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Calciphylaxis is a confusing disease process that affects people with end-stage renal disease. The prognosis of this increasingly common condition is poor and mortality rates range from 60% to 80% related to wound infection, sepsis, and organ failure. Its presenting sign is skin necrosis related to calcification of the arteriole microvasculature. The disease is painful and debilitating, particularly due to the necrotic wounds. Aggressive wound care to prevent infection is vital when eschar does not protect the wound and drainage is present, but debridement is contraindicated for wounds covered with dry, noninfected eschars. The decision to debride is based on the patient's total clinical picture. Patients with calciphylaxis have poor healing potential due to ischemia and comorbidity factors such as diabetes mellitus, peripheral vascular disease, and obesity. The goal of care is prevention of infection and pain management. Some of the sensitizers and challengers responsible for the chemical imbalance leading to the arteriole calcification, as well as risk factors and clinical manifestations of calciphylaxis, are reviewed. A discussion of treatment focuses on wound care of stable necrotic ulcers and a case report illustrating the progression of calciphylaxis is presented.
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PMID:Mysterious calciphylaxis: wounds with eschar--to debride or not to debride? 1525 2

The number of people with diabetes grows worldwide. The complications resulting from this disease are a significant cause of morbidity and mortality. World Health Organization estimates that, while in the year 2000 the number of people with diabetes was about 177 million, by 2025, this will increase to at least 300 million. The diabetes epidemic, without primary prevention, will continue to grow. Individuals with type 2 diabetes are at a significantly higher risk for coronary heart disease, peripheral vascular disease, and stroke, and they have a greater probability of having hypertension, dyslipidemia, and obesity. A number of clinical trials provide evidences that RAAS inhibition could be helpful at preventing new onset of type 2 diabetes mellitus. Pharmacologic treatment that antagonize the renin-angiotensin system (RAS) provide more benefits, not only in patients after myocardial infarction and in congestive heart failure, but also in persons with hypertension and type 2 diabetes mellitus.
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PMID:Renin-Angiotensin-Aldosterone system inhibition in prevention of diabetes mellitus. 1552 18

Hyperlipidaemia is a pivotal risk factor for the development of atherosclerotic disease. A large number of studies have demonstrated that the treatment of abnormalities in lipoprotein levels reduces the risk for myocardial infarction, peripheral vascular disease, carotid artery disease, stroke, and cardiovascular mortality. Despite the development of multiple drug classes to treat dyslipidaemias and the promulgation of clearly defined guidelines for the management of lipid disorders, dyslipidaemia tends to be undertreated in the majority of patients at risk for cardiovascular disease. A part of the reluctance to treat different lipoprotein fractions to goal levels is attributable to physician- and patient-related concerns over the increasing toxicity of available therapies, as their dosages are increased. The risks of hepatotoxicity, myalgia, and rhabdomyolysis are fairly well characterised in patients receiving statins, fibrates and niacin. Another issue affecting treatment success rates is the fact that many patients with complex dyslipidaemias are inadequately responsive to single-agent therapy. As the epidemics of obesity, metabolic syndrome and diabetes mellitus continue to worsen, physicians will encounter severe, mixed dyslipidaemias more frequently. Many of these patients will require combinations of drugs to address the various metabolic derangements causing changes in multiple lipoprotein fractions. Although the need for combination therapy is well-established in the management of disorders, such as hypertension and diabetes, it is less often used for the treatment of dyslipidaemias. The development of safe, cost-effective, and efficacious combination dyslipidaemic therapy is an important goal in cardiovascular medicine. Simvastatin plus ezetimibe has recently been combined as a fixed dose therapy, which offers clinicians the opportunity to simultaneously inhibit two key pathways in cholesterol metabolism: hepatic cholesterol biosynthesis and the absorption of cholesterol at the level of the proximal jejunum. This dual mechanism of inhibition substantially increases the capacity to decrease serum levels of atherogenic low-density lipoproteins and increase high-density lipoprotein, compared with that observed when either drug is used alone. This combination increases the likelihood of therapeutic success in patients with dyslipidaemia.
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PMID:Simvastatin plus ezetimibe: combination therapy for the management of dyslipidaemia. 1570 90

