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Background: In patients with myocardial infarction, beta-adrenergic blockers reduce recurrent myocardial infarction and total mortality rates. However, whether a direct influence of beta-blockers on coronary atherosclerosis contributes to reduced recurrent myocardial infarction and total mortality rates is not known.Objective: To assess whether beta-blocker therapy is associated with reduced atheroma progression in adults with known coronary artery disease.Design: Post hoc, pooled analysis of individual patient data from 4 intravascular ultrasonography (IVUS) trials.Setting: Four IVUS trials conducted in the United States, Europe, and Australia.Patients: 1515 patients with coronary artery disease.Intervention: The original trials used 3 different statins, a calcium-channel blocker, an angiotensin-converting enzyme inhibitor, or an acyl coenzyme A-cholesterol acyltransferase inhibitor.Measurements: Changes in atheroma volume, as determined by IVUS after adjustment for possible confounders by using linear mixed-effects models, were compared in patients who did and did not receive concomitant beta-blocker treatment.Results: Patients who received beta-blockers (n = 1154) were more likely to have histories of myocardial infarction, angina, and hypertension than were patients who did not receive beta-blockers (n = 361). The estimated annual change in atheroma volume was statistically significantly less in patients who received beta-blockers. This was true for univariate and multivariable analyses that controlled for history of myocardial infarction, angina, and hypertension (mean [+/-SE] atheroma volume, -2.4 +/- 0.5 mm3/y in treated patients vs. -0.4 +/- 0.8 mm3/y in untreated patients; P = 0.034). Accordingly, atheroma volume statistically significantly decreased at follow-up IVUS in patients who received beta-blockers (P < 0.001) and did not change in patients who did not receive beta-blockers (P = 0.86). Additional adjustments for low-density lipoprotein cholesterol level, concomitant medications, and clinical trial did not change the results.Limitations: Patients were not randomly assigned to beta-blocker therapy, and interventions other than beta-blocker therapy could have influenced the changes in atheroma volume. Whether progression rate of atherosclerosis as detected by IVUS predicts cardiovascular outcomes is unknown.Conclusions: The analysis demonstrates that beta-blockers can slow progression of coronary atherosclerosis. The findings provide additional support for the current clinical guidelines advocating long-term use of beta-blockers to treat most forms of coronary artery disease. [ABSTRACT FROM AUTHOR]

Coronary angiography is the gold standard for the detection of coronary artery disease, but it only gives information about the lumen of the coronary arteries. Intravascular ultrasound (IVUS) has provided a new perspective for imaging the coronary arteries. It allows assessment of not only the lumen but also the vessel wall and atherosclerotic plaque. In this article, we review the technique, measurements and current applications of IVUS imaging of the coronaries in a question-answer format. [ABSTRACT FROM AUTHOR]

