Arterial pathophysiology and comparison of two devices for pulse wave velocity assessment in elderly men: the British regional heart study.

Objective: Vascular disease is highly prevalent in the elderly. This study aimed to evaluate arterial phenotype in elderly men and compare carotid-femoral pulse wave velocity (cfPWV) assessed by two techniques (Sphygmocor (S)and Vicorder (V)). Methods: 1722 men (72-92 years), participants in the British Regional Heart Study, underwent ultrasound assessment of carotid intima-media thickness (cIMT), carotid distensibility coefficient and presence of carotid plaque. cfPWV and ankle brachial pressure index (ABPI) were also assessed. 123 men returned for between visit reproducibility assessments. Results: Good reproducibility was demonstrated in all measures (Gwet's agreement=0.8 for plaque, intraclass correlation=0.65 for ABPI and coefficient of variation 90% of men for all measures except cfPWV(S) and ABPI. In 1122 men with both cfPWV(V) and cfPWV(S) data, cfPWV(S) was greater than cfPWV(V) (mean difference=0.23,95%CI 0.10 to 0.37 m/s). cfPWV(V) was higher at low cfPWV values and cfPWV(S) was higher at high cfPWV values. Correlation of V transit time (TT) against S carotid and femoral TT demonstrated that the slope of the regression line for femoral TT was steeper than for carotid TT, resulting in a proportionally greater subtraction of carotid TT from femoral TT at higher PWVs. Conclusions: Reproducible, satisfactory quality non-invasive measurements of vascular phenotype were obtainable in a large proportion of elderly men. The discrepancy in results between the two PWV measures may partly be due to the differential impact of subtracting carotid TT when deriving cfPWV(S) across the clinical PWV range

Impact of Vitamin D Supplementation on Arterial Vasomotion, Stiffness and Endothelial Biomarkers in Chronic Kidney Disease Patients

Background: Cardiovascular events are frequent and vascular endothelial function is abnormal in patients with chronic kidney disease (CKD). We demonstrated endothelial dysfunction with vitamin D deficiency in CKD patients; however the impact of cholecalciferol supplementation on vascular stiffness and vasomotor function, endothelial and bone biomarkers in CKD patients with low 25-hydroxy vitamin D [25(OH)D] is unknown, which this study investigated. Methods: We assessed non-diabetic patients with CKD stage 3/4, age 17–80 years and serum 25(OH)D ,75 nmol/L. Brachial artery Flow Mediated Dilation (FMD), Pulse Wave Velocity (PWV), Augmentation Index (AI) and circulating blood biomarkers were evaluated at baseline and at 16 weeks. Oral 300,000 units cholecalciferol was administered at baseline and 8-weeks. Results: Clinical characteristics of 26 patients were: age 50614 (mean61SD) years, eGFR 41611 ml/min/1.73 m2, males 73%, dyslipidaemia 36%, smokers 23% and hypertensives 87%. At 16-week serum 25(OH)D and calcium increased (43616 to 84629 nmol/L, p,0.001 and 2.3760.09 to 2.4260.09 mmol/L; p = 0.004, respectively) and parathyroid hormone decreased (10.868.6 to 7.464.4; p = 0.001). FMD improved from 3.163.3% to 6.163.7%, p = 0.001. Endothelial biomarker concentrations decreased: E-Selectin from 566662123 to 525662058 pg/mL; p = 0.032, ICAM-1, 3.4560.01 to 3.1061.04 ng/mL; p = 0.038 and VCAM-1, 54633 to 42633 ng/mL; p = 0.006. eGFR, BP, PWV, AI, hsCRP, von Willebrand factor and Fibroblast Growth Factor-23, remained unchanged. Conclusion: This study demonstrates for the first time improvement of endothelial vasomotor and secretory functions with vitamin D in CKD patients without significant adverse effects on arterial stiffness, serum calcium or FGF-23. Trial Registration: ClinicalTrials.gov NCT0200571

Omega-3 Fatty Acids and Mortality Outcome in Patients With and Without Type 2 Diabetes After Myocardial Infarction: A Retrospective, Matched-Cohort Study