Peripheral vascular disease (PVD) is very prevalent in the United States and is part of a global vascular problem. PVD patients have a heightened inflammatory state and are at high risk of death from acute cardiovascular problems rather than from progression of PVD. Modifiable risk factors for PVD include smoking, hypertension, diabetes, hyperlipidemia, elevated high sensitivity C-reactive protein, obesity, and the metabolic syndrome. Symptomatic treatment of claudication includes smoking cessation, exercise, cilostazol, statins, and revascularization with percutaneous or surgical therapy. Antithrombotic therapy with aspirin or clopidogrel is important to reduce cardiovascular events but does not affect symptoms of claudication. Patients with rest limb ischemia or ulceration should be revascularized to minimize the chance of limb loss. Percutaneous revascularization is not without significant complications, however, and future research needs to focus on inflammation, thrombosis, and restenosis in the PVD patient. Finally, new devices that tackle difficult lesions, drug-eluting stents, and pharmacologic agents that reduce global atherosclerosis are on the horizon and are likely to become critical components in the management of the PVD patient.
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PMID:Evidence-based management of peripheral vascular disease. 1610 78

Insufficient blood flow through end-resistance arteries leads to symptoms associated with peripheral vascular disease. This may be caused in part by poor macrocirculatory inflow or impaired microcirculatory function. Dysfunction of the microcirculation occurs in a similar fashion in multiple tissue beds long before the onset of atherosclerotic symptoms. Impaired microcirculatory vasodilatation has been shown to occur in certain disease states including peripheral vascular disease, diabetes mellitus, hypercholesterolemia, hypertension, chronic renal failure, abdominal aortic aneurysmal disease, and venous insufficiency, as well as in menopause, advanced age, and obesity. Microcirculatory structure and function can be evaluated with transcutaneous oxygen, pulp skin flow, iontophoresis, and capillaroscopy. We discuss the importance of the microcirculation, investigative methods for evaluating its function, and clinical applications and review the literature of the microcirculation in these different states.
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PMID:Evaluation of the microcirculation in vascular disease. 1617 12

The Cochrane Collaboration provides growing and readily accessible resources to help ensure that medical decision-making is based on detailed, methodical, and up-to-date reviews of the best available evidence. We analyzed systematic reviews in the field of pediatric cardiology published by the Cochrane Collaboration's 50 Collaborative Review Groups. We found a total of 20 systematic reviews: 13 published by the Cochrane Neonatal Group, 6 by the Cochrane Heart Group, and 1 by the Cochrane Peripheral Vascular Disease Group. Systematic reviews in pediatric cardiology appear infrequently. They only concern evidence-based decision-making in the therapeutic management of patent ductus arteriosus and arterial hypotension in preterm infants, and in the management of children with Kawasaki disease. The quality of the clinical trials contained in the systematic reviews of acute rheumatic fever or obesity in children is limited. Consequently, the reviewers' conclusions provide an inadequate basis for inferring probable effects in clinical practice. In pediatric cardiology, many therapies continue to be used without supportive evidence. We found no systematic reviews of important cardiologic topics in childhood such as heart failure, shock, hypertension, congenital cardiopathy, and arrhythmia. Clinical practice guidelines complement systematic reviews, which can recommend only strategies that are supported by strong evidence or suggest further research when scientific evidence is inadequate.
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PMID:[Usefulness of Cochrane Collaboration for pediatric cardiology]. 1618 20