Context: Statins reduce low-density lipoprotein cholesterol (LDL-C) levels and slow progression of coronary atherosclerosis. However, no data exist describing the relationship between statin-induced changes in high-density lipoprotein cholesterol (HDL-C) and disease progression.Objective: To investigate the relationship between changes in LDL-C and HDL-C levels and atheroma burden.Design, Setting, and Patients: Post-hoc analysis combining raw data from 4 prospective randomized trials (performed in the United States, North America, Europe, and Australia between 1999 and 2005), in which 1455 patients with angiographic coronary disease underwent serial intravascular ultrasonography while receiving statin treatment for 18 months or for 24 months. Ultrasound analysis was performed in the same core laboratory for all of the studies.Main Outcome Measure: Relationship between changes in lipoprotein levels and coronary artery atheroma volume.Results: During statin therapy, mean (SD) LDL-C levels were reduced from 124.0 (38.3) mg/dL (3.2 [0.99] mmol/L) to 87.5 (28.8) mg/dL (2.3 [0.75] mmol/L) (a 23.5% decrease; P<.001), and HDL-C levels increased from 42.5 (11.0) mg/dL (1.1 [0.28] mmol/L) to 45.1 (11.4) mg/dL (1.2 [0.29] mmol/L) (a 7.5% increase; P<.001). The ratio of LDL-C to HDL-C was reduced from a mean (SD) of 3.0 (1.1) to 2.1 (0.9) (a 26.7% decrease; P<.001). These changes were accompanied by a mean (SD) increase in percent atheroma volume from 39.7% (9.8%) to 40.1% (9.7%) (a 0.5% [3.9%] increase; P = .001) and a mean (SD) decrease in total atheroma volume of 2.4 (23.6) mm3 (P<.001). In univariate analysis, mean levels and treatment-mediated changes in LDL-C, total cholesterol, non-HDL cholesterol, apolipoprotein B, and ratio of apolipoprotein B to apolipoprotein A-I were significantly correlated with the rate of atherosclerotic progression, whereas treatment-mediated changes in HDL-C were inversely correlated with atheroma progression. In multivariate analysis, mean levels of LDL-C (beta coefficient, 0.11 [95% confidence interval, 0.07-0.15]) and increases in HDL-C (beta coefficient, -0.26 [95% confidence interval, -0.41 to -0.10]) remained independent predictors of atheroma regression. Substantial atheroma regression (> or =5% reduction in atheroma volume) was observed in patients with levels of LDL-C less than the mean (87.5 mg/dL) during treatment and percentage increases of HDL-C greater than the mean (7.5%; P<.001). No significant differences were found with regard to clinical events.Conclusions: Statin therapy is associated with regression of coronary atherosclerosis when LDL-C is substantially reduced and HDL-C is increased by more than 7.5%. These findings suggest that statin benefits are derived from both reductions in atherogenic lipoprotein levels and increases in HDL-C, although it remains to be determined whether the atherosclerotic regression associated with these changes in lipid levels will translate to meaningful reductions in clinical events and improved clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: The enzyme acyl-coenzyme A:cholesterol acyltransferase (ACAT) esterifies cholesterol in a variety of tissues. In some animal models, ACAT inhibitors have antiatherosclerotic effects. Methods: We performed intravascular ultrasonography in 408 patients with angiographically documented coronary disease. All patients received usual care for secondary prevention, including statins, if indicated. Patients were randomly assigned to receive the ACAT inhibitor pactimibe (100 mg per day) or matching placebo. Ultrasonography was repeated after 18 months to measure the progression of atherosclerosis. Results: The primary efficacy variable analyzing the progression of atherosclerosis--the change in percent atheroma volume--was similar in the pactimibe and placebo groups (0.69 percent and 0.59 percent, respectively; P=0.77). However, both secondary efficacy variables assessed by means of intravascular ultrasonography showed unfavorable effects of pactimibe treatment. As compared with baseline values, the normalized total atheroma volume showed significant regression in the placebo group (-5.6 mm3, P=0.001) but not in the pactimibe group (-1.3 mm3, P=0.39; P=0.03 for the comparison between groups). The atheroma volume in the most diseased 10-mm subsegment regressed by 3.2 mm3 in the placebo group, as compared with a decrease of 1.3 mm3 in the pactimibe group (P=0.01). The combined incidence of adverse cardiovascular outcomes was similar in the two groups (P=0.53). Conclusions: For patients with coronary disease, treatment with an ACAT inhibitor did not improve the primary efficacy variable (percent atheroma volume) and adversely affected two major secondary efficacy measures assessed by intravascular ultrasonography. ACAT inhibition is not an effective strategy for limiting atherosclerosis and may promote atherogenesis. (ClinicalTrials.gov number, NCT00268515.). [ABSTRACT FROM AUTHOR]

Background: Carotid artery stenting (CAS) with a carotid protection device (CPD) has become the standard practice in patients with severe carotid stenosis and high surgical risk. However, the clinical efficacy and safety of CPDs are still controversial issues. We aimed to compare the clinical outcomes of the CAS without CPD with CAS combined with CPD., Methods: This is a multicenter randomized prospective study registered with http://clinicaltrials.gov (NCT02781181). After the exclusion, 279 patients were enrolled (139 patients in the CAS with CPD group and 140 patients in the CAS without CPD group). The primary outcome was a combination of peri-procedural in-hospital transient ischemic attack (TIA), ipsilateral stroke, or death. The secondary outcome was new ischemic brain lesions on post-procedural diffusion-weighted magnetic resonance imaging (DW-MRI)., Results: Two patients died in CAS without CPD group, one patient died in CAS with CPD group. TIA was only seen in patients who underwent CAS under protection (n = 5). The combined primary outcome of TIA, ipsilateral stroke, and death rate was not different between groups (5.7% vs. 2.8%; p = 0.254). New defects were noted on the post-procedural DW-MRI in 28% of patients in the CPD group and 27% of patients in the no CPD group (p = 0.881)., Conclusions: This study suggests that CAS without CPD is not associated with higher rates of peri-procedural TIA, stroke, and death or new ischemic brain lesions on post-procedural DW-MRI compared to CAS with CPD in selected symptomatic and asymptomatic patients with significant carotid artery stenosis provided that there is no visible thrombus.

