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JAMA Internal Medicine Jul 2023Asymptomatic blood pressure (BP) elevations are common in hospitalized older adults, and widespread heterogeneity in the clinical management of elevated inpatient BPs...
IMPORTANCE
Asymptomatic blood pressure (BP) elevations are common in hospitalized older adults, and widespread heterogeneity in the clinical management of elevated inpatient BPs exists.
OBJECTIVE
To examine the association of intensive treatment of elevated inpatient BPs with in-hospital clinical outcomes of older adults hospitalized for noncardiac conditions.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study examined Veterans Health Administration data between October 1, 2015, and December 31, 2017, for patients aged 65 years or older hospitalized for noncardiovascular diagnoses and who experienced elevated BPs in the first 48 hours of hospitalization.
INTERVENTIONS
Intensive BP treatment following the first 48 hours of hospitalization, defined as receipt of intravenous antihypertensives or oral classes not used prior to admission.
MAIN OUTCOME AND MEASURES
The primary outcome was a composite of inpatient mortality, intensive care unit transfer, stroke, acute kidney injury, B-type natriuretic peptide elevation, and troponin elevation. Data were analyzed between October 1, 2021, and January 10, 2023, with propensity score overlap weighting used to adjust for confounding between those who did and did not receive early intensive treatment.
RESULTS
Among 66 140 included patients (mean [SD] age, 74.4 [8.1] years; 97.5% male and 2.6% female; 17.4% Black, 1.7% Hispanic, and 75.9% White), 14 084 (21.3%) received intensive BP treatment in the first 48 hours of hospitalization. Patients who received early intensive treatment vs those who did not continued to receive a greater number of additional antihypertensives during the remainder of their hospitalization (mean additional doses, 6.1 [95% CI, 5.8-6.4] vs 1.6 [95% CI, 1.5-1.8], respectively). Intensive treatment was associated with a greater risk of the primary composite outcome (1220 [8.7%] vs 3570 [6.9%]; weighted odds ratio [OR], 1.28; 95% CI, 1.18-1.39), with the highest risk among patients receiving intravenous antihypertensives (weighted OR, 1.90; 95% CI, 1.65-2.19). Intensively treated patients were more likely to experience each component of the composite outcome except for stroke and mortality. Findings were consistent across subgroups stratified by age, frailty, preadmission BP, early hospitalization BP, and cardiovascular disease history.
CONCLUSIONS AND RELEVANCE
The study's findings indicate that among hospitalized older adults with elevated BPs, intensive pharmacologic antihypertensive treatment was associated with a greater risk of adverse events. These findings do not support the treatment of elevated inpatient BPs without evidence of end organ damage, and they highlight the need for randomized clinical trials of inpatient BP treatment targets.
Topics: Humans; Male; Female; Aged; Antihypertensive Agents; Blood Pressure; Inpatients; Retrospective Studies; Hospitalization; Stroke
PubMed: 37252732
DOI: 10.1001/jamainternmed.2023.1667 -
Reviews in Endocrine & Metabolic... Aug 2023Emerging evidence suggests that treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) could be an interesting treatment strategy to reduce neurological... (Review)
Review
Emerging evidence suggests that treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) could be an interesting treatment strategy to reduce neurological complications such as stroke, cognitive impairment, and peripheral neuropathy. We performed a systematic review to examine the evidence concerning the effects of GLP-1 RAs on neurological complications of diabetes. The databases used were Pubmed, Scopus and Cochrane. We selected clinical trials which analysed the effect of GLP-1 RAs on stroke, cognitive impairment, and peripheral neuropathy. We found a total of 19 studies: 8 studies include stroke or major cardiovascular events, 7 involve cognitive impairment and 4 include peripheral neuropathy. Semaglutide subcutaneous and dulaglutide reduced stroke cases. Liraglutide, albiglutide, oral semaglutide and efpeglenatide, were not shown to reduce the number of strokes but did reduce major cardiovascular events. Exenatide, dulaglutide and liraglutide improved general cognition but no significant effect on diabetic peripheral neuropathy has been reported with GLP-1 RAs. GLP-1 RAs are promising drugs that seem to be useful in the reduction of some neurological complications of diabetes. However, more studies are needed.
