Nicole R. Fowler, Katherine A. Partrick, James Taylor, Michael Hornbecker, Kevin Kelleher, Malaz Boustani, Jeffrey L. Cummings, Tim MacLeod, Michelle M. Mielke, Jared R. Brosch, Janice Lee, Eli Shobin, James E. Galvin, Howard Fillit, Chinedu Udeh-Momoh, Deanna R. Willis
Primary care is the ideal setting for early detection of mild cognitive impairment (MCI) and Alzheimer's disease and related dementias (ADRD), as it serves as the primary point of care for most older adults. With the growing aging population, reliance on specialists for detection and diagnosis is unsustainable, highlighting the need for primary care-led assessment. Recent research findings on successful brain health prevention strategies, AD diagnostic tools, and anti-amyloid treatments empower primary care to play a central role in early detection and intervention. Primary care-focused resources are being developed, including tools for cognitive assessments and materials designed to educate patients about brain health and initiate discussions on lifestyle modifications, thereby making early detection more feasible and efficient. Identifying risk factors early enables providers to implement interventions that can slow cognitive decline and improve outcomes for patients and caregivers. If left undetected and unmanaged, MCI and ADRD can lead to worse outcomes, including increased falls, hospitalizations, financial vulnerability, and caregiver stress. Early detection enables the identification of reversible causes of cognitive impairment, supports the management of comorbidities worsened by cognitive decline, mitigates safety risks, and can preserve quality of life. Importantly, primary care is essential for addressing ADRD-related health disparities that disproportionately affect racial minorities, rural populations, and those of lower socioeconomic status. With a focus on the United States healthcare system, this perspective addresses how implementing early detection practices into primary care can improve outcomes for patients and caregivers, reduce societal burdens, and promote health equity in ADRD care.
{"title":"Implementing early detection of cognitive impairment in primary care to improve care for older adults","authors":"Nicole R. Fowler, Katherine A. Partrick, James Taylor, Michael Hornbecker, Kevin Kelleher, Malaz Boustani, Jeffrey L. Cummings, Tim MacLeod, Michelle M. Mielke, Jared R. Brosch, Janice Lee, Eli Shobin, James E. Galvin, Howard Fillit, Chinedu Udeh-Momoh, Deanna R. Willis","doi":"10.1111/joim.20098","DOIUrl":"10.1111/joim.20098","url":null,"abstract":"<p>Primary care is the ideal setting for early detection of mild cognitive impairment (MCI) and Alzheimer's disease and related dementias (ADRD), as it serves as the primary point of care for most older adults. With the growing aging population, reliance on specialists for detection and diagnosis is unsustainable, highlighting the need for primary care-led assessment. Recent research findings on successful brain health prevention strategies, AD diagnostic tools, and anti-amyloid treatments empower primary care to play a central role in early detection and intervention. Primary care-focused resources are being developed, including tools for cognitive assessments and materials designed to educate patients about brain health and initiate discussions on lifestyle modifications, thereby making early detection more feasible and efficient. Identifying risk factors early enables providers to implement interventions that can slow cognitive decline and improve outcomes for patients and caregivers. If left undetected and unmanaged, MCI and ADRD can lead to worse outcomes, including increased falls, hospitalizations, financial vulnerability, and caregiver stress. Early detection enables the identification of reversible causes of cognitive impairment, supports the management of comorbidities worsened by cognitive decline, mitigates safety risks, and can preserve quality of life. Importantly, primary care is essential for addressing ADRD-related health disparities that disproportionately affect racial minorities, rural populations, and those of lower socioeconomic status. With a focus on the United States healthcare system, this perspective addresses how implementing early detection practices into primary care can improve outcomes for patients and caregivers, reduce societal burdens, and promote health equity in ADRD care.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 1","pages":"31-45"},"PeriodicalIF":9.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20098","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adrian Post, Wendy A. Dam, Dion Groothof, Casper F. M. Franssen, Stephan J. L. Bakker, Robin P. F. Dullaart
Background and Objectives
This population-based study explores associations of fibroblast growth factor 21 (FGF21), a key modulator of processes linked to protein metabolism, with protein intake and muscle mass, and their relationships with all-cause mortality.
