the interplay among metabolic risk factors, chronic kidney disease, and the cardiovascular system and has profound... (Review)
Review
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.
Topics: United States; Humans; Cardiovascular Diseases; Metabolic Syndrome; American Heart Association; Risk Factors; Cardiovascular System; Kidney
PubMed: 37807924
DOI: 10.1161/CIR.0000000000001184 -
Current Problems in Cardiology Feb 2024The correlation between obesity, type 2 diabetes mellitus (DM), cardiovascular disease (CVD), and chronic kidney disease (CKD) is an escalating and widely acknowledged... (Review)
Review
The correlation between obesity, type 2 diabetes mellitus (DM), cardiovascular disease (CVD), and chronic kidney disease (CKD) is an escalating and widely acknowledged epidemic in industrialized nations. Recently, this complex web of interrelated health conditions has been collectively defined as the Cardiovascular-Kidney-Metabolic (CKM) syndrome by the American Heart Association (AHA). The molecular mechanisms underlying CKM disease contain a spectrum of interconnected factors, including hyperglycemia, insulin resistance, heightened activity of the renin-angiotensin-aldosterone system (RAAS), the generation of advanced glycation end-products, oxidative stress, lipotoxicity, endoplasmic reticulum stress, abnormalities in calcium handling, malfunctioning of mitochondria and impaired energy production, as well as persistent chronic inflammation. Addressing their prevention, management, and treatment is of paramount importance to promote better patient health outcomes. The objective of this review is to provide a comprehensive and critical examination of the current state-of-the-art regarding the recently defined CKM syndrome. This includes an exploration of epidemiological evidence establishing connections between cardio-renal-metabolic diseases, an examination of the underlying pathophysiological mechanisms, and a comprehensive overview of existing treatment modalities.
Topics: Humans; Diabetes Mellitus, Type 2; Metabolic Syndrome; Kidney; Insulin Resistance; Obesity
PubMed: 38103820
DOI: 10.1016/j.cpcardiol.2023.102344 -
British Journal of Anaesthesia Aug 2023Metabolic syndrome and its components are risk factors for cognitive impairment, but their contribution to perioperative neurocognitive disorders is unknown. We examined...
BACKGROUND
Metabolic syndrome and its components are risk factors for cognitive impairment, but their contribution to perioperative neurocognitive disorders is unknown. We examined their associations with the risk of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) in older patients.
METHODS
In 765 male and female participants aged ≥65 years, we measured preoperative metabolic parameters and screened for POD for 7 days or until discharge. POCD was defined through comparison of cognitive change on six neuropsychological tests with non-surgical controls. Multiple logistic regression analyses examined the association of metabolic parameters with risk of POD and POCD with adjustment for age, sex, and surgery type.
RESULTS
A total of 149 patients (19.5% of 765) developed POD and 53 (10.1% of 520 attendees) had POCD at 3 months. Patients with metabolic syndrome were at 1.85-fold higher risk of POD (95% confidence interval [CI] 1.26-2.70). Each 1 mM higher high-density lipoprotein cholesterol (HDL-C) was associated with a 0.47-fold lower POD risk (95% CI 0.30-0.74). Each 1 kg m higher body mass index (BMI) was associated with a 1.09-fold higher POCD risk (95% CI 1.02- 1.16).
CONCLUSIONS
Older surgical patients with metabolic syndrome were at increased risk of POD. Only reduced HDL-C was significantly associated with POD. For POCD, a higher preoperative BMI was identified as a risk factor. These findings add to mounting evidence of a distinct epidemiology of POD and POCD. Screening programmes taking advantage of HDL-C and BMI measurements and of metabolic interventions in reducing perioperative neurocognitive disorders should be evaluated.
CLINICAL TRIAL REGISTRATION
NCT02265263.
Topics: Humans; Male; Female; Aged; Emergence Delirium; Postoperative Cognitive Complications; Delirium; Metabolic Syndrome; Cohort Studies; Postoperative Complications
PubMed: 37344340
DOI: 10.1016/j.bja.2023.04.031 -
Cell Metabolism Dec 2023In a recent Presidential Advisory report, the American Heart Association (AHA) defined cardiovascular-kidney-metabolic (CKM) syndrome as a spectrum of pathology...
