Yousef Shahin

Angiotensin converting enzyme inhibitors effect on arterial stiffness and wave reflections: A meta-analysis and meta-regression of randomised controlled trials

OBJECTIVEnSeveral studies have assessed the effect of angiotensin converting enzyme inhibitors (ACEIs) on arterial stiffness and wave reflections as measured by pulse wave velocity (PWV) and augmentation index (AIx), respectively. We conducted a meta-analysis to investigate this effect in comparison to placebo and to other antihypertensive agents. Additionally, we investigated this effect when ACEIs are combined with other antihypertensive agents and in comparison to a combination of antihypertensive agents.nnnMETHODSnMEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from inception to May 2011 on randomised controlled trials (RCTs) which assessed the effect of ACEIs on arterial stiffness vs. placebo or no treatment and ACEIs vs. angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), β-blockers and diuretics. RCTs which assessed the effect of ACEIs combined with other antihypertensives or compared ACEIs with a combination of antihypertensives were also sought. Data from included RCTs were pooled with use of fixed and random effects meta-analysis of the weighted mean change differences between the comparator groups. Heterogeneity across studies was assessed with the I(2) statistic.nnnRESULTSnIn 5 trials including 469 patients, treatment with ACEIs (n=227) vs. placebo (n=216) significantly reduced PWV (pooled mean change difference -1.69, 95% C.I. -2.05, -1.33, p<0.00001 with insignificant heterogeneity). In 9 trials which included 378 patients, treatment with ACEIs (n=178) insignificantly reduced PWV when compared with other antihypertensives (ARBs, CCBs, β-blockers, diuretics and a combination of ACEI and ARB) (n=220) (pooled mean change difference -0.19, 95% C.I. -0.59, 0.21, p=0.36, I(2)=0%). ACEI effect on AIx in comparison to placebo was assessed in 7 trials. Treatment with ACEIs significantly reduced AIx (pooled mean change difference -3.79, 95% C.I. -5.96, -1.63, p=0.0006) with significant heterogeneity. In 7 trials, treatment with ACEIs significantly reduced AIx when compared with other antihypertensives (pooled mean change difference -1.84, 95% C.I. -3, -0.68, p=0.002, I(2)=32%, p for heterogeneity=0.11). However, this effect was only significant when compared with β-blockers (pooled mean change difference -1.6, 95% C.I. -2.84, -0.36, p=0.01). Mean BP differences between baseline and end of treatment did not predict the treatment (ACEI) induced changes in PWV.nnnCONCLUSIONSnACEIs reduce PWV and AIx which are markers of arterial stiffness and wave reflections in patients with different pathological conditions. However, due to the lack of high quality and properly powered RCTs, it is not clear whether ACEIs are superior to other antihypertensive agents in their effect on arterial stiffness. The ability of ACEIsxa0to reduce arterial stiffness (PWV) seems to be independent of its ability to reduce BP.

Angiotensin converting enzyme inhibitors effect on endothelial dysfunction: A meta-analysis of randomised controlled trials

OBJECTIVEnSeveral studies have assessed the effect of angiotensin converting enzyme inhibitors (ACEIs) on endothelial dysfunction as measured by brachial flow-mediated vasodilatation (FMD). We conducted a meta-analysis to investigate this effect in comparison to placebo or no treatment and to other antihypertensive agents.nnnMETHODSnMEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from 1996 to October 2010 on randomised controlled trials (RCTs) that assessed the effect of ACEIs on brachial FMD versus placebo or no treatment and ACEIs versus angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs) and β-blockers. Data from included studies were pooled with use of random effects meta-analysis of the weighted mean change differences between the comparator groups. Heterogeneity across studies was assessed with the I(2) statistic.nnnRESULTSnIn 10 trials including 1129 patients, treatment with ACEIs (n = 498) versus placebo or no treatment (n = 503) significantly improved brachial FMD (pooled mean change difference 1.26%, 95% C.I. 0.46-2.07, p = 0.002 with significant heterogeneity). In 11 trials which included 805 patients, treatment with ACEIs (n = 264) had a significant effect on brachial FMD when compared with other antihypertensives (ARBs, CCBs and β-blockers) (n = 420) (pooled mean change difference 0.89%, 95% C.I. 0.22-1.56, p = 0.009, I(2) = 83%, p for heterogeneity < 0.00001). In 7 trials, treatment with ACEIs had no significant effect on FMD when compared with ARBs (pooled mean change difference = 0.21%, 95% C.I. -0.24 to 0.66, p = 0.36, I(2) = 0%). However, in 4 trials ACEIs significantly improved FMD when compared with CCBs (pooled mean change difference 2.15%, 95% C.I. 0.55-3.75, p = 0.009, I(2) = 90%, p for heterogeneity < 0.00001). When compared with β-blockers in 4 trials, ACEIs also had a significant effect on FMD (pooled mean change difference = 0.59%, 95% C.I. 0.05-1.13, p = 0.03, I(2) = 34%, p for heterogeneity = 0.21).nnnCONCLUSIONSnThis study shows that ACEIs improve brachial FMD which is a marker of endothelial function in patients with endothelial dysfunction caused by various conditions and are superior to CCBs and β-blockers. There was no significant difference between ACEIs and ARBs effect on brachial FMD.