Methods
In 6395 participants (mean age 54 years; 50% women), circulating FGF21 (immunoassay), protein intake (Maroni equation using 24-h urinary urea excretion; low intake defined as <0.8 g/kg/day), and muscle mass (24-h creatinine excretion rate indexed to height squared (CERI)) were documented.
Results
FGF21 concentration was 896 (540–1384) pg/mL, protein intake was 1.01 (0.85–1.19) g/kg/day, and CERI was 4.1 ± 0.9 mmol/day/m2. Higher FGF21 was associated with higher odds of low protein intake (odds ratio per doubling: 1.48; 95% confidence interval [CI]: 1.38–1.58; p < 0.0001) and lower muscle mass (standardized beta: −0.08; 95% CI: −0.10; −0.06; p < 0.001). Over 10.4 years of follow-up, 955 deaths were registered. Higher FGF21 was associated with increased mortality (hazard ratio (HR) per doubling: 1.09; 95% CI: 1.02–1.16; p = 0.009). Conversely, higher protein intake (HR per doubling: 0.67; 95% CI: 0.56–0.81; p < 0.0001) and higher CERI (HR per standard deviation increase: 0.83; 95% CI: 0.76–0.90; p < 0.0001) were associated with a lower risk of mortality, independent of potential confounders. However, the FGF21-mortality association became non-significant after adjusting for protein intake.
Conclusion
Higher FGF21 was associated with higher odds of low protein intake. The observed association of higher FGF21 concentrations and risk mortality was predominantly attributable to lower protein intake. In contrast, both higher protein intake and higher muscle mass were independently associated with lower mortality risk, highlighting the potential relevance of protein intake and maintenance of muscle mass in long-term health.
{"title":"Higher circulating FGF21, lower protein intake, and lower muscle mass: Associations with a higher risk of mortality","authors":"Adrian Post, Wendy A. Dam, Dion Groothof, Casper F. M. Franssen, Stephan J. L. Bakker, Robin P. F. Dullaart","doi":"10.1111/joim.20099","DOIUrl":"10.1111/joim.20099","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Objectives</h3>\u0000 \u0000 <p>This population-based study explores associations of fibroblast growth factor 21 (FGF21), a key modulator of processes linked to protein metabolism, with protein intake and muscle mass, and their relationships with all-cause mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In 6395 participants (mean age 54 years; 50% women), circulating FGF21 (immunoassay), protein intake (Maroni equation using 24-h urinary urea excretion; low intake defined as <0.8 g/kg/day), and muscle mass (24-h creatinine excretion rate indexed to height squared (CERI)) were documented.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>FGF21 concentration was 896 (540–1384) pg/mL, protein intake was 1.01 (0.85–1.19) g/kg/day, and CERI was 4.1 ± 0.9 mmol/day/m<sup>2</sup>. Higher FGF21 was associated with higher odds of low protein intake (odds ratio per doubling: 1.48; 95% confidence interval [CI]: 1.38–1.58; <i>p</i> < 0.0001) and lower muscle mass (standardized beta: −0.08; 95% CI: −0.10; −0.06; <i>p</i> < 0.001). Over 10.4 years of follow-up, 955 deaths were registered. Higher FGF21 was associated with increased mortality (hazard ratio (HR) per doubling: 1.09; 95% CI: 1.02–1.16; <i>p</i> = 0.009). Conversely, higher protein intake (HR per doubling: 0.67; 95% CI: 0.56–0.81; <i>p</i> < 0.0001) and higher CERI (HR per standard deviation increase: 0.83; 95% CI: 0.76–0.90; <i>p</i> < 0.0001) were associated with a lower risk of mortality, independent of potential confounders. However, the FGF21-mortality association became non-significant after adjusting for protein intake.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Higher FGF21 was associated with higher odds of low protein intake. The observed association of higher FGF21 concentrations and risk mortality was predominantly attributable to lower protein intake. In contrast, both higher protein intake and higher muscle mass were independently associated with lower mortality risk, highlighting the potential relevance of protein intake and maintenance of muscle mass in long-term health.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 1","pages":"2-15"},"PeriodicalIF":9.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alfonso Giaquinto, Veronica Abate, Anita Vergatti, Riccardo Muscariello, Adelaide Iervolino, Martina Pucci, Guido Cavati, Filippo Pirrotta, Gianpaolo De Filippo, Roberta Esposito, Lanfranco D'Elia, Daniela Merlotti, Luigi Gennari, Domenico Rendina
Background
Paget's disease of the bone (PDB) is a metabolic bone disorder involving one or more skeletal sites. Cardiovascular diseases (CVDs) have been described in patients with PDB but have not been systematically analysed.