Angiotensin-receptor blockers (ARBs) are a class of drugs approved for the treatment of several common conditions, such as hypertension and heart failure. Recently, regulatory agencies have started to identify possibly carcinogenic nitrosamines and azido compounds in a multitude of formulations of several ARBs, resulting in progressive recalls. Furthermore, data from several randomized controlled trials suggested that there is also a clinically increased risk of cancer and specifically lung cancer with ARBs; whereas other trials suggested no increased risk. The purpose of this analysis was to provide additional insight into the ARB-cancer link by examining whether there is a relationship between degree of cumulative exposure to ARBs and risk of cancer in randomized trials. Trial-level data from ARB Trialists Collaboration including 15 randomized controlled trials was extracted and entered into meta-regression analyses. The two co-primary outcomes were the relationship between cumulative exposure to ARBs and risk of all cancers combined and the relationship between cumulative exposure and risk of lung cancer. A total of 74,021 patients were randomized to an ARB resulting in a total cumulative exposure of 172,389 person-years of exposure to daily high dose (or equivalent). 61,197 patients were randomized to control. There was a highly significant correlation between the degree of cumulative exposure to ARBs and risk of all cancers combined (slope = 0.07 [95% CI 0.03 to 0.11], p<0.001), and also lung cancer (slope = 0.16 [95% CI 0.05 to 0.27], p = 0.003). Accordingly, in trials where the cumulative exposure was greater than 3 years of exposure to daily high dose, there was a statistically significant increase in risk of all cancers combined (I2 = 31.4%, RR 1.11 [95% CI 1.03 to 1.19], p = 0.006). There was a statistically significant increase in risk of lung cancers in trials where the cumulative exposure was greater than 2.5 years (I2 = 0%, RR 1.21 [95% CI 1.02 to 1.44], p = 0.03). In trials with lower cumulative exposure to ARBs, there was no increased risk of all cancers combined or lung cancer. Cumulative exposure-risk relationship with ARBs was independent of background angiotensin-converting enzyme inhibitor treatment or the type of control (i.e. placebo or non-placebo control). Since this is a trial-level analysis. the effects of patient characteristics such as age and smoking status could not be examined due to lack of patient-level data. In conclusion, this analysis, for the first time, reveals that risk of cancer with ARBs (and specifically lung cancer) increases with increasing cumulative exposure to these drugs. The excess risk of cancer with long-term ARB use has public health implications., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Dr. Sipahi has received lecture honoraria from Novartis, Boehringer-Ingelheim, Sanofi, Sandoz, Bristol-Myers Squibb, Bayer, Pfizer, Ranbaxy, Servier and ARIS and served on advisory board for Novartis, Sanofi, Servier, Bristol-Myers Squibb, Pfizer, Bayer and I.E. Ulagay. This does not alter my adherence to PLOS ONE policies on sharing data and materials.

Background: We planned a three arm randomized study to evaluate the safety and efficacy of a new blood stopper, Ankaferd blood stopper (ABS) along with short-time compression, compared to either short-time compression with conventional sterile gauzes (CSG) or with a TR band after transradial (TRA) procedures., Methods: The Ankaferd blood stopper as a new strategy to avoid early complications. After transradial procedures (ABS transradial) trial is designed in a prospective, randomized, placebo-controlled fashion and registered with http://clinicaltrials.gov (NCT02982733). Six hundred and thirty patients were randomized into three arms in a 1:1:1 fashion corresponding to three different strategies of patent hemostasis techniques after diagnostic or interventional catheterization., Results: One (0.49%) patient in the CSG group and one patient (0.48%) in the TR Band group developed RAO at the end of the hemostasis, compared with 0 (0%) in the ABS group. At 30 days follow-up none of the groups had any patients with RAO. As a secondary end-points the difference was not statistically significant regarding hematoma among the three groups (P = 0.70). Bleeding during deflation of the TR Band or removal of the elastic bandage occurred in 55 patients (26.96%) in the CSG group and in 56 (27.31%) patients in the TR Band group compared to 19 patients (9.40%) in the ABS group (P < 0.001)., Conclusion: Ankaferd blood stopper is a promising device for use in patent hemostasis, with no evidence on RAO at short-term or long term and with reduced risk of re-bleeding at the end of hemostasis., (© 2018 Wiley Periodicals, Inc.)

