Arterial stiffness in hypertensive and type 2 diabetes patients in Ghana: comparison of the cardio-ankle vascular index and central aortic techniques

Background Diabetes and hypertension increase arterial stiffness and cardiovascular events in all societies studied so far; sub-Saharan African studies are sparse. We investigated factors affecting arterial function in Ghanaians with diabetes, hypertension, both or neither. Method Testing the hypothesis that arterial stiffness would progressively increase from controls to multiply affected patients, 270 participants were stratified into those with diabetes or hypertension only, with both, or without either. Cardio-ankle vascular index (CAVI), heart–ankle pulse wave velocity (haPWV), aortic PWV (PWVao) by Arteriograph, aortic and brachial blood pressures (BP), were measured. Results In patients with both diabetes and hypertension compared with either alone, values were higher of CAVI (mean ± SD, 8.3 ± 1.2 vs 7.5 ± 1.1 and 7.4 ± 1.1 units; p < 0.05), PWVao (9.1 ± 1.4 vs 8.7 ± 1.9 and 8.1 ± 0.9 m/s; p < 0.05) and haPWV (8.5 ± 1 vs 7.9 ± 1 and 7.2 ± 0.7 m/s; p < 0.05) respectively. In multivariate analysis, age, having diabetes or hypertension and BMI were independently associated with CAVI in all participants (β = 0.49, 0.2, 0.17 and -0.2 units; p < 0.01, respectively). Independent determinants of PWVao were heart rate, systolic BP and age (β = 0.42, 0.27 and 0.22; p < 0.01), and for haPWV were systolic BP, age, BMI, diabetes and hypertension status (β = 0.46, 0.32, -0.2, 0.2 and 0.11; p < 0.01). Conclusion In this sub-Saharan setting with lesser atherosclerosis than the western world, arterial stiffness is significantly greater in patients with coexistent diabetes and hypertension but did not differ between those with either diabetes or hypertension only. Simple, reproducibly measured PWV/CAVI may offer effective and efficient targets for intervention

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Clinical pharmacokinetics of perhexiline.

A sensitive, ultraviolet, spectrophotometric, high-performance liquid chromatographic method (using dinitrophenyl derivatives of drug and metabolites) for the simultaneous determination of perhexiline and its major metabolites in biological fluids was developed and validated. The procedure was employed successfully in pharmacokinetic studies of perhexiline in healthy, adult volunteers. Following oral administration of perhexiline to human volunteers, considerable inter-individual variation in the rates of drug absorption occurs. Extensive pre-systemic metabolism was observed following drug ingestion, with considerable individual variation in the AUC of plasma perhexiline. Significantly more unchanged perhexiline was available in the systemic circulation following the administration of (+) perhexiline than after either its optical antipode or the racemate; of the three dosage forms the (-) enantiomer was associated with the lowest plasma perhexiline levels. Perhexiline is metabolized by the cytochrome P-450 dependent mixed function oxidase system in the liver. In humans, cis-hydroxylation is generally the predominant metabolic pathway for racemic perhexiline with trans-hydroxylation probably playing a major role in individuals with impaired drug oxidative capacity. Cis-hydroxylation of perhexiline in humans may exhibit saturable kinetics. The metabolism of perhexiline exhibits complex stereoselectivity. In man, cis- and trans-hydroxylation are the preferred routes of metabolism following ingestion of (-) and (+) perhexiline respectively. The (-) enantiomer is metabolized at a faster rate than its optical antipode either in in vivo in humans, or in vitro in man and the rat. Drug accumulation and hence drug induced-toxicity, on prolonged Pexid therapy in angina patients is more likely to occur with the (+) than with either the (-)enantiomer or racemate and least with the (-) enantiomer. Defective function of the liver monooxygenase system possibly due to defective cytochrome P-450-substrate interaction and/or abnormal microenviroment of cytochrome P-450 may be the molecular mechanism of impaired hydroxylation of perhexiline

Clinical pharmacokinetics of perhexiline.

