Neil R Poulter’s research while affiliated with Imperial College London and other places

Background Sex differences in cognitive abilities have been reported; however, the underlying reasons remain unclear. Objective To (i) investigate sex differences in cognitive performance, (ii) evaluate the contributions of established dementia risk factors to these differences, and (iii) examine the role of non-modifiable risk factors on sex differences in cognitive performance. Methods Among 964 cognitively unimpaired participants (aged 60–85) of the UK CHARIOT-PRO Main Study, we assessed cross-sectional and longitudinal associations, over up to 3 years of follow-up, between sex and cognitive performance, using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Results Sex differences, mostly favoring women were observed at baseline across almost all RBANS indices including the total scale (Cohen's d = 0.3, adjusted mean difference in score = −5.4, p < 0.001). Sex differences were observed in Practice effects (PEs), with men showing less PE in almost all cognitive domains including the total scale (adjusted 1.3, p = 0.002). Greater sex differences in PEs, were documented among the ‘older’ participants in two out of five cognitive domains including the immediate memory index (mean difference: older (69–85 years) group = −3.2, p = 0.002); younger (60–68 years) group = −0.8, p = 0.4). Sex differences were more pronounced among ‘Apolipoprotein-Ꜫ4 -carriers’ in three out of five domains including the total scale (mean difference in carriers = −2.6, p = 0.002); non-carriers = −0.7, p = 0.3). Conclusions Sex differences in cognition and PE were observed after adjusting for risk factors associated with Alzheimer's disease. Future studies should also consider the effects of sex on non-modifiable risk factors and PEs to identify potential ‘masked’ neuropathology.

EU-Wide Cross-Sectional Observational Study of Lipid-Modifying Therapy Use in Secondary and Primary Care: the DA VINCI study.

BACKGROUND Glucagon-like peptide 1 receptor agonists (GLP-1RA) reduce the incidence of major adverse cardiovascular events (MACE) in type 2 diabetes (T2D), although whether benefits extend to both subcutaneous and oral formulations remains unclear. PURPOSE In these meta-analyses, including new data from the Semaglutide cardiOvascular oUtcomes triaL (SOUL) (oral semaglutide) and Evaluate Renal Function with Semaglutide Once Weekly (FLOW) trial, we examined cardiovascular (CV) and kidney benefits and risks of long-acting (defined as having pharmacokinetics sufficient to provide 24-h activity) GLP-1RA in T2D. DATA SOURCES A systematic review of PubMed was conducted (to 7 February 2025). STUDY SELECTION Randomized placebo-controlled CV and kidney outcomes trials of GLP-1RA with ≥500 individuals with T2D were included. DATA EXTRACTION A random-effects model was used to estimate hazard ratios (HRs) for MACE, its components, all-cause mortality, hospitalization for heart failure (HHF), a composite kidney outcome (kidney failure [kidney replacement therapy or persistent estimated glomerular filtration rate [eGFR] <15 mL/min/1.73 m2], sustained ≥50% eGFR decline or nearest equivalent, or kidney-related death), worsening kidney function, and safety outcomes. DATA SYNTHESIS Across 10 trials (n = 71,351), long-acting GLP-1RA reduced incidence rate of MACE by 14% (HR 0.86 [95% CI 0.81, 0.90]; I2 = 27.6%), HHF by 14% (0.86 [0.79, 0.93]; I2 = 2.1%), and the composite kidney outcome by 17% (0.83 [0.75, 0.92]; I2 = 20.4%) and all-cause mortality by 12% (0.88 [0.82, 0.93]; I2 = 17.5%). A consistent 14% reduction was seen for all MACE components. There was no significant heterogeneity by GLP-1RA administration route (subcutaneous vs. oral). There were no increased risks of severe hypoglycemia, retinopathy, or pancreatic events. LIMITATIONS Trial-level meta-analyses preclude detailed subgroup analyses and may introduce ecological bias. CONCLUSIONS As a group, long-acting GLP-1RA, including both injectable and oral formulations, reduce incidence of MACE, HHF, and kidney events and all-cause mortality in T2D.

