Endothelial function: ready for prime time?

The strategic location of the endothelium allows it to detect changes in hemodynamic forces and blood-borne signals, and to respond by releasing a number of autocrine and paracrine substances. The balanced release of these bioactive factors facilitates vascular homeostasis. If disrupted, endothelial cell dysfunction ensues. This predisposes the vessel wall to vasoconstriction, leukocyte adherence, platelet activation, thrombosis, vascular inflammation and atherosclerosis. Given the central role of the endothelium in the development and progression of atherosclerosis, endothelial function testing may serve as a useful biomarker of atherosclerotic disease. The present review highlights the current modalities used in assessing endothelial function, explores how endothelial function may serve as a biomarker for atherosclerosis, comments on the prognostic relevance of endothelial function and describes its use in the clinical setting.     

Relationship between carotid artery intima-media thickness and brachial artery flow-mediated dilation in middle-aged healthy men

OBJECTIVES: We aimed to determine the relationship between carotid intima-media thickness (IMT) and brachial artery flow-mediated dilation (FMD) in healthy middle-age men. BACKGROUND: Carotid IMT and brachial artery FMD are frequently used as surrogate measures of subclinical atherosclerosis. Whereas carotid IMT identifies early structural abnormalities, brachial artery FMD, considered a bioassay of endothelial function, measures functional vascular integrity. The relationship between carotid IMT and brachial artery FMD has not been well studied. METHODS: We measured traditional risk factors, carotid IMT, and brachial artery FMD in 1,578 middle-aged men without known cardiovascular disease and analyzed the relationship between carotid IMT and brachial FMD. RESULTS: Carotid IMT correlated with age, systolic blood pressure, body mass index, fasting glucose, total and low-density lipoprotein (LDL) cholesterol, and with the overall Framingham risk score (p < 0.001 for all), whereas impaired brachial artery FMD correlated with systolic and diastolic blood pressure (p < 0.01). No relationship was observed between carotid IMT and brachial artery FMD for the entire cohort (r = -0.006, p = 0.82) and in subgroups defined by traditional risk factors or by quintiles of carotid IMT and brachial FMD. CONCLUSIONS: In middle-aged healthy men, there is no significant correlation between carotid IMT and brachial artery FMD. This finding suggests that these are unique, independent surrogates that measure different aspects and stages of early atherosclerosis. Further studies are needed to define their role in clinical research and in cardiovascular risk assessment.     

The endocannabinoid system and cardiometabolic risk

Worldwide, the rates of obesity are rapidly rising. Abdominal obesity in particular is associated with increased cardiovascular risk factors, namely increased triglycerides, low high-density lipoprotein (HDL) cholesterol, elevated blood pressure and increased plasma glucose. The cluster of these obesity-related metabolic disorders identifies individuals with the cardiometabolic syndrome, who are at particular risk for cardiovascular disease and type 2 diabetes. The accumulation of intra-abdominal fat and the subsequent development of visceral obesity rely on the body's mechanisms to store energy and to stimulate appetite. The endocannabinoid system has been implicated in the regulation of energy balance and has emerged as a critical target for the modulation of visceral obesity and insulin resistance. Its overactivity appears to be associated with the development of obesity. The current review examines the role of the endocannabinoid system in cardiometabolic disease and its basis as a target for modulating cardiovascular risk.     

Uracil excision repair in Mycobacterium tuberculosis cell-free extracts

Uracil excision repair is ubiquitous in all domains of life and initiated by uracil DNA glycosylases (UDGs) which excise the promutagenic base, uracil, from DNA to leave behind an abasic site (AP-site). Repair of the resulting AP-sites requires an AP-endonuclease, a DNA polymerase, and a DNA ligase whose combined activities result in either short-patch or long-patch repair. Mycobacterium tuberculosis, the causative agent of tuberculosis, has an increased risk of accumulating uracils because of its G + C-rich genome, and its niche inside host macrophages where it is exposed to reactive nitrogen and oxygen species, two major causes of cytosine deamination (to uracil) in DNA. In vitro assays to study DNA repair in this important human pathogen are limited. To study uracil excision repair in mycobacteria, we have established assay conditions using cell-free extracts of M. tuberculosis and M. smegmatis (a fast-growing mycobacterium) and oligomer or plasmid DNA substrates. We show that in mycobacteria, uracil excision repair is completed primarily via long-patch repair. In addition, we show that M. tuberculosis UdgB, a newly characterized family 5 UDG, substitutes for the highly conserved family 1 UDG, Ung, thereby suggesting that UdgB might function as backup enzyme for uracil excision repair in mycobacteria.     

Liver tests,cardiovascular outcomes and effects of empagliflozin in patients with heart failure and preserved ejection fraction: The EMPEROR-Preserved trial

Aim

The prognostic implication of elevated liver tests in heart failure with preserved ejection fraction (HFpEF) is uncertain. This analysis investigates the association of liver markers with hospitalization for heart failure (HHF) and cardiovascular death (CVD), and the treatment effect of empagliflozin across the range of liver marker levels.