Background There are conflicting data regarding the benefits of omega-3 (n-3) fatty acids, most recently in patients with type 2 diabetes. Objective Our goal was to evaluate the impact of licensed, highly purified n-3 fatty acids on all-cause mortality after myocardial infarction (MI). Methods This was a retrospective, matched-cohort study using data from the General Practice Research Database. Patients initiating treatment with 1 g of n-3 fatty acids in the 90 days after first MI were identified and each matched to 4 nonexposed patients. Progression to death was compared using time-dependent Cox models to account for potential differences in exposure to other cardiovascular risk–modifying treatments. Results A total of 2466 eligible subjects exposed to n-3 fatty acids were matched. The majority of patients had concurrent treatment with lipid-lowering therapies, antihypertensives, and antiplatelets after first MI, with subjects exposed to n-3 fatty acids having a greater likelihood of concurrent exposure. For those initiating n-3 fatty acids within 90 days of first MI, the adjusted hazard ratio (aHR) was 0.782 (95% CI, 0.641–0.995; P = 0.0159); for those initiating treatment within 14 days, the aHR was 0.680 (95% CI, 0.481–0.961; P = 0.0288). In patients with type 2 diabetes at baseline, the aHRs were 0.714 (95% CI, 0.454–1.124) and 0.597 (95% CI, 0.295–1.211) when initiation was within 90 and 14 days, respectively. Use of n-3 fatty acids resulted in a consistent survival benefit under a range of scenarios quantitatively consistent with the overall effect. Conclusion After MI, early treatment with licensed n-3 fatty acids was associated with improvement in all-cause mortality in patients with and without type 2 diabetes, against a background of contemporary cardiovascular risk–modifying treatments

C-reactive protein levels in patients at cardiovascular risk: EURIKA study

Background: Elevated C-reactive protein (CRP) levels are associated with high cardiovascular risk, and might identify patients who could benefit from more carefully adapted risk factor management. We have assessed the prevalence of elevated CRP levels in patients with one or more traditional cardiovascular risk factors. Methods: Data were analysed from the European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice (EURIKA, ClinicalTrials.gov Identifier: NCT00882336), which included patients (aged ≥50 years) from 12 European countries with at least one traditional cardiovascular risk factor but no history of cardiovascular disease. Analysis was also carried out on the subset of patients without diabetes mellitus who were not receiving statin therapy. Results: In the overall population, CRP levels were positively correlated with body mass index and glycated haemoglobin levels, and were negatively correlated with high-density lipoprotein cholesterol levels. CRP levels were also higher in women, those at higher traditionally estimated cardiovascular risk and those with greater numbers of metabolic syndrome markers. Among patients without diabetes mellitus who were not receiving statin therapy, approximately 30% had CRP levels ≥3 mg/L, and approximately 50% had CRP levels ≥2 mg/L, including those at intermediate levels of traditionally estimated cardiovascular risk. Conclusions: CRP levels are elevated in a large proportion of patients with at least one cardiovascular risk factor, without diabetes mellitus who are not receiving statin therapy, suggesting a higher level of cardiovascular risk than predicted according to conventional risk estimation systems

Ready-to-use food supplement, with or without arginine and citrulline, with daily chloroquine in Tanzanian children with sickle-cell disease: a double-blind, random order crossover trial

