Currently, pathophysiological mechanisms of post-acute sequelae of coronavirus disease-19-cardiovascular syndrome (PASC-CVS) remain unknown.
Methods and results
Patients with PASC-CVS exhibited significantly higher circulating levels of severe acute respiratory syndrome-coronavirus-2 spike protein S1 than the non-PASC-CVS patients and healthy controls. Moreover, individuals with high plasma spike protein S1 concentrations exhibited elevated heart rates and normalized low frequency, suggesting cardiac β-adrenergic receptor (β-AR) hyperactivity. Microscale thermophoresis (MST) assay revealed that the spike protein bound to β1- and β2-AR, but not to D1-dopamine receptor. These interactions were blocked by β1- and β2-AR blockers. Molecular docking and MST assay of β-AR mutants revealed that the spike protein interacted with the extracellular loop 2 of both β-ARs. In cardiomyocytes, spike protein dose-dependently increased the cyclic adenosine monophosphate production with or without epinephrine, indicating its allosteric effects on β-ARs.
Conclusion
Severe acute respiratory syndrome-coronavirus-2 spike proteins act as an allosteric β-AR agonist, leading to cardiac β-AR hyperactivity, thus contributing to PASC-CVS.
{"title":"SARS-CoV-2 spike protein acts as a β-adrenergic receptor agonist: A potential mechanism for cardiac sequelae of long COVID","authors":"Xiangning Deng, Hongtu Cui, Hao Liang, Xinyu Wang, Haiyi Yu, Jingjia Wang, Wenyao Wang, Dongyang Liu, Youyi Zhang, Erdan Dong, Yida Tang, Han Xiao","doi":"10.1111/joim.20000","DOIUrl":"10.1111/joim.20000","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Currently, pathophysiological mechanisms of post-acute sequelae of coronavirus disease-19-cardiovascular syndrome (PASC-CVS) remain unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>Patients with PASC-CVS exhibited significantly higher circulating levels of severe acute respiratory syndrome-coronavirus-2 spike protein S1 than the non-PASC-CVS patients and healthy controls. Moreover, individuals with high plasma spike protein S1 concentrations exhibited elevated heart rates and normalized low frequency, suggesting cardiac β-adrenergic receptor (β-AR) hyperactivity. Microscale thermophoresis (MST) assay revealed that the spike protein bound to β<sub>1</sub>- and β<sub>2</sub>-AR, but not to D1-dopamine receptor. These interactions were blocked by β<sub>1</sub>- and β<sub>2</sub>-AR blockers. Molecular docking and MST assay of β-AR mutants revealed that the spike protein interacted with the extracellular loop 2 of both β-ARs. In cardiomyocytes, spike protein dose-dependently increased the cyclic adenosine monophosphate production with or without epinephrine, indicating its allosteric effects on β-ARs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Severe acute respiratory syndrome-coronavirus-2 spike proteins act as an allosteric β-AR agonist, leading to cardiac β-AR hyperactivity, thus contributing to PASC-CVS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 3","pages":"291-297"},"PeriodicalIF":9.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141786658","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}
Ji-Hoon Sim, Sang-Min Kim, Hong-Rae Kim, Pil-Je Kang, Hwa Jung Kim, Donghee Lee, Sang-Wook Lee, In-Cheol Choi
Background
Cardiopulmonary resuscitation (CPR) is the cornerstone intervention for cardiac arrest, with extracorporeal CPR (ECPR) demonstrating enhanced survival and neurologic outcomes in in-hospital cardiac arrest. This study explores the time interval between CPR initiation and the onset of extracorporeal membrane oxygenation (ECMO) in ECPR recipients, investigating its impact on survival outcomes.
Methods
This retrospective analysis included 1950 adults who received CPR at a single medical center between March 2019 and April 2023. Data from 198 adult patients who had ECMO inserted during CPR were analyzed. The interval from CPR initiation to ECMO initiation was quantified and categorized as ≤20, 20–40, and >40 min. Cox regression analysis assessed associations between CPR-to-ECMO time and short- and long-term mortalities.
Results
Among the 198 patients who underwent ECPR, 116 (58.6%) experienced 30-day mortality. Initiation of ECMO within 20 min occurred in 46 (23.2%), whereas 74 (37.4%) had ECMO initiated after 40 min. Cox regression revealed a significant association between time from CPR to ECMO initiation and 30-day mortality (adjusted hazard ratio [HR]: 2.20 in >40 min, HR: 2.63 in 20–40 min, p = 0.006) and 6-month mortality (HR: 1.81, in >40 min, HR: 1.99 in 20–40 min, p = 0.021).
Conclusions
This study revealed that, in ECPR recipients, a shorter duration between CPR initiation and ECMO flow commencement is associated with improved short- and long-term patient prognoses. These findings emphasize the critical role of timely ECMO application in optimizing outcomes for patients undergoing ECPR.