Background: QRS duration is an important risk factor for both sudden cardiac death and all-cause mortality in patients with moderate to severe left ventricular systolic dysfunction. However, it is unknown whether baseline QRS duration can help predict the mortality benefit from implantable cardioverter-defibrillators (ICDs) when used for primary prevention purposes., Objective: Our objective was to examine the relationship between baseline QRS duration and mortality reduction with ICDs implanted for primary prevention by performing a meta-analysis of all available randomized clinical trials., Methods: A systematic literature search of SCOPUS (covering MEDLINE and EMBASE) was conducted for randomized controlled clinical trials involving ICDs. Primary prevention trials of systolic dysfunction that reported all-cause mortality according to subgroups on the basis of baseline QRS duration were included., Results: A total of four randomized controlled clinical trials enrolling 3561 patients were included. Patients with QRS durations less than 120 ms [n = 2002, hazard ratio 0.78, 95% confidence interval (CI) 0.63-0.96, P = 0.018] and at least 120 ms (n = 1559, hazard ratio 0.59, 95% CI 0.48-0.73, P = 0.0000009) had significant decreases in all-cause mortality. On heterogeneity analysis, a strong trend for greater magnitude of benefit in patients with QRS at least 120 ms was observed (22% risk reduction vs. 41% risk reduction, P = 0.066)., Conclusion: For primary prevention purposes, ICDs are effective in reducing all-cause mortality in moderate to severe systolic dysfunction regardless of QRS duration. However, patients with a baseline QRS duration of at least 120 ms seem to derive a greater mortality benefit from ICDs.

Whether stenting or coronary artery bypass grafting (CABG) is the best revascularization strategy in patients with multivessel disease has been a heavily debated controversy. The trials comparing the two methods were unfortunately underpowered for mortality. Moreover, results of clinical trials appeared to contradict with each other. Because CABG is unequivocally a more cumbersome method, stenting became commonly preferred in the absence of evidence for mortality difference. Meta-analysis is a powerful tool, especially when several high-quality randomized trials are available on the same issue. In these instances, meta-analyses can overcome the power limitation of the individual trials. Our recent meta-analysis reveals that, as compared to stenting, CABG leads to unequivocal reductions in mortality and myocardial infarctions in patients with multivessel disease. These benefits are seen regardless of whether patients are diabetic or not and also do not depend on whether bare-metal or drug-eluting stents are used.

Objectives: Although heparin is highly effective in reducing the rate of radial artery occlusion after transradial catheterization, the optimal heparin dose is still controversial. The aim of this study was to evaluate the efficacy and safety of two different heparin doses during transradial coronary angiography., Methods: 490 consecutive patients undergoing transradial coronary angiography were prospectively enrolled into this double-blind randomized trial. A total of 202 patients enrolled in the low-dose (LD; 2,500 U of heparin) group and 202 patients enrolled in the high-dose (HD; 5,000 U of heparin) group were included in the final analysis. The primary endpoint of the study was radial artery occlusion. Bleeding and hematomas were the secondary outcome measures., Results: At day 7, radial artery occlusion occurred in 5.9% of the patients in the LD group and in 5.4% of the patients in the HD group (p = 0.83). Bleeding during deflation of the transradial band occurred in 6.4% of the patients in the LD group and in 18.3% of the patients in the HD group; the difference was statistically significant (p < 0.001). Higher-dose heparin was found to be an independent predictor of bleeding (p = 0.007)., Conclusion: A lower dose of heparin (i.e. 2,500 U) decreases bleeding during transradial band deflation without an increase in radial artery occlusion., (© 2015 S. Karger AG, Basel.)

