Statins decrease perioperative cardiac complications in patients undergoing noncardiac vascular surgery: the Statins for Risk Reduction in Surgery (StaRRS) study

OBJECTIVES: We sought to assess whether statins may decrease cardiac complications in patients undergoing noncardiac vascular surgery. BACKGROUND: Cardiovascular complications account for considerable morbidity in patients undergoing noncardiac surgery. Statins decrease cardiac morbidity and mortality in patients with coronary disease, and the beneficial treatment effect is seen early, before any measurable increase in coronary artery diameter. METHODS: A retrospective study recorded patient characteristics, past medical history, and admission medications on all patients undergoing carotid endarterectomy, aortic surgery, or lower extremity revascularization over a two-year period (January 1999 to December 2000) at a tertiary referral center. Recorded perioperative complication outcomes included death, myocardial infarction, ischemia, congestive heart failure, and ventricular tachyarrhythmias occurring during the index hospitalization. Univariate and multivariate logistic regressions identified predictors of perioperative cardiac complications and medications that might confer a protective effect. RESULTS: Complications occurred in 157 of 1,163 eligible hospitalizations and were significantly fewer in patients receiving statins (9.9%) than in those not receiving statins (16.5%, p = 0.001). The difference was mostly accounted by myocardial ischemia and congestive heart failure. After adjusting for other significant predictors of perioperative complications (age, gender, type of surgery, emergent surgery, left ventricular dysfunction, and diabetes mellitus), statins still conferred a highly significant protective effect (odds ratio 0.52, p = 0.001). The protective effect was similar across diverse patient subgroups and persisted after accounting for the likelihood of patients to have hypercholesterolemia by considering their propensity to use statins. CONCLUSIONS: Use of statins was highly protective against perioperative cardiac complications in patients undergoing vascular surgery in this retrospective study.     

Incidence of noncardiac vascular disease in rheumatoid arthritis and relationship to extraarticular disease manifestations

OBJECTIVE: To investigate the incidence of noncardiac vascular disease in patients with rheumatoid arthritis (RA) and its relationship to systemic extraarticular disease in a community-based cohort. METHODS: A retrospective medical record review of 609 patients with incident RA diagnosed during 1955-1994 was carried out in Olmsted County, Minnesota. Patients were followed up from 1955 to 2000 (median followup 11.8 years). Incident noncardiac vascular disease and severe extraarticular RA manifestations (including pericarditis, pleuritis, and vasculitis) were recorded according to predefined criteria, and incidence rates were estimated. Using Cox proportional hazards models, the risk (hazard ratio [HR]) of developing vascular events was assessed in patients with and without severe extraarticular RA. RESULTS: Cerebrovascular and peripheral arterial events occurred in 139 patients (22.8%). The 30-year cumulative incidence rates of peripheral arterial events, cerebrovascular events, and venous thromboembolic events were estimated to be 19.6%, 21.6%, and 7.2%, respectively. The presence of severe extraarticular RA manifestations was found to be associated with all subgroups of noncardiac vascular disease except cerebrovascular disease alone (HR 2.3, 95% confidence interval [95% CI] 1.2-4.3 for peripheral arterial events; HR 3.7, 95% CI 1.3-10.3 for venous thromboembolic events; HR 1.5, 95% CI 0.7-3.2 for cerebrovascular events) after adjusting for age, sex, body mass index, smoking, and rheumatoid factor status. CONCLUSION: This is the first study to assess the incidence of noncardiac vascular disease in RA. Severe extraarticular RA was associated with all forms of noncardiac vascular disease except cerebrovascular disease alone. Similar to cardiac disease, the excess risk of noncardiac vascular disease in RA is likely to be related, in part, to the systemic inflammation associated with the extraarticular manifestations of RA.     

Statins and kidney disease

The prevalence of chronic kidney disease (CKD) is increasing worldwide. This clinical and social problem is mainly related to the ongoing epidemic of obesity and metabolic syndrome resulting in hypertension and diabetes mellitus. CKD is a well-recognized risk multiplier for the development of cardiovascular disease (CVD), and it is widely known that CVD is the leading cause of morbidity and mortality in patients with CKD. Lipid metabolism abnormalities are commonly associated with CKD. These consist of increased levels of low-density lipoproteins (LDL), triglycerides, very-low-density lipoproteins (VLDL) and lipoprotein(a), and reduced levels of HDL cholesterol. Lipid abnormalities contribute to cardiovascular morbidity and mortality in CKD patients. Some evidence also suggests that dyslipidemia may contribute to the progression of renal disease associated with type 1 and type 2 diabetic as well as non-diabetic renal disease. In the general population, HMG-CoA reductase inhibitors (statins) reduce the cardiovascular risk and prevent CVD. Similar data from secondary analyses of CKD subgroups of larger prospective trials using statins suggest a beneficial effect on cardiovascular outcomes and - albeit with more conflicting evidence - the progression of renal disease. Statins reduce blood levels of LDL cholesterol but also have multiple effects above and beyond cholesterol lowering, including direct effects on vascular tissue, kidney, bone, and glucose metabolism. The evidence linking dyslipidemia management with statins to cardiovascular disease and the decline in renal function in CKD patients will be presented in this review.     

