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The peripheral arterial disease (PAD) accounts for very significant medical issue in the world. Various clinical disorders due to coronary, cerebrovascular, abdominal and obliterative arteriosclerosis of extremities can be classified as the most important medical challenges. This review summarises the etiopathogenesis of this systemic problem including the function of endothelium as well as the anatomic, physiologic relevance, and major risk factors of atherosclerosis (diabetes mellitus, hypertension, obesity, smoking etc.). The first step is the dysfunction of endothelial monolayer, later on the plaques caused by humoral and cellular reactions can produce abnormal blood flow. The atherosclerosis in relation to plaque rupture with intraarterial thrombosis constitutes acute and chronic circulation disturbances and tissue damage. Diagnostic procedures are also presented regarding not only the symptomatic, but focusing on the early, asymptomatic phase of the disease, as well. By giving full details of the acute and chronic treatment the author emphasizes its basic concepts. He also points out the importance of evidence based medicine.
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PMID:[Peripheral arterial disease]. 1671 Dec 57

The effect of obesity on atherosclerotic burden and its modulation by lipid-lowering therapy is unknown. The Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) study was analyzed to determine the influence of increasing body mass index (BMI) on plasma lipids, C-reactive protein, plaque burden as determined by intravascular ultrasound, and the serial change in these parameters with a moderate or intensive lipid-lowering strategy. Patients with a higher BMI were younger, more likely to be women, and had a greater prevalence of hypertension, diabetes, and the metabolic syndrome. Although a higher BMI was associated with a lower high-density lipoprotein level and higher triglyceride and C-reactive protein levels, there was no apparent influence of BMI on plaque burden. However, with the intensive lipid-lowering strategy, a greater BMI was associated with a lower proportionate decrease in low-density lipoprotein (49.1 +/- 21.4% vs 43.0 +/- 22.4%, p = 0.008) and a greater proportionate decrease in C-reactive protein (39.7% vs 33.3%, p <0.04). Further, although moderate and intensive lipid-lowering strategies halted plaque progression in subjects with a lower BMI (median progression rates +1.5% and +1.2%, respectively), a significant effect on plaque progression rates was seen only with adoption of an intensive lipid-lowering strategy in the most obese subjects (median progression rate -1.88% vs +6.5% with the moderate lipid-lowering strategy, p = 0.01). In conclusion, plaque progression in obese patients is attenuated using an intensive, but not moderate, lipid-lowering strategy. These results highlight the need for aggressive risk factor modification and a decrease in vascular inflammation in obese patients.
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PMID:Effects of obesity on lipid-lowering, anti-inflammatory, and antiatherosclerotic benefits of atorvastatin or pravastatin in patients with coronary artery disease (from the REVERSAL Study). 1672 12

Type 2 diabetes and atherosclerotic vascular disease develop in parallel. Prospective epidemiologic studies have shown a striking communality of major risk factors for both diseases. This raises the question of a "common soil". The traits of the metabolic syndrome including dyslipidemia, visceral obesity and hypertension are predictors of type 2 diabetes as well as coronary heart disease. The same applies to the environmental factors: overnutrition, physical inertia and smoking. Visceral obesity, insulin resistance and low-grade inflammation are known as major components of the common soil for metabolic syndrome and coronary heart disease. Depending on the quality of metabolic control diabetes will accelerate the progression of atherosclerosis via unstable plaque formation. The "common soil" concept provides a paradigm for an integrated therapeutic approach. This applies to a lifestyle intervention as well as a rational use of drugs in diseases of the metabolic syndrome. The medication should consider coexisting disorders of the metabolic syndrome to use pleiotropic effects. On the other hand, side effect such as the worsening of blood glucose levels caused by beta-blockers and diuretics should be avoided. The following medication should be preferred in context of the metabolic syndrome: oral antidiabetics such as acarbose, metformin and thiazolidinediones, antihypertensives such as ACE inhibitors and ARBs (angiotensin receptor blockers) and lipid-lowering drugs such as atorvastatin, rosuvastatin, and the modern nicotinic acid derivative Niaspan, respectively. The strategy using synergies in drug treatment can reduce polypharmacy and costs and improve the patients' compliance.
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PMID:[Metabolic syndrome: "common soil" for diabetes and atherosclerosis. Novel approaches to an integrated therapy]. 1677 May 62