Topics: Humans; Hypoglycemic Agents; Liraglutide; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide 1; Cardiovascular Diseases; Stroke; Diabetes Complications
PubMed: 37231200
DOI: 10.1007/s11154-023-09807-3 -
American Heart Journal Jan 2024Tirzepatide, a once-weekly GIP/GLP-1 receptor agonist, reduces blood glucose and body weight in people with type 2 diabetes. The cardiovascular (CV) safety and efficacy... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison of tirzepatide and dulaglutide on major adverse cardiovascular events in participants with type 2 diabetes and atherosclerotic cardiovascular disease: SURPASS-CVOT design and baseline characteristics.
BACKGROUND
Tirzepatide, a once-weekly GIP/GLP-1 receptor agonist, reduces blood glucose and body weight in people with type 2 diabetes. The cardiovascular (CV) safety and efficacy of tirzepatide have not been definitively assessed in a cardiovascular outcomes trial.
METHODS
Tirzepatide is being studied in a randomized, double-blind, active-controlled CV outcomes trial. People with type 2 diabetes aged ≥40 years, with established atherosclerotic CV disease, HbA1c ≥7% to ≤10.5%, and body mass index ≥25 kg/m were randomized 1:1 to once weekly subcutaneous injection of either tirzepatide up to 15 mg or dulaglutide 1.5 mg. The primary outcome is time to first occurrence of any major adverse cardiovascular event (MACE), defined as CV death, myocardial infarction, or stroke. The trial is event-driven and planned to continue until ≥1,615 participants experience an adjudication-confirmed component of MACE. The primary analysis is noninferiority for time to first MACE of tirzepatide vs dulaglutide by demonstrating an upper confidence limit <1.05, which will also confirm superiority vs a putative placebo, and also to determine whether tirzepatide produces a greater CV benefit than dulaglutide (superiority analysis).
RESULTS
Over 2 years, 13,299 people at 640 sites in 30 countries across all world regions were randomized. The mean age of randomized participants at baseline was 64.1 years, diabetes duration 14.7 years, HbA1c 8.4%, and BMI 32.6 kg/m. Overall, 65.0% had coronary disease, of whom 47.3% reported prior myocardial infarction and 57.4% had prior coronary revascularization. 19.1% of participants had a prior stroke and 25.3% had peripheral artery disease. The trial is fully recruited and ongoing.
CONCLUSION
SURPASS-CVOT will provide definitive evidence as to the CV safety and efficacy of tirzepatide as compared with dulaglutide, a GLP-1 receptor agonist with established CV benefit.
Topics: Humans; Middle Aged; Atherosclerosis; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide-1 Receptor Agonists; Glycated Hemoglobin; Hypoglycemic Agents; Myocardial Infarction; Stroke; Treatment Outcome; Double-Blind Method
PubMed: 37758044
DOI: 10.1016/j.ahj.2023.09.007 -
JAMA Aug 2023Whether protein risk scores derived from a single plasma sample could be useful for risk assessment for atherosclerotic cardiovascular disease (ASCVD), in conjunction... (Comparative Study)
Comparative Study
IMPORTANCE
Whether protein risk scores derived from a single plasma sample could be useful for risk assessment for atherosclerotic cardiovascular disease (ASCVD), in conjunction with clinical risk factors and polygenic risk scores, is uncertain.
OBJECTIVE
To develop protein risk scores for ASCVD risk prediction and compare them to clinical risk factors and polygenic risk scores in primary and secondary event populations.
DESIGN, SETTING, AND PARTICIPANTS
The primary analysis was a retrospective study of primary events among 13 540 individuals in Iceland (aged 40-75 years) with proteomics data and no history of major ASCVD events at recruitment (study duration, August 23, 2000 until October 26, 2006; follow-up through 2018). We also analyzed a secondary event population from a randomized, double-blind lipid-lowering clinical trial (2013-2016), consisting of individuals with stable ASCVD receiving statin therapy and for whom proteomic data were available for 6791 individuals.
EXPOSURES
Protein risk scores (based on 4963 plasma protein levels and developed in a training set in the primary event population); polygenic risk scores for coronary artery disease and stroke; and clinical risk factors that included age, sex, statin use, hypertension treatment, type 2 diabetes, body mass index, and smoking status at the time of plasma sampling.
MAIN OUTCOMES AND MEASURES
Outcomes were composites of myocardial infarction, stroke, and coronary heart disease death or cardiovascular death. Performance was evaluated using Cox survival models and measures of discrimination and reclassification that accounted for the competing risk of non-ASCVD death.