Background Sickle-cell disease increases the risk of malnutrition. Low arginine and nitric oxide bioavailability are implicated in morbidity related to sickle-cell disease. Simple interventions are required, especially in low-income settings. We aimed to test the hypotheses that: (1) supplementary arginine, citrulline, and daily chloroquine increase bioavailable arginine and flow-mediated dilatation (FMD; maximal diameter change; FMDmax%), a measure of nitric oxide-dependent endothelial function; and (2) protein energy supplementation in the form of ready-to-use supplementary food (RUSF) improves the height-for-age and body-mass index-for-age Z-scores in children with sickle-cell disease. Methods We performed a double-blind, random order crossover trial with two 4-month intervention periods (each followed by 4-month washout periods) in Muhimbili National Hospital in Dar-es-Salaam, Tanzania. We enrolled 119 children from the Muhimbili Sickle Cohort who were aged 8–12 years, naive to hydroxyurea, and had documented HbSS phenotype. Two formulations of RUSF (providing 500 kcal/day) were tested: basic (RUSF-b), with which children also received weekly chloroquine (150 mg or 225 mg chloroquine base, dependent on bodyweight); and vascular (RUSF-v), which was fortified with arginine and citrulline (designed to achieve mean intakes of 0·2 g/kg per day of arginine and 0·1 g/kg per day of citrulline), and with which children received daily chloroquine (maximum 3 mg chloroquine base/kg per day). Children were randomly allocated to receive either RUSF-b first or RUSF-v first and, after a washout period, were then given the other treatment. The primary outcomes in comparing the two RUSF formulations were mean plasma arginine, arginine to ornithine ratio, and arginine to asymmetric dimethylarginine ratio, and mean FMDmax%. The primary outcomes of the combined effect of both RUSF interventions were mean height-for-age Z-score and body-mass index-for-age Z-score. Analyses were done on the eligible intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01718054; and with ISRCTN74331412. Findings Between Aug 9, 2012, and Feb 26, 2014, 145 children were randomised (71 children to RUSF-v first and 74 children to RUSF-b first) and 119 children were treated, of whom 114 children yielded complete data for all reported endpoints. The ratio of arginine to ornithine (mean of individual differences –8·67%, 95% CI –19·55 to 2·20; p=0·12) and the mean FMDmax% (1·00, –0·47 to 2·47; p=0·18) did not significantly differ between the RUSF-b and RUSF-v treatments. However, the arginine to asymmetric dimethylarginine ratio was significantly increased by RUSF-v compared with RUSF-b (56·26%, 31·13 to 81·38; p<0·0001). In planned analyses that used mixed effects models to estimate the effect of each intervention compared with the participants at baseline or during washout periods, the arginine to asymmetric dimethylarginine ratio increased following both RUSF-v treatment (86%; p<0·0001) and RUSF-b treatment (40%; p<0·0001). However, FMDmax% was higher after treatment with RUSF-v (0·92; p<0·0001) but not RUSF-b (0·39; p=0·22). Following either intervention (RUSF-b and RUSF-v, pooled) body-mass index-for-age Z-score (0·091; p=0·001) and height-for-age Z-score (0·013; p=0·081) increased compared with baseline and washout timepoints. In 83 participants in the treated population, there were 71 adverse events during the intervention, of which 21 (30%) were serious, and 81 adverse events during the washout periods, of which 26 (32%) were serious (p=0·31), including one patient who died in the second washout period. Interpretation RUSF providing 500 kcal/day results in small weight gains in children with sickle-cell disease. However, even without arginine and citrulline fortification, RUSF seems to ameliorate arginine dysregulation and might improve endothelial function. Long-term studies are required to assess whether these physiological effects translate to improved clinical outcomes and better growth and development in patients with sickle-cell disease

Early influences on cardiovascular and renal development

The hypothesis that a developmental component plays a role in subsequent disease initially arose from epidemiological studies relating birth size to both risk factors for cardiovascular disease and actual cardiovascular disease prevalence in later life. The findings that small size at birth is associated with an increased risk of cardiovascular disease have led to concerns about the effect size and the causality of the associations. However, recent studies have overcome most methodological flaws and suggested small effect sizes for these associations for the individual, but an potential important effect size on a population level. Various mechanisms underlying these associations have been hypothesized, including fetal undernutrition, genetic susceptibility and postnatal accelerated growth. The specific adverse exposures in fetal and early postnatal life leading to cardiovascular disease in adult life are not yet fully understood. Current studies suggest that both environmental and genetic factors in various periods of life may underlie the complex associations of fetal growth retardation and low birth weight with cardiovascular disease in later life. To estimate the population effect size and to identify the underlying mechanisms, well-designed epidemiological studies are needed. This review is focused on specific adverse fetal exposures, cardiovascular adaptations and perspectives for new studies. Copyrigh

Routine measurement of cardiometabolic disease risk factors in primary care in England before, during, and after the COVID-19 pandemic: A population-based cohort study.