Methods and results

The double-blind, placebo-controlled EMPEROR-Preserved (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure with Preserved Ejection Fraction) enrolled 5988 patients with HFpEF (ejection fraction >40%). Patients in New York Heart Association class II–IV and elevated N-terminal pro-B-type natriuretic peptide were randomized to receive empagliflozin 10 mg daily or placebo in addition to usual therapy. Patients with significant liver disease were excluded. The primary endpoint was time to first adjudicated HHF or CVD. We explored the association of liver function abnormalities with heart failure outcomes in patients on placebo, the effects of empagliflozin on liver tests and the treatment effects of empagliflozin on heart failure outcomes across categories of liver laboratory values. High alkaline phosphatase (p trend < 0.0001), low albumin (p trend < 0.0001) and high bilirubin (p = 0.02) were associated with poorer outcomes for HHF or CVD, while high aspartate aminotransferase was not, and high alanine aminotransferase was associated with better outcomes. Empagliflozin had no significant effects on liver tests compared to placebo except for albumin which was significantly increased. The treatment effect of empagliflozin on outcomes was not modified by liver tests.

Conclusion

Abnormalities of liver function tests are associated differently with heart failure outcomes. Salutary effects of empagliflozin on liver tests were not observed although albumin increased. The treatment benefits of empagliflozin were not affected by baseline values of liver parameters.     

A cross-sectional study of the prevalence and clinical management of atherosclerotic cardiovascular diseases in patients with type 2 diabetes across the Middle East and Africa (PACT-MEA): Study design and rationale

Aim

To investigate the epidemiology and clinical management of patients with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease (eASCVD) or high/very high ASCVD risk, defined by the 2021 European Society of Cardiology Guidelines, in seven countries in the Middle East and Africa (PACT-MEA; NCT05317845), and to assess physicians' attitudes and the basis for their decision-making in the management of these patients.

Materials and Methods

PACT-MEA is a cross-sectional, observational study undertaken in Bahrain, Egypt, Jordan, Kuwait, Qatar, South Africa and the United Arab Emirates based on a medical chart review of approximately 3700 patients with T2D in primary and secondary care settings, and a survey of approximately 400 physicians treating patients with T2D.

Results

The primary and secondary objectives are to determine the prevalence of eASCVD and high/very high ASCVD risk in patients with T2D. Current treatment with cardioprotective antidiabetic medication, the proportion of patients meeting the treatment criteria for reimbursement in the study countries where there is an applicable reimbursement guideline, and physician-reported factors in clinical decision-making in T2D management, will also be assessed.

Conclusions

This large cross-sectional study will establish the estimated prevalence and management of eASCVD and high/very high ASCVD risk in patients with type 2 diabetes across the Middle East and Africa.     

Peri-operative outcomes for pancreatoduodenectomy in India: a multi-centric study

Background:

There have been an increasing number of reports world-wide relating improved outcomes after pancreatic resections to high volumes thereby supporting the idea of centralization of pancreatic resectional surgery. To date there has been no collective attempt from India at addressing this issue. This cohort study analysed peri-operative outcomes after pancreatoduodenectomy (PD) at seven major Indian centres.

Materials and Methods:

Between January 2005 and December 2007, retrospective data on PDs, including intra-operative and post-operative factors, were obtained from seven major centres for pancreatic surgery in India.

Results:

Between January 2005 and December 2007, a total of 718 PDs were performed in India at the seven centres. The median number of PDs performed per year was 34 (range 9–54). The median number of PDs per surgeon per year was 16 (range 7–38). Ninety-four per cent of surgeries were performed for suspected malignancy in the pancreatic head and periampullary region. The median mortality rate per centre was four (range 2–5%). Wound infections were the commonest complication with a median incidence per centre of 18% (range 9.3–32.2%), and the median post-operative duration of hospital stay was 16 days (range 4–100 days).

Conclusions:

This is the first multi-centric report of peri-operative outcomes of PD from India. The results from these specialist centers are very acceptable, and appear to support the thrust towards centralization.     

Gender differences,outcomes and trends among nonagenarian with atrial fibrillation: insight from National Inpatient Sample database

BACKGROUND Nonagenarians(NG),individuals aged≥90 years,constitute an increasing proportion of hospitalizations presenting with atrial fibrillation(AF).However,not much is known about demographics,clinical outcomes,and trends of hospitalizations.Therefore,we analyzed data about hospitalizations and clinical outcomes among NGs with AF over ten years from 2005 to 2014 using a publically available database,the National Inpatient Sample.METHODS All hospitalizations and major outcomes of subjects≥90 years with a primary diagnosis of AF(ICD-9-CM code 427.31)over a ten-year period were assessed in this study by multivariate logistic regression analysis.RESULTS There were more females than males(176,268 females,51,384 males)in this analysis.The number of hospitalizations for AF among NG increased by 50%(17,295 in 2005 to 25,830 in 2014).Males were more likely to undergo cardioversion(6.14%of males vs.5.06%of females,P<0.0001).Over this period,in-hospital mortality declined from 3.21%in 2005 to 2.38%in 2014(P=0.0041),with higher in-hospital mortality in males(3.23%in males vs.2.76%in females,P=0.0138),mean length of hospitalization decreased from 4.53 days to 4.13 days(P<0.0001),the prevalence of congestive heart failure fell from 0.48%to 0.23%(P=0.0257),and the use of anticoagulation increased from 6.09%to 14.54%(P<0.0001).In a multivariate analysis,hospital admission on the weekend,Elixhauser comorbidity index,CHA2DS2VASc score,acute respiratory failure,and the length of hospital stay were associated with a higher risk of in-hospital mortality.CONCLUSIONS From 2005 to 2014,AF-related hospitalizations among NGs increased,more so in in females population,mortality trends improved,rates of anticoagulation increased,and cardioversions increased.Despite the decreasing trend of in-hospital mortality since 2005,the relatively high mortality rate in males warrants further studies.