Importance: Recent trials of percutaneous coronary intervention (PCI) vs coronary artery bypass grafting (CABG) for multivessel disease were not designed to detect a difference in mortality and therefore were underpowered for this outcome. Consequently, the comparative effects of these 2 revascularization methods on long-term mortality are still unclear. In the absence of solid evidence for mortality difference, PCI is oftentimes preferred over CABG in these patients, given its less invasive nature., Objectives: To determine the comparative effects of CABG vs PCI on long-term mortality and morbidity by performing a meta-analysis of all randomized clinical trials of the current era that compared the 2 treatment techniques in patients with multivessel disease., Data Sources: A systematic literature search was conducted for all randomized clinical trials directly comparing CABG with PCI., Study Selection: To reflect current practice, we included randomized trials with 1 or more arterial grafts used in at least 90%, and 1 or more stents used in at least 70% of the cases that reported outcomes in patients with multivessel disease., Data Extraction: Numbers of events at the longest possible follow-up and sample sizes were extracted., Data Synthesis: A total of 6 randomized trials enrolling a total of 6055 patients were included, with a weighted average follow-up of 4.1 years. There was a significant reduction in total mortality with CABG compared with PCI (I2 = 0%; risk ratio [RR], 0.73 [95% CI, 0.62-0.86]) (P < .001). There were also significant reductions in myocardial infarction (I2 = 8.02%; RR, 0.58 [95% CI, 0.48-0.72]) (P < .001) and repeat revascularization (I2 = 75.6%; RR, 0.29 [95% CI, 0.21-0.41]) (P < .001) with CABG. There was a trend toward excess strokes with CABG (I2 = 24.9%; RR, 1.36 [95% CI, 0.99-1.86]), but this was not statistically significant (P = .06). For reduction in total mortality, there was no heterogeneity between trials that were limited to and not limited to patients with diabetes or whether stents were drug eluting or not. Owing to lack of individual patient-level data, additional subgroup analyses could not be performed., Conclusions and Relevance: In patients with multivessel coronary disease, compared with PCI, CABG leads to an unequivocal reduction in long-term mortality and myocardial infarctions and to reductions in repeat revascularizations, regardless of whether patients are diabetic or not. These findings have implications for management of such patients.

Echocardiography-guided pericardiocentesis is the first choice method for relieving cardiac tamponade, but the exact role of the echocardiography at the moment of the puncture is still controversial. In this report, detailed echocardiographic evaluation was performed in 21 consecutive patients with cardiac tamponade just before the pericardiocentesis. Appropriate needle position was determined according to the probe position using imaginary x, y, and z axes. Pericardiocentesis was performed successfully using this technique without simultaneous echocardiography and no complications were observed. We concluded that bedside echocardiography with detailed evaluation of the puncture site and angle is enough for pericardiocentesis instead of real time guiding., (© 2013, Wiley Periodicals, Inc.)

Background: Cardiac resynchronization therapy (CRT) is effective in reducing clinical events in systolic heart failure patients with a wide QRS. Previous retrospective studies suggest only patients with QRS prolongation due to a left bundle-branch block (LBBB) benefit from CRT. Our objective was to examine this by performing a meta-analysis of all randomized controlled trials of CRT., Methods: Systematic searches of MEDLINE and the Food and Drug Administration official website were conducted for randomized controlled CRT trials. Trials reporting adverse clinical events (eg, all-cause mortality, heart failure hospitalizations) according to QRS morphology were included in the meta-analysis., Results: Four randomized trials totaling 5,356 patients met the inclusion criteria. In patients with LBBB at baseline, there was a highly significant reduction in composite adverse clinical events with CRT (RR = 0.64 [95% CI (0.52-0.77)], P = .00001). However no such benefit was observed for patients with non-LBBB conduction abnormalities (RR = 0.97 [95% CI (0.82-1.15)], P = .75). When examined separately, there was no benefit in patients with right-bundle branch block (RR = 0.91 [95% CI (0.69-1.20)], P = .49) or non-specific intraventricular conduction delay (RR = 1.19 [95% CI (0.87-1.63)], P = .28). There was no heterogeneity among the clinical trials with regards to the lack of benefit in non-LBBB patients (I(2) = 0%). When directly compared, the difference in effect of CRT between LBBB versus non-LBBB patients was highly statistically significant (P = .0001 by heterogeneity analysis)., Conclusions: While CRT was very effective in reducing clinical events in patients with LBBB, it did not reduce such events in patients with wide QRS due to other conduction abnormalities., (Copyright © 2012 Mosby, Inc. All rights reserved.)