Objectives
This study aimed to compare standard and advanced (speckle-tracking) echocardiographic parameters measured in patients with PDB and controls matched for age, weight, height and history of hypertension but without metabolic bone disorders.
Methods
This multicentre case–control study included all patients with PDB referred to the Federico II and Siena Universities, Italy, from March 2019 to October 2022. During the same time, we enrolled at least one control for each patient, matched for age, sex, body mass index (BMI) and history of hypertension.
Results
Sixty-nine patients with PDB and 115 healthy controls were enrolled in this study. All patients with PDB were treated with zoledronic acid at the time of diagnosis. Compared with controls, on standard echocardiography, patients with PDB showed a high prevalence of aortic and mitral valve calcifications and/or sclerosis, reduced left ventricular (LV) ejection fraction, stroke volume, cardiac output, increased interventricular septum thickness, posterior wall thickness, LV mass index, relative wall thickness, relative diastolic wall thickness, E/e′ ratio and systemic vascular resistance. Using speckle-tracking echocardiography, patients with PDB showed a lower global longitudinal strain and global myocardial work efficiency than controls. There was no relationship between the PDB activity and extent and severity of cardiac abnormalities.
Conclusion
Overall, the myocardial function and structure were impaired in patients with PDB. Additionally, PDB was associated with early subclinical myocardial damage.
{"title":"Standard and advanced echocardiographic study of patients with Paget's disease of bone: Evidence of a pagetic heart disease?","authors":"Alfonso Giaquinto, Veronica Abate, Anita Vergatti, Riccardo Muscariello, Adelaide Iervolino, Martina Pucci, Guido Cavati, Filippo Pirrotta, Gianpaolo De Filippo, Roberta Esposito, Lanfranco D'Elia, Daniela Merlotti, Luigi Gennari, Domenico Rendina","doi":"10.1111/joim.20069","DOIUrl":"10.1111/joim.20069","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Paget's disease of the bone (PDB) is a metabolic bone disorder involving one or more skeletal sites. Cardiovascular diseases (CVDs) have been described in patients with PDB but have not been systematically analysed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study aimed to compare standard and advanced (speckle-tracking) echocardiographic parameters measured in patients with PDB and controls matched for age, weight, height and history of hypertension but without metabolic bone disorders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This multicentre case–control study included all patients with PDB referred to the Federico II and Siena Universities, Italy, from March 2019 to October 2022. During the same time, we enrolled at least one control for each patient, matched for age, sex, body mass index (BMI) and history of hypertension.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Sixty-nine patients with PDB and 115 healthy controls were enrolled in this study. All patients with PDB were treated with zoledronic acid at the time of diagnosis. Compared with controls, on standard echocardiography, patients with PDB showed a high prevalence of aortic and mitral valve calcifications and/or sclerosis, reduced left ventricular (LV) ejection fraction, stroke volume, cardiac output, increased interventricular septum thickness, posterior wall thickness, LV mass index, relative wall thickness, relative diastolic wall thickness, <i>E</i>/<i>e</i>′ ratio and systemic vascular resistance. Using speckle-tracking echocardiography, patients with PDB showed a lower global longitudinal strain and global myocardial work efficiency than controls. There was no relationship between the PDB activity and extent and severity of cardiac abnormalities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Overall, the myocardial function and structure were impaired in patients with PDB. Additionally, PDB was associated with early subclinical myocardial damage.