A sensitive, ultraviolet, spectrophotometric, high-performance liquid chromatographic method (using dinitrophenyl derivatives of drug and metabolites) for the simultaneous determination of perhexiline and its major metabolites in biological fluids was developed and validated. The procedure was employed successfully in pharmacokinetic studies of perhexiline in healthy, adult volunteers. Following oral administration of perhexiline to human volunteers, considerable inter-individual variation in the rates of drug absorption occurs. Extensive pre-systemic metabolism was observed following drug ingestion, with considerable individual variation in the AUC of plasma perhexiline. Significantly more unchanged perhexiline was available in the systemic circulation following the administration of (+) perhexiline than after either its optical antipode or the racemate; of the three dosage forms the (-) enantiomer was associated with the lowest plasma perhexiline levels. Perhexiline is metabolized by the cytochrome P-450 dependent mixed function oxidase system in the liver. In humans, cis-hydroxylation is generally the predominant metabolic pathway for racemic perhexiline with trans-hydroxylation probably playing a major role in individuals with impaired drug oxidative capacity. Cis-hydroxylation of perhexiline in humans may exhibit saturable kinetics. The metabolism of perhexiline exhibits complex stereoselectivity. In man, cis- and trans-hydroxylation are the preferred routes of metabolism following ingestion of (-) and (+) perhexiline respectively. The (-) enantiomer is metabolized at a faster rate than its optical antipode either in in vivo in humans, or in vitro in man and the rat. Drug accumulation and hence drug induced-toxicity, on prolonged Pexid therapy in angina patients is more likely to occur with the (+) than with either the (-)enantiomer or racemate and least with the (-) enantiomer. Defective function of the liver monooxygenase system possibly due to defective cytochrome P-450-substrate interaction and/or abnormal microenviroment of cytochrome P-450 may be the molecular mechanism of impaired hydroxylation of perhexiline

Assessing the vibration perception threshold in a community sample of adult Ghanaians.

BackgroundThe vibration perception threshold (VPT) helps evaluate human somatosensory function and diagnose peripheral neuropathy. To optimize its use as a primary neurologic tool, it is imperative to establish its typical values in healthy subjects and assess the factors affecting its variability in an individual to ensure consistency in its application.MethodsDemographic data and a brief medical history were collected from 391 non-diabetic adults aged 30-80 at Kpone-on-Sea in Ghana. The VPT was measured at the tip of the big toe, the medial malleolus, the tip of the middle finger, and the head of the ulna of each participant using a Horwell Neurothesiometer. The variability of VPT was assessed vis-à-vis the following factors: gender, age, fasting plasma sugar and body mass index.ResultsThe mean age of participants was 48.4 ± 0.7 years, and the female-to-male ratio was 1.46. The overall VPT values ranged from 5.74 ± 0.14 volts to 8.55 ± 0.18 volts in the lower limbs and 3.61 ± 0.06 volts to 5.00 ± 0.08 volts in the upper limbs. Age was found to be the only factor that could predict VPT for both the lower and upper limbs (P ConclusionsGenerally, the VPT was high on proximal sites and low on distal sites indicating that the vibration sensation increased from proximal to distal direction. Therefore, distal areas should be used for VPT testing with a Neurothesiomer. Age was found to be the only factor that affected VPT variability. Hence, the practical application of VPT will require age-specific reference ranges to cater for older adults

Associations between macrovascular and renal microvascular dysfunction in type 2 diabetes and non-diabetes: the HELIUS study

Background: Although the associations between measures of macrovascular and microvascular dysfunctions are well characterized in diabetes, there is limited data on these associations in individuals without diabetes. We compared the associations between macrovascular dysfunction and renal microvascular dysfunction in individuals with type 2 diabetes (T2D) and without diabetes. Methods: Cross-sectional analyses of baseline data from the multiethnic Healthy Life in an Urban Setting (HELIUS) study (Amsterdam, the Netherlands), including 986 participants with T2D and 7680 participants without diabetes were done. Logistic regression analyses were used to examine the associations between macrovascular dysfunction [aortic stiffness, coronary artery disease (CAD), peripheral artery disease (PAD), and stroke] and renal microvascular dysfunction [albuminuria] with adjustments for age, sex, ethnicity, waist-to-hip ratio, systolic blood pressure, LDL-cholesterol, and smoking (and HbA1c and diabetes duration for the T2D group). Results: In the fully adjusted models, aortic stiffness was associated with albuminuria in individuals with T2D [OR 2.55; 95% CI,1.30–4.98], but not without diabetes [0.96; 0.63–1.45]; stroke was associated with albuminuria in T2D [2.40;1.10–5.25], but not in non-diabetes [1.39;0.83–2.33]. In age-sex adjusted models, CAD was associated with albuminuria in T2D [1.65;1.09–2.50] and in non-diabetes [1.56;1.13–2.15]; the associations were no longer significant in the fully adjusted model. There were no associations between PAD and albuminuria in T2D and non-diabetes. Conclusions: Our study shows important differences in the associations between measures of macrovascular and renal microvascular dysfunction in T2D and non-diabetes. These findings provide opportunities for future research aimed at prevention and treatment strategies for individuals with vascular dysfunction