Intraluminal thrombus has a selective influence on matrix metalloproteinases and their inhibitors (tissue inhibitors of matrix metalloproteinases) in the wall of abdominal aortic aneurysms.

BACKGROUNDnThe influence of intraluminal thrombus (ILT) on the proteolytic environment within the wall of an abdominal aortic aneurysm (AAA) is unknown. This is the first study to examine the correlation between ILT thickness and the levels of matrix metalloproteinases (MMPs) and their natural inhibitors (tissue inhibitors of matrix metalloproteinases [TIMPs]) within the adjacent AAA wall.nnnMETHODSnThirty-five patients undergoing elective repair of AAAs were studied. A single full-thickness infrarenal aortic sample was obtained uniformly from the arteriotomy site from each patient. All samples were snap frozen and analyzed for total and active MMP 2, 8, and 9 and TIMP 1 and 2. Thrombus thickness at the specimen site was measured on the preoperative contrast computed tomographic angiograms.nnnRESULTSnThere was a statistically significant correlation between ILT thickness, concentration of TIMP 1, and active concentration of MMP 9. MMP 2 (active and total) and TIMP 2 demonstrated a positive correlation with ILT thickness, although not statistically significant.nnnCONCLUSIONnIn this novel study, we found a significant positive correlation of ILT thickness with active MMP 9 and TIMP 1 concentration in the adjacent AAA wall, and this may have implications for AAA expansion and eventual rupture.

Electrical stimulation vs. standard care for chronic ulcer healing: a systematic review and meta-analysis of randomised controlled trials

We conducted a systematic review to investigate the effect of electrical stimulation on ulcer healing compared to usual treatment and/or sham stimulation. This systematic review also aimed to investigate the effect of different types of electrical stimulation on ulcer size reduction.

Endovenous laser ablation in the treatment of small saphenous varicose veins: does site of access influence early outcomes?

Objective: The study was performed to evaluate the clinical and technical efficacy of endovenous laser ablation (EVLA) of small saphenous varicosities, particularly in relation to the site of endovenous access. Methods: Totally 59 patients with unilateral saphenopopliteal junction incompetence and small saphenous vein reflux underwent EVLA (810 nm, 14 W diode laser) with ambulatory phlebectomies. Small saphenous vein access was gained at the lowest site of truncal reflux. Patients were divided into 2 groups: access gained above mid-calf (AMC, n = 33) and below mid-calf (BMC, n = 26) levels. Outcomes included Venous Clinical Severity Scores (VCSS), Aberdeen Varicose Vein Questionnaire (AVVQ), patient satisfaction, complications, and recurrence rates. Results: Both groups demonstrated significant improvement in VCSS, AVVQ, generic quality of life Short Form 36, and EuroQol scores (P < .05) up to 1 year. No differences were seen between AMC and BMC groups for complications (phlebitis: 2 [6%] and 1 [3.8%], P > .05; paresthesia: 2 [6%] and 5 [19%], P = .223) and recurrence (3 [9%] and 1 [3.8%], P = .623), respectively. Conclusions: The site of access in our study does not appear to influence complications specifically neural injury or recurrence rates.