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"297 6","pages":"630-641"},"PeriodicalIF":9.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>The article by Wu et al. [<span>1</span>] in the <i>Journal of Internal Medicine</i> investigates the relation between clonal hematopoiesis of indeterminate potential (CHIP) and autoimmune diseases. The reason behind such relation might be attributed to changes in the immune system occurring with advanced age.</p><p>Indeed, CHIP is common in the elderly and asymptomatic. Individuals with CHIP have an increased risk of hematologic malignancies and chronic inflammatory diseases, such as cardiovascular disease [<span>2, 3</span>]. The latter has been associated to enhanced production of proinflammatory cytokines and accelerated atherosclerosis. More recently, studies have found associations between CHIP and multiple autoimmune diseases; specifically, large CHIP clones (>10% or >15%) were associated with an increased risk of seropositive rheumatoid arthritis (RA) and, to a lesser extent, RA [<span>4</span>]. Of note is that 60% of patients with the notable hemato-immunoinflammatory VEXAS syndrome have CHIP [<span>5</span>]. Observations from studies of Behçet's disease, a chronic inflammatory immune-mediated disorder, indicate that some extent of inflammation is associated with CHIP emergence [<span>6</span>].</p><p>Wu et al. [<span>1</span>] set out to address the interplay between CHIP and autoimmune diseases. To do so, the authors analyzed data collected from whole blood-derived exome sequencing (WES) of 456,692 UK Biobank participants after exclusion of (a) individuals with hematologic malignancies, (b) individuals with more than 10 third-degree relatives, (c) heterozygous outliers, and (d) participants with a baseline autoimmune disease. Overall, 19 immune-mediated inflammatory diseases were selected (Addison's disease, ankylosing spondylitis, coeliac disease, type 1 diabetes, Graves’ disease, Crohn's disease, ulcerative colitis, multiple sclerosis, myasthenia gravis, pernicious anemia, polymyalgia rheumatica, primary biliary cholangitis, psoriasis, RA, Sjögren's syndrome, systemic lupus erythematosus, systemic sclerosis, vasculitis, and vitiligo). Association between CHIP (with a variant allele frequency [VAF] more than (a) 2%, (b) 10%, and (c) specific CHIP mutation) was analyzed. In total, 58 CHIP genes were included.</p><p>Overall, 17,433 (3.82%) individuals had any CHIP (<i>DNMT3A</i> [2.40%] with p.R882H being the most common mutation, <i>TET2</i> [0.47%], <i>ASXL1</i> variants [0.25%], spliceosomal genes [0.11%], and <i>PPM1D</i> [0.11%] variants). More than one CHIP mutation was detected in 6.10% of individuals. Specific CHIP mutations were associated with different autoimmune diseases. A large part of the study focuses on making inflammation the central node between CHIP and autoimmune disorders. However, as per today, this connection is still very vague and rather inconclusive due to the high number of inflammatory markers possibly involved in the process and the inability to assess all of them.</p><p>A point of discussion rem
{"title":"The yin–yang between clonal hematopoiesis of indeterminate potential and autoimmune diseases","authors":"Zachary Brady, Valeria Visconte","doi":"10.1111/joim.20091","DOIUrl":"10.1111/joim.20091","url":null,"abstract":"<p>The article by Wu et al. [<span>1</span>] in the <i>Journal of Internal Medicine</i> investigates the relation between clonal hematopoiesis of indeterminate potential (CHIP) and autoimmune diseases. The reason behind such relation might be attributed to changes in the immune system occurring with advanced age.