{"title":"Time to initiation of extracorporeal membrane oxygenation in conventional cardiopulmonary resuscitation affects the patient survival prognosis","authors":"Ji-Hoon Sim, Sang-Min Kim, Hong-Rae Kim, Pil-Je Kang, Hwa Jung Kim, Donghee Lee, Sang-Wook Lee, In-Cheol Choi","doi":"10.1111/joim.20002","DOIUrl":"10.1111/joim.20002","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cardiopulmonary resuscitation (CPR) is the cornerstone intervention for cardiac arrest, with extracorporeal CPR (ECPR) demonstrating enhanced survival and neurologic outcomes in in-hospital cardiac arrest. This study explores the time interval between CPR initiation and the onset of extracorporeal membrane oxygenation (ECMO) in ECPR recipients, investigating its impact on survival outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective analysis included 1950 adults who received CPR at a single medical center between March 2019 and April 2023. Data from 198 adult patients who had ECMO inserted during CPR were analyzed. The interval from CPR initiation to ECMO initiation was quantified and categorized as ≤20, 20–40, and >40 min. Cox regression analysis assessed associations between CPR-to-ECMO time and short- and long-term mortalities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 198 patients who underwent ECPR, 116 (58.6%) experienced 30-day mortality. Initiation of ECMO within 20 min occurred in 46 (23.2%), whereas 74 (37.4%) had ECMO initiated after 40 min. Cox regression revealed a significant association between time from CPR to ECMO initiation and 30-day mortality (adjusted hazard ratio [HR]: 2.20 in >40 min, HR: 2.63 in 20–40 min, <i>p</i> = 0.006) and 6-month mortality (HR: 1.81, in >40 min, HR: 1.99 in 20–40 min, <i>p</i> = 0.021).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study revealed that, in ECPR recipients, a shorter duration between CPR initiation and ECMO flow commencement is associated with improved short- and long-term patient prognoses. These findings emphasize the critical role of timely ECMO application in optimizing outcomes for patients undergoing ECPR.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 4","pages":"350-361"},"PeriodicalIF":9.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141786677","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}
Hypertensive disorders of pregnancy (HDP), especially preeclampsia, and diabetes during pregnancy pose significant risks for both maternal and infant health, extending to long-term outcomes such as early-onset cardiovascular disease and metabolic disorders. Current strategies for managing HDP focus on screening, prevention, surveillance, and timely intervention. No disease-modifying therapies exist so far for established preeclampsia; delivery remains the definitive resolution. Preventive measures—including early pregnancy screening, exercise, and low-dose aspirin—show promise. Antihypertensive treatments reduce severe hypertension risks, whereas magnesium sulfate remains the standard for preventing eclampsia. Planned delivery from gestational week 37 can balance maternal benefits and neonatal risks in women with established preeclampsia. Delivery between 34 and 37 weeks gestation in women with preeclampsia has to balance risks for mother and infant. Lifestyle interventions—particularly diet and physical activity—are pivotal in managing gestational diabetes mellitus and type 2 diabetes. The oral antidiabetic metformin has shown benefits in glycaemic control and reducing maternal weight gain, although its long-term effects on offspring remain uncertain. The safety of other peroral antidiabetics in pregnancy is less studied. Advancements in glucose monitoring and insulin administration present encouraging prospects for enhancing outcomes in women with diabetes types 1 and 2. Both HDP and diabetes during pregnancy necessitate vigilant management through a combination of lifestyle modifications, pharmacological interventions, and timely obstetric care. Although certain treatments such as low-dose aspirin and metformin show efficacy in risk reduction, further research is ongoing to ensure safety for both mothers and their offspring to reduce short- and long-term adverse effects.
{"title":"Can short- and long-term maternal and infant risks linked to hypertension and diabetes during pregnancy be reduced by therapy?","authors":"Olof Stephansson, Anna Sandström","doi":"10.1111/joim.13823","DOIUrl":"10.1111/joim.13823","url":null,"abstract":"<p>Hypertensive disorders of pregnancy (HDP), especially preeclampsia, and diabetes during pregnancy pose significant risks for both maternal and infant health, extending to long-term outcomes such as early-onset cardiovascular disease and metabolic disorders. Current strategies for managing HDP focus on screening, prevention, surveillance, and timely intervention. No disease-modifying therapies exist so far for established preeclampsia; delivery remains the definitive resolution. Preventive measures—including early pregnancy screening, exercise, and low-dose aspirin—show promise. Antihypertensive treatments reduce severe hypertension risks, whereas magnesium sulfate remains the standard for preventing eclampsia. Planned delivery from gestational week 37 can balance maternal benefits and neonatal risks in women with established preeclampsia. Delivery between 34 and 37 weeks gestation in women with preeclampsia has to balance risks for mother and infant. Lifestyle interventions—particularly diet and physical activity—are pivotal in managing gestational diabetes mellitus and type 2 diabetes. The oral antidiabetic metformin has shown benefits in glycaemic control and reducing maternal weight gain, although its long-term effects on offspring remain uncertain. The safety of other peroral antidiabetics in pregnancy is less studied. Advancements in glucose monitoring and insulin administration present encouraging prospects for enhancing outcomes in women with diabetes types 1 and 2. Both HDP and diabetes during pregnancy necessitate vigilant management through a combination of lifestyle modifications, pharmacological interventions, and timely obstetric care. Although certain treatments such as low-dose aspirin and metformin show efficacy in risk reduction, further research is ongoing to ensure safety for both mothers and their offspring to reduce short- and long-term adverse effects.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 3","pages":"216-233"},"PeriodicalIF":9.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.13823","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750676","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>In the July 2020 issue of the <i>Journal of Internal Medicine</i>, Wu et al. conducted a retrospective study including 280 confirmed cases of COVID-19 at the early stage of the pandemic. They found that comorbidity, early antiviral treatment, and age were three major risk factors resulting in the poor prognosis of COVID-19 patients [<span>1</span>]. Although the benefits of addressing comorbidity and early antiviral treatment are clear, the impact of age is more complex. The clinical trial indicated that people older than 65 years have a higher risk of progressing to severe disease. However, there is a discrepancy in children's low mortality despite their immature immune systems being as weak as those of older adults [<span>2</span>].