Meta-analysis of angiotensin converting enzyme inhibitors effect on walking ability and ankle brachial pressure index in patients with intermittent claudication

OBJECTIVEnThe aim of this meta-analysis was to investigate the effect of angiotensin converting enzyme (ACE) inhibitors on maximum walking distance (MWD), pain-free walking distance (PFWD) and ankle brachial pressure index (ABPI) in patients with intermittent claudication (IC).nnnMETHODSnMEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from inception to July 2013 on randomised controlled trials (RCTs) that assessed the effect of ACE inhibitors on MWD, PFWD and ABPI in patients with IC.nnnRESULTSnOf 348 publications found, a meta-analysis was conducted of 6 RCTs comprising 821 patients. Treatment with ACE inhibitors improved MWD by mean difference (95 per cent confidence interval) of 120.8 (2.95-238.68) m (P = 0.040), improved PFWD by 74.87 (25.24-124.50) m (P = 0.003) and insignificantly improved ABPI by 0.07 (-0.02-0.17) (P = 0.110) compared to placebo. Heterogeneity across studies was significant. Maximum treatment benefit was achieved after a 6-months treatment period with ramipril as the ACE inhibitor.nnnCONCLUSIONnTreatment with ACE inhibitors improved walking ability in patients with IC. However, this was not associated with significant improvement in ABPI. Patients with IC might benefit from treatment with a high tissue affinity ACE inhibitor for a period of 6 months.

Supervised Exercise Program Improves Aerobic Fitness in Patients Awaiting Abdominal Aortic Aneurysm Repair

BACKGROUNDnAerobic fitness is an important predictor of postoperative outcome in major surgery. In this study, we assess the effects of a period of preoperative exercise on aerobic fitness as measured by cardiopulmonary exercise testing (CPET) in patients scheduled for abdominal aortic aneurysm (AAA) repair.nnnMETHODSnAs part of a randomized trial, the first patients recruited in the intervention group were enrolled in a supervised exercise program of six week duration. Treadmill CPET parameters were measured before and after exercise preoperatively for these patients. These parameters were as follows: peak oxygen uptake (VO2 peak), anaerobic threshold (AT), and ventilator equivalents for oxygen and carbon dioxide (VE/VO2 and VE/VCO2, respectively). Total exercise time and the time at which AT was achieved were also recorded. A comparison between pre- and postexercise parameters was made to detect for a possible improvement in aerobic fitness.nnnRESULTSnTwenty patients with AAA (17 men; mean age: 74.9 ± 5.9 years) were included in this study. Thirty-five percent of patients had a history of ischemic heart disease, 25% of obstructive airway disease, and 15% of cerebral vascular events. Seventy percent were previous smokers, and 15% were current smokers. Fifty-five percent of patients were taking aspirin and 75% were undergoing statin therapy. The median (interquartile range) VO2 peak at baseline was 18.2 (15.4-19.9) mL/kg/min, and after exercise was 19.9 (17.1-21.1; Pxa0=xa00.048). Median AT at baseline was 12.2 (10.5-14.9), and 14.4 (12.3-15.4) after exercise (Pxa0=xa00.023). Time of exercise tolerated also improved from a median of 379xa0to 604xa0sec (Pxa0=xa00.001). No significant changes were seen in VE/VO2, VE/VCO2, or the time at which AT was achieved.nnnCONCLUSIONnThis study shows that cardiopulmonary aerobic fitness improves after a period of supervised exercise in patients scheduled for AAA repair. This is justification for a randomized trial to assess whether this affects morbidity and mortality after AAA repair.

Prediction of organ‐specific complications following abdominal aortic aneurysm repair using cardiopulmonary exercise testing

This study aimed at assessing whether measures of aerobic fitness can predict postoperative cardiac and pulmonary complications, 30‐day mortality and length of hospital stay following elective abdominal aortic aneurysm repair. We prospectively collected cardiopulmonary exercise testing data over two years for 130 patients. Upon multivariate analysis, a decreased anaerobic threshold (OR (95% CI) 0.55 (0.37–0.84); p = 0.005) and open repair (OR (95% CI) 6.99 (1.56–31.48); p = 0.011) were associated with cardiac complications. Similarly, an increased ventilatory equivalent for carbon dioxide (OR (95% CI) 1.18 (1.05–1.33); p = 0.005) and open repair (OR (95% CI) 14.29 (3.24–62.90); p < 0.001) were associated with pulmonary complications. Patients who had an endovascular repair had shorter hospital and critical care lengths of stay (p < 0.001). Measures of fitness were not associated with 30‐day mortality or length of hospital stay. Cardiopulmonary exercise testing variables, therefore, seem to predict different postoperative complications following abdominal aortic aneurysm repair, which adds value to their routine use in risk stratification and optimisation of peri‐operative care.