</p><p>Indeed, CHIP is common in the elderly and asymptomatic. Individuals with CHIP have an increased risk of hematologic malignancies and chronic inflammatory diseases, such as cardiovascular disease [<span>2, 3</span>]. The latter has been associated to enhanced production of proinflammatory cytokines and accelerated atherosclerosis. More recently, studies have found associations between CHIP and multiple autoimmune diseases; specifically, large CHIP clones (>10% or >15%) were associated with an increased risk of seropositive rheumatoid arthritis (RA) and, to a lesser extent, RA [<span>4</span>]. Of note is that 60% of patients with the notable hemato-immunoinflammatory VEXAS syndrome have CHIP [<span>5</span>]. Observations from studies of Behçet's disease, a chronic inflammatory immune-mediated disorder, indicate that some extent of inflammation is associated with CHIP emergence [<span>6</span>].</p><p>Wu et al. [<span>1</span>] set out to address the interplay between CHIP and autoimmune diseases. To do so, the authors analyzed data collected from whole blood-derived exome sequencing (WES) of 456,692 UK Biobank participants after exclusion of (a) individuals with hematologic malignancies, (b) individuals with more than 10 third-degree relatives, (c) heterozygous outliers, and (d) participants with a baseline autoimmune disease. Overall, 19 immune-mediated inflammatory diseases were selected (Addison's disease, ankylosing spondylitis, coeliac disease, type 1 diabetes, Graves’ disease, Crohn's disease, ulcerative colitis, multiple sclerosis, myasthenia gravis, pernicious anemia, polymyalgia rheumatica, primary biliary cholangitis, psoriasis, RA, Sjögren's syndrome, systemic lupus erythematosus, systemic sclerosis, vasculitis, and vitiligo). Association between CHIP (with a variant allele frequency [VAF] more than (a) 2%, (b) 10%, and (c) specific CHIP mutation) was analyzed. In total, 58 CHIP genes were included.</p><p>Overall, 17,433 (3.82%) individuals had any CHIP (<i>DNMT3A</i> [2.40%] with p.R882H being the most common mutation, <i>TET2</i> [0.47%], <i>ASXL1</i> variants [0.25%], spliceosomal genes [0.11%], and <i>PPM1D</i> [0.11%] variants). More than one CHIP mutation was detected in 6.10% of individuals. Specific CHIP mutations were associated with different autoimmune diseases. A large part of the study focuses on making inflammation the central node between CHIP and autoimmune disorders. However, as per today, this connection is still very vague and rather inconclusive due to the high number of inflammatory markers possibly involved in the process and the inability to assess all of them.</p><p>A point of discussion rem","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"297 6","pages":"558-559"},"PeriodicalIF":9.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20091","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Annie Pedersen, Anna Skarin Nordenvall, Giorgio Tettamanti, Ann Nordgren
Background
Life expectancy for individuals with Down syndrome (DS) has increased dramatically. To improve detection and prevention, the risk of age-related cardiovascular disease in this population needs to be better defined.
Methods
We performed a population-based matched cohort study. Through the National Patient Register (NPR) and/or the Medical Birth Register, we identified all individuals born in Sweden between 1946 and 2000 with a diagnosis of DS. Each individual with DS was matched to 50 comparators by sex, birth year, and county of birth. Data on ischemic and hemorrhagic stroke, acute myocardial infarction (AMI), and covariates indicating cardiovascular risk were retrieved from the NPR. Associations between DS and cardiovascular outcomes were estimated using Cox proportional hazards models. We also assessed the influence of cardiovascular risk factors.
Results
We included 5155 individuals with DS, of which 55% were male. The median age at the end of follow-up was 35 in the DS population and 42 among the comparisons. DS was associated with increased risk of ischemic stroke (hazard ratios [HR] 4.41, 95% confidence intervals [CI] 3.53–5.52) and hemorrhagic stroke (HR 5.14, 95% CI 3.84–6.89). The overall risk of AMI was similar in DS and comparators but increased in young individuals with DS. The risk of ischemic stroke was elevated in individuals with DS with selected atherosclerotic (HR 12.67, 95% CI 7.04–22.78) as well as embolic (HR 10.35, 95% CI 6.69–16.01) risk factors, as compared to comparators without risk factors.