</p><p>Recently, Woodall et al. conducted an in vitro study using nasal epithelial cells (NECs)—the primary target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—to study the age-related immune response to SARS-CoV-2 infections, ruling out the confounding factors in the immune system. They found age-specific nasal epithelial responses across different age groups [<span>3</span>]. The authors first identified characteristics of pediatric (<12 years), adult (30–50 years), and older adult (>70 years) cohorts. The adult cohort exhibited a higher abundance of basal/progenitor subtypes compared to pediatric cultures. Notably, NECs from pediatric subjects had the most goblet 2 cells, whereas basaloid-like cells were predominant in NECs from older adults, indicating a shift from goblet 2 cells to basaloid-like cells. Additionally, the receptors for SARS-CoV-2 entry into cells—transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2) [<span>4</span>]—were differently expressed in pediatric (higher SARS-CoV-2 receptors expression in goblet 2 cells) and older adult cohorts (higher SARS-CoV-2 receptors expression in secretory and basal 2 cell types), suggesting that the virus targets are age-specific.</p><p>The authors then examined the speed of virus spread in varied age groups. Interestingly, they found a promotion of virus production in NECs from older adults compared to pediatric groups, including more virus-targeted cell types, more viral protein translation, and stronger total viral spread. As the cellular landscape of NECs is age-stratified, the authors reasoned that the pathological effect of SARS-CoV-2 infections is age-related and confirmed this hypothesis. They infected NECs from all three groups with SARS-CoV-2 and found negative effects on the morphology of NECs, including decreased culture thickness and epithelial integrity. Notably, damaged NECs in older adult cultures exhibited a compensatory effect, such as increased basal cell mobilization and epithelial escape. The escaped epithelial cells carried newly packaged viral particles, which may account for SARS-CoV-2 spread from the lung to other organs in older adults. Additionally, the results confirmed the upre
{"title":"Why does severe acute respiratory syndrome coronavirus 2 attack the aged more severely?","authors":"Yiwen Xie, Hongcui Cao","doi":"10.1111/joim.13825","DOIUrl":"10.1111/joim.13825","url":null,"abstract":"<p>In the July 2020 issue of the <i>Journal of Internal Medicine</i>, Wu et al. conducted a retrospective study including 280 confirmed cases of COVID-19 at the early stage of the pandemic. They found that comorbidity, early antiviral treatment, and age were three major risk factors resulting in the poor prognosis of COVID-19 patients [<span>1</span>]. Although the benefits of addressing comorbidity and early antiviral treatment are clear, the impact of age is more complex. The clinical trial indicated that people older than 65 years have a higher risk of progressing to severe disease. However, there is a discrepancy in children's low mortality despite their immature immune systems being as weak as those of older adults [<span>2</span>].</p><p>Recently, Woodall et al. conducted an in vitro study using nasal epithelial cells (NECs)—the primary target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—to study the age-related immune response to SARS-CoV-2 infections, ruling out the confounding factors in the immune system. They found age-specific nasal epithelial responses across different age groups [<span>3</span>]. The authors first identified characteristics of pediatric (<12 years), adult (30–50 years), and older adult (>70 years) cohorts. The adult cohort exhibited a higher abundance of basal/progenitor subtypes compared to pediatric cultures. Notably, NECs from pediatric subjects had the most goblet 2 cells, whereas basaloid-like cells were predominant in NECs from older adults, indicating a shift from goblet 2 cells to basaloid-like cells. Additionally, the receptors for SARS-CoV-2 entry into cells—transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2) [<span>4</span>]—were differently expressed in pediatric (higher SARS-CoV-2 receptors expression in goblet 2 cells) and older adult cohorts (higher SARS-CoV-2 receptors expression in secretory and basal 2 cell types), suggesting that the virus targets are age-specific.</p><p>The authors then examined the speed of virus spread in varied age groups. Interestingly, they found a promotion of virus production in NECs from older adults compared to pediatric groups, including more virus-targeted cell types, more viral protein translation, and stronger total viral spread. As the cellular landscape of NECs is age-stratified, the authors reasoned that the pathological effect of SARS-CoV-2 infections is age-related and confirmed this hypothesis. They infected NECs from all three groups with SARS-CoV-2 and found negative effects on the morphology of NECs, including decreased culture thickness and epithelial integrity. Notably, damaged NECs in older adult cultures exhibited a compensatory effect, such as increased basal cell mobilization and epithelial escape. The escaped epithelial cells carried newly packaged viral particles, which may account for SARS-CoV-2 spread from the lung to other organs in older adults. Additionally, the results confirmed the upre","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 4","pages":"308-310"},"PeriodicalIF":9.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.13825","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141730856","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}
Yin Zhang, Mingyang Song, Molin Wang, Ellen Hertzmark, Kana Wu, A. Heather Eliassen, Lorelei A. Mucci, Qi Sun, Meir J. Stampfer, Walter C. Willett, Frank B. Hu, Edward L. Giovannucci
Background
Evidence on type 2 diabetes onset age and duration on mortality risk has been limited by short follow-up, inadequate control for confounding, missing repeated measurements, and inability to cover the full range of onset age, duration, and major causes of death. Moreover, scarce data dissect how type 2 diabetes onset age and duration shape life expectancy.
Methods
We evaluate prospectively these topics based on 270,075 eligible participants in the Nurses’ Health Studies and Health Professionals Follow-up Study, leveraging repeated measurements throughout up to 40 years of follow-up. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).