Aortic Augmentation Index is Independently Associated With N-Terminal Pro B-type Natriuretic Peptide in Patients With Peripheral Arterial Disease

Objectives: To investigate the relationship of aortic augmentation index (AIx) with N-terminal pro B-type natriuretic peptide (NTproBNP) plasma levels in patients with peripheral arterial disease (PAD) with normal left ventricular (LV) function. Methods: Totally, 31 patients (23 males, mean age 65 ± 7.4) with a confirmed diagnosis of PAD of the lower limbs (ankle–brachial pressure index [ABPI] <0.90 in at least 1 leg) were enrolled in this study. All patients underwent pulse wave analysis by applanation tonometry of the radial artery using the SphygmoCor system and had a measurement of plasma NTproBNP levels. Results: Patients had a mean resting ABPI of 0.62 ± 0.19 and a mean AIx 32.6% ± 6.9. Median (interquartile range) NTproBNP plasma level was 75 (44-210) pg/mL. In a univariate analysis which included age, brachial systolic blood pressure (BSBP), brachial diastolic blood pressure (BDBP), ejection duration index (ED%), heart rate (HR), and NTproBNP, aortic AIx was significantly associated (Spearman rho) with NTproBNP, HR, and ED% (r = .49, P = .006; r = −.72, P = .000, and r = −.42, P = .02, respectively). Multivariate linear regression analysis showed that AIx was associated with NTproBNP (β = 0.38, P = .02) independent of gender, HR, ED%, and use of β-blockers. N-terminal pro B-type natriuretic peptide explained 8% of the variance in aortic AIx, whereas HR explained 15% of the variance. Conclusion: In patients with PAD with normal LV systolic function, AIx is independently associated with NTproBNP. Structural changes in the myocardium might occur due to increased LV afterload as a result of increased wave reflections and arterial stiffness due to atherosclerosis leading to an increase in NTproBNP plasma levels.

Outcomes after Open Repair of Ruptured Abdominal Aortic Aneurysms in Octogenarians: A 20-Year, Single-Center Experience

BACKGROUNDnThe purpose of this study was to evaluate morbidity, mortality, and survival in octogenarians undergoing open repair of ruptured abdominal aortic aneurysms (RAAAs) in comparison to younger patients.nnnMETHODSnThis investigation was a retrospective analysis of a prospectively maintained database from a tertiary referral center. We included all consecutive RAAA patients who underwent open repair from 1990 to 2011. Univariate and multivariate analyses were used to identify predictors of inferior short- and long-term outcomes.nnnRESULTSnOverall, 463 patients were identified, of whom 138 (30%) were octogenarians (group 2), with a mean age of 84 ± 0.47 years. There were 96 (69%) men and 42 women (31%). There were more women in group 2 (31%) compared with the <80-year-old patients of group 1 (14%) (P < 0.001). The 30-day mortality for group 2 was 43.5% compared with 28.0% for group 1 (P < 0.001). Preoperatively, 63% of group 1 patients presented with shock compared with 65% of those in group 2 (P = 0.751). There was no difference between the two groups in terms of preoperative systolic blood pressure (SBP), duration of operation, and intraoperative blood loss (P > 0.05). Median preoperative hemoglobin (P < 0.001) and creatinine (P = 0.031) levels were significantly different between the groups. There was no significant difference between the two groups in terms of postoperative complications and length of hospital stay. Median long-term survival for octogenarians (group 2) was 5.4 years compared with 12.4 years for the younger patient group (group 1) (P < 0.001). Multivariate analysis identified age as an independent predictor of 30-day mortality (odds ratio [OR] = 1.154, 95% confidence interval [CI] 1.037-1.285) and inferior long-term survival (OR = 1.074, 95% CI 1.011-1.141). History of cigarette smoking also predicted worse long-term outcomes (OR = 3.044, 95% CI 1.318-7.032) as did multiorgan failure in the postoperative course (OR = 1.363, 95% CI 1.080-14.130).nnnCONCLUSIONSnAdvanced age is associated with high surgical mortality; however, for octogenarians surviving surgical repair, long-term outcome is acceptable. Therefore, with responsible decision-making, surgical intervention is justifiable in the elderly. Smoking and multiorgan failure were both predictive of worse survival.