The renin-angiotensin system is an important mediator of tumor progression and metastasis. A recent meta-analysis of randomized controlled trials reported an increased risk of cancer with angiotensin receptor blockers. It is unknown whether angiotensin-converting enzyme (ACE) inhibitors may have a similar effect. Our primary objective was to determine the effect of ACE inhibitors on cancer occurrence and cancer death. Our secondary objective was to determine the effect of ACE inhibitors on occurrence of gastrointestinal (GI) cancers given previous concerns of increased risk. Systematic searches of SCOPUS (covering MEDLINE, EMBASE, and other databases) and the Food and Drug Administration official web site were conducted for all randomized controlled trials of ACE inhibitors. Trials with ≥1 year of follow-up and enrolling a minimum of 100 patients were included. Fourteen trials reported cancer data in 61,774 patients. This included 10 trials of 59,004 patients providing information on cancer occurrence, 7 trials of 37,515 patients for cancer death, and 5 trials including 23,291 patients for GI cancer. ACE inhibitor therapy did not have an effect on occurrence of cancer (I(2) 0%, risk ratio [RR] 1.01, 95% confidence interval [CI] 0.95 to 1.07, p = 0.78), cancer death (I(2) 0%, RR 1.00, 95% CI 0.88 to 1.13, p = 0.95), or GI cancer (RR 1.09, 95% CI 0.88 to 1.35, p = 0.43). In conclusion, ACE inhibitors did not significantly increase or decrease occurrence of cancer or cancer death. There was also no significant difference in risk of GI cancer., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Heart failure with preserved ejection fraction (HF-PEF) is the clinical syndrome of heart failure associated with normal or near-normal systolic function. Because inhibition of the adrenergic and renin-angiotensin-aldosterone systems has been so effective in the treatment of systolic heart failure, these same therapies have been the subject of recent clinical trials of HF-PEF. In this review, we examine the current evidence about treatment of HF-PEF, with particular emphasis on reviewing the literature for large-scale randomized clinical studies. The lack of significant benefit with neurohormonal antagonism in HF-PEF suggests that this condition might not involve neurohormonal activation as a critical pathophysiologic mechanism. Perhaps heart failure as we traditionally think of it is the wrong paradigm to pursue as we try to understand this condition of volume overload known as HF-PEF.

Ventricular assist devices (VADs) and intra-aortic balloon pumps (IABPs) are important tools that provide hemodynamic support to patients in cardiogenic shock. The Impella Recover 2.5 is a percutaneous VAD that provides temporary circulatory support. We report the case of a patient who required the combined support of both an IABP and the Impella device.

Background: Angiotensin-receptor blockers (ARBs) are a widely used drug class approved for treatment of hypertension, heart failure, diabetic nephropathy, and, recently, for cardiovascular risk reduction. Experimental studies implicate the renin-angiotensin system, particularly angiotensin II type-1 and type-2 receptors, in the regulation of cell proliferation, angiogenesis, and tumour progression. We assessed whether ARBs affect cancer occurrence with a meta-analysis of randomised controlled trials of these drugs., Methods: We searched Medline, Scopus (including Embase), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and the US Food and Drug Administration website for studies published before November, 2009, that included any of the seven currently available ARBs. Randomised controlled trials with an ARB given in at least one group, with a follow-up of at least 1 year, and that enrolled at least 100 patients were included. New-cancer data were available for 61,590 patients from five trials. Data on common types of solid organ cancers were available for 68,402 patients from five trials, and data on cancer deaths were available for 93,515 patients from eight trials., Findings: Telmisartan was the study drug in 30,014 (85.7%) patients who received ARBs as part of the trials with new cancer data. Patients randomly assigned to receive ARBs had a significantly increased risk of new cancer occurrence compared with patients in control groups (7.2%vs 6.0%, risk ratio [RR] 1.08, 95% CI 1.01-1.15; p=0.016). When analysis was limited to trials where cancer was a prespecified endpoint, the RR was 1.11 (95% CI 1.04-1.18, p=0.001). Among specific solid organ cancers examined, only new lung-cancer occurrence was significantly higher in patients randomly assigned to receive ARBs than in those assigned to receive control (0.9%vs 0.7%, RR 1.25, 1.05-1.49; p=0.01). No statistically significant difference in cancer deaths was observed (1.8%vs 1.6%, RR 1.07, 0.97-1.18; p=0.183)., Interpretation: This meta-analysis of randomised controlled trials suggests that ARBs are associated with a modestly increased risk of new cancer diagnosis. Given the limited data, it is not possible to draw conclusions about the exact risk of cancer associated with each particular drug. These findings warrant further investigation., (2010 Elsevier Ltd. All rights reserved.)