Results
In fully adjusted analyses, incident early onset type 2 diabetes (diagnosed <40 years of age) was associated with significantly higher mortality from all-causes (HR, 95% CI was 3.16, 2.64–3.79; vs. individuals without type 2 diabetes), cardiovascular disease (6.56, 4.27–10.1), respiratory disease (3.43, 1.38–8.51), neurodegenerative disease (5.13, 2.09–12.6), and kidney disease (8.55, 1.98–36.9). The relative risk elevations declined dramatically with each higher decade of age at diagnosis for deaths from most of these causes, though the absolute risk difference increased continuously. A substantially higher cumulative incidence of mortality and a greater loss in life expectancy were associated with younger age at type 2 diabetes diagnosis. Longer disease duration was associated with generally higher relative and absolute risk of mortality.
Conclusion
Early onset of type 2 diabetes and longer disease duration are associated with substantially increased risk of all-cause and cause-specific mortality and greater loss in life expectancy.
{"title":"All-cause and cause-specific mortality risk and loss in life expectancy associated with incident type 2 diabetes onset age and duration","authors":"Yin Zhang, Mingyang Song, Molin Wang, Ellen Hertzmark, Kana Wu, A. Heather Eliassen, Lorelei A. Mucci, Qi Sun, Meir J. Stampfer, Walter C. Willett, Frank B. Hu, Edward L. Giovannucci","doi":"10.1111/joim.13817","DOIUrl":"10.1111/joim.13817","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Evidence on type 2 diabetes onset age and duration on mortality risk has been limited by short follow-up, inadequate control for confounding, missing repeated measurements, and inability to cover the full range of onset age, duration, and major causes of death. Moreover, scarce data dissect how type 2 diabetes onset age and duration shape life expectancy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We evaluate prospectively these topics based on 270,075 eligible participants in the Nurses’ Health Studies and Health Professionals Follow-up Study, leveraging repeated measurements throughout up to 40 years of follow-up. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In fully adjusted analyses, incident early onset type 2 diabetes (diagnosed <40 years of age) was associated with significantly higher mortality from all-causes (HR, 95% CI was 3.16, 2.64–3.79; vs. individuals without type 2 diabetes), cardiovascular disease (6.56, 4.27–10.1), respiratory disease (3.43, 1.38–8.51), neurodegenerative disease (5.13, 2.09–12.6), and kidney disease (8.55, 1.98–36.9). The relative risk elevations declined dramatically with each higher decade of age at diagnosis for deaths from most of these causes, though the absolute risk difference increased continuously. A substantially higher cumulative incidence of mortality and a greater loss in life expectancy were associated with younger age at type 2 diabetes diagnosis. Longer disease duration was associated with generally higher relative and absolute risk of mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Early onset of type 2 diabetes and longer disease duration are associated with substantially increased risk of all-cause and cause-specific mortality and greater loss in life expectancy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 3","pages":"260-279"},"PeriodicalIF":9.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632161","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}
Hans-Kittil Viermyr, Bente Halvorsen, Ellen Lund Sagen, Annika E Michelsen, Andreas Barrat-Due, Trine Kåsine, Katerina Nezvalova-Henriksen, Anne Ma Dyrhol-Riise, The Nor-Solidarity Consortium, Tøri Vigeland Lerum, Fredrik Müller, Kristian Tonby, Anders Tveita, Pål Aukrust, Marius Trøseid, Thor Ueland, Tuva Børresdatter Dahl
Objectives
To investigate temporal changes in the association between SARS-CoV2 viral load (VL) and markers of inflammation during hospitalization, as well as the ability of these markers alone or in combination to predict severe outcomes.
Methods
Serial oropharyngeal and blood samples were obtained from hospitalized COVID-19 patients (n = 160). Levels of inflammatory markers and oropharyngeal VL were measured during hospitalization (admission, days 3–5, and days 7–10) and related to severe outcomes (respiratory failure/intensive care unit admission).
Results
Elevated admission levels of IL (interleukin)-6, IL-33, IL-8, monocyte chemoattractant protein-1 (MCP-1), interferon-γ-induced protein 10 (IP-10), IL-1β, and IL-1Ra were associated with severe outcomes during hospitalization. Although no inflammatory markers correlated with VL at baseline, there was a significant correlation between VL and levels of IP-10 and MCP-1 at days 3–5, accompanied by IL-8 and IL-6 at days 7–10. Finally, there was a seemingly additive effect of IP-10, MCP-1, and IL-6 in predicting severe outcomes when combined with high VL at baseline.
Conclusions
An increasing number of inflammatory markers were associated with VL during the first 10 days of hospitalization, and several of these markers were associated with severe outcomes, in particular when combined with elevated VL. Future studies should assess the potential for combining antiviral and immunomodulatory treatment, preferably guided by viral and inflammatory biomarkers, for the selection of high-risk patients.
