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At least 1 in 40 people in the UK have type 2 diabetes mellitus, and the prevalence is increasing. Such people are more likely than others to develop, and to die from, cardiovascular disease. Statin therapy helps to prevent cardiovascular disease events among patients at increased risk, with or without diabetes, and is standard treatment for patients needing secondary prevention. Here we discuss whether statins should be used routinely for primary prevention of cardiovascular disease in patients with type 2 diabetes irrespective of other risk factors.
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PMID:Statins for primary prevention in type 2 diabetes. 1690 86

This analysis of the Ezetimibe Add-on to Statin for Effectiveness (EASE) trial examined the effectiveness and safety of ezetimibe 10 mg added to ongoing statin therapy in patients with diabetes, metabolic syndrome without diabetes, or neither disorder who had low-density lipoprotein cholesterol (LDL-C) levels exceeding National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) goals. After six weeks of treatment, ezetimibe added to statin reduced LDL-C in patients with diabetes by 28%, metabolic syndrome by 24%, or neither by 26%, compared with a 3% reduction for placebo for each group. In each group, more patients receiving ezetimibe plus statin reached LDL-C goal (67-74%) compared with those receiving placebo plus statin (19-22%). Other parameters demonstrating greater improvement with ezetimibe included triglycerides, apolipoprotein (Apo)B/Apo A-I ratio, high-density lipoprotein cholesterol (HDL-C), and C-reactive protein. Ezetimibe plus statin was well tolerated in each group. Ezetimibe added to ongoing statin therapy offers a new treatment option that is consistently effective in improvement of lipid profiles and attainment of LDL-C goals in patients with without diabetes or metabolic syndrome.
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PMID:Ezetimibe added to ongoing statin therapy improves LDL-C goal attainment and lipid profile in patients with diabetes or metabolic syndrome. 1705 29

Statins have been described as miracle drugs, but such "beatification" is not justified. Changes in lifestyle should be considered the cornerstone in cardiovascular prevention. However, trends in mortality from coronary heart disease have not effectively changed since statins were approved in the United States, while obesity has risen significantly. Have these drugs contributed to a deterioration in lifestyle among those who believe a pill will protect them? Adherence to healthful lifestyle has been shown to be associated with reductions in the rates of coronary disease, diabetes in women, and mortality in elderly. Patients with major lifestyle problems enrolled in recent statin trials were given only drugs, and no statin has ever been compared with a nonatherogenic lifestyle and shown to be superior or additive. Furthermore, there is no evidence for a total mortality benefit in women and elderly persons from dyslipidemia therapy. Side effects are often presented as relative, not absolute risk, and are suggested to be low. However, there is reason to believe that their numbers are much larger in clinical practice where the drugs may be given to most patients usually excluded in randomised trials. Statin-related side effects may be considered as a complication to the primary disease. However, these complaints may be statin therapy related. Finally, the relationship between long-standing statin therapy and cancerogenesis is not fully understood. Investigators should carefully resist the natural tendency to highlight the most positive findings in their studies while minimising harm, especially when commercially sponsored.
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PMID:Questioning the "beatification" of statins. 1732 Feb 17

Peripheral arterial disease (PAD) is strongly associated with atherosclerosis in the coronary and carotid arteries, leading to a highly increased incidence of myocardial infarction, ischaemic stroke and cardiovascular death. Fortunately, pharmacological interventions in large clinical trials have been as effective in subgroups of patients with PAD as in subjects with other atherosclerotic disease. Antiplatelet treatment is indicated in virtually all patients with PAD. Aspirin 75-325 mg day(-1) is considered as first-line treatment, and clopidogrel 75 mg day(-1) is an effective alternative. Statin therapy is indicated to achieve a target low-density lipoprotein cholesterol level of < or = 2.5 mmol L(-1) in patients with PAD and there is emerging evidence that even lower levels are beneficial. Lowering of plasma homocysteine by supplementing folic acid, vitamin B(12) and vitamin B(6) is not recommended in patients with mild to moderate hyperhomocysteinaemia in the 12-25 micromol L(-1) range, since it does not reduce the incidence of cardiovascular events. Antihypertensive treatment is indicated to achieve a goal blood pressure of < or = 140/90 mmHg or < or = 130/80 mmHg in the presence of diabetes or chronic kidney disease. All classes of antihypertensive drugs are acceptable for treatment of hypertension in patients with PAD, but angiotensin-converting enzyme inhibitors ramipril or perindopril are especially appropriate because they reduce the incidence of cardiovascular events beyond their blood pressure-lowering effects. Beta-blockers should not be used as first-line antihypertensive treatment. Diabetic patients with PAD should reduce their glycosylated haemoglobin to < or = 7%. In conclusion, pharmacological secondary prevention of cardiovascular morbidity and mortality in patients with PAD should be as comprehensive as that in patients with established coronary or cerebrovascular disease.
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PMID:Pharmacological prevention of atherothrombotic events in patients with peripheral arterial disease. 1735 82