Cardiovascular diseases (CVDs) may have their origin before birth: the combination of being small at birth and having an overly rich post-natal diet increases the likelihood of obesity and of acquiring a specific metabolic syndrome in adulthood that carries an increased risk of CVD. The incidence of CVD and mortality is very low in women of reproductive age but rises to a significant level in older women. In this article, we discuss CVD in relation to hormonal contraception, pregnancy and polycystic ovarian syndrome (PCOS) in younger women and menopause in older women. Women with PCOS have a higher risk of diabetes and hypertension, but studies to date have not shown an effect on CVD events. Use of combined hormonal contraception has only small effects on CVD because of the low baseline incidence of myocardial infarction (MI), stroke and venous thromboembolism (VTE) among young women. Women with existing risk factors or existing CVD, however, should consider alternative contraception. In pregnancy, CVD is rare, although, in the West, it now accounts for a significant proportion of maternal mortality as the frequency of obstetrical causes of mortality has substantially declined. The frequency of VTE is 15 per 10,000 during pregnancy and the post-partum period. In older women, menopause causes a slightly higher risk of MI after allowing for age, although there is substantial heterogeneity in the results of studies on menopause and age at menopause and MI. A larger effect might have been expected, because estrogen reduces the risk of developing atherosclerosis in premenopausal women, whereas in post-menopausal women who may have established atherosclerotic disease, estrogen increases the risk of myocardial disease through the effects on plaque stability and clot formation. Recent trial results indicate that hormone treatment in menopause does not favourably affect the risk of MI, stroke or other vascular disease. Thus, prevention of CVD should rely on diet and fitness, low-dose aspirin and treatment of hypertension, hyperglycaemia and hyperlipidaemia.
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PMID:Hormones and cardiovascular health in women. 1680 76

Cardiovascular disease is associated with the aging of the population, obesity, metabolic syndrome, and diabetes. Therefore, it is important to develop non-invasive imaging systems to detect "at-risk" populations. New data suggest that contrast-enhanced ultrasound (CU) imaging of the carotid arteries enhances luminal irregularities (i.e., ulcers and plaques), improves near-wall, carotid intima-media thickness, and uniquely permits direct, real-time visualization of neovasculature of the atherosclerotic plaque and associated adventitial vasa vasorum. With continued clinical investigation, CU imaging of the carotid artery may afford an effective means to non-invasively identify atherosclerosis in "at-risk" populations while providing new standard for therapeutic monitoring.
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PMID:Contrast ultrasound imaging of the carotid artery vasa vasorum and atherosclerotic plaque neovascularization. 1684 69

Patients with peripheral vascular disease are less likely to receive optimal medical management than patients with coronary artery disease. However, early medical treatment is critical because it is profoundly beneficial and the benefits are maximized. Even in patients with advanced disease requiring invasive intervention, medical management has been proven to improve outcome, prolong the success of the intervention, improve functional capacity, and prolong life. The vascular surgeon should be knowledgeable enough to initiate basic medical therapy and to define for their patients the goals that need to be met to optimize their medical management. The vascular surgeon should be instrumental in assuring that the peripheral vascular patient receives medical therapy of the same standard as the patient with coronary disease. The major modifiable risk factors in the vascular patient are: smoking, high blood pressure, hyperlipidemia, physical inactivity, obesity, and diabetes. In addition, the use of beta blockers for patients with coronary disease and antiplatelet therapy as well as angiotensin-converting enzyme (ACE) inhibitors are recommended for all patients with peripheral vascular disease. Statins have favorable effects on multiple interrelated aspects of vascular biology important in atherosclerosis. In particular they have beneficial effects on inflammation, plaque stabilization, endothelial dysfunction, and thrombosis. Statins have also been shown to be beneficial in acute vascular events. Angiotensin-converting enzyme inhibitors have been shown to reduce cardiovascular morbidity and mortality in patients with peripheral arterial disease regardless of the presence or absence of hypertension. A number of the pleiotropic effects of statins are shared by ACE inhibitors. In summary, patients with known vascular disease should be treated aggressively with a combination of a HMG CoA reductase inhibitor, an angiotensin-converting enzyme inhibitor, an antiplatelet agent and a beta blocker if there is a history of coronary disease. They should also receive tight control of their blood pressure and blood sugar. Smokers should be encouraged to stop smoking and should be provided with pharmaceutical and emotional support by their physicians. All of these patients should have their body mass index as close to normal as possible and be on a therapeutic lifestyle diet. Regular aerobic exercise is also indicated. Patients with symptomatic claudication should be considered for cilostazol. Patients with multiple risk factors for vascular disease, but who do not have documented disease should also be on statin therapy. As more studies define the linear relationship between lower LDL-C levels and lowered risk of vascular events, indicating that the lower the LDL-C level, the lower the risk, experts are advocating more aggressive lipid-lowering therapy. In patients with peripheral arterial disease, some experts now advocate lowering the goal of LDL therapy to 70 mg/dL.
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PMID:Optimal medical management of peripheral arterial disease. 1727 51