Statins, and the vascular and valvular calcification

Statins are currently approved for reducing the risk of cardiovascular diseases, clinically. These evidences were thought to be due to the lipid-lowering effects of the statins. But recently, the growing evidences showed the various effects of statins, such as inhibition of vascular and valvular calcification. How statins affects the bone forming proteins and genes are still not known.     

Statins, inflammation and kidney disease

Inflammation is highly prevalent in patients with chronic kidney disease (CKD) and is consistently associated with cardiovascular morbidity and mortality. Clinical event rates increase with declining renal function and activation of the acute-phase response. Statins are potent anti-inflammatory drugs that reduce the incidence of cardiovascular events. Owing to the increased prevalence of inflammation in patients with CKD and the potent effect of statins in individuals with elevated levels of C-reactive protein, these drugs should be especially effective in patients with CKD. Whereas data indicate that pravastatin may prevent loss of kidney function to a greater extent in individuals with evidence of increased inflammation than in those who show no inflammation, two large, randomized statin trials in patients on hemodialysis found no benefit of statin therapy, neither in the whole study group nor after stratifying for inflammation. Irrespective of inflammation, guidelines recommend treatment of dyslipidemia in early stages of CKD, which is supported by results from recent meta-analyses, and the Study of Heart and Renal Protection (SHARP), a large, randomized, placebo-controlled trial.     

慢性阻塞性肺疾病与他汀类药物

慢性阻塞性肺疾病的关键特征是气道、肺实质与全身的慢性炎症及进行性肺功能减退,他汀类药物是一种广泛用于治疗高脂血症与预防动脉粥样硬化的有效药物,近期研究提示,他汀类药物独立于降脂作用之外的多效性如抗炎、抗氧化、抗细胞凋亡和改善血管内皮功能等效应可能对慢性肺部炎症性疾病以及增强吸入性皮质激素抗炎效应、延缓慢性阻塞性肺疾病患...     

Gastroesophageal reflux disease in noncardiac chest pain

After a cardiac source has been excluded, the most likely cause of NCCP is GERD. Clinical history often cannot make the diagnosis of GERD-related NCCP. The PPI test is a simple, highly sensitive, and cost-effective tool that should be the first diagnostic test used in evaluating these patients.Patients with GERD-related NCCP require long-term therapy with a PPI,commonly double the standard dose. The introduction of the wireless pH system and the multi-channel intraluminal impedance will help us to further understand the role of GERD in NCCP. Treatment of NCCP has dramatically improved since the introduction of the PPI class of drugs.However, better therapeutic modalities should be sought out to further improve our current treatment of GERD-related NCCP.     

Preoperative assessment of cardiac risk in noncardiac major vascular surgery

We evaluated whether a preoperative clinical algorithm allows an adequate stratification in cardiac risk and the predictive value of dipyridamole thallium-201 scintigraphy and rest echocardiography for postoperative adverse cardiac outcomes. Three hundred twenty patients undergoing 338 vascular surgery procedures were prospectively stratified into low, intermediate, and high risk. The low- and intermediate-risk patients underwent surgery without further diagnostic evaluation. In 7 high-risk patients the vascular procedure was canceled (1 died of myocardial infarction at 6-month follow-up), 9 underwent presurgical myocardial revascularization (1 died of myocardial infarction), and 49 underwent vascular surgery with perioperative intensive care treatment. Hospital mortality was 3.8%. Cardiac mortality and morbidity were 1.5% and 10.4%, respectively. We observed a significant difference in "hard" (death, myocardial infarction, pulmonary edema, major arrhythmias) and "soft" (myocardial ischemia, minor arrhythmias) events between groups, p <0.001. Previous pulmonary edema was a predictive variable of cardiac outcomes (multiple logistic regression analysis). Ninety-nine of 220 intermediate-risk patients randomly underwent dipyridamole thallium-201 scintigraphy: 37 had redistribution, 10 persistent, and 52 no defects; 7 of 13 soft and hard cardiac events occurred in patients without redistribution defects. Sensitivity, specificity, and positive and negative predictive values of redistribution defects for postoperative adverse outcomes were 38%, 63%, 14%, 87%, respectively. This algorithm may provide a safe and cost-effective approach (average cost saving per patient $1,500) to cardiac risk stratification. These results suggest that routine use of dipyridamole thallium-201 scintigraphy for screening of intermediate-risk patients may not be warranted.     

