Renal artery stenosis - an update.

Renal artery stenosis (RAS) is a common form of peripheral arterial disease. The most common cause of RAS is atherosclerosis. It is predominantly unilateral. The pathophysiologic mechanism stems from renal underperfusion resulting in the activation of the renin- angiotensin-aldosterone pathway. Even though the majority of patients with RAS are asymptomatic, it can clinically present with hypertension, nephropathy and congestive heart failure. This progressive disease can lead to resistant hypertension and end stage kidney failure. Screening patients for RAS with either Doppler ultrasonography, computed tomographic angiography, or magnetic resonance angiography is preferred. Adequate blood pressure control, goal-directed lipid-lowering therapy, smoking cessation, and other preventive measures form the foundation of management of patients with RAS. Catheter-based percutaneous revascularization with angioplasty and stenting showed modest clinical benefit for patients in small retrospective studies, but data from randomized clinical trials failed to confirm these beneficial results. The current ongoing Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial may provide more concrete data regarding the role of stenting in RAS. Surgical revascularization is considered only if catheter-based revascularization is unsuitable or unsuccessful. The American College of Cardiology/American Heart Association guidelines on evaluation and management of patients with RAS provide the framework for determining individualized assessment and treatment plans for patients with RAS.

Is atherosclerosis regression a realistic goal of statin therapy and what does that mean?

Atherosclerosis is a complex disease associated with aberrant lipoprotein metabolism and leukocyte infiltration into arterial tissue that leads to cardiovascular diseases. Statins have emerged as among the most effective means of reducing the risk of cardiovascular disease in both primary and secondary prevention settings. Statins are the only pharmacological agents that have been consistently shown to have antiatherosclerotic effects. Statins slow atherosclerosis progression and can even induce atherosclerosis regression. Technological advances in imaging modalities to assess atherosclerosis have made possible direct visualization of atherosclerotic plaques and estimation of plaque burden and permit the evaluation of the impact of medical therapies on the natural history of plaque progression. However, owing to several limiting factors as discussed in this review, presently atherosclerotic plaque progression cannot be used as a therapeutic goal for reduction of the risk of cardiovascular disease. In this review we discuss the evidence for the use of imaging modalities in the detection of atherosclerotic plaque regression, the effects of statins on the atherosclerotic process, and the clinical relevance of atherosclerosis regression.

Tirofiban use with clopidogrel and aspirin decreases adverse cardiovascular events after percutaneous coronary intervention for ST-elevation myocardial infarction: a meta-analysis of randomized trials.

Current guidelines deemed usefulness of routine early glycoprotein IIb/IIIa inhibitor (GPI) administration in ST-elevation myocardial infarction (STEMI) before primary percutaneous coronary intervention (PCI) with dual antiplatelet therapy as uncertain. We aimed to examine the current evidence for the use of tirofiban, a nonpeptide glycoprotein IIb/IIIa inhibitor, in STEMI patients treated with dual antiplatelet therapy. We performed systematic searches of MEDLINE, EMBASE, and CENTRAL databases for randomized controlled trials (RCTs) of tirofiban use in STEMI patients treated with aspirin and clopidogrel which reported clinical and/or angiographic outcomes after primary PCI. Data were combined using random effect and fixed effect models for heterogeneous and homogeneous outcomes respectively using Review Manager 5 (The Nordic Cochrane Centre, The Cochrane Collaboration, 2008). Six randomized controlled trials were eligible for the inclusion; involving 708 patients in tirofiban group and 721 control subjects. Routine tirofiban use decreased the major adverse cardiovascular events (odds ratio [OR] 0.50; 95% confidence interval [CI], 0.26-0.94). Corrected thrombolysis in myocardial infarction (TIMI) frame count was also reduced with tirofiban (mean difference -8.48 [95% CI, -12.62 to -4.34]). There were no significant differences in the rates of postprocedure TIMI flow grade 3 and TIMI myocardial perfusion/blush grade 3, major bleeding by TIMI criteria, or mortality in the 2 groups. Current analysis of available studies suggests that routine and early tirofiban use before primary PCI may decrease the major cardiovascular events in STEMI patients treated with aspirin and clopidogrel without any significant increase in major bleeding. An adequately powered randomized trial is urgently needed to confirm the above findings and estimate the effect size.