RESULTS
In the primary event population test set (4018 individuals [59.0% women]; 465 events; median follow-up, 15.8 years), the protein risk score had a hazard ratio (HR) of 1.93 per SD (95% CI, 1.75 to 2.13). Addition of protein risk score and polygenic risk scores significantly increased the C index when added to a clinical risk factor model (C index change, 0.022 [95% CI, 0.007 to 0.038]). Addition of the protein risk score alone to a clinical risk factor model also led to a significantly increased C index (difference, 0.014 [95% CI, 0.002 to 0.028]). Among White individuals in the secondary event population (6307 participants; 432 events; median follow-up, 2.2 years), the protein risk score had an HR of 1.62 per SD (95% CI, 1.48 to 1.79) and significantly increased C index when added to a clinical risk factor model (C index change, 0.026 [95% CI, 0.011 to 0.042]). The protein risk score was significantly associated with major adverse cardiovascular events among individuals of African and Asian ancestries in the secondary event population.
CONCLUSIONS AND RELEVANCE
A protein risk score was significantly associated with ASCVD events in primary and secondary event populations. When added to clinical risk factors, the protein risk score and polygenic risk score both provided statistically significant but modest improvement in discrimination.
Topics: Female; Humans; Male; Atherosclerosis; Diabetes Mellitus, Type 2; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Proteomics; Retrospective Studies; Stroke; Cardiovascular Diseases; Risk Assessment; Adult; Middle Aged; Aged; Iceland; Randomized Controlled Trials as Topic
PubMed: 37606673
DOI: 10.1001/jama.2023.13258 -
Frontiers in Neurology 2023The objective of our study was to evaluate vaccine type, COVID-19 infection, and their association with stroke soon after COVID-19 vaccination.
BACKGROUND
The objective of our study was to evaluate vaccine type, COVID-19 infection, and their association with stroke soon after COVID-19 vaccination.
METHODS
In a retrospective cohort study, we estimated the 21-day post-vaccination incidence of stroke among the recipients of the first dose of a COVID-19 vaccine. We linked the Georgia Immunization Registry with the Georgia Coverdell Acute Stroke Registry and the Georgia State Electronic Notifiable Disease Surveillance System data to assess the relative risk of stroke by the vaccine type.
RESULTS
Approximately 5 million adult Georgians received at least one COVID-19 vaccine between 1 December 2020 and 28 February 2022: 54% received BNT162b2, 41% received mRNA-1273, and 5% received Ad26.COV2.S. Those with concurrent COVID-19 infection within 21 days post-vaccination had an increased risk of ischemic (OR = 8.00, 95% CI: 4.18, 15.31) and hemorrhagic stroke (OR = 5.23, 95% CI: 1.11, 24.64) with no evidence for interaction between the vaccine type and concurrent COVID-19 infection. The 21-day post-vaccination incidence of ischemic stroke was 8.14, 11.14, and 10.48 per 100,000 for BNT162b2, mRNA-1273, and Ad26.COV2.S recipients, respectively. After adjusting for age, race, gender, and COVID-19 infection status, there was a 57% higher risk (OR = 1.57, 95% CI: 1.02, 2.42) for ischemic stroke within 21 days of vaccination associated with the Ad26.COV2.S vaccine compared to BNT162b2; there was no difference in stroke risk between mRNA-1273 and BNT162b2.
CONCLUSION
Concurrent COVID-19 infection had the strongest association with early ischemic and hemorrhagic stroke after the first dose of COVID-19 vaccination. Although not all determinants of stroke, particularly comorbidities, were considered in this analysis, the Ad26.COV2.S vaccine was associated with a higher risk of early post-vaccination ischemic stroke than BNT162b2.
PubMed: 37448752
DOI: 10.3389/fneur.2023.1199745 -
Journal of Advanced Research Apr 2024The causal association between modifiable risk factors and erectile dysfunction (ED) remains unclear, which hinders the early identification and intervention of patients...
INTRODUCTION
The causal association between modifiable risk factors and erectile dysfunction (ED) remains unclear, which hinders the early identification and intervention of patients with ED. The present study aimed to clarify the causal association between 42 predominant risk factors and ED.
METHODS
Univariate Mendelian Randomization (MR), multivariate MR, and mediation MR analyses were used to investigate the causal association between 42 modifiable risk factors and ED. Combined results were pooled from two independent ED genome-wide association studies to verify the findings.
