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There is growing evidence that increased plasma concentrations of CRP strongly predict cardiovascular death in both non-renal and renal patient populations. The interleukin-6 (IL-6) system activity, which is the major mediator of the acute phase response, is often markedly up-regulated in uremic patients and has also been shown to predict outcome. This raises the issue of whether or not IL-6 per se may contribute to increased mortality from malnutrition and atherosclerotic cardiovascular disease in uremic patients. The causes of elevated IL-6 levels in the uremic circulation are not fully understood, although a number of factors prevalent in uremic patients, such as hypertension, adiposity, infections, and chronic heart failure may all contribute. However, factors associated with the dialysis procedure, such as bioincompatibility and non-sterile dialysate, may stimulate IL-6 production. Furthermore, available evidence suggests that genetic factors may also have an impact on circulating plasma IL-6 levels. We advance the hypothesis that IL-6 may play a central role in the genesis of inflammatory-driven malnutrition and that it may be regarded as a significant proatherogenic cytokine. This hypothesis may provide a rationale to test if targeted anti-cytokine therapy may be one way to combat the unacceptable high cardiovascular mortality rate among dialysis patients.
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PMID:Mortality, malnutrition, and atherosclerosis in ESRD: what is the role of interleukin-6? 1198 23

Pathogenesis of the atherosclerotic process is deemed as multifactorial. To the most important risk factors, besides certain family predisposition, there belongs hypercholesterolemia, arterial hypertension, obesity, diabetes mellitus, smoking and others. In the last years there are more and more data about the role of inflammation and infection in the whole development of atherosclerosis. The witness for this hypothesis is the findings of high parameters of inflammation in involved vessels as well as in the blood of atherosclerosis suffering persons. Opinions about the inflammation theory appear from the 90th. Local sterile inflammation in the subendotelium of the middle and big arteries has been proved to consist of specific immune reaction (activation of the T-lymphocytes) as well as nonspecific characteristic by elevated monocytes in the artery wall during the whole process of atherogenesis. Inflammation in the plaque can trigger and hold several factors engaged in the atherosclerotic process, such as oxidized LDL cholesterol, elevated production of various superoxides, activated macrophages, activated T-lymphocytes, cytokines (IL-1, IL-6, interferon gamma) and lipoprotein Lp (a). In this inflammation process levels of CRP (acute phase protein), fibrinogen and erythrocyte sedimentation are elevated as a reaction of the organism to nonspecific chronic infections. Because of this it is thought that elevated fibrinogen and erythrocyte sedimentation are markers of the cardiovascular risk. Some papers deal with antiinflammatory effects of statins, because these lower CRP levels so they also lower atherosclerotic risk through not only lowering of cholesterol levels. Also asprine, as an antiinflammation agent, changing the CRP levels, would be of benefit for patients with vascular disease because its antiaggregation and antiinflammatory effects. ACE inhibitors are also antiinflamatory through blocking of tissue production of angiotensin II (artery wall and atherosclerotic plaque). Enzymatic inhibitors changing angiotensin can also have a partial antiinflammatory effect. The infection theory is supported also by tracing of some microorganisms in the atherosclerotic plaque or in the blood, as e.g. Helicobacter pylori or Chlamydia pneumoniae; to the autoimmune origin is indicated the presence of the specific immunity reaction against heat shock proteins (HSP) or oxidized LDL. This infection theory offers new therapy possibilities. Therefore eradication for example by antibiotics can lead to stabilization of the atherosclerotic plaque with positive consequences, as it was discovered by many studies.
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PMID:[The role of infection and inflammation in the pathogenesis of atherosclerosis]. 1219 10

Coronary artery disease is common in diabetic patients and remains the major cause of death in these patients. However myocardial ischaemia resulting from coronary lesions does not always give rise to symptoms. The managing physician must therefore consider the benefit of screening for silent myocardial ischaemia in diabetic patients. Screening all diabetic patients is not recommended. The challenge to the physician is to select the patient subgroups likely to benefit from screening. Patients with more than one cardiac risk factor (dyslipidaemia, hypertension, smoking, family history, micro-albuminuria) in addition to diabetes, as well as patients with established macrovascular disease, e.g. peripheral vascular disease, will benefit most from screening. A standard treadmill stress ECG is the recommended screening test. A number of additional tests have been proposed to select high-risk patients for screening. Of these, testing for microalbuminuria and elevated CRP levels are most likely to influence decision-making. Once silent ischaemia has been detected in a diabetic patient, the mainstay of treatment remains the aggressive control of risk factors, improvement of glycaemic control and aspirin therapy. The use of beta-blockers and ACE-inhibitors often need consideration. The attending physician must then consider referring the patient to a cardiologist for angiography and possible intervention. This decision is based on the presence of poor prognostic signs during the stress ECG and the number of risk factors present. Microalbuminuria and elevated CRP levels are helpful in assisting with the risk stratification process.
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PMID:Managing the asymptomatic diabetic patient with silent myocardial ischaemia. 1238 62