Effects of statins on progression of coronary artery disease as measured by intravascular ultrasound.

Intravascular ultrasound (IVUS) is a novel technique that provides an accurate and reproducible method to measure atheroma burden. Statin drugs reduce both atherogenic lipoproteins and cardiovascular morbidity and mortality. Studies assessing the effect of statin treatment on atheroma burden have shown conflicting results. Hence, this meta-analysis was conducted to evaluate the impact of statin therapy on coronary atherosclerosis progression. A systematic search using PubMed, EMBASE, and Cochrane Library databases was performed. Heterogeneity of the studies was analyzed by Cochran's Q statistics. The significance of common treatment effect was assessed by computing common mean difference between the control and treatment groups. A two-sided α error of <0.05 was considered statistically significant (P<.05). Eight trials composed of 919 patients including a placebo group with 458 patients and a treatment group with 461 patients were used. Characteristics of both groups at baseline were similar without any significant difference between them. In the pooled analysis, the common mean difference of coronary atheroma volume between statin therapy and the placebo arm was -3.573 (confidence interval, -4.46 to -2.68; P<.01). This meta-analysis demonstrates that treatment with statins not only slows atherosclerotic plaque progression but may also lead to plaque regression.

Outcomes of nonemergent percutaneous coronary intervention with and without on-site surgical backup: a meta-analysis.

Despite major advances in percutaneous coronary intervention (PCI) techniques, the current guidelines recommend against elective PCI at hospitals without on-site cardiac surgery backup. Nonetheless, an increasing number of hospitals without on-site cardiac surgery in the United States have developed programs for elective PCI. Studies evaluating outcome in this setting have yielded mixed results, leaving the question unanswered. Hence, a meta-analysis comparing outcomes of nonemergent PCI in hospitals with and without on-site surgical backup was performed. A systematic review of literature identified four studies involving 6817 patients. Three clinical end points were extracted from each study and included in-hospital death, myocardial infarction, and the need for emergency coronary artery bypass grafting. The studies were homogenous for each outcome studied. Therefore, the combined relative risks (RRs) across all the studies and the 95% confidence intervals (CIs) were computed using the Mantel-Haenszel fixed-effect model. A two-sided alpha error less than 0.05 was considered to be statistically significant. Compared with facilities with on-site surgical backup, the risk of in-hospital death (RR, 2.7; CI, 0.6-12.9; P = 0.18), nonfatal myocardial infarction (RR, 1.3; CI, 0.7- 2.2; P = 0.29), and need of emergent coronary artery bypass grafting (RR, 0.46; CI, 0.06- 3.1; P = 0.43) was similar in those lacking on-site surgical backup. The present meta-analysis suggests that there is no difference in the outcome with regard to risk of nonfatal myocardial infarction, need for emergency coronary artery bypass grafting, and the risk of death in patients undergoing elective PCI in hospitals with and without on-site cardiac surgery backup.

Safety and efficacy of triple antithrombotic therapy after percutaneous coronary intervention in patients needing long-term anticoagulation.

BACKGROUND: Optimal antithrombotic therapy after percutaneous coronary intervention (PCI) is currently undefined in patients requiring long-term anticoagulation. Previous studies comparing triple therapy (TT) of warfarin, aspirin and clopidogrel with standard dual therapy (DT) of aspirin and clopidogrel have yielded conflicting results. Meta-analysis of these studies was performed to evaluate safety and efficacy of TT. METHODS: A total of 1482 patients from 6 studies were analyzed using the Mantel-Haenszel random effect model to extract incidence of major bleeding. The secondary end point assessed by three of these studies was major adverse cardiac events (MACEs: cardiovascular death, myocardial infarction and thromboembolic complications). The incidence of MACEs was computed using the Mantel-Haenszel fixed effect model. Combined relative risks (RRs) across all of the studies and the 95% confidence intervals (CIs) were determined. A two-sided alpha error <0.05 was considered statistically significant. RESULTS: Baseline characteristics were similar in both groups. Compared with patients receiving DT, the risk of major bleeding was significantly higher in the TT group (RR: 2.74, CI: 1.08-6.98; p=0.034). However, risk of MACE was significantly lower in the TT group (RR: 0.72, CI: 0.56-0.98; p=0.014). CONCLUSION: In patients requiring long-term anticoagulation after PCI, TT may be superior to DT in reducing the incidence of MACEs, however risk of major bleeding complications is increased significantly.