Conclusion
Individuals with DS were at increased risk of cardiovascular outcomes.
背景：唐氏综合症（DS）患者的预期寿命急剧增加。为了改进检测和预防，需要更好地定义这一人群中与年龄相关的心血管疾病的风险。方法：我们进行了一项基于人群的匹配队列研究。通过国家患者登记（NPR）和/或医疗出生登记，我们确定了1946年至2000年间在瑞典出生的所有诊断为DS的个体。每个患有DS的个体按性别、出生年份和出生县与50个比较者相匹配。缺血性和出血性卒中、急性心肌梗死（AMI）和指示心血管风险的协变量数据从NPR中检索。使用Cox比例风险模型估计DS和心血管结局之间的关联。我们还评估了心血管危险因素的影响。结果：纳入5155例DS患者，其中55%为男性。随访结束时，DS人群的中位年龄为35岁，对照组为42岁。DS与缺血性卒中（风险比[HR] 4.41, 95%可信区间[CI] 3.53-5.52）和出血性卒中（风险比[HR] 5.14, 95%可信区间[CI] 3.84-6.89）的风险增加相关。AMI的总体风险在DS和比较组中相似，但在年轻DS患者中增加。与没有危险因素的比较者相比，伴有动脉粥样硬化（HR 12.67, 95% CI 7.04-22.78）和栓塞（HR 10.35, 95% CI 6.69-16.01）危险因素的DS患者发生缺血性卒中的风险升高。结论：退行性椎体滑移患者心血管结局风险增加。
{"title":"Age-related cardiovascular disease in Down syndrome: A population-based matched cohort study","authors":"Annie Pedersen, Anna Skarin Nordenvall, Giorgio Tettamanti, Ann Nordgren","doi":"10.1111/joim.20093","DOIUrl":"10.1111/joim.20093","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Life expectancy for individuals with Down syndrome (DS) has increased dramatically. To improve detection and prevention, the risk of age-related cardiovascular disease in this population needs to be better defined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a population-based matched cohort study. Through the National Patient Register (NPR) and/or the Medical Birth Register, we identified all individuals born in Sweden between 1946 and 2000 with a diagnosis of DS. Each individual with DS was matched to 50 comparators by sex, birth year, and county of birth. Data on ischemic and hemorrhagic stroke, acute myocardial infarction (AMI), and covariates indicating cardiovascular risk were retrieved from the NPR. Associations between DS and cardiovascular outcomes were estimated using Cox proportional hazards models. We also assessed the influence of cardiovascular risk factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We included 5155 individuals with DS, of which 55% were male. The median age at the end of follow-up was 35 in the DS population and 42 among the comparisons. DS was associated with increased risk of ischemic stroke (hazard ratios [HR] 4.41, 95% confidence intervals [CI] 3.53–5.52) and hemorrhagic stroke (HR 5.14, 95% CI 3.84–6.89). The overall risk of AMI was similar in DS and comparators but increased in young individuals with DS. The risk of ischemic stroke was elevated in individuals with DS with selected atherosclerotic (HR 12.67, 95% CI 7.04–22.78) as well as embolic (HR 10.35, 95% CI 6.69–16.01) risk factors, as compared to comparators without risk factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Individuals with DS were at increased risk of cardiovascular outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"297 6","pages":"683-692"},"PeriodicalIF":9.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20093","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhiqi Yao, Beverly G. Tchang, Kacey Chae, Michael Albert, Jeanne M. Clark, Michael J. Blaha
Background
Population-level adverse effects of obesity beyond commonly considered chronic conditions need to be characterized to understand its overall burden.
Objective
To assess the cross-sectional associations between obesity and self-reported status of overall health, quality of life, pain, fatigue, ability of physical activity, and the risks of developing chronic pain syndrome, chronic fatigue syndrome, fibromyalgia, and insomnia.