{"title":"High viral loads combined with inflammatory markers predict disease severity in hospitalized COVID-19 patients: Results from the NOR-Solidarity trial","authors":"Hans-Kittil Viermyr, Bente Halvorsen, Ellen Lund Sagen, Annika E Michelsen, Andreas Barrat-Due, Trine Kåsine, Katerina Nezvalova-Henriksen, Anne Ma Dyrhol-Riise, The Nor-Solidarity Consortium, Tøri Vigeland Lerum, Fredrik Müller, Kristian Tonby, Anders Tveita, Pål Aukrust, Marius Trøseid, Thor Ueland, Tuva Børresdatter Dahl","doi":"10.1111/joim.13820","DOIUrl":"10.1111/joim.13820","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To investigate temporal changes in the association between SARS-CoV2 viral load (VL) and markers of inflammation during hospitalization, as well as the ability of these markers alone or in combination to predict severe outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Serial oropharyngeal and blood samples were obtained from hospitalized COVID-19 patients (<i>n</i> = 160). Levels of inflammatory markers and oropharyngeal VL were measured during hospitalization (admission, days 3–5, and days 7–10) and related to severe outcomes (respiratory failure/intensive care unit admission).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Elevated admission levels of IL (interleukin)-6, IL-33, IL-8, monocyte chemoattractant protein-1 (MCP-1), interferon-γ-induced protein 10 (IP-10), IL-1β, and IL-1Ra were associated with severe outcomes during hospitalization. Although no inflammatory markers correlated with VL at baseline, there was a significant correlation between VL and levels of IP-10 and MCP-1 at days 3–5, accompanied by IL-8 and IL-6 at days 7–10. Finally, there was a seemingly additive effect of IP-10, MCP-1, and IL-6 in predicting severe outcomes when combined with high VL at baseline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>An increasing number of inflammatory markers were associated with VL during the first 10 days of hospitalization, and several of these markers were associated with severe outcomes, in particular when combined with elevated VL. Future studies should assess the potential for combining antiviral and immunomodulatory treatment, preferably guided by viral and inflammatory biomarkers, for the selection of high-risk patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 3","pages":"249-259"},"PeriodicalIF":9.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.13820","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141618797","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}
In this multi-professional review, we will provide the in-depth knowledge required to work in the expanding field of obesity treatment. The prevalence of obesity has doubled in adults and quadrupled in children over the last three decades. The most common treatment offered has been lifestyle treatment, which has a modest or little long-term effect. Recently, several new treatment options—leading to improved weight loss—have become available. However, long-term care is not only about weight loss but also aims to improve health and wellbeing overall. In the era of personalized medicine, we have an obligation to tailor the treatment in close dialogue with our patients. The main focus of this review is new pharmacological treatments and modern metabolic surgery, with practical guidance on what to consider when selecting and guiding the patients and what to include in the follow-up care. Furthermore, we discuss common clinical challenges, such as patients with concurrent eating disorder or mental health problems, and treatment in the older adults. We also provide recommendations on how to deal with obesity in a non-stigmatizing way to diminish weight stigma during treatment. Finally, we present six microcases—obesity treatment for persons with neuropsychiatric disorders and/or intellectual disability; obesity treatment in the nonresponsive patient who has “tried everything”; and hypoglycemia, abdominal pain, and weight regain after metabolic surgery—to highlight common problems in weight-loss treatment and provide personalized treatment suggestions.
{"title":"Obesity treatment in adolescents and adults in the era of personalized medicine","authors":"Magnus Sundbom, Kajsa Järvholm, Lovisa Sjögren, Paulina Nowicka, Ylva Trolle Lagerros","doi":"10.1111/joim.13816","DOIUrl":"10.1111/joim.13816","url":null,"abstract":"<p>In this multi-professional review, we will provide the in-depth knowledge required to work in the expanding field of obesity treatment. The prevalence of obesity has doubled in adults and quadrupled in children over the last three decades. The most common treatment offered has been lifestyle treatment, which has a modest or little long-term effect. Recently, several new treatment options—leading to improved weight loss—have become available. However, long-term care is not only about weight loss but also aims to improve health and wellbeing overall. In the era of personalized medicine, we have an obligation to tailor the treatment in close dialogue with our patients. The main focus of this review is new pharmacological treatments and modern metabolic surgery, with practical guidance on what to consider when selecting and guiding the patients and what to include in the follow-up care. Furthermore, we discuss common clinical challenges, such as patients with concurrent eating disorder or mental health problems, and treatment in the older adults. We also provide recommendations on how to deal with obesity in a non-stigmatizing way to diminish weight stigma during treatment. Finally, we present six microcases—obesity treatment for persons with neuropsychiatric disorders and/or intellectual disability; obesity treatment in the nonresponsive patient who has “tried everything”; and hypoglycemia, abdominal pain, and weight regain after metabolic surgery—to highlight common problems in weight-loss treatment and provide personalized treatment suggestions.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 2","pages":"139-155"},"PeriodicalIF":9.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.13816","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615435","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}
Sining Xie, Federica Galimberti, Elena Olmastroni, Alberico L. Catapano, Manuela Casula
