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Diabetic patients have a two- to four-fold increase in macrovascular disease compared with non-diabetic subjects, with coronary heart disease (CHD) and stroke being the most common causes of death in type 2 diabetes. Diabetic nephropathy has become the most common single cause of end-stage renal disease in industrialized countries. Risk factors, including hyperglycaemia, high blood lipids and high blood pressure (BP), often co-exist in diabetic subjects. One recent metaanalysis, including more than 90,000 patients with a 12.4-year follow-up, has demonstrated a continuous increase in the relative risks of morbidity and mortality with increasing blood glucose concentration. Both the Multiple Risk Factor Intervention Trial (MRFIT) and the United Kingdom Prospective Diabetes Study (UKPDS) have confirmed in diabetes the close relationship between total cholesterol levels and elevated risk of cardiovascular events. For every 1 mmol/l increase in low-density lipoprotein cholesterol in type 2 diabetes, the relative risk of CHD increases by 1.57. Furthermore, about 40% of newly diagnosed diabetic patients are also hypertensive. Elevated BP is related to the presence of left ventricular hypertrophy (LVH) and, indeed, LVH is observed in more than 70% of diabetic patients with hypertension. Several studies in diabetes have proven treatment benefits when different risk factors are addressed. The need for tighter control of cardiovascular risk factors in diabetic patients is clear. This may include better control of raised BP, hyperlipidaemia and hyperglycaemia as well as closer monitoring for the appearance of LVH and microalbuminuria. There is a clear need to translate the results of clinical trials into everyday clinical practice.
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PMID:The need for tighter control of cardiovascular risk factors in diabetic patients. 1276 60

About 60% of patients with mild and moderate hypertension have insulin resistance and half of them have clinically manifest metabolic syndrome which comprises abdominal obesity, hyperlipidemia, impaired glucose tolerance, hypertension and insulin resistance. In a framework of metabolic syndrome hypertension is characterized by disturbed circadian profile without nocturnal blood pressure lowering and concentric left ventricular hypertrophy. There exist 2 mechanisms of linkage between hypertension and metabolic syndrome: impaired ion transport and neurohormonal and humoral activation. Antihypertensive drugs for correction of hypertension in metabolic syndrome should be long acting, provide protection of target organs, and induce positive or neutral metabolic effect. Together with normalization of blood pressure these actions can cause lowering of risk of atherosclerosis development. Representatives of the following classes of antihypertensive agents can be used as drugs of choice: angiotensin converting enzyme inhibitors, long-acting calcium antagonists, selective beta1-adrenoblockers, and thiazide diuretics.
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PMID:[Arterial hypertension in a framework of metabolic syndrome: special features and principles of drug correction]. 1511 79

Appropriate initiation of dialysis is of an outstanding importance in the treatment of patients with end-stage renal disease. It prevents development of irreversible uremic complication and enables selection of the most appropriate dialysis modality for the individual patient. The major causes of morbidity and mortality in dialysis patients are cardiovascular diseases. Hypertension and hyperlipidemia are commonly found in dialysis patients as well as anemia, chronic inflammation and fluid overload, all of which are found to be risk factors for the development of cardiovascular diseases. Arterial hypertension is the main risk factor for left ventricular hypertrophy, and there is clear evidence that control of hypertension has a beneficial effect on left ventricular hypertrophy. It is best achieved by correction of overhydration and maintenance of dry weight. Modern dialysis machines are capable of changing electrolyte concentrations, which reduces intradialytic cardiovascular complications, incidence of cardiac arrhythmias and hypotension. Correction of anemia with erythropoietin results in regression of left ventricular hypertrophy and improvement of the quality of life and defense against microorganisms. Chronic inflammation can be prevented with the use of biocompatible high-flux dialysis membranes and sterile dialysate, which are also important for the prevention of oxidative stress involved in the increase of LDL oxygenation and incorporation into the intimal layer of the vessels. Low molecular weight heparins by their action on lipoprotein lipase serve as an additional factor that suppresses development of atherosclerotic plaque in dialysis patients. Optimal dialysis dose decreases the mortality and morbidity rates. High-flux membranes or prolongation of dialysis session are modalities for dialysis dose improvement. Individualized approach to preparation of dialysis solutions has resulted in better control of fluid overload and intradialytic hyper- or hypotension, reduction in the incidence of arrhythmias, improvement of hemodynamic stability, and delay of renal osteodystrophy. Malnutrition is a relatively common problem in dialysis patients that may be secondary to poor nutritional intake, inadequate amount of dialysis, lack of appetite, acidosis, associated disease, and/or increase in protein catabolism. The most appropriate approach includes individualization of dietary prescription according to the nutritionist's advice, increase of dialysis dose with biocompatible membranes, and use of sterile bicarbonate dialysate with glucose and erythropoietin. The major goal of adequate dialysis is not just improvement in survival of dialysis patients, but also improvement in the quality of their lives.
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PMID:[Biological adequacy--what does it mean?]. 1512 86