BACKGROUND: This study estimated to what extent the number of measurements of cardiometabolic risk factors (e.g., blood pressure, cholesterol, glycated haemoglobin) were impacted by the COVID-19 pandemic and whether these have recovered to expected levels. METHODS AND FINDINGS: A cohort of individuals aged ≥18 years in England with records in the primary care-COVID-19 General Practice Extraction Service Data for Pandemic Planning and Research (GDPPR) were identified. Their records of 12 risk factor measurements were extracted between November 2018 and March 2024. Number of measurements per 1,000 individuals were calculated by age group, sex, ethnicity, and area deprivation quintile. The observed number of measurements were compared to a composite expectation band, derived as the union of the 95% confidence intervals of 2 estimates: (1) a projected trend based on data prior to the COVID-19 pandemic; and (2) an assumed stable trend from before pandemic. Point estimates were calculated as the mid-point of the expectation band. A cohort of 49,303,410 individuals aged ≥18 years were included. There was sharp drop in all measurements in March 2020 to February 2022, but overall recovered to the expected levels during March 2022 to February 2023 except for blood pressure, which had prolonged recovery. In March 2023 to March 2024, blood pressure measurements were below expectation by 16% (-19 per 1,000) overall, in people aged 18 to 39 (-23%; -18 per 1,000), 60 to 79 (-17%; -27 per 1,000), and ≥80 (-31%; -57 per 1,000). There was suggestion that recovery in blood pressure measurements was socioeconomically patterned. The second most deprived quintile had the highest deviation (-20%; -23 per 1,000) from expectation compared to least deprived quintile (-13%; -15 per 1,000). CONCLUSIONS: There was a substantial reduction in routine measurements of cardiometabolic risk factors following the COVID-19 pandemic, with variable recovery. The implications for missed diagnoses, worse prognosis, and health inequality are a concern

Carotid artery wave intensity in mid- to late-life predicts cognitive decline: the Whitehall II study

© The Author(s) 2019. Aims: Excessive arterial pulsatility may contribute to cognitive decline and risk of dementia via damage to the fragile cerebral microcirculation. We hypothesized that the intensity of downstream-travelling pulsatile waves measured by wave intensity analysis in the common carotid artery during mid- to late-life would be associated with subsequent cognitive decline. ......................................................................................................................................................... Methods and results: Duplex Doppler ultrasound was used to calculate peak forward-travelling compression wave intensity (FCWI) within the common carotid artery in 3191 individuals [mean ± standard deviation (SD), age = 61 ± 6 years; 75% male] assessed as part of the Whitehall II study in 2003–05. Serial measures of cognitive function were taken between 2002–04 and 2015–16. The relationship between FCWI and cognitive decline was adjusted for sociodemographic variables, genetic and health-related risk factors, and health behaviours. Mean (SD) 10-year change in standardized global cognitive score was -0.39 (0.18). Higher FCWI at baseline was associated with accelerated cognitive decline during follow-up [difference in 10-year change of global cognitive score per 1 SD higher FCWI = -0.02 (95% confidence interval -0.04 to -0.00); P = 0.03]. This association was largely driven by cognitive changes in individuals with the highest FCWI [Q4 vs. Q1–Q3 = -0.05 (-0.09 to -0.01), P = 0.01], equivalent to an age effect of 1.9 years. Compared to other participants, this group was 50% more likely to exhibit cognitive decline (defined as the top 15% most rapid reductions in cognitive function during follow-up) even after adjustments for multiple potential confounding factors [odds ratio 1.49 (1.17–1.88)]. ............................................................................................................................................... Conclusion: Elevated carotid artery wave intensity in mid- to late-life predicts faster cognitive decline in long-term follow-up independent of other cardiovascular risk factors.Whitehall II study was supported by the UK Medical Research Council [MR/R024227/1]; the US National Institute on Aging [NIA, R01AG056477], the British Heart Foundation [32334]; and European Commission [LIFEPATH 633666]. S.T.C. receives research funding from the Brain Protection Company Ltd (Australia). M.K. was supported by the Medical Research Council, NIA, NordForsk, and Helsinki Institute of Life Sciences (Finland). J.E.D. was a BHF-funded Professor from 2003 to 2017. A.D.H. receives support from the British Heart Foundation [PG/15/75/31748, CS/15/6/31468, and CS/13/1/30327], the National Institute for Health Research University College London Hospitals Biomedical Research Centre, and works in a unit that receives support from the UK Medical Research Council [Programme Code MC_UU_12019/1]

Prevalence and outcomes of atrial fibrillation in older people living in care homes in Wales: a routine data linkage study 2003-2018.