The prevalence of marked obesity is increasing rapidly among adults and has more than doubled in 10 years. Sixty-one percent of the adult population of the United States is overweight or obese. Americans are the fattest people on earth. Paradoxically these increases in the numbers of persons who are obese or overweight have occurred during recent years when Americans have been preoccupied with numerous dietary programs, diet products, weight control, health clubs, home exercise equipment, and physical fitness videos, each "guaranteed" to bring rapid results. Overweight and obesity are also world problems. The World Health Organization estimates that 1 billion people around the world are now overweight or obese. Westernization of diets has been part of the problem. Fruits, vegetables, and whole grains are being replaced by readily accessible foods high in saturated fat, sugar, and refined carbohydrates. Since class 3 obesity (morbid or extreme obesity) is associated with the most severe health complications, the incidence of hypertension, stroke, heart disease, diabetes, and peripheral vascular disease will increase substantially in the future. Recently, obesity alone has been implicated in the development of cardiac hypertrophy and CHF. The metabolic syndrome associated with abdominal obesity, which includes insulin resistance, dyslipidemia, and elevated CRP levels, identifies subjects who have an increase in cardiovascular morbidity and mortality. Twenty to 25% of the adult population in the United States have the metabolic syndrome, and in some older groups this prevalence approaches 50%. The prevalence of overweight children in the United States has also been increasing dramatically, especially among non-Hispanic blacks and Mexican-American adolescents. Overweight children usually become overweight adults. Atherosclerosis begins in childhood. The degree of atherosclerotic changes in children and young adults can be correlated with the presence of the same risk factors seen in adults. As health providers, our direction is obvious!
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PMID:Obesity and the metabolic syndrome. 1262 76

Arteriosclerosis, atherosclerosis and vascular calcification are causally related to the high morbidity and mortality of patients with chronic renal failure. Oxidative stress and carbonyl stress of uremia, dialysis procedure and/or intravenous iron therapy result in AGE (advanced glycation end-product), ALE (advanced lipoxidation end-product) and AOPP (advanced oxidation protein product) formation, favouring together with elevated CRP (C-reactive protein) levels the development of cardiovascular and cerebrovascular complications. Enhanced plasma levels of homocysteine and ADMA (asymmetric dimethylarginine) contribute to this process. In addition, in chronic renal insufficiency hyperphosphatemia and an enhanced calcium x phosphorus ion product are associated with the morbidity and mortality of the patients, particularly in the presence of fetuin deficiency. Phosphorus, AGEs and AOPPs, beside other factors, catalyze the conversion of vascular smooth muscle cells to osteoblast--like cells (particularly in the presence of monocytes/macrophages), resulting in bone matrix protein formation. Other risk factors, such as age, male sex, smoking, hypertension, diabetes, chronic inflammation, insulin resistance or dyslipidemia (enhanced non-HDL-cholesterol) also contribute to the atherosclerotic risk profile of the patient with chronic renal insufficiency. While there is growing understanding of the mechanisms involved in arteriosclerosis, atherosclerosis and vascular calcification in uremia, we are still missing effective therapeutic maneuvers for reduction of excess mortality in uremic patients.
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PMID:[Atherosclerosis and uremia: signifance of non-traditional risk factors]. 1277 74

Current topics and new developments in risk factors for ischemic stroke were reviewed. Hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation, cigarrette smoking, and heavy alcohol drinking have been established as being common treatable risk factors for stroke. Recent studies have clarified that homocysteine, various cardiac sources of embolism such as patent foramen ovale, antiphopholipid antibodies, lipoprotein (Lp) abnormalities including Lp(a) and remnant-like particle, insulin resistance or hyperinsulinemia, infectious diseases such as Chlamydia Pneumoniae, and CRP are additional risk factors for stroke. In addition, genetic studies using single nucleotide polymorphisms have suggested that many gene polymorphisms are significant risk factors for certain subpopulations of stroke, which is recognized to be a polygenic disease. Management of these risk factors is crucial for primary prevention of stroke, which is the leading cause of death or disability all over the developed countries.
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PMID:[Risk factors for cerebral infarction: current topics and new developments]. 1278 67