The role of chronic inflammation causing metabolic and vascular disorders is increasingly recognized. It is hypothesized that proinflammatory cytokines contribute to atherogenesis, peripheral insulin resistance, and the development of hypertension and type II diabetes. Psoriasis as a chronic inflammatory skin disorder is characterized by a variety of immunologic and inflammatory changes and may similarly predispose for those disorders. The objective of this study was to elucidate the association of psoriasis with chronic vascular and metabolic disorders. We investigated a total of 581 adult patients hospitalised for plaque type psoriasis as compared to 1,044 hospital-based controls. A distinct pattern of chronic disorders was found to be significantly associated with psoriasis, including diabetes mellitus type II [odds ratio (OR)=2.48], arterial hypertension (OR = 3.27), hyperlipidemia (OR = 2.09), and coronary heart disease (OR = 1.95). The combined presence of these conditions together with obesity, known as the metabolic syndrome, was clearly more prevalent in psoriasis patients (OR = 5.29). In addition, psoriasis patients were significantly more likely to be smokers (OR = 2.96) and to have a regular or heavy consumption of alcohol (OR = 3.33 and 3.61, respectively). In conclusion, psoriasis patients appear to be at higher risk for diabetes mellitus and cardiovascular disease. This could likely be due to the effects of chronic inflammatory changes, in particular the secretion of proinflammatory cytokines. The risk of late term cardiovascular complications might support the use of systemic treatment in psoriasis.
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PMID:Increased prevalence of the metabolic syndrome in patients with moderate to severe psoriasis. 1702 63

Type 2 diabetes is a global epidemic contributing to significant cardiovascular morbidity and mortality. The high prevalence of cardiovascular disease can largely be attributed to the metabolic syndrome with its multiple cardiovascular risk factors, including central obesity, hypertension, glucose intolerance, chronic inflammation, and dyslipidemia. The peroxisome proliferator-activated receptor-gamma agonists, the thiazolidinediones, may potentially correct the inflammatory disarray, endothelial dysfunction, dyslipidemia, and plaque vulnerability associated with diabetic cardiovascular disease through their effects on insulin resistance and fat metabolism, yet they can also exacerbate congestive heart failure. This review summarizes basic science, animal, and human data on the effects of thiazolidinediones on cardiovascular disease.
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PMID:Are thiazolidinediones good or bad for the heart? 1707 99

A model of chronic kidney disease (CKD)-induced vascular calcification (VC) that complicates the metabolic syndrome was produced. In this model, the metabolic syndrome is characterized by severe atherosclerotic plaque formation, hypertension, type 2 diabetes, obesity, and hypercholesterolemia, and CKD stimulates calcification of the neointima and tunica media of the aorta. The CKD in this model is associated the adynamic bone disorder form of renal osteodystrophy. The VC of the model is associated with hyperphosphatemia, and control of the serum phosphorus both in this animal model and in humans has been preventive in the development of VC. This article reports studies that demonstrate reduction of established VC by the addition of sevelamer carbonate to the diets of this murine metabolic syndrome model with CKD. Sevelamer, besides normalizing the serum phosphorus, surprisingly, reversed the CKD-induced trabecular osteopenia. Sevelamer therapy increased osteoblast surfaces in the metaphyseal trabeculae of the tibia and femur. It also increased osteoid surfaces and, importantly, bone formation rates. In addition, sevelamer was found to be effective in decreasing serum cholesterol levels. These results suggest that sevelamer may have important actions in decreasing diabetic and uremic vasculopathy and that sevelamer carbonate may be capable of increasing bone formation rates that are suppressed by diabetic nephropathy.
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PMID:Reversal of the adynamic bone disorder and decreased vascular calcification in chronic kidney disease by sevelamer carbonate therapy. 1718 86

Non-alcoholic fatty liver disease (NAFLD) affects a substantial proportion of the general population and is frequently associated with many features of the metabolic syndrome (MetS). Currently, the importance of NAFLD and its relationship with the MetS is being increasingly recognized, and this has stimulated an interest in the possible role of NAFLD in the development of atherosclerosis. Recent studies have reported the association of NAFLD with multiple classical and non-classical risk factors for cardiovascular disease (CVD). Moreover, there is a strong association between the severity of liver histopathology in NAFLD patients and greater carotid artery intima-media thickness and plaque, and lower endothelial flow-mediated vasodilation (as markers of subclinical atherosclerosis) independent of obesity and other MetS components. Finally, it has recently been demonstrated that NAFLD is associated with an increased risk of all-cause death and predicts future CVD events independently of other prognostic factors, including MetS components. Overall, therefore, the evidence from these recent studies strongly emphasizes the importance of assessing the global CVD risk in patients with NAFLD. Moreover, these novel findings suggest a more complex picture and raise the possibility that NAFLD, as a component of the MetS, might not only be a marker but also an early mediator of CVD.
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PMID:Non-alcoholic fatty liver disease, the metabolic syndrome and the risk of cardiovascular disease: the plot thickens. 1722 17


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