Background: Both glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) improve cardiovascular (CV) outcomes in people with type 2 diabetes (T2D) and CV or chronic kidney disease (CKD). However, there are limited data about the effect of combining these agents on CV and safety outcomes. Methods: The SOUL trial (NCT03914326) randomised 9650 participants with T2D and atherosclerotic CV disease and/or CKD to oral semaglutide or placebo. As prespecified, participants were analysed according to baseline use of SGLT2i (Yes: n=2596, No: n=7054) and, subsequently for any use of SGLT2i during the trial (Yes: n=4718, No: n=4932). The primary outcome was time to first major adverse cardiovascular event (MACE), defined as cardiovascular death, non-fatal myocardial infarction or non-fatal stroke. Safety was evaluated by comparing the incidence of serious adverse events. Results: Over a mean follow-up of 47.5±10.9 months, the risk of the primary outcome in the overall trial population was 14% lower for oral semaglutide vs placebo (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.77; 0.96). In those taking SGLT2i at baseline, there were 143/1296 (semaglutide) versus 158/1300 (placebo) primary outcome events (HR 0.89; 95% CI 0.71; 1.11); and 436/3529 versus 510/3525, respectively, in participants not taking SGLT2i at baseline (HR 0.84; 95% CI 0.74; 0.95; P -interaction 0.66). An analysis of MACE by any in-trial SGLT2i use versus no use also showed no evidence of heterogeneity in the effects of oral semaglutide. The adverse event profiles of oral semaglutide with or without concomitant SGLT2i were similar. Conclusions: Oral semaglutide reduced MACE outcomes independently of concomitant SGLT2i treatment and this combination appeared to be safe.

The May Measurement Month (MMM) campaign was carried out in Kazakhstan in 2022 with the aim of raising awareness of raised blood pressure (BP). Here, we report on the findings of the campaign. Adults aged ≥ 18 years were recruited opportunistically at hypermarkets in Almaty. Three seated BP readings were taken for each participant, along with completion of a questionnaire on demographics, lifestyle factors, and comorbidities. Hypertension was defined as a systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg or being on antihypertensive medication. Controlled BP was defined as being on antihypertensive medication with a BP <140/90 mmHg. Multiple imputation was used to estimate any missing BP readings. In total, 2133 adults were screened, with a mean age of 46.5 years and 49.8% were female. Of all participants, 843 (39.5%) had hypertension, of whom 469 (55.6%) were aware, and 396 (47.0%) were on antihypertensive medication. Of those on antihypertensive medication, 172 (43.4%) had controlled BP, and of all participants with hypertension, 20.4% had controlled BP. In total, 671 (31.5%) were found to have either untreated or inadequately treated hypertension. The MMM campaign in Kazakhstan identified significant numbers of participants with either untreated or inadequately treated hypertension. The findings highlight the urgent need for improved screening, treatment, and management strategies for hypertension in Kazakhstan. Strengthening public health initiatives and increasing awareness can significantly reduce the burden of cardiovascular disease and improve population health outcomes.

Background: The cardiovascular safety of oral semaglutide, a glucagon-like peptide 1 receptor agonist, has been established in persons with type 2 diabetes and high cardiovascular risk. An assessment of the cardiovascular efficacy of oral semaglutide in persons with type 2 diabetes and atherosclerotic cardiovascular disease, chronic kidney disease, or both is needed. Methods: In this double-blind, placebo-controlled, event-driven, superiority trial, we randomly assigned participants who were 50 years of age or older, had type 2 diabetes with a glycated hemoglobin level of 6.5 to 10.0%, and had known atherosclerotic cardiovascular disease, chronic kidney disease, or both to receive either once-daily oral semaglutide (maximal dose, 14 mg) or placebo, in addition to standard care. The primary outcome was major adverse cardiovascular events (a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke), assessed in a time-to-first-event analysis. The confirmatory secondary outcomes included major kidney disease events (a five-point composite outcome). Results: Among the 9650 participants who had undergone randomization, the mean (±SD) follow-up was 47.5±10.9 months, and the median follow-up was 49.5 months. A primary-outcome event occurred in 579 of the 4825 participants (12.0%; incidence, 3.1 events per 100 person-years) in the oral semaglutide group, as compared with 668 of the 4825 participants (13.8%; incidence, 3.7 events per 100 person-years) in the placebo group (hazard ratio, 0.86; 95% confidence interval, 0.77 to 0.96; P = 0.006). The results for the confirmatory secondary outcomes did not differ significantly between the two groups. The incidence of serious adverse events was 47.9% in the oral semaglutide group and 50.3% in the placebo group; the incidence of gastrointestinal disorders was 5.0% and 4.4%, respectively. Conclusions: Among persons with type 2 diabetes and atherosclerotic cardiovascular disease, chronic kidney disease, or both, the use of oral semaglutide was associated with a significantly lower risk of major adverse cardiovascular events than placebo, without an increase in the incidence of serious adverse events. (Funded by Novo Nordisk; SOUL ClinicalTrials.gov number, NCT03914326.).