In the control of acute rejection, attention is being focused more and more on the long-term adverse effects of the immunosuppressive agents used. Since cardiovascular disease is the main cause of death in renal transplant recipients, optimal control of cardiovascular risk factors is essential in the long-term management of these patients. Unfortunately, several commonly used immunosuppressive drugs interfere with the cardiovascular system. In this review, the cardiovascular adverse effects of the immunosuppressive agents currently used for maintenance immunosuppression are thoroughly discussed. Optimising immunosuppression means finding a balance between efficacy and safety. Corticosteroids induce endothelial dysfunction, hypertension, hyperlipidaemia and diabetes mellitus, and impair fibrinolysis. The use of corticosteroids in transplant recipients is undesirable, not only because of their cardiovascular effects, but also because they induce such adverse effects as osteoporosis, obesity, and atrophy of the skin and vessel wall. Calcineurin inhibitors are the most powerful agents for maintenance immunosuppression. The calcineurin inhibitor ciclosporin (cyclosporine) not only induces these same adverse effects as corticosteroids but is also nephrotoxic. Tacrolimus has a more favourable cardiovascular risk profile than ciclosporin and is also less nephrotoxic. It has little or no effect on blood pressure and serum lipids; however, its diabetogenic effect is more prominent in the period immediately following transplantation, although at maintenance dosages, the diabetogenic effect appears to be comparable to that of ciclosporin. The diabetogenic effect of tacrolimus can be managed by reducing the dose of tacrolimus and early corticosteroid withdrawal. The effect of tacrolimus on endothelial function has not been completely elucidated. The proliferation inhibitors azathioprine and mycophenolate mofetil (MMF) have little effect on the cardiovascular system. Yet, indirectly, by inducing anaemia, they may lead to left ventricular hypertrophy. MMF is an attractive alternative to azathioprine because of its higher potency and possibly lower risk of malignancies. Sirolimus also induces anaemia, but may be promising because of its antiproliferative features. Whether the hyperlipidaemia induced by sirolimus counteracts its beneficial effects is, as yet, unknown. It may be combined with MMF, however, initial attempts resulted in severe mouth ulcers.
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PMID:Effect of immunosuppressive agents on long-term survival of renal transplant recipients: focus on the cardiovascular risk. 1534 97

Epidemiological studies showed that hypercholesterolemia is associated with higher left ventricular mass. Endothelin signaling is activated in hyperlipidemic animals and may contribute to progressive ventricular hypertrophy. Simvastatin has been shown to inhibit endothelin-1. However, the behavior of simvastatin on ventricular hypertrophy in hyperlipidemic animals is not well understood. In this study, we evaluated the hemodynamic, biochemical, and morphological responses to simvastatin in cholesterol-fed (1%) rabbits. The left ventricular weight increased 8 wk after cholesterol feeding compared with that in normocholesterolemic rabbits. Simvastatin at a clinical therapeutic dose (1.2 mg x kg(-1) x day(-1)) significantly decreased left ventricular weight by 14% and left ventricular myocyte sizes by 14% as isolated by enzymatic dissociation. Hypercholesterolemia upregulated ventricular preproendothelin-1 mRNA as assessed by real-time quantitative RT-PCR and elevated production of cardiac endothelin-1 concentration. The increased endothelin-1 responses can be inhibited after simvastatin administration. Left ventricular mass indexed by body weight positively correlated with tissue endothelin-1 levels (P = 0.0003). In Langendorff-perfused rabbit hearts, hyperlipidemia led to significant QT prolongation compared with normocholesterolemia, which can be reversed by administering simvastatin. In contrast, simvastatin-induced beneficial effects were reversed by the addition of mevalonate. The addition of bosentan, a nonspecific endothelin receptor blocker, improved the response in hypercholesterolemic rabbits and did not have additional beneficial effects in simvastatin-treated rabbits. The results of the present study suggest that the antihypertropic and electrocardiographic effects of simvastatin at a clinical therapeutic dose are mediated through inhibition of tissue endothelin-1 expression, which is linked to mevalonate metabolism, and result in an amelioration of cardiomyocyte hypertrophy development by an atherogenic diet.
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PMID:Effect of simvastatin on left ventricular mass in hypercholesterolemic rabbits. 1548 36