Fifty type 2 diabetes patients (25 of them being hypertensive) who had no cardiac symptoms had their left ventricular function assessed. There were 24 female and 26 male diabetes patients evaluated, along with a control group of 50 healthy subjects. The patients and controls underwent full clinical evaluation, which included physical examination, blood biochemistry (urea and electrolyte; creatinine, creatinine clearance; fasting blood and two-hour postprandial glucose levels, lipid profile), electrocardiograph, chest radiograph, and echocardiograph. The hypertensive diabetes patients had higher cholesterol levels, and 50% had levels >5.0 mmol/L. Sixteen patients had cataracts, 14 had background retinopathy, 12 had peripheral neuropathy, and 7 had peripheral vascular disease. The subjects had significantly lower ejection fraction than controls, and fractional shortening showed a similar pattern. Eight patients had ejection fraction <50% compared to none of the controls. Sixty-six percent of the subjects and 30% of the controls had diastolic dysfunction (reverse E/A ratio, prolonged deceleration time, and lower deceleration rate), respectively, but the diabetes patients did not show any difference. Diastolic dysfunction correlated significantly with age, fasting blood glucose, and two-hour postprandial glucose. The subjects had higher left ventricular mass (LVM) than controls. The LVM correlated significantly positively with diastolic blood pressure, systolic blood pressure, and pulse pressure. Subclinical diabetic cardiomyopathy exists in our patients; in addition, other risk factors for cardiomyopathy and coronary artery disease exist, including hypertension, hypercholesterolemia, and obesity.
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PMID:Left ventricular function in type 2 diabetes patients without cardiac symptoms in Zaria, Nigeria. 1626 87

Diabetes (particularly type 2 diabetes) represents a global health problem of epidemic proportions. Individuals with diabetes are not only more likely to develop hypertension, dyslipidemia, and obesity, but are also at a significantly higher risk for coronary heart disease, peripheral vascular disease, and stroke. Angiotensin II plays a key pathophysiological role in the progression of diabetic renal disease, and blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II antagonists has therefore become an important therapeutic strategy to reduce renal and cardiovascular events in patients with diabetes. Several studies have demonstrated the effects of angiotensin II antagonists on the reduction of albuminuria and the progression of renal disease from microalbuminuria to macroalbuminuria. More importantly, several endpoint trials have shown that the antiproteinuric effects of losartan and irbesartan translate into cardiovascular and renoprotective benefits beyond blood pressure lowering, thereby delaying the need for dialysis or kidney transplantation by several years. These and other studies indicate that angiotensin II antagonists not only improve survival and quality of life of patients with diabetic nephropathy, but also have the potential to reduce the substantial healthcare burden associated with managing these patients. ACEi also appear to exert similar beneficial effects in diabetic patients, but whether clinically significant differences in renoprotection or mortality exist between angiotensin II antagonists and ACEi in patients with type 2 diabetes remains to be fully investigated in appropriate head-to-head studies.
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PMID:Blockade of the renin-angiotensin-aldosterone system: a key therapeutic strategy to reduce renal and cardiovascular events in patients with diabetes. 1633 Oct 93

Patients with acute coronary syndromes (ACSs) may develop serious multiorgan complications and require prolonged intensive care. Our aim was to characterize and identify factors that are associated with outcomes in these patients. We retrospectively identified 267 consecutive patients admitted to the coronary care unit for an ACS who required >3 days of mechanical ventilation. Multiple clinical and laboratory variables were correlated with mortality. Patients' ages were 68.3 +/- 10.9 years (mean +/- SD) and 165 (62%) were men. Seventy-six patients (29%) died within 30 days of admission, and the 1 year mortality was 46%. Moderate or severe left ventricular systolic dysfunction was found in 72% of the patients. Eighty-nine patients (33.3%) required vasopressors, of whom 64 (72%) did not survive 30 days. Among 127 patients who required antibiotics (48.3%), 30-day mortality was 53% compared with 4% among patients who did not require antibiotics (p <0.001). The 30-day mortality among patients who received both antibiotics and vasopressors was 64 of 87 patients (74%), and the 1-year mortality in this subgroup was 86.2%. Parameters found to be independent predictors of 30-day mortality were (in descending order): vasopressor requirement, use of antibiotics, peripheral vascular disease, ST-elevation myocardial infarction, renal failure, obesity and Killip class on admission. In conclusion, mortality among patients who require prolonged mechanical ventilation after an ACS is substantial. The main independent predictors of with mortality are the severity of heart failure and the presence of co-morbidities.
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PMID:Clinical characteristics and prognostic factors in patients with complicated acute coronary syndromes requiring prolonged mechanical ventilation. 1636 Mar 51

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


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