RESULTS
Genetically predicted body mass index (BMI), waist circumference, trunk fat mass, whole body fat mass, poor overall health rating, type 2 diabetes, basal metabolic rate, adiponectin, cigarette consumption, insomnia, snoring, hypertension, stroke, ischemic stroke, coronary heart disease, myocardial infarction, heart failure, and major depressive disorder were found to increase the risk of ED (all P < 0.05). Additionally, genetic liability to higher body fat percentage and alcohol consumption were suggestively associated with an increased risk of ED (P < 0.05 and adjusted P > 0.05). Genetic predisposition to higher sex hormone-binding globulin (SHBG) levels could decrease the risk of ED (P < 0.05). No significant association was detected between lipid levels and ED. Multivariate MR identified type 2 diabetes, basal metabolic rate, cigarette consumption, hypertension, and coronary heart disease as risk factors for ED. The combined results confirmed that waist circumference, whole body fat mass, poor overall health rating, type 2 diabetes, basal metabolic rate, adiponectin, cigarette consumption, snoring, hypertension, ischemic stroke, coronary heart disease, myocardial infarction, heart failure, and major depressive disorder could increase the risk of ED (all P < 0.05), while higher SHBG decreased the risk of ED (P = 0.004). There were suggestive significances of BMI, insomnia, and stroke on ED (P < 0.05 and adjusted P > 0.05).
CONCLUSION
This comprehensive MR study supported the causal role of obesity, type 2 diabetes, basal metabolic rate, poor self-health rating, cigarette and alcohol consumption, insomnia and snoring, depression, hypertension, stroke, ischemic stroke, coronary heart disease, myocardial infarction, heart failure, SHBG, and adiponectin in the onset and development of ED.
Topics: Male; Humans; Diabetes Mellitus, Type 2; Adiponectin; Depressive Disorder, Major; Erectile Dysfunction; Genome-Wide Association Study; Mendelian Randomization Analysis; Sleep Initiation and Maintenance Disorders; Snoring; Risk Factors; Hypertension; Ischemic Stroke; Myocardial Infarction; Stroke; Coronary Disease; Heart Failure
PubMed: 37236543
DOI: 10.1016/j.jare.2023.05.008 -
Cardiovascular Diabetology Jan 2024This study used a bidirectional 2-sample Mendelian randomization study to investigate the potential causal links between mtDNA copy number and cardiometabolic disease... (Review)
Review
BACKGROUND
This study used a bidirectional 2-sample Mendelian randomization study to investigate the potential causal links between mtDNA copy number and cardiometabolic disease (obesity, hypertension, hyperlipidaemia, type 2 diabetes [T2DM], coronary artery disease [CAD], stroke, ischemic stroke, and heart failure).
METHODS
Genetic associations with mtDNA copy number were obtained from a genome-wide association study (GWAS) summary statistics from the UK biobank (n = 395,718) and cardio-metabolic disease were from largest available GWAS summary statistics. Inverse variance weighting (IVW) was conducted, with weighted median, MR-Egger, and MR-PRESSO as sensitivity analyses. We repeated this in the opposite direction using instruments for cardio-metabolic disease.
RESULTS
Genetically predicted mtDNA copy number was not associated with risk of obesity (P = 0.148), hypertension (P = 0.515), dyslipidemia (P = 0.684), T2DM (P = 0.631), CAD (P = 0.199), stroke (P = 0.314), ischemic stroke (P = 0.633), and heart failure (P = 0.708). Regarding the reverse directions, we only found that genetically predicted dyslipidemia was associated with decreased levels of mtDNA copy number in the IVW analysis (β= - 0.060, 95% CI - 0.044 to - 0.076; P = 2.416e-14) and there was suggestive of evidence for a potential causal association between CAD and mtDNA copy number (β= - 0.021, 95% CI - 0.003 to - 0.039; P = 0.025). Sensitivity and replication analyses showed the stable findings.
CONCLUSIONS
Findings of this Mendelian randomization study did not support a causal effect of mtDNA copy number in the development of cardiometabolic disease, but found dyslipidemia and CAD can lead to reduced mtDNA copy number. These findings have implications for mtDNA copy number as a biomarker of dyslipidemia and CAD in clinical practice.
Topics: Humans; DNA, Mitochondrial; DNA Copy Number Variations; Diabetes Mellitus, Type 2; Genome-Wide Association Study; Mendelian Randomization Analysis; Coronary Artery Disease; Hypertension; Heart Failure; Ischemic Stroke; Stroke; Obesity; Dyslipidemias
PubMed: 38282013
DOI: 10.1186/s12933-023-02074-1