Statins differentially regulate vascular endothelial growth factor synthesis in endothelial and vascular smooth muscle cells

Objectives: HMG-CoA reductase inhibitors (statins) can modulate the formation of new blood vessels, but the reports on their contribution to angiogenesis are contradictory. Therefore, we investigated whether the effect of statins is dependent either on the concentration of the drug or on the cell type. Methods and results: Under basal conditions human vascular smooth muscle cells (HVSMC) and microvascular endothelial cells (HMEC-1) constitutively generate and release vascular endothelial growth factor (VEGF). In contrast, primary macrovascular endothelial cells (HUVEC) produce minute amounts of VEGF. Different statins (atorvastatin, simvastatin and lovastatin, 1–10 μmol/l) significantly reduced basal and cytokine-, nitric oxide- or lysophosphatidylcholine (LPC)-induced VEGF synthesis in HMEC-1 and HVSMC. Interestingly, at the same concentrations statins upregulated VEGF generation in HUVEC. Furthermore, statins exerted dual, concentration-dependent influence on angiogenic activities of HUVEC as determined by tube formation assay. At low concentrations (0.03–1 μmol/l) the pro-angiogenic activity of statins is prevalent, whereas at higher concentrations statins inhibit angiogenesis, despite increasing VEGF synthesis. Conclusion: Our data show that statins exert concentration- and cell type-dependent effects on angiogenic activity of endothelial cells and on VEGF synthesis. The data are of relevance for elucidating the differential activity of statins on angiogenesis in cardiovascular diseases and cancer.     

Statins and their use in preventing carotid disease

Carotid disease may be evaluated by surrogate outcomes, such as intima-media thickness and carotid plaque features, and by clinical end points. Statins stop progression or may induce regression of intima-media thickness, and statins may also stop plaque growth or even induce reduction of plaque volume. Areas rich in lipids within plaques may be reduced in size and/or in number of inflammatory cells. Ultrasound reflectivity may be reduced by statin treatment, indicating less lipid/inflammatory content. Finally, statins appear to reduce the risk of all cardiovascular events (eg, stroke, myocardial infarction, need for revascularization) in patients with carotid stenosis. This review summarizes and discusses the existing data.     

慢性肾脏病脂质异常的治疗及意义

血脂异常是慢性肾脏病患者的常见表现,它与慢性肾脏病的进展互为因果,共同参与慢性肾脏病高发心血管并发症和病死率。治疗中除了生活方式改变,强调他汀类药物治疗在慢性肾脏病患者血脂异常的早期治疗,副反应较一般人群无明显增加。已经看到他汀类药物治疗能够降低慢性肾脏病患者高发心血管事件和全因病死率,对降低尿蛋白和延缓肾脏病进展的益处还需要更多证据来证实。     

Statins in the spectrum of neurologic disease

Overwhelming evidence now shows that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (ie, statins) are safe and effective in primary and secondary prevention of cardiovascular disease. Atherosclerosis, the primary cause of heart disease, is directly and independently related to hypercholesterolemia and inflammation, and statins have multiple and independent effects on these conditions. New evidence for the use of statins in neurologic disease is mounting, and the range of therapeutic applications is formidable. Statins are beginning to show benefits in a wide range of neurologic conditions, from common ischemic stroke to rare congenital neurometabolic storage diseases, from acute brain injury to chronic central nervous system inflammation, and from prevention of neurodegenerative disease to acute neuroprotection. A diverse therapeutic spectrum is explained by shared pathogenetic mechanisms of neurologic disease and the manifold pharmacodynamic effects of statins.     

Statins, ACE inhibitors and ARBs in cardiovascular disease

Several trials have indicated that classical cardiovascular risk factors, including hyperlipidemia and hypertension, are not associated with a great number of acute cardiovascular events. Given the crucial role of inflammation in atherogenesis, inflammatory factors have been proposed to better define and predict acute cardiovascular events. In this promising context, treatments with lipid-lowering drugs (statins) and anti-hypertensive drugs (ACE inhibitors and ARBs) have been also investigated from an ‘anti-inflammatory’ point of view, with some encouraging results. At present, statins are recommended by the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III guidelines as the first-line choice for drug therapy lowering LDL cholesterol in high-risk patients (LDL goal <70 mg/dL, <1.8 mmol/L). In moderate-risk patients (LDL goal <100 mg/dL, <2.6 mmol/L), statin therapy is indicated mainly in metabolic syndrome and in diabetic patients. Treatment with ACE inhibitors or ARBs is recommended in both hypertension and cardiovascular diseases, particularly in diabetic patients. The use of ACE inhibitors is recommended in all patients with ST-elevation myocardial infarction with LVEF ≤40%, with normal LVEF in the presence of well-controlled cardiovascular risk factors and revascularization, hypertension, diabetes or chronic kidney disease. On the other hand, the use of ARBs is recommended in patients intolerant of ACE inhibitors or who have heart failure or hypertension. In the future, these recommendations will probably be frequently updated as the pleiotropic activities of statins, ACE inhibitors and ARB are also taken into account.