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Background In patients with vasodilatory shock, plasma concentrations of angiotensin I (ANG I) and II (ANG II) and their ratio may reflect differences in the response to severe vasodilation, provide novel insights into its biology, and predict clinical outcomes. The objective of these protocol prespecified and subsequent post hoc analyses was to assess the epidemiology and outcome associations of plasma ANG I and ANG II levels and their ratio in patients with catecholamine-resistant vasodilatory shock (CRVS) enrolled in the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) study. Methods We measured ANG I and ANG II levels at baseline, calculated their ratio, and compared these results to values from healthy volunteers (controls). We dichotomized patients according to the median ANG I/II ratio (1.63) and compared demographics, clinical characteristics, and clinical outcomes. We constructed a Cox proportional hazards model to test the independent association of ANG I, ANG II, and their ratio with clinical outcomes. Results Median baseline ANG I level (253 pg/mL [interquartile range (IQR) 72.30–676.00 pg/mL] vs 42 pg/mL [IQR 30.46–87.34 pg/mL] in controls; P  <  0.0001) and median ANG I/II ratio (1.63 [IQR 0.98–5.25] vs 0.4 [IQR 0.28–0.64] in controls; P  <  0.0001) were elevated, whereas median ANG II levels were similar (84 pg/mL [IQR 23.85–299.50 pg/mL] vs 97 pg/mL [IQR 35.27–181.01 pg/mL] in controls; P  = 0.9895). At baseline, patients with a ratio above the median (≥1.63) had higher ANG I levels ( P  <  0.0001), lower ANG II levels ( P  <  0.0001), higher albumin concentrations ( P  = 0.007), and greater incidence of recent (within 1 week) exposure to angiotensin-converting enzyme inhibitors ( P  <  0.00001), and they received a higher norepinephrine-equivalent dose ( P  = 0.003). In the placebo group, a baseline ANG I/II ratio <1.63 was associated with improved survival (hazard ratio 0.56; 95% confidence interval 0.36–0.88; P  = 0.01) on unadjusted analyses. Conclusions Patients with CRVS have elevated ANG I levels and ANG I/II ratios compared with healthy controls. In such patients, a high ANG I/II ratio is associated with greater norepinephrine requirements and is an independent predictor of mortality, thus providing a biological rationale for interventions aimed at its correction. Trial registration ClinicalTrials.gov identifier NCT02338843 . Registered 14 January 2015.

Phenolic acids, found in cereals, legumes, vegetables, and fruits, have various biological functions. We aimed to compare the antihypertensive potential of different phenolic acids by evaluating their ACE inhibitory activity and cytoprotective capacity in EA.hy 926 endothelial cells. In addition, we explored the mechanism underlying the antihypertensive activity of sinapic acid. Of all the phenolic acids studied, sinapic acid, caffeic acid, coumaric acid, and ferulic acid significantly inhibited ACE activity. Moreover, gallic acid, sinapic acid, and ferulic acid significantly enhanced intracellular NO production. Based on the results of GSH depletion, ROS production, and MDA level analyses, sinapic acid was selected to study the mechanism underlying the antihypertensive effect. Sinapic acid decreases endothelial dysfunction by enhancing the expression of antioxidant-related proteins. Sinapic acid increased phosphorylation of eNOS and Akt in a dose-dependent manner. These findings indicate the potential of sinapic acid as a treatment for hypertension.