Impact of statins on cardiovascular outcomes in renal transplant recipients: a systematic review.

Patients with chronic kidney disease including renal transplant recipients (RTRs) have a markedly higher prevalence of cardiovascular disease than the general population. Many trials have established the role of statins in the prevention of cardiovascular mortality, not only by decreasing the low density lipoprotein-cholesterol levels but also by their pleotropic effects. These data from the general population may not be applicable to RTRs as these patients have different cardiovascular risk profiles. Till date, only a few prospective, randomized trials have assessed the use of statins in RTRs with regards to cardiovascular outcomes. The Assessment of Lescol in Renal Transplant trial, the largest trial so far, suggested that dyslipidemia management with statins in RTRs is associated with a significant reduction in the incidence of cardiac death and nonfatal myocardial infarction (although differences in the combined primary end point were not statistically significant). The current guidelines from National Kidney Foundation for managing dyslipidemia in RTRs recommend managing all chronic kidney disease patients as a coronary heart disease equivalent. The task group for drafting these guidelines concluded that based on the currently available evidence, additional studies may be needed in RTRs to confirm and extend the results of Assessment of Lescol in Renal Transplant trial.

Effects of statins on progression of carotid atherosclerosis as measured by carotid intimal--medial thickness: a meta-analysis of randomized controlled trials.

BACKGROUND: Carotid intimal-medial thickness (CIMT) as measured by B-mode ultrasonography is a surrogate marker for carotid atherosclerosis. Studies have found conflicting results for the effect of statins on carotid atherosclerosis progression by measuring CIMT. Hence, this meta-analysis was conducted to evaluate the impact of statin therapy on CIMT progression. METHODS: A systematic search using PubMed, EMBASE, and Cochrane library databases was performed. Heterogeneity of the studies was analyzed by the Cochran Q statistics. The significance of common treatment effect was assessed by computing common mean difference between the control and treatment groups. A 2-sided alpha error of less than 0.05 was considered to be statistically significant. RESULTS: In all, 11 trials (N = 3806) fulfilled the criteria for inclusion in the analysis. The study population included 67.2% males and 22.8% females. The mean age was 58.7 years. Treatment with statins (mean treatment duration of 25.6 months) resulted in a significant reduction in the mean low-density lipoprotein ([LDL]; mg/dL, before treatment 168.6 ± 33.3, after treatment 102.33 ± 27.9, P < .05). No significant changes in the levels of LDL cholesterol were noted in the control group. A total of 7 trials showed regression and 4 trials showed slowing of progression of CIMT. Pooled analysis of all 11 trials showed that there was a statistically significant benefit with statin therapy in slowing down the progression of CIMT and the common mean difference between statin therapy arm and placebo arm was -0.040 (CI: -0.052--0.028; P value < .001). CONCLUSIONS: Statins therapy slows down the progression of carotid atherosclerosis as measured by CIMT, indicating benefits at subclinical stage of the disease process.

Safety and efficacy of prolonged use of unfractionated heparin after percutaneous coronary intervention.