Methods
Using data from the All of Us Research Program (the United States), we included participants with a body mass index (BMI) ≥18.5 kg/m2 and available Overall Health Survey or electronic health records. Cross-sectional analyses of self-reported variables were conducted using multivariable logistic and linear regression models. Cox proportional-hazard models were used to assess risks for incident outcomes.
Results
Among 323,640 participants (60.3% were female, mean age: 51.3 years), 20.7%, 11.0%, and 9.5% were with Classes I, II, and III obesity, respectively. Higher BMI categories were correlated with worse health metrics, with Class III obesity exhibiting the greatest disparities. Among those with Class III obesity, 9.6% (vs. 3.2% for normal weight) reported poor overall health, 28.3% (vs. 13.2%) reported severe pain, and 11.8% (vs. 8.4%) had prevalent insomnia. Graded associations were observed across high BMI categories, with Class III obesity showing the strongest effects. Compared with normal weight, in Class III obesity, the odds ratio (95% CI) was 3.82 (3.69–3.96) for fair/poor overall health, 3.93 (3.71–4.17) for severe pain, and 3.13 (2.98–3.29) for severely limited physical activity; the hazard ratio (95% CI) was 2.83 (2.36–3.40) for fibromyalgia and 1.53 (1.41–1.65) for insomnia.
Conclusion
Obesity imposes a substantial burden on broad aspects of well-being in the US population.
{"title":"Adverse effects of obesity on overall health, quality of life, and related physical health metrics: A cross-sectional and longitudinal study from the All of Us Research Program","authors":"Zhiqi Yao, Beverly G. Tchang, Kacey Chae, Michael Albert, Jeanne M. Clark, Michael J. Blaha","doi":"10.1111/joim.20083","DOIUrl":"10.1111/joim.20083","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Population-level adverse effects of obesity beyond commonly considered chronic conditions need to be characterized to understand its overall burden.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To assess the cross-sectional associations between obesity and self-reported status of overall health, quality of life, pain, fatigue, ability of physical activity, and the risks of developing chronic pain syndrome, chronic fatigue syndrome, fibromyalgia, and insomnia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using data from the All of Us Research Program (the United States), we included participants with a body mass index (BMI) ≥18.5 kg/m<sup>2</sup> and available Overall Health Survey or electronic health records. Cross-sectional analyses of self-reported variables were conducted using multivariable logistic and linear regression models. Cox proportional-hazard models were used to assess risks for incident outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 323,640 participants (60.3% were female, mean age: 51.3 years), 20.7%, 11.0%, and 9.5% were with Classes I, II, and III obesity, respectively. Higher BMI categories were correlated with worse health metrics, with Class III obesity exhibiting the greatest disparities. Among those with Class III obesity, 9.6% (vs. 3.2% for normal weight) reported poor overall health, 28.3% (vs. 13.2%) reported severe pain, and 11.8% (vs. 8.4%) had prevalent insomnia. Graded associations were observed across high BMI categories, with Class III obesity showing the strongest effects. Compared with normal weight, in Class III obesity, the odds ratio (95% CI) was 3.82 (3.69–3.96) for fair/poor overall health, 3.93 (3.71–4.17) for severe pain, and 3.13 (2.98–3.29) for severely limited physical activity; the hazard ratio (95% CI) was 2.83 (2.36–3.40) for fibromyalgia and 1.53 (1.41–1.65) for insomnia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Obesity imposes a substantial burden on broad aspects of well-being in the US population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"297 6","pages":"657-671"},"PeriodicalIF":9.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jonas Brinck, Karin Littmann, Daniel Eriksson Hogling, Linnea Widman, Kenneth Caidahl, Maria Eriksson, Jonas Johnson, Karolina Szummer, Magnus Bäck