Objectives: We investigated coronary atheroma progression in patients with low levels of low-density lipoprotein cholesterol (LDL-C) and systolic blood pressure (SBP)., Background: Low LDL-C and SBP beneficially impact coronary atherosclerosis. However, the association between intensive control of both risk factors and coronary plaque progression remains unclear., Methods: Changes in atheroma burden monitored by intravascular ultrasound were studied in 3,437 patients with coronary artery disease (CAD) who were stratified according to on-treatment LDL-C and SBP., Results: Patients with very low LDL-C (< or =70 mg/dl) and normal SBP (< or =120 mm Hg) had less progression in percent atheroma volume (PAV) (p < 0.001) and total atheroma volume (TAV) (p < 0.001), more frequent plaque regression (p = 0.01), and less frequent plaque progression (p < 0.001). In patients with SBP >120 mm Hg, very low LDL-C was associated with less progression of PAV (+0.30%, 95% confidence interval [CI]: -0.17% to 0.77% vs. +0.61%, 95% CI: 0.17% to 1.05%, p = 0.01) and TAV (-3.9 mm3, 95% CI: -7.24 to -0.63 mm3 vs. -1.2 mm3, 95% CI: -4.31 to 1.92 mm3, p = 0.001). In patients with LDL-C >70 mg/dl, normal SBP was not associated with less progression of PAV (+0.51%, 95% CI: 0.04% to 0.99% vs. +0.61%, 95% CI: 0.17% to 1.05%, p = 0.159) or TAV (-2.3 mm3, 95% CI: -5.59 to 1.05 mm3 vs. -1.2 mm3, 95% CI: -4.31 to 1.92 mm3, p = 0.617)., Conclusions: Very low LDL-C and normal SBP are associated with the slowest progression of coronary atherosclerosis. Although a greater beneficial association is observed in patients with very low LDL-C, these findings suggest the need for intensive control of global risk in patients with CAD.

Objectives: Our goal was to characterize coronary atherosclerosis progression and arterial remodeling in diabetic patients., Background: The mechanisms that underlie adverse cardiovascular outcomes in diabetic patients have not been well characterized., Methods: A systematic analysis was performed in 2,237 subjects in randomized controlled studies of atherosclerosis progression. The pattern of arterial remodeling, extent of coronary atherosclerosis, and disease progression was compared in subjects with and without diabetes., Results: In association with more risk factors, diabetic patients demonstrated a greater percent atheroma volume (PAV) (40.2 +/- 0.9% vs. 37.5 +/- 0.8%, p < 0.0001) and total atheroma volume (TAV) (199.4 +/- 7.9 mm(3) vs. 189.4 +/- 7.1 mm(3), p = 0.03) on multivariate analysis. A stronger correlation was observed between PAV and glycated hemoglobin (r = 0.22, p = 0.0003) than fasting glucose (r = 0.09, p < 0.0001), although the difference just failed to meet statistical significance after controlling for study. Diabetic patients exhibited a smaller lumen (291.1 +/- 104.8 mm(3) vs. 306.5 +/- 108.2 mm(3), p = 0.005) but no difference in external elastic membrane (494.9 +/- 166.9 mm(3) vs. 498.8 +/- 167.2 mm(3), p = 0.61) volumes. More rapid progression of PAV (0.6 +/- 0.4% vs. 0.05 +/- 0.3%, p = 0.0001) and TAV (-0.6 +/- 2.5 mm(3) vs. -2.7 +/- 2.4 mm(3), p = 0.03) was observed in diabetic patients on multivariate analysis. Smaller external elastic membrane (482.5 +/- 160.7 mm(3) vs. 519.9 +/- 166.9 mm(3), p = 0.03) and lumen (276.0 +/- 100.3 mm(3) vs. 310.1 +/- 105.6 mm(3), p = 0.001) volumes were observed in diabetic patients treated with insulin despite the presence of a similar TAV (206.5 +/- 88.6 mm(3) vs. 209.9 +/- 90.2 mm(3), p = 0.84). Intensive low-density lipoprotein cholesterol lowering in patients improved the rate of plaque progression, but only to the level observed in nondiabetic patients with suboptimal lipid control., Conclusions: Diabetes is accompanied by more extensive atherosclerosis and inadequate compensatory remodeling. Accelerated plaque progression, despite use of medical therapies, supports the need to develop new antiatherosclerotic strategies in diabetic patients.