There is increasing evidence that statins reduce cardiovascular events such as coronary artery disease or stroke in hypercholesterolemic patients in both primary and secondary prevention. The striking benefit achieved with statin treatments in patients with a wide range of cholesterol levels cannot be attributed to their cholesterol lowering effect alone. Substantial data has recently accumulated showing that statins exert various effects on multiple targets, namely pleiotropic effects, especially targeting the concept of 'vascular failure', including the improvement of vascular endothelial function, inhibition of vascular smooth muscle cell proliferation and migration, anti-inflammatory actions, anti-oxidative effects or stabilization of vulnerable plaques. These effects have potential in the treatments of coronary artery disease in various settings, such as prevention of its onset as well as its progression, or plaque rupture. Statin therapy should be more extensively applied even in normolipidemic patients if there are additional risk factors such as hypertension, diabetes mellitus, or others. Furthermore, statins may be used to intervene in earlier stage risk conditions such as postprandial hyperlipidemia or hyperglycemia, insulin resistant state, masked hypertension, or metabolic syndrome to further reduce mortality or morbidity of coronary artery disease and heart failure.
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PMID:Statin therapy for vascular failure. 1768 28

Graft surveillance aims to identify those grafts that are at risk of failure as intervention in a patent but failing graft results in improved long-term patency and limb salvage rates compared to rescue of an occluded graft. Controversy exists as to which types of graft benefit the most from surveillance and whether patient factors such as diabetes and smoking status have an effect on graft survival. Our aims were (1) to clarify the natural history of midterm graft failure as a consequence of myointimal hyperplasia and (2) to identify which patients and grafts are at a higher risk of failure and at what time points this is most prevalent. Serial vascular laboratory and clinical data of 212 infrainguinal lower limb grafts in 197 patients were analyzed. Follow-up within the surveillance program was by focused examination with color flow duplex ultrasound at 0, 1, 3, 6, 12, and 18 months with respect to surgery. Outcomes were correlated with retrospectively collected data regarding patient demographics, smoking status, concurrent medication, comorbidity, and operative factors such as distal target vessel and conduit. During the program, 21.6% of grafts occluded. Overall, 16% of grafts underwent a salvage procedure, 40.5% of which were carried out at the 6-month time point. There were 56.6% of occlusions preceded by a stenotic lesion. Primary occlusions accounted for 95.9% in the prosthetic group and 66.5% in the femorocrural group. As a group, vein grafts were more likely to develop a progressive stenosis prior to occlusion, with 58.3% in this group predated by a stenotic lesion. Fewer than 75% of stenoses were common and had a variable natural history, with over 40% resolving or failing to progress. Throughout the study period, 56.2% of grafts remained stenosis-free. Stenoses were more common at the proximal anastomosis in the vein graft cohort. There were low rates of significant stenoses within the prosthetic group. These lesions were more likely to occur at the distal anastomosis but were poor predictors of occlusion. Statin use postoperatively was protective against the development of significant stenosis and occlusions, particularly in the above-knee grafts (p = 0.03). Surprisingly, preoperative smoking status was predictive of neither occlusion nor development of significant stenosis. The presence of diabetes was not predictive of poor outcome. Our findings suggest that graft surveillance is a valid method for detecting the presence of significant stenoses in vein grafts at high risk of failure without intervention. Despite the intensive follow-up, the program failed to detect lesions prior to occlusion in a large percentage of prosthetic and femorocrural grafts, so perhaps this group is poorly served by graft surveillance.
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PMID:The natural history of stenoses within lower limb arterial bypass grafts using a graft surveillance program. 1798 Jul 93

Statin therapy for aggressive low-density lipoprotein cholesterol (LDL-C) reduction reduces cardiovascular morbidity and mortality. However, even on maximal statin therapy, high-risk patients have substantial residual risk of coronary heart disease (CHD). Certain subgroups, such as individuals with diabetes mellitus, low high-density lipoprotein cholesterol (HDL-C), metabolic syndrome, or other comorbidities, have a particularly high residual risk. Patients at high risk for future CHD events often require multiple aggressive risk-reduction therapies (eg, antiplatelet agents, an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, beta-blockade, cholesterol and/or diabetes management, and lifestyle interventions) to further lower their overall cardiovascular risk. For cholesterol management, combination therapy may be required to attain optimal levels of LDL-C, HDL-C, and non-HDL-C.
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PMID:Residual risk in statin-treated patients: future therapeutic options. 1799 76