Background This study explores the relationship between angiotensin-converting enzyme ( ACE ) gene polymorphisms and early diastolic dysfunction in patients with hypertension utilizing four-dimensional echocardiography and assesses the prognosis. Methods This study consecutively selected 470 patients with hypertension who visited the Fourth Affiliated Hospital of Soochow University between September 2021 and August 2022, with 274 meeting the inclusion criteria. Hypertension gene testing was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) techniques, and the Hardy–Weinberg equilibrium test was used to confirm genetic equilibrium. Patients were categorized into the D allele group ( n  = 163) and the non-D allele group ( n  = 111). Diastolic function was assessed using four-dimensional echocardiography, which included averaging the E/e’ ratio over three cardiac cycles, measuring the left atrial (LA) maximum volume index (LA volume), tricuspid regurgitation velocity (TR velocity), LA strain, and left ventricular isovolumic relaxation time (IVRT). Patients were subsequently classified into the diastolic dysfunction group ( n  = 133) and the normal diastolic function group ( n  = 141). Chi-square tests were used to analyze differences in diastolic function indicators between the groups, Logistic regression was applied to control for potential confounding factors, and receiver operating characteristic (ROC) curves were plotted to assess the predictive value of different ACE alleles for diastolic dysfunction in patients with hypertension. Results The genotype distribution in both the D allele group and the non-D allele group was consistent with Hardy–Weinberg equilibrium ( P  >  0.05 ). Compared to the non-D allele group, echocardiographic indicators in the D allele group showed a decline in diastolic function: the average E/e' ratio over three cardiac cycles (14.67 [13.82, 15.80] vs. 9.30 [8.12, 12.00]), LA volume (32.76 [29.34, 34.61] vs. 25.61 [22.63, 29.64] ml/m 2 ), TR velocity (2.90 [2.40, 2.90] vs. 1.40 [1.10, 2.40] cm/s), LA strain (18.00 [14.00, 25.00] vs. 37.00 [24.00, 40.00] %), and IVRT (104.25 [95.87, 106.25] vs. 88.09 [80.99, 96.56] ms). Differences between each group were statistically significant (all P  <  0.05 ). The number of patients with diastolic dysfunction was higher in the D allele group ( n  = 102; 62.6%) compared to the non-D allele group ( n  = 31; 27.9%). In the logistic regression model, the D allele was associated with an increased risk of early diastolic dysfunction in hypertension (OR = 4.32, 95% CI = 2.56–7.27, P  < 0.01). In the adjusted model, the D allele remained associated with an elevated risk of early diastolic dysfunction in hypertension (OR = 3.83, 95% CI = 2.24–6.54, P  < 0.01). ROC curve analysis indicated that the D allele has predictive value for early diastolic dysfunction in patients with hypertension (area under the curve [AUC], 0.667; 95% confidence interval [CI], 0.608–0.723; sensitivity, 76.7%; and specificity, 56.7%; P  <  0.05 ). Conclusions The ACE -D allele is associated with early diastolic dysfunction in hypertension. ACE gene testing can enhance the predictive value for diastolic dysfunction in patients with hypertension.

It is known that the angiotensin-converting–enzyme inhibitor captopril is beneficial in patients with myocardial infarction complicated by left ventricular dysfunction or heart failure. This study compared captopril with valsartan, an angiotensin-receptor blocker, and the combination of the two drugs in such patients. Mortality was the same in the three groups, but there were more side effects with the combination therapy. In patients with heart failure, valsartan is an alternative. Multiple randomized, placebo-controlled trials involving a total of more than 100,000 patients have demonstrated that angiotensin-converting–enzyme (ACE) inhibitors reduce the risk of death as well as the risk of major nonfatal cardiovascular events after myocardial infarction. 1 – 8 The greatest relative and absolute benefits have been obtained with long-term ACE-inhibitor therapy in high-risk patients — specifically, in those with left ventricular dysfunction, signs or symptoms of heart failure, or both. 9 , 10 Angiotensin-receptor blockers offer an alternative approach to the inhibition of the renin–angiotensin system. 11 The identification of a functioning chymase in humans that is capable of generating angiotensin II independently of . . .