A 41-year-old man was admitted to our hospital suffering from generalized convulsion with a high fever and disturbed consciousness one week after exhibiting flu-like symptoms. We made a diagnosis of acute viral encephalitis, based on the clinical features and the evidence of pleocytosis with an increase in protein in the CSF. On admission, MRI was normal and CRP was negative. The levels of transaminase, ammonia, and blood sugar were normal, so that an adult Reye's syndrome could be ruled out. Herpes simplex encephalitis and influenza encephalopathy were also ruled out because of viral examinations, and specific agents could not be determined. Clinical symptoms subsided once after he was treated with dexamethasone, acyclovir, and anti-convulsants, until generalized convulsion accompanied by a high fever again occurred on the 9th day. On the 18th day, the patient showed anisocoria and ataxic respiration due to severe brain edema. Mild hypothermia therapy to rectal temperature 35 degrees C was induced under mechanical ventilation. Cranial CT taken 3 days after the therapy began to show the improvement of the brain edema. After 7 days of the therapy, his clinical symptoms began to recover dramatically. On the 46th day, he was discharged from hospital without showing almost any neurological symptoms. Mild hypothermia therapy should be considered for adult patients as well as non-adult patients suffering from acute encephalitis with severe intracranial hypertension.
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PMID:[Successful use of mild hypothermia therapy in an adult patient of non-herpetic acute encephalitis with severe intracranial hypertension]. 1283 82

Advantages and risks related to the use of selective COX-2 inhibitors when treating arthritis are currently being scrutinized by authorities and public. The discussion tends towards exaggerated claims for or against their usefulness. The issue of cardiovascular safety is still not finally settled. In an experimental study using patients with severe coronary disease, administration of celecoxib resulted in improved endothelial function together with reduced CRP levels. Gastrointestinal tolerance was studied in patients who had recently recovered from peptic ulcer bleeding. In this group of high risk patients, celecoxib was as safe as combined therapy using omeprazol and diclofenac when given for 6 months. However, both COX inhibitors caused hypertension and adverse renal effects. The second generation of selective inhibitors is being launched. Etoricoxib--related to rofecoxib--was shown to be as potent as indomethacin in the treatment of acute gout, but it caused fewer adverse reactions. In general, however, any advantage of second generation as compared to first generation COX-2 inhibitors remains to be proven. The Swedish Council on Technology Assessment in Health Care, in its "SBU Alert", has published an appraisal of celecoxib and rofecoxib, in which the need for further long-term safety studies is emphasized.
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PMID:[New studies of COX-inhibitors, yet issues remain]. 1455 11

Infection with Chlamydia pneumoniae has been suggested to play a role in the development and maintenance of atherosclerosis based on differences in the prevalence of antibodies against Chlamydia pneumoniae in patients with and without atherosclerotic lesions. We evaluated the prevalence of Chlamydia pneumoniae DNA in the white cells of the peripheral blood in 194 patients with diabetes mellitus, 50 patients with acute coronary syndrome, 102 hypertensive patients, 193 patients having suffered a stroke and in 368 healthy subjects with a nested polymerase chain reaction (nPCR). Overall the prevalence of Chlamydia pneumoniae DNA in peripheral blood cells was: diabetes mellitus (11.9%), stroke (10.4%), hypertension (6.9%), acute coronary syndrome (4.0%) and healthy subjects (7.9%). The prevalence of Chlamydia pneumoniae DNA in the patients was not significantly different from prevalence in the healthy subjects. However, a significant association was found between high levels of triglycerides and presence of C. pneumoniae DNA (OR = 3.27, p < 0.04). The prevalence of C. pneumoniae DNA was not associated with age, gender, smoking, BMI, HDL, CRP, plasma creatinine and symptoms or signs of ischaemic heart disease. The association between high levels of triglycerides and C. pneumoniae DNA suggests that infection by C. pneumoniae affects lipid metabolism.
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PMID:Chlamydia pneumoniae DNA in peripheral blood mononuclear cells in healthy control subjects and patients with diabetes mellitus, acute coronary syndrome, stroke, and arterial hypertension. 1460 8

Women who have had preeclampsia (PE) or gestational hypertension (GH) exhibit relatively high rates of circulatory diseases. PE is a disease associated with inflammation and vascular endothelial dysfunction. We therefore hypothesised that women with a history of PE or GH might have abnormal levels of markers of endothelial activation or inflammation, reflecting either an innate predisposition to preeclampsia or changes induced by the eclamptic process. Levels of von Willebrand factor, fibrinogen and C-reactive protein were compared in 392 women with a history of PE between 1951 and 1970, 297 women with a history of GH and 163 matched controls. Although no significant differences between those with either PE or GH and controls were noted, subjects with a history of PE had significantly higher CRP values than those with GH. No significant differences were found when the three groups were compared for von Willebrand factor or fibrinogen. Overall, the data do not support our hypothesis. In addition, our data document increasing von Willebrand factor levels increase with age, which may help explain the age dependent increase in venous or arterial thrombosis. Moderate alcohol consumption was also associated with lower levels of inflammatory markers.
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PMID:Markers of endothelial activation and atherothrombosis in women with history of preeclampsia or gestational hypertension. 1465 56


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