<p>Dear Editor,</p><p>Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality worldwide. Although several therapeutic options are available to reduce LDL-cholesterol (LDL-C), many patients continue to experience major cardiovascular (CV) events. In ASCVD, inflammation plays a critical role, contributing significantly to residual CV risk [<span>1</span>]. Several anti-inflammatory therapies have been evaluated to reduce CV risk, and recently, the U.S. Food and Drug Administration approved the use of low-dose colchicine to reduce the risk of myocardial infarction (MI), stroke, coronary revascularization, or CV death in adult patients with established ASCVD or multiple CV risk factors [<span>2, 3</span>]. Meta-analyses have shown that low-dose colchicine (0.5–1.0 mg) can lead to a reduction in C-reactive protein (CRP) levels by −0.36 mg/L (95%CI, −0.51 to −0.20) in patients with coronary artery disease [<span>4, 5</span>], and by −0.66 mg/L (95%CI, −0.98 to −0.35) in patients with acute MI [<span>6</span>], which translates into a 35% and 44% reduction in major CV events, respectively. Nevertheless, some studies have suggested an anti-inflammatory effect with some lipid-lowering therapies. In a recent meta-analysis involving 171,668 subjects from 53 randomized control trials (RCTs), we demonstrated a reduction in serum CRP concentration with statins (−0.65 mg/L [95%CI, −0.87 to −0.43]), bempedoic acid (−0.43 mg/L [95%CI, −0.67 to −0.20]), and ezetimibe (−0.28 mg/L [95%CI, −0.48 to −0.08]), which was independent of LDL-C changes [<span>7</span>].</p><p>Given the growing interest in targeting inflammation to further reduce CV risk and the recent inclusion of colchicine among CV preventive therapies [<span>8</span>], it appears of interest to compare the effect of available therapies on plasma CRP levels. Therefore, we sought to quantify the additional effect of adding colchicine to statins on CRP levels and to compare the effect of bempedoic acid, ezetimibe, or colchicine added to background statin treatment.</p><p>Because no trial directly compares the impact on CRP levels of colchicine versus lipid-lowering therapies, we performed a network meta-analysis according to the PRISMA guidelines. PubMed, Web of Science, EMBASE, Cochrane Library, and ClinicalTrial.gov were searched from inception to November 2023. Inclusion criteria were as follows: (1) RCTs in human, parallel design, phase II, III, or IV; (2) English language; (3) using ezetimibe, bempedoic acid, or colchicine as interventions on top of statin treatment (defined as more than 80% patients treated with statins at baseline); (4) reporting the effect on CRP levels; (5) with an intervention duration of more than 3 weeks.</p><p>Pooled estimates were assessed by both fixed-effect and random-effects models within a Bayesian hierarchical setting, assuming equal heterogeneity across all comparisons. When significant heterogeneity was detected (as determine
{"title":"Effect on C-reactive protein levels of the addition of ezetimibe, bempedoic acid, or colchicine to statin treatment: A network meta-analysis","authors":"Sining Xie, Federica Galimberti, Elena Olmastroni, Alberico L. Catapano, Manuela Casula","doi":"10.1111/joim.13824","DOIUrl":"10.1111/joim.13824","url":null,"abstract":"<p>Dear Editor,</p><p>Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality worldwide. Although several therapeutic options are available to reduce LDL-cholesterol (LDL-C), many patients continue to experience major cardiovascular (CV) events. In ASCVD, inflammation plays a critical role, contributing significantly to residual CV risk [<span>1</span>]. Several anti-inflammatory therapies have been evaluated to reduce CV risk, and recently, the U.S. Food and Drug Administration approved the use of low-dose colchicine to reduce the risk of myocardial infarction (MI), stroke, coronary revascularization, or CV death in adult patients with established ASCVD or multiple CV risk factors [<span>2, 3</span>]. Meta-analyses have shown that low-dose colchicine (0.5–1.0 mg) can lead to a reduction in C-reactive protein (CRP) levels by −0.36 mg/L (95%CI, −0.51 to −0.20) in patients with coronary artery disease [<span>4, 5</span>], and by −0.66 mg/L (95%CI, −0.98 to −0.35) in patients with acute MI [<span>6</span>], which translates into a 35% and 44% reduction in major CV events, respectively. Nevertheless, some studies have suggested an anti-inflammatory effect with some lipid-lowering therapies. In a recent meta-analysis involving 171,668 subjects from 53 randomized control trials (RCTs), we demonstrated a reduction in serum CRP concentration with statins (−0.65 mg/L [95%CI, −0.87 to −0.43]), bempedoic acid (−0.43 mg/L [95%CI, −0.67 to −0.20]), and ezetimibe (−0.28 mg/L [95%CI, −0.48 to −0.08]), which was independent of LDL-C changes [<span>7</span>].</p><p>Given the growing interest in targeting inflammation to further reduce CV risk and the recent inclusion of colchicine among CV preventive therapies [<span>8</span>], it appears of interest to compare the effect of available therapies on plasma CRP levels. Therefore, we sought to quantify the additional effect of adding colchicine to statins on CRP levels and to compare the effect of bempedoic acid, ezetimibe, or colchicine added to background statin treatment.</p><p>Because no trial directly compares the impact on CRP levels of colchicine versus lipid-lowering therapies, we performed a network meta-analysis according to the PRISMA guidelines. PubMed, Web of Science, EMBASE, Cochrane Library, and ClinicalTrial.gov were searched from inception to November 2023. Inclusion criteria were as follows: (1) RCTs in human, parallel design, phase II, III, or IV; (2) English language; (3) using ezetimibe, bempedoic acid, or colchicine as interventions on top of statin treatment (defined as more than 80% patients treated with statins at baseline); (4) reporting the effect on CRP levels; (5) with an intervention duration of more than 3 weeks.</p><p>Pooled estimates were assessed by both fixed-effect and random-effects models within a Bayesian hierarchical setting, assuming equal heterogeneity across all comparisons. When significant heterogeneity was detected (as determine","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 3","pages":"302-305"},"PeriodicalIF":9.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.13824","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589086","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}
Nada Maaziz, Laurent Martin, Alexandre Marchand, Betty Gardie, François Girodon