Cardiovascular diseases are the leading causes of mortality among patients with end-stage renal disease (ESRD), with arterial disease and left ventricular hypertrophy being the two principal factors of the high mortality rate in this population. In addition to traditional risk factors (age, gender, diabetes, hypertension, lifestyle, hyperlipidemia, smoking, hyperhomocystinemia), inflammation, oxidative stress and disorders of mineral metabolism may contribute to cardiovascular risk in patients with uremic syndrome. High serum phosphate may influence vascular calcifications directly and indirectly, by worsening secondary hyperparathyroidism. Several treatment options are available for the treatment of hyperphosphatemia and secondary hyperparathyroidism in patients with ESRD. The treatment approach includes a diet low in phosphorus, with less than 1 g/kg/day of protein. Vitamin D supplementation is an important part of treatment. Phosphate binding agents are in most of the patients necessary in addition to diet. Aluminum hydroxide has been widely used for many years. It is very potent, but also very toxic, with severe encephalopathy as the most dangerous side effect. Calcium salts are less potent, and were considered safe for use in patients on dialysis. However, improvement in the understanding of vascular calcifications has demonstrated that calcium overload significantly contributes to widespread atherosclerosis in patients with ESRD. Sevelamer-hydrochloride is a novel non-aluminum, non-calcium containing phosphate binder, which is capable of reducing the levels of phosphorus as well as of low-density lipoprotein cholesterol, and increasing high-density lipoprotein cholesterol.
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PMID:[Hyperphosphatemia and cardiovascular risk in patients on dialysis]. 1550 84

Left ventricular hypertrophy is an important risk factor of cardiovascular complications during the course of hypertension. Increased QT dispersion is associated with sudden cardiac death in congestive heart failure and in other cardiovascular diseases. Our aim was to compare QT dispersion from routine ECG in hypertensive patients with and without left ventricular hypertrophy defined by echocardiography. Authors examined 71 hypertensives treated in our medical department. Left ventricular hypertrophy was defined by echocardiography (Penn convention) as left ventricular mass index > 134 g/m2 in men and > 110 g/m2 in women. QT dispersion was defined from routine ECG (QTmax - QTmin). Presence of LVH was found in 26 patients (mean age 59.3 years), absence of LVH in 45 patients (mean age 57.8 years). Hypertensives with secondary hypertension, hypertrophic cardiomyopathy, sings of ischemia in ECG, arrhythmias, myocardial infarction, heart failure, diabetes mellitus and patients treated by antiarrhythmic drugs of the Ic and III groups were excluded. Both groups of hypertensives were matched by demographic parameters, and by the presence of hypertension, obesity, hyperlipidemia and smoking habites. There were statistically significant longer QT dispersion and QTc dispersion (59.0 +/- 20.1 ms, 64.0 +/- 23.7 ms) in LVH-positive patients than in LVH-negative once (43.2 +/- 9.5 ms, 48.4 +/- 11.1 ms). Left ventricular hypertrophy in patients with hypertension brings usually a complicated course of the disease. Authors recommend to look after left ventricular hypertrophy presence in hypertensives as it carries much more complicated course of the disease. Measurment of QT dispersion adds farther stratificational information to these patients.
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PMID:[QT dispersion intervals in hypertensives with left ventricular hypertrophy]. 1563 64

Obesity, now an epidemic in the USA, northern Europe, and Italy, is associated with several co-morbidities that shorten life expectancy, in particular type 2 diabetes mellitus (T2DM), arterial hypertension, and hyperlipidemia. The impact of obesity on mortality is evident in all ages, and is especially strong in young persons. Obesity, especially visceral obesity, associated with a sedentary lifestyle, is among the strongest risk factors for T2DM, and a diagnosis of T2DM seems to increase linearly as a function of duration of obesity. The pathogenesis of T2DM is based on a dual defect, i.e. increased insulin resistance coupled with defective insulin release. The main abnormality in obesity is increased insulin resistance, while insulin release, even though defective compared with body needs, is usually abundant. The incidence of obesity among children aged 6-16 years is now even greater than that among adults: in Italy, figures up to 30% have been reported. As in adults, obesity is a cause, among children, of arterial hypertension, left ventricular hypertrophy, hyperlipidemia, non-alcoholic-steato hepatitis, sleep apnea syndrome (SAS), and orthopedic, psychological, and social problems. Together with an increase in body weight, there is an increase of visceral fat. Obesity in children has also led to a tremendous increase in the prevalence of impaired glucose tolerance (IGT); the percentages span from 25% in a multiethnic cohort in the USA, to 4% in Italian Caucasians. Management of obesity and of T2DM in children has to face the issue of poor compliance; there is consensus that dietary treatment of obese T2DM children is a failure, so that drugs are required; the only drug evaluated in a formal trial is metformin, that behaves in terms of efficacy and of minor side effects as in adults. In conclusion, obesity in children is not pure obesity, but is accompanied by co-morbidities that cluster to form the "metabolic syndrome" just like in the adults. If this epidemics continues and is not properly challenged, in the next decades we will face an epidemic of early cardiovascular morbidity and mortality.
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PMID:Type 2 diabetes mellitus is becoming the most common type of diabetes in school children. 1566 74

Artery calcification occurring in atherosclerosis is connected with a high risk of