In a recent Presidential Advisory report, the American Heart Association (AHA) defined cardiovascular-kidney-metabolic (CKM) syndrome as a spectrum of pathology associated with dysfunctional or excess adiposity and leading to adverse cardiovascular outcomes. Implementing the guidelines set forth by the AHA has the potential to improve population-wide CKM health.
Topics: Humans; Metabolic Syndrome; Kidney; Cardiovascular Diseases
PubMed: 38056429
DOI: 10.1016/j.cmet.2023.10.015 -
Fertility and Sterility Dec 2023The impact of paternal obesity and metabolic disease on semen quality and fertility outcomes is not fully appreciated. With increasing obesity rates, researchers have... (Review)
Review
The impact of paternal obesity and metabolic disease on semen quality and fertility outcomes is not fully appreciated. With increasing obesity rates, researchers have studied the intricate relationship between paternal body mass index, metabolic health, and male fertility. This systematic review identified 112 articles in the MEDLINE database between 2013 and 2023 that investigated the effects of body mass index, diabetes, metabolic syndrome, exercise, weight loss medication, or bariatric surgery on semen parameters, sperm quality, or fertility outcomes. This review suggests that obesity, diabetes, and metabolic syndrome have a negative impact on various parameters of male fertility, from semen quality to sperm deoxyribonucleic acid integrity. There is also mounting evidence that male obesity is correlated negatively with live births via both natural conception and assisted reproductive technologies. Lifestyle interventions, such as physical exercise, generally appear to improve male fertility markers; however, the type and intensity of exercise may play a crucial role. Pharmacologic treatments for weight loss, such as metformin and glucagon-like peptide 1 agonists, present a more complex picture, with studies suggesting both beneficial and detrimental effects on male reproductive health. Similarly, surgical interventions, such as gastric bypass surgery, show promise in improving hormonal imbalances but have mixed effects on semen parameters. Future research is needed to clarify these associations and inform clinical guidelines. In the interim, health practitioners should incorporate these insights into clinical practices, encouraging proactive lifestyle changes and providing targeted treatments to improve male reproductive health.
Topics: Male; Humans; Semen Analysis; Semen; Metabolic Syndrome; Obesity; Infertility, Male; Fertility; Weight Loss; Diabetes Mellitus
PubMed: 37839720
DOI: 10.1016/j.fertnstert.2023.10.017 -
Cell Reports. Medicine Jul 2023Direct diagnosis and accurate assessment of metabolic syndrome (MetS) allow for prompt clinical interventions. However, traditional diagnostic strategies overlook the...
Direct diagnosis and accurate assessment of metabolic syndrome (MetS) allow for prompt clinical interventions. However, traditional diagnostic strategies overlook the complex heterogeneity of MetS. Here, we perform metabolomic analysis in 13,554 participants from the natural cohort and identify 26 hub plasma metabolic fingerprints (PMFs) associated with MetS and its early identification (pre-MetS). By leveraging machine-learning algorithms, we develop robust diagnostic models for pre-MetS and MetS with convincing performance through independent validation. We utilize these PMFs to assess the relative contributions of the four major MetS risk factors in the general population, ranked as follows: hyperglycemia, hypertension, dyslipidemia, and obesity. Furthermore, we devise a personalized three-dimensional plasma metabolic risk (PMR) stratification, revealing three distinct risk patterns. In summary, our study offers effective screening tools for identifying pre-MetS and MetS patients in the general community, while defining the heterogeneous risk stratification of metabolic phenotypes in real-world settings.
Topics: Humans; Metabolic Syndrome; Risk Factors; Obesity; Hypertension; Risk Assessment
PubMed: 37467725
DOI: 10.1016/j.xcrm.2023.101109 -
The Journal of Clinical Endocrinology... Nov 2023Thyroid function has been associated with metabolic syndrome (MetS) in a number of observational studies but the direction of effects and the exact causal mechanism of...