<p>Dear Editor,</p><p>The upcoming Olympic Games will be accompanied by intense testing for doping, which is unfortunately not uncommon in top-level sporting circles. Among classic doping products used in endurance sports, erythropoietin (EPO) drug, the biological copy of the main EPO hormone responsible for substantial increases in haemoglobin (Hb) concentration and haematocrit (Ht), is one of the originals, both in terms of its age (available since the 1980s) and frequency of use (61 doping cases worldwide in 2022) [<span>1</span>].</p><p>The history of the Olympic Games is associated with the discovery of mutations in the EPO receptor gene, <i>EPOR</i>, in the 1990s. The first mutation was identified in Eero Mäntyranta, who won multiple Olympic and world champion medals in cross-country skiing [<span>2</span>]. At that time, no technique was available to identify blood doping using EPO drug, or transfusion, for which methods were validated in the early 2000s [<span>3</span>].</p><p>Here, we report two cases in which top-level athletes were disqualified solely on the basis of high Hb and Ht values. These athletes were found to be carriers of familial polycythaemia associated with functionally tested pathogenic mutations in genes involved in the hypoxia-sensing pathway several years after their disqualification from the sporting world, underlining the importance of having recourse to specialized testing before making serious accusations.</p><p>A 34-year-old male, who started playing soccer at a young age, applied to enter a sports-study high school when he was 16 years old. His application was rejected due to the presence of high Hb and Ht values (Table 1). The doctor overseeing his case suspected doping, leading to the man's subsequent ban from sports study in high school and competitions. Eighteen years later, his son was diagnosed with polycythaemia, suggesting familial erythrocytosis and samples from the father and son were analysed using NGS sequencing with a gene panel dedicated to the exploration of polycythaemia. A pathogenic mutation (p.Asp525Gly) in <i>EPAS1</i> was identified in the father and son and three other relatives segregating with a polycythaemia phenotype. The <i>EPAS1</i> gene encodes the hypoxia-inducible factor HIF2α, which regulates the expression of EPO when oxygen concentrations go down.</p><p>The second medical record concerns a top-level national Taekwondo athlete, for whom a routine examination revealed high Ht and Hb values (Table 1), leading to definitive banishment from competition. Ten years later, the patient's sister was referred to the hospital for absolute idiopathic polycythaemia. Given the sister's history of polycythaemia, the hypoxia-regulating genes were sequenced, which revealed a pathogenic mutation in the <i>EGLN1</i> gene (p.Trp334Arg). <i>EGLN1</i> encodes the PHD2 protein, which plays a major role in the degradation of HIF2α. This mutation was found in the athlete and her sister, as well as in thr
{"title":"Olympic Games: When the haematocrit does not fit, the athlete is not always a cheat","authors":"Nada Maaziz, Laurent Martin, Alexandre Marchand, Betty Gardie, François Girodon","doi":"10.1111/joim.13822","DOIUrl":"10.1111/joim.13822","url":null,"abstract":"<p>Dear Editor,</p><p>The upcoming Olympic Games will be accompanied by intense testing for doping, which is unfortunately not uncommon in top-level sporting circles. Among classic doping products used in endurance sports, erythropoietin (EPO) drug, the biological copy of the main EPO hormone responsible for substantial increases in haemoglobin (Hb) concentration and haematocrit (Ht), is one of the originals, both in terms of its age (available since the 1980s) and frequency of use (61 doping cases worldwide in 2022) [<span>1</span>].</p><p>The history of the Olympic Games is associated with the discovery of mutations in the EPO receptor gene, <i>EPOR</i>, in the 1990s. The first mutation was identified in Eero Mäntyranta, who won multiple Olympic and world champion medals in cross-country skiing [<span>2</span>]. At that time, no technique was available to identify blood doping using EPO drug, or transfusion, for which methods were validated in the early 2000s [<span>3</span>].</p><p>Here, we report two cases in which top-level athletes were disqualified solely on the basis of high Hb and Ht values. These athletes were found to be carriers of familial polycythaemia associated with functionally tested pathogenic mutations in genes involved in the hypoxia-sensing pathway several years after their disqualification from the sporting world, underlining the importance of having recourse to specialized testing before making serious accusations.</p><p>A 34-year-old male, who started playing soccer at a young age, applied to enter a sports-study high school when he was 16 years old. His application was rejected due to the presence of high Hb and Ht values (Table 1). The doctor overseeing his case suspected doping, leading to the man's subsequent ban from sports study in high school and competitions. Eighteen years later, his son was diagnosed with polycythaemia, suggesting familial erythrocytosis and samples from the father and son were analysed using NGS sequencing with a gene panel dedicated to the exploration of polycythaemia. A pathogenic mutation (p.Asp525Gly) in <i>EPAS1</i> was identified in the father and son and three other relatives segregating with a polycythaemia phenotype. The <i>EPAS1</i> gene encodes the hypoxia-inducible factor HIF2α, which regulates the expression of EPO when oxygen concentrations go down.</p><p>The second medical record concerns a top-level national Taekwondo athlete, for whom a routine examination revealed high Ht and Hb values (Table 1), leading to definitive banishment from competition. Ten years later, the patient's sister was referred to the hospital for absolute idiopathic polycythaemia. Given the sister's history of polycythaemia, the hypoxia-regulating genes were sequenced, which revealed a pathogenic mutation in the <i>EGLN1</i> gene (p.Trp334Arg). <i>EGLN1</i> encodes the PHD2 protein, which plays a major role in the degradation of HIF2α. This mutation was found in the athlete and her sister, as well as in thr","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 2","pages":"213-214"},"PeriodicalIF":9.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.13822","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562198","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}
Ann Bugeja, Celine Girard, Manish M Sood, Claire E Kendall, Ally Sweet, Ria Singla, Pouya Motazedian, Amanda J Vinson, Marcel Ruzicka, Gregory L. Hundemer, Greg Knoll, Daniel I McIsaac
Background
Sex-based disparities in cardiovascular outcomes may be improved with appropriate hypertension management.