Angiotensin II type 1 receptor blockers have favourable effects on haemodynamic measurements, neurohumoral activity, and left-ventricular remodelling when added to angiotensin-converting-enzyme (ACE) inhibitors in patients with chronic heart failure (CHF). We aimed to find out whether these drugs improve clinical outcome. Between March, 1999, and November, 1999, we enrolled 2548 patients with New York Heart Association functional class II–IV CHF and left-ventricular ejection fraction 40% or lower, and who were being treated with ACE inhibitors. We randomly assigned patients candesartan (n=1276, target dose 32 mg once daily) or placebo (n=1272). At baseline, 55% of patients were also treated with β blockers and 17% with spironolactone. The primary outcome of the study was the composite of cardiovascular death or hospital admission for CHF. Analysis was done by intention to treat. The median follow-up was 41 months. 483 (38%) patients in the candesartan group and 538 (42%) in the placebo group experienced the primary outcome (unadjusted hazard ratio 0·85 [95% CI 0·75–0·96], p=0·011; covariate adjusted p=0·010). Candesartan reduced each of the components of the primary outcome significantly, as well as the total number of hospital admissions for CHF. The benefits of candesartan were similar in all predefined subgroups, including patients receiving baseline β blocker treatment. The addition of candesartan to ACE inhibitor and other treatment leads to a further clinically important reduction in relevant cardiovascular events in patients with CHF and reduced left-ventricular ejection fraction. Published online Sept 1, 2003 http://image.thelancet.com/extras/03art7417web.pdf

Angiotensin-converting-enzyme (ACE) inhibitors improve outcome of patients with chronic heart failure (CHF). A substantial proportion of patients, however, experience no benefit from ACE inhibitors because of previous intolerance. We aimed to find out whether candesartan, an angiotensin-receptor blocker, could improve outcome in such patients not taking an ACE inhibitor. Between March, 1999, and March, 2001, we enrolled 2028 patients with symptomatic heart failure and left-ventricular ejection fraction 40% or less who were not receiving ACE inhibitors because of previous intolerance. Patients were randomly assigned candesartan (target dose 32 mg once daily) or matching placebo. The primary outcome of the study was the composite of cardiovascular death or hospital admission for CHF. Analysis was by intention to treat. The most common manifestation of ACE-inhibitor intolerance was cough (72%), followed by symptomatic hypotension (13%) and renal dysfunction (12%). During a median follow-up of 33·7 months, 334 (33%) of 1013 patients in the candesartan group and 406 (40%) of 1015 in the placebo group had cardiovascular death or hospital admission for CHF (unadjusted hazard ratio 0·77 [95% CI 0·67–0·89], p=0·0004; covariate adjusted 0·70 [0·60–0·81], p<0·0001). Each component of the primary outcome was reduced, as was the total number of hospital admissions for CHF. Study-drug discontinuation rates were similar in the candesartan (30%) and placebo (29%) groups. Candesartan was generally well tolerated and reduced cardiovascular mortality and morbidity in patients with symptomatic chronic heart failure and intolerance to ACE inhibitors. Published online Sept 1, 2003 http://image.thelancet.com/extras/03art7418web.pdf

The purposes of this review were to give the optimal cutoffs of the Montreal Cognitive Assessment (MoCA) by comparing sensitivity and specificity under different cutoffs and compare the MoCA with other screening tools in post-stroke cognitive impairment (PSCI) determined by a neuropsychological evaluation. Articles were derived from a systematic search in PubMed, Web of science, Embase, and CINAHL and were assessed for internal validity by the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). The figure of risk of bias was made by Review Manager 5.3, and data of selected studies were synthesized by MetaDisc 1.4. Twelve diagnostic studies, involving 2130 patients, were included. The area under the curve (AUC) under cutoffs of 20v19, 21v20, and 26v25 are 0.90, 0.90, and 0.95, showing high predictive validity for PSCI screening within 1 month. When the sensitivity and specificity are equal important, the optimal cutoff is 20v19 (Youden Index = 0.58). Compared to the Mini-Mental State Examination (MMSE), the MoCA has higher sensitivity but lower specificity. The optimal cutoff differs in different stages of stroke. Both the MMSE and MoCA are appropriate screening tools for PSCI, and the use of these two tools should be in accordance with the aim of screening. The Addenbrooke’s Cognitive Examination-Revised (ACE-R) can act as a supplement for the MoCA.