Inflammation and its associations with aortic stiffness, coronary artery disease and peripheral artery disease in different ethnic groups: The HELIUS Study

Background: evidence shows important ethnic differences in vascular dysfunction rates; however, the mechanisms driving these differences remain unclear. One potential factor is the ethnic differences in the role of inflammation in vascular injury. We tested the hypothesis that low-grade inflammation is unequally associated with vascular dysfunction in different ethnic groups. Methods: we included 5698 participants (similar-sized Dutch, African Surinamese, South-Asian Surinamese, Ghanaians, Turkish, and Moroccans) of the HELIUS study (the Netherlands) conducted between 2011 and 2015. Logistic regression was used to examine the associations of Z-score inflammatory biomarker concentration (high sensitivity C-reactive protein [hs-CRP], fibrinogen, and D-dimer) with vascular dysfunction (aortic stiffness, coronary artery disease [CAD], and peripheral artery disease [PAD]), with adjustments for age, sex, smoking (pack-years), BMI, hypertension, HbA1c, total cholesterol, and statin use Findings: in the fully adjusted models, higher Z-score hs-CRP was positively associated with CAD in Dutch [OR 1·63, (95% CI 1·21–2·18)] and PAD in South Asians [1·25(1·03–1·53)], respectively. Higher Z-score fibrinogen was positively associated with CAD in African Surinamese [1·28(1·03–1·59)] while higher Z-score D-dimer was positively associated with PAD in Moroccans [1·39(1·01–1·93)]. Higher Z-score hs-CRP [0·71(0·54–0·94)] and fibrinogen [0·75(0·58–0·97)] concentrations were negatively associated with PAD in African Surinamese. Interpretation: our study shows that inflammatory biomarkers are unequally associated with vascular dysfunction in different ethnic groups. These observations provide opportunities for future studies aimed at assessing the predictive roles of inflammation on vascular disease in different ethnic groups

Inflammation and its associations with aortic stiffness, coronary artery disease and peripheral artery disease in different ethnic groups: The HELIUS Study

Background: evidence shows important ethnic differences in vascular dysfunction rates; however, the mechanisms driving these differences remain unclear. One potential factor is the ethnic differences in the role of inflammation in vascular injury. We tested the hypothesis that low-grade inflammation is unequally associated with vascular dysfunction in different ethnic groups. Methods: we included 5698 participants (similar-sized Dutch, African Surinamese, South-Asian Surinamese, Ghanaians, Turkish, and Moroccans) of the HELIUS study (the Netherlands) conducted between 2011 and 2015. Logistic regression was used to examine the associations of Z-score inflammatory biomarker concentration (high sensitivity C-reactive protein [hs-CRP], fibrinogen, and D-dimer) with vascular dysfunction (aortic stiffness, coronary artery disease [CAD], and peripheral artery disease [PAD]), with adjustments for age, sex, smoking (pack-years), BMI, hypertension, HbA1c, total cholesterol, and statin use Findings: in the fully adjusted models, higher Z-score hs-CRP was positively associated with CAD in Dutch [OR 1·63, (95% CI 1·21–2·18)] and PAD in South Asians [1·25(1·03–1·53)], respectively. Higher Z-score fibrinogen was positively associated with CAD in African Surinamese [1·28(1·03–1·59)] while higher Z-score D-dimer was positively associated with PAD in Moroccans [1·39(1·01–1·93)]. Higher Z-score hs-CRP [0·71(0·54–0·94)] and fibrinogen [0·75(0·58–0·97)] concentrations were negatively associated with PAD in African Surinamese. Interpretation: our study shows that inflammatory biomarkers are unequally associated with vascular dysfunction in different ethnic groups. These observations provide opportunities for future studies aimed at assessing the predictive roles of inflammation on vascular disease in different ethnic groups