Objective
To compare the evidence-based evaluation and management of females with late-onset hypertension compared to males in the contemporary era.
Participants: Residents aged ≥66 years with newly diagnosed hypertension between January 1, 2010, and December 31, 2017.
Exposure: Sex (female vs. male).
Outcomes and Measures: We used Poisson and logistic regression to estimate adjusted sex-attributable differences in the performance of guideline-recommended lab investigations. We estimated adjusted differences in time to the prescription of, and type of, first antihypertensive medication prescribed between females and males, using Cox regression.
Results
Among 111,410 adults (mean age 73 years, 53% female, median follow-up 6.8 years), females underwent a similar number of guideline-recommended investigations (adjusted incidence rate ratio, 0.997 [95% confidence interval [CI] 0.99–1.002]) compared to males. Females were also as likely to complete all investigations (0.70% females, 0.77% males; adjusted odds ratio, 0.96 [95% CI 0.83–1.11]). Females were slightly less likely to be prescribed medication (adjusted hazard ratio [aHR] 0.98 [95% CI 0.96–0.99]) or, among those prescribed, less likely to be prescribed first-line medication (aHR, 0.995 [95% CI 0.994–0.997]).
Conclusions
Compared to males, females with late-onset hypertension were equally likely to complete initial investigations with comparable prescription rates. These findings suggest that there may be no clinically meaningful sex-based differences in the initial management of late-onset hypertension to explain sex-based disparities in cardiovascular outcomes.
背景：适当的高血压管理可改善心血管疾病预后中的性别差异：通过适当的高血压管理可改善心血管预后中的性别差异：比较当代对晚发高血压女性患者与男性患者的循证评估和管理：方法：设计：设计：基于人群的回顾性队列研究：地点：加拿大安大略省：2010年1月1日至2017年12月31日期间新诊断出高血压的年龄≥66岁的居民.暴露：性别（女性与男性）.结果与测量：我们使用泊松回归和逻辑回归估算了指南推荐的实验室检查结果的调整后性别可归因差异。我们使用 Cox 回归估算了调整后的女性和男性首次处方抗高血压药物的时间和类型差异：在 111,410 名成年人（平均年龄 73 岁，53% 为女性，中位随访时间 6.8 年）中，女性接受指南推荐检查的次数与男性相似（调整后发病率比为 0.997 [95% 置信区间 [CI]0.99-1.002]）。女性完成所有检查的几率也与男性相当（女性为 0.70%，男性为 0.77%；调整后的几率比为 0.96 [95% CI 0.83-1.11]）。女性接受处方药物治疗的可能性略低（调整后危险比[aHR] 0.98 [95% CI 0.96-0.99]），在处方药物中，女性接受一线药物治疗的可能性较低（aHR，0.995 [95% CI 0.994-0.997]）：结论：与男性相比，女性晚发性高血压患者同样有可能完成初步检查，且处方率相当。这些研究结果表明，在晚发性高血压的初始管理中，可能不存在临床上有意义的性别差异，从而无法解释心血管结果的性别差异。
{"title":"Adherence to guideline-recommended care of late-onset hypertension in females versus males: A population-based cohort study","authors":"Ann Bugeja, Celine Girard, Manish M Sood, Claire E Kendall, Ally Sweet, Ria Singla, Pouya Motazedian, Amanda J Vinson, Marcel Ruzicka, Gregory L. Hundemer, Greg Knoll, Daniel I McIsaac","doi":"10.1111/joim.13821","DOIUrl":"10.1111/joim.13821","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sex-based disparities in cardiovascular outcomes may be improved with appropriate hypertension management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To compare the evidence-based evaluation and management of females with late-onset hypertension compared to males in the contemporary era.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p><i>Design</i>: Retrospective population-based cohort study.</p>\u0000 \u0000 <p><i>Setting</i>: Ontario, Canada.</p>\u0000 \u0000 <p><i>Participants</i>: Residents aged ≥66 years with newly diagnosed hypertension between January 1, 2010, and December 31, 2017.</p>\u0000 \u0000 <p><i>Exposure</i>: Sex (female vs. male).</p>\u0000 \u0000 <p><i>Outcomes and Measures</i>: We used Poisson and logistic regression to estimate adjusted sex-attributable differences in the performance of guideline-recommended lab investigations. We estimated adjusted differences in time to the prescription of, and type of, first antihypertensive medication prescribed between females and males, using Cox regression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 111,410 adults (mean age 73 years, 53% female, median follow-up 6.8 years), females underwent a similar number of guideline-recommended investigations (adjusted incidence rate ratio, 0.997 [95% confidence interval [CI] 0.99–1.002]) compared to males. Females were also as likely to complete all investigations (0.70% females, 0.77% males; adjusted odds ratio, 0.96 [95% CI 0.83–1.11]). Females were slightly less likely to be prescribed medication (adjusted hazard ratio [aHR] 0.98 [95% CI 0.96–0.99]) or, among those prescribed, less likely to be prescribed first-line medication (aHR, 0.995 [95% CI 0.994–0.997]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Compared to males, females with late-onset hypertension were equally likely to complete initial investigations with comparable prescription rates. These findings suggest that there may be no clinically meaningful sex-based differences in the initial management of late-onset hypertension to explain sex-based disparities in cardiovascular outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 3","pages":"280-290"},"PeriodicalIF":9.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.13821","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141553822","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}
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