<p>Elevated lipoprotein(a) (Lp(a)) is a dyslipoproteinaemia that causes atherosclerotic cardiovascular disease and calcified aortic valve stenosis (AS) [<span>1, 2</span>]. AS develops over decades and can lead to valve obstruction requiring an aortic valve procedure. Both genetic variations in the LPA gene and an elevated plasma Lp(a) level are associated with an increased incidence of AS [<span>3, 4</span>]. Measurement of peak aortic jet velocity (<i>V</i><sub>max</sub>; m/s) with Doppler echocardiography is used to assess and monitor AS in clinical routine. In the ASTRONOMER trial, a limited number of participants (<i>n</i> = 220) with mild-to-moderate AS (initial <i>V</i><sub>max</sub> ≥ 2.5 m/s) who underwent repeated echocardiography exhibited faster <i>V</i><sub>max</sub> progression with elevated Lp(a) [<span>5-7</span>]. Similar faster haemodynamic progression at higher Lp(a) levels was reported in 129 subjects with AS (initial <i>V</i><sub>max</sub> ≥ 2.0 m/s) from the SATIRE trial and Ring of Fire study [<span>8</span>]. However, the impact of Lp(a) on AS progression in an unselected population has remained unexplored. The aim of the present study was to determine the effect of elevated plasma Lp(a) on AS progression measured as <i>V</i><sub>max</sub> by repeated Doppler echocardiography in a large cohort with and without AS at any stage.</p><p>We performed an observational retrospective cohort study by linking two databases of individuals who had had their plasma Lp(a) level measured 2003–2017 (<i>n</i> = 23,398) and who had ≥2 Doppler echocardiography <i>V</i><sub>max</sub> measurements with ≥6 months of interval 2003–2018 (<i>n</i> = 9889) in the clinical routine in Region Stockholm, Sweden (Fig. S1). Lp(a) was analysed using accredited laboratory methods, reporting values in nmol/L or mg/dL as previously described [<span>9</span>]. Participants were subdivided into three Lp(a) strata defined as low (<70 nmol/L or <30 mg/dL), intermediate (70–169 nmol/L or 30–69 mg/dL) and high (≥170 nmol/L or ≥70 mg/dL). Transthoracic Doppler echocardiography was performed at Karolinska University Hospital using standard equipment. The current European Society of Cardiology guidelines recommendation on AS management in relation to AS progression is based on the change in <i>V</i><sub>max</sub>, measured in m/s/year, which was calculated in the present study as the difference between the first and the last Doppler measurement divided by the time interval. Individuals who underwent aortic valve replacement (AVR) were excluded if the procedure was performed before the first echocardiography and censored if undergoing AVR during the observational period. The individuals’ cardiovascular status was specified by the International Classification of Diseases diagnoses. Differences between individuals in Lp(a) strata were compared using the Kruskal–Wallis test, Dunn's post hoc test and unbalanced adjusted analysis of covariance with ranked transformed
本研究强调了Lp(a)暴露对AS发展的长期影响，并确定Lp(a)是一般人群中AS进展的潜在生物标志物。这些结果确定高Lp(a)可能是需要超声心动图监测as发展的一个指标。然而，临床意义受到限制，因为目前还没有治疗方法可以减缓AS的进展。Jonas Brinck， Karin Littmann和Magnus Bäck：概念化；可视化;调查;写作;编辑和审查。Jonas Brinck和Magnus Bäck：项目管理和资金获取。Linnea Widman：方法论/统计；回顾。丹尼尔·埃里克森·霍格林，肯尼斯·凯达尔，玛丽亚·埃里克森和卡罗琳娜·夏莫：回顾；编辑。所有作者同意出版最终版本，并同意对工作的各个方面负责。JB报告了安进、诺华和Ionis在提交工作之外的机构资助，以及安进、诺华、赛诺菲和Ultragenyx的酬金。DEH获得了安进的机构荣誉。在提交的工作和安进和赛诺菲的酬金之外，KL报告了来自安进和斯德哥尔摩创新基金的研究资助资金。MBs的机构已经从Amarin、安进（Amgen）、Heel、诺华（Novartis）和费森尤斯卡比（Fresenius Kabi）获得了演讲和咨询费。其余的作者对这项工作没有什么可透露的。MB由瑞典研究委员会资助，资助号：2023-02652；心肺基金会，资助号：20240697。这项研究得到了伦理审查机构的批准。
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