May Measurement Month (MMM) is a global campaign initiated by the International Society of Hypertension aimed at raising awareness of high blood pressure (BP) and to act as a temporary solution to the lack of screening programmes worldwide. We provide the results of the MMM 2022 (MMM22) campaign in Mauritius. Adults aged ≥ 18 years were recruited opportunistically at workplaces and community centres, in both rural and urban areas across Mauritius. Three seated BP readings were taken for each participant, along with completion of a questionnaire on demographics, lifestyle factors, and comorbidities. Hypertension was defined as a systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg or being on antihypertensive medication. Controlled BP was defined as being on antihypertensive medication with a BP <140/90 mmHg. Multiple imputation was used to estimate any missing BP readings. In total, 8953 were screened, with a mean age of 43.6 years and 62.2% of whom were female. Out of 8953 participants, 2024 participants (22.6%) had hypertension, of whom 1066 (52.7%) were aware, and 884 (43.7%) were on antihypertensive medication. Of those on antihypertensive medication, 550 (62.2%) had controlled BP, and of all participants with hypertension, 550 (27.2%) had controlled BP. The MMM campaign in Mauritius identified significant numbers of participants with either untreated or inadequately treated hypertension. MMM22 was the largest BP screening campaign undertaken in Mauritius. These results suggest that MMM22 was useful in the identification of patients with raised BP for further investigation and follow-up.

Aims Cardiovascular (CV) deaths were reduced by atorvastatin during a 16-year follow-up of participants in the Anglo-Scandinavian Cardiac Outcomes Trial-lipid-lowering arm. We now extend these observations over 20 years and report both non-fatal and fatal CV outcomes. Methods A cohort of 4605 UK hypertensive participants with total cholesterol <6.5 mmol/L (2317 atorvastatin vs 2288 placebo) was followed for up to 21 years (IQR 9.1–19.3). Cox proportional hazard models assessed HRs for non-fatal and fatal CV events. At the end of the original trial (3.3 years), all participants were offered atorvastatin. Lipid profiles were obtained from all subjects 2 years later and from subgroups approximately 9 years post-trial. Results Patients allocated to atorvastatin had a significant reduction in non-fatal myocardial infarction (MI) and fatal coronary heart disease (CHD) events (HR (95% CI) 0.81 (0.69 to 0.94, p=0.006)), total coronary events (0.88 (0.80 to 0.98, p=0.017)) and CV deaths (0.86 (0.74 to 0.99, p=0.048)). No significant reduction in heart failure (HF), strokes, total CV events and all-cause mortality was observed. In participants assigned atorvastatin in the trial, 3-year mean low-density lipoprotein-cholesterol was strongly associated with long-term CV outcomes. The HRs per 1 mmol/L decrease were for non-fatal MI and fatal CHD (0.69 (0.57 to 0.85, p<0.001)), total coronary events (0.70 (0.61 to 0.79, p<0.001)), non-fatal and fatal HF (0.68 (0.57 to 0.81, p<0.001)), non-fatal and fatal stroke (0.74 (0.59 to 0.92, p=0.006)), total CV events and procedures (0.74 (0.66 to 0.81, p<0.001)), CV mortality (0.66 (0.55 to 0.81, p<0.001)) and all-cause mortality (0.81 (0.71 to 0.90, p<0.001)). Two years after the trial, approximately two-thirds of subjects in each arm were taking atorvastatin. At this time point and approximately 9 years post-trial, lipid profiles were similar between those formerly assigned atorvastatin or placebo. Conclusions These observations provide further evidence for the long-term legacy effects of statins and have implications for the early introduction of statins to prevent CV events and mortality.

Hypertension is the leading modifiable risk factor for atrial fibrillation (AF) and is estimated to be present in >70% of AF patients. This Frontiers Review was prepared by 29 expert members of the AF-SCREEN International Collaboration to summarize existing evidence and knowledge gaps on links between hypertension, AF, and their cardiovascular sequelae; simultaneous screening for hypertension and AF; and the prevention of AF through antihypertensive therapy. Hypertension and AF are inextricably connected. Both are easily diagnosed, often silent, and frequently treated inadequately. Together, they additively increase the risk of ischemic stroke, heart failure, and many types of dementia, resulting in greater all-cause mortality, considerable disease burden, and increased health care expenditures. Automated upper arm cuff blood pressure devices with implemented technology can be used to simultaneously detect both hypertension and AF. However, positive screening for AF with an oscillometric blood pressure monitor still requires ECG confirmation. The current evidence suggests that high-risk individuals aged ≥65 years or with treatment-resistant hypertension could benefit from AF screening. Since antihypertensive therapy effectively lowers AF risk, particularly in individuals with left ventricular dysfunction, hypertension should be the key target for AF prediction and prevention rather than merely a comorbidity of AF. Nevertheless, several important gaps in knowledge need to be filled over the next years, including the ideal method and selection of patients for simultaneous screening of hypertension and AF and the optimal antihypertensive drug class and blood pressure targets for AF prevention.