Objective: To determine atrial fibrillation (AF) prevalence and temporal trends, and examine associations between AF and risk of adverse health outcomes in older care home residents. Methods: Retrospective cohort study using anonymised linked data from the Secure Anonymised Information Linkage Databank on CARE home residents in Wales with AF (SAIL CARE-AF) between 2003 and 2018. Fine-Gray competing risk models were used to estimate the risk of health outcomes with mortality as a competing risk. Cox regression analyses were used to estimate the risk of mortality. Results: There were 86,602 older care home residents (median age 86.0 years [interquartile range 80.8-90.6]) who entered a care home between 2003 and 2018. When the pre-care home entry data extraction was standardised, the overall prevalence of AF was 17.4% (95% confidence interval 17.1-17.8) between 2010 and 2018. There was no significant change in the age- and sex-standardised prevalence of AF from 16.8% (15.9-17.9) in 2010 to 17.0% (16.1-18.0) in 2018. Residents with AF had a significantly higher risk of cardiovascular mortality (adjusted hazard ratio [HR] 1.27 [1.17-1.37], P < 0.001), all-cause mortality (adjusted HR 1.14 [1.11-1.17], P < 0.001), ischaemic stroke (adjusted sub-distribution HR 1.55 [1.36-1.76], P < 0.001) and cardiovascular hospitalisation (adjusted sub-distribution HR 1.28 [1.22-1.34], P < 0.001). Conclusions: Older care home residents with AF have an increased risk of adverse health outcomes, even when higher mortality rates and other confounders are accounted for. This re-iterates the need for appropriate oral anticoagulant prescription and optimal management of cardiovascular co-morbidities, irrespective of frailty status and predicted life expectancy

Association of cytokines with endothelium dependent flow mediated vasodilation (FMD) of systemic arteries in patients with non-ischemic cardiomyopathy

<p>Abstract</p> <p>Background</p> <p>Aim of this study was to elucidate the relation between localised inflammatory heart disease and endothelial dysfunction in the peripheral circulation, considering circulating cytokines as a potential link.</p> <p>Methods</p> <p>In 38 patients with non-ischemic heart disease, myocardial biopsies were examined for myocardial inflammation (immunohistology) and virus persistence (PCR). Cytokines (sIL-4, IFN-g, IFN-b, IFN-a, sIL-12p7, TNF-a) were measured by ELISA in venous serum. Endothelial function of the radial artery was examined by ultrasound, measuring diameter changes in response to reactive hyperemia (FMD), compared to glyceroltrinitrate (GTN-MD). Patients with EF < 35% were excluded.</p> <p>Results</p> <p>Age 44 ± 14 years, 19 male, 19 female, EF 63.5[16]%. FMD 4.38 [4.82]%. 30 patients had myocardial inflammation (8 not), 23 virus persistence (15 not). FMD correlated significantly with sIL-12p7 (p = 0.024, r = -0.365), but not with other cytokines. sIL-12p7 levels were significantly higher in patients with severely impaired FMD (n = 17), compared with normal FMD (n = 21): 10.70 [10.72] vs. 4.33 [7.81] pg/ml (p = 0.002). Endothelium independent vasodilation (GTN-MD 23.67 [8.21]%) was not impaired.</p> <p>Conclusion</p> <p>Endothelial dysfunction of peripheral arteries in patients with non-ischemic cardiomyopathy is associated with elevated serum concentrations of sIL-12p7, but not of other cytokines. Circulating sIL-12p7 may partly explain, that endothelial dysfunction is not restricted to the coronary circulation, but involves systemic arteries.</p