CONTEXT
Thyroid function has been associated with metabolic syndrome (MetS) in a number of observational studies but the direction of effects and the exact causal mechanism of this relationship is still unknown.
OBJECTIVE
To examine genetically predicted effects of thyroid function on MetS risk and its components, and vice versa, using large-scale summary genetic association data.
METHODS
We performed a two-sample bidirectional Mendelian randomization (MR) study using summary statistics from the most comprehensive genome-wide association studies (GWAS) of thyroid-stimulating hormone (TSH, n = 119 715), free thyroxine (fT4, n = 49 269), MetS (n = 291 107), and components of MetS: waist circumference (n = 462 166), fasting blood glucose (n = 281 416), hypertension (n = 463 010), triglycerides (TG, n = 441 016) and high-density lipoprotein cholesterol (HDL-C, n = 403 943). We chose the multiplicative random effects inverse variance weighted (IVW) method as the main analysis. Sensitivity analysis included weighted median and mode analysis, as well as MR-Egger and Causal Analysis Using Summary Effect estimates (CAUSE).
RESULTS
Our results suggest that higher fT4 levels lower the risk of developing MetS (OR = 0.96, P = .037). Genetically predicted fT4 was also positively associated with HDL-C (β = 0.02, P = .008), while genetically predicted TSH was positively associated with TG (β = 0.01, P = .044). These effects were consistent across different MR analyses and confirmed with the CAUSE analysis. In the reverse direction MR analysis, genetically predicted HDL-C was negatively associated with TSH (β = -0.03, P = .046) in the main IVW analysis.
CONCLUSION
Our study suggests that variations in normal-range thyroid function are causally associated with the diagnosis of MetS and with lipid profile, while in the reverse direction, HDL-C has a plausible causal effect on reference-range TSH levels.
Topics: Humans; Genome-Wide Association Study; Mendelian Randomization Analysis; Metabolic Syndrome; Thyroid Gland; Thyrotropin
PubMed: 37339283
DOI: 10.1210/clinem/dgad371 -
Innere Medizin (Heidelberg, Germany) Jul 2023
Topics: Humans; Metabolic Syndrome; Dyslipidemias; Diabetes Mellitus, Type 2
PubMed: 37341737
DOI: 10.1007/s00108-023-01545-7 -
Alzheimer's & Dementia : the Journal of... Jan 2024The association between metabolic syndrome (MetS) and incident dementia remains inconclusive.
INTRODUCTION
The association between metabolic syndrome (MetS) and incident dementia remains inconclusive.
METHODS
In 176,249 dementia-free UK Biobank participants aged ≥60 years at baseline, Cox proportional-hazards models were used to investigate the association between MetS and incident dementia. MetS was defined as the presence of ≥3 of the following: elevated waist circumference, triglycerides, blood pressure, blood glucose, and reduced high-density lipoprotein cholesterol.
RESULTS
Over 15 years of follow-up (median = 12.3), 5255 participants developed dementia. MetS was associated with an increased risk of incident dementia (hazard ratio [HR]: 1.12, 95% confidence interval [CI]: 1.06, 1.18). The association remained consistent when restricting to longer follow-up intervals: >5 to 10 years (HR: 1.17, 95% CI: 1.07, 1.27) and >10 years (HR: 1.22, 95% CI: 1.12, 1.32). Stronger associations were observed in those with ≥4 MetS components and in apolipoprotein-E (APOE)-ε4 non-carriers.
DISCUSSION
In this large population-based prospective cohort, MetS was associated with an increased risk of dementia.
HIGHLIGHTS
MetS was associated with a 12% increased risk of incident all-cause dementia. Associations remained similar after restricting the analysis to those with longer follow-up. The presence of four or five MetS components was significantly associated with dementia. Stronger associations were observed in those with a low genetic risk for dementia.
Topics: Humans; Metabolic Syndrome; Prospective Studies; Biological Specimen Banks; UK Biobank; Risk Factors; Dementia; Incidence
PubMed: 37675869
DOI: 10.1002/alz.13439