The current guidelines for percutaneous coronary intervention do not address the prolonged postprocedural use of unfractionated heparin (UFH) to prevent acute occlusion. However, recently published small studies have yielded mixed results, leaving the question unanswered. Hence, we performed a meta-analysis of the existing evidence to assess the safety and efficacy of prolonged infusion of UFH after percutaneous coronary intervention. A systematic review of literature revealed seven studies involving 2412 patients. End points analyzed were ischemic complications (acute closure, myocardial infarction, and repeat revascularization) and major vascular complications (hematoma, arteriovenous fistula, pseudoaneurysm, and retroperitoneal bleed). Because the studies were homogenous for outcomes, combined relative risks across all the studies and the 95% confidence intervals were computed using the Mantel-Haenszel fixed-effect model. A two-sided alpha error <0.05 was considered to be statistically significant. There were no significant differences in patient demographics between both groups. Compared with placebo, the risk of major vascular complication was significantly higher in patients getting postprocedural UFH for prolonged hours (relative risk, 2.24; confidence interval, 1.68-3.48; P = 0.001). However, the risk of ischemic complications was similar in both groups (relative risk, 0.95; confidence interval, 0.46-1.96; P = 0.89). The meta-analysis suggests that routine infusion of UFH after uncomplicated percutaneous coronary intervention may result in increased vascular complications without any reduction in incidence of ischemic complications.

Leptin and the clinical cardiovascular risk.

Obesity is a universal health problem of increasing prevalence and represents a major public health concern. Obesity is associated with a high risk of developing cardiovascular and metabolic diseases such as hypertension, coronary atherosclerosis, myocardial hypertrophy, diabetes, dyslipidemia, and increased cardiovascular morbidity and mortality. There has been an ongoing search for mediators between obesity and cardiovascular disease. Leptin is a novel and very promising molecule of research that may link these pathologic conditions. Since its discovery in 1994, major advances have been made in the understanding of neuroendocrine mechanisms regulating appetite, metabolism, adiposity, sympathetic tone and blood pressure. In this review, we discuss the physiological and pathophysiological roles of leptin in the causation of various cardiovascular diseases.

Cardiovascular manifestations of posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) involves the onset of psychiatric symptoms after exposure to a traumatic event. PTSD has an estimated lifetime prevalence of 7.8% among adult Americans, and about 15.2% of the men and 8.5% of the women who served in Vietnam suffered from posttraumatic stress disorder (PTSD) > or =15 years after their military service. Physiological responses (increase in heart rate, blood pressure, tremor and other symptoms of autonomic arousal) to reminders of the trauma are a part of the DSM-IV definition of PTSD. Multiple studies have shown that patients suffering from PTSD have increased resting heart rate, increased startle reaction, and increased heart rate and blood pressure as responses to traumatic slides, sounds and scripts. Some researchers have studied the sympathetic nervous system even further by looking at plasma norepinephrine and 24-hour urinary norepinephrine and found them to be elevated in veterans with PTSD as compared to those without PTSD. PTSD is associated with hyperfunctioning of the central noradrenergic system. Hyperactivity of the sympathoadrenal axis might contribute to cardiovascular disease through the effects of the catecholamines on the heart, the vasculature and platelet function. A psychobiological model based on allostatic load has also been proposed and states that chronic stressors over long durations of time lead to increased neuroendocrine responses, which have adverse effects on the body. PTSD has also been shown to be associated with an increased prevalence of substance abuse. With this review, we have discussed the effects of PTSD on the cardiovascular system.

Coronary artery disease in South Asians: an emerging risk group.

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide and was responsible for 7.2 million deaths in 2003. Various studies have pointed out that South Asians have a higher prevalence of CAD as compared with other ethnicities. South Asians may have a genetic predisposition to CAD; however, environmental, nutritional, and lifestyle factors may also be responsible. South Asians have a much higher prevalence of metabolic syndrome, diabetes, insulin resistance (and resultant hyperinsulinemia), central obesity, dyslipidemias (lower high-density lipoprotein, increased lipoprotein[a], higher triglyceride levels), increased thrombotic tendency (increased plasminogen activator inhibitor-1 and decreased tissue plasminogen activator levels), decreased levels of physical activity, and low birth weights ("fetal origins hypothesis"). In addition, the dietary indiscretions and sedentary lifestyle practiced by most South Asians puts them at a higher risk. A multidisciplinary approach involving the population at risk, healthcare personnel, and the government is required to diminish the incidence. Educational programs regarding the genetic predisposition as well as risk factors for CAD, physical activity, and dietary modifications need to be encouraged. There is a need for implementation of newer guidelines as well as a lower threshold for initiating therapeutic interventions in this population. Mass media should be involved to bring about behavioral changes, and these changes should be reinforced at the physician's level.