Duchenne Muscular Dystrophy (DMD) is a severe X-linked recessive disorder characterized by progressive muscle degeneration due to dystrophin deficiency. Cardiac involvement, particularly dilated cardiomyopathy, significantly impacts morbidity and mortality, typically manifesting after age 10. This case report presents a rare instance of early-onset cardiac involvement in a 3-year-old male with a confirmed deletion in exon 55 of the dystrophin gene. The patient developed dilated cardiomyopathy at 3 years and 8 months, with progressive left ventricular dysfunction despite early treatment with corticosteroids, ACE inhibitors, and beta-blockers. Genetic mechanisms and genotype–phenotype correlations related to cardiac involvement were reviewed, highlighting emerging therapies such as exon skipping, vamorolone, ifetroban, and rimeporide. Studies indicate that variants in exons 12, 14–17, 31–42, 45, and 48–49 are associated with more severe cardiac impairment. This case emphasizes the need for early, ongoing cardiac assessment and personalized treatment to address disease heterogeneity. While current DMD care standards improve survival, optimizing management through early intervention and novel therapies remains essential. Further research is needed to better understand genotype–phenotype correlations and improve cardiac outcomes for patients with DMD.

Background Vision impairment affects the accuracy of cognitive test outcomes, emphasizing the need for developing cognitive screening tools designed for visually impaired individuals, especially considering global aging trends. This study aimed to develop a modified, validated version of the Vision-Impairment version of Addenbrooke's Cognitive Examination III (VI-ACE-III) for Arabic-speaking elderly individuals with vision impairment in Egypt. In addition, the study aimed to assess the accuracy of VI-ACE-III in diagnosing dementia and mild cognitive impairment (MCI). Methods The VI-ACE-III was developed using large printed formats and verbal substitution of the vision-dependent items. One hundred and eighty participants aged ≥ 60, with varying degrees of vision impairment (including moderate, severe, and blindness), were divided into three equal groups: 60 individuals with MCI, 60 with mild to moderate dementia, and 60 with cognitively intact controls. Receiver operating characteristics (ROC) curves were plotted to assess the accuracy of the test screening. Results ROC analysis for dementia established an optimal cut-off point of 84 out of 115, demonstrating 100.0% sensitivity, 98.3% specificity, and an area under the curve (AUC) of 0.983, based on the comparison between the dementia and MCI groups. The analysis for MCI determined an optimal cut-off point of 94 out of 115, with 95.0% sensitivity, 96.7% specificity, and an AUC of 0.983 compared to controls. The VI-ACE-III demonstrated significant Cronbach's alpha values (α = 0.866, α = 0.771), indicating strong internal consistency within the dementia and MCI groups. Conclusions The VI-ACE-III showed good sensitivity and specificity for assessing dementia and MCI in Arabic-speaking elderly individuals with visual impairment (VI) in Egypt. Regular screening and interventions are crucial for managing and preventing the deterioration of cognitive dysfunction and vision impairment in the elderly population.

INTRODUCTION Lifelong bilingualism is associated with a delayed age at onset of dementia, but evidence from community‐based studies is limited. We investigated the relationship between bilingualism and the prevalence of cognitive impairment in a linguistically diverse community. METHODS A door‐to‐door community study was conducted from January to December 2021 in urban Bengaluru, India. 1234 individuals aged ≥60 years participated in the study. Participants were diagnosed with no cognitive impairment (NCI), mild cognitive impairment (MCI), or dementia using established diagnostic criteria. RESULTS Dementia prevalence was higher in monolinguals (4.9%) than bilinguals (0.4%) (P = .001). The prevalence of MCI was also higher in monolinguals (8.5%) than bilinguals (5.3%) (P = .001). The study also revealed better cognitive function in bilinguals than monolinguals with NCI, after controlling for confounding variables. DISCUSSION The current study provides significant support for the protective effect of bilingualism on cognitive impairment in an urban community with extensive bilingual interactional contexts in everyday life. Highlights Bilingualism has been demonstrated to protect against dementia and mild cognitive impairment in a linguistically diverse community with extensive code‐switching contexts. Bilingual older individuals had superior baseline cognitive performance compared to monolingual older individuals. Bilingualism was found to have an independent effect on general cognition after adjusting for major social determinants of health in the group without cognitive impairment.