Statin treatment markedly reduces the incidence of acute coronary events in patients with coronary atherosclerosis. Although imaging studies have indirectly shown the beneficial effects of statins on plaque morphology, there has to our knowledge been no reported histologic comparison of the morphology of coronary plaque in statin-treated versus untreated patients who had substantial coronary artery atherosclerosis. We retrospectively studied arterial sections from the native hearts of patients who had experienced end-stage ischemic heart disease and subsequent cardiac transplantation. Of 44 qualified patients, 33 study patients had received pre-transplantation statin therapy, and 11 control patients had not. Pathologic examination of each explanted heart confirmed coronary artery disease and previous myocardial infarction in all patients. Diabetes mellitus was more prevalent in the study group. The groups were similar in levels of total and low-density lipoprotein cholesterol, and in the available number of arterial cross-sections per patient. All patients had plaques. High-grade lesions were found in 66.3% of cross-sections in the control group, and in 34.6% in the study group (P=0.011). Conversely, the degree of inflammation was markedly lower in the study group: low-grade fibrous plaques occurred in 45.7% of cross-sections in the study group, versus 11.3% in the control group (P=0.006). The study group had significantly fewer high-grade plaques and more fibrous plaques than did the control group at the time of transplantation. Our findings show that statin therapy substantially enhances plaque stabilization. We further suggest that reduction of plaque inflammation is an important aspect of this stabilization.
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PMID:Statins improve human coronary atherosclerotic plaque morphology. 1861 39

The prevalence of type 2 diabetes mellitus continues to increase rapidly. Persons with diabetes face a 2-fold greater absolute risk of cardiovascular disease (CVD) than those without diabetes. Many diabetic patients die before reaching the hospital after a cardiovascular event. Use of statin therapy for intensive control of diabetic dyslipidemia has produced relative reductions in CVD risk of about 25% in randomized, controlled clinical trials. This is true even though low-density lipoprotein cholesterol, the primary target of statin therapy, might not be markedly elevated in diabetic patients. Most patients with diabetes or diabetes plus established CVD warrant intensive statin therapy. Statin therapy has the ability to achieve low-density lipoprotein cholesterol goals recommended in treatment guidelines. Alone or in combination with an additional lipid-lowering drug, statins may also improve triglyceride and high-density lipoprotein cholesterol abnormalities in patients with diabetes.
Diabetes Educ
PMID:Do people with diabetes need statins? 1866 8

Atherothrombosis of the coronary and cerebral vessels is understood to be a disorder of inflammation and innate immunity, as well as a disorder of lipid accumulation. From a vascular biology perspective, the processes of cellular adhesion, monocyte and macrophage attachment, and transmigration of immune cells across the endothelium are crucial steps in early atherogenesis and in the later stages of mature plaque rupture, particularly the transition of unstable plaque at the time of acute thrombosis. There is abundant clinical evidence demonstrating that many biomarkers of inflammation are elevated years in advance of first ever myocardial infarction (MI) or thrombotic stroke and that these same biomarkers are highly predictive of recurrent MI, recurrent stroke, diabetes, and cardiovascular death. In daily practice, the inflammatory biomarker in widest use is high-sensitivity C-reactive protein (hsCRP); when interpreted within the context of usual risk factors, levels of hsCRP <1, 1 to 3, and >3 mg/l denote lower, average, and higher relative risk for future vascular events. Risk-prediction models that incorporate hsCRP, such as the Reynolds Risk Score, have been developed that improve risk classification and the accuracy for global risk prediction, particularly for those deemed at "intermediate risk" by usual algorithms, such as the Framingham Risk Score. With regard to cerebral vessels, increased biomarkers of inflammation, including hsCRP, have been associated with increased stroke risk as well as an increased rate of atherosclerosis progression in the carotid vessels. Although the proportion of variation in hsCRP explained by genetic factors may be as large as 20% to 40%, diet, exercise, and smoking cessation remain critical tools for risk reduction and CRP reduction. Statin therapy reduces hsCRP in a largely low-density lipoprotein (LDL)-independent manner, and the "anti-inflammatory" properties of these agents have been suggested as a potential mechanism beyond LDL reduction for the efficacy of these agents. The ongoing multinational Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial of 17,802 initially healthy men and women with low levels of LDL cholesterol but increased levels of hsCRP will help to define whether vascular protection can be achieved with statin therapy, even in the absence of hyperlipidemia. Targeted anti-inflammatory therapies are being developed that may provide a direct method of translating the biology of inflammation into new clinical treatments across multiple vascular beds. This article summarizes data supporting a role for inflammation in cardiovascular disease and offers the possibility that other disorders characterized by inflammation, such as periodontal disease, may have an indirect role by influencing the risk, manifestation, and progression of vascular events.
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PMID:Inflammation, C-reactive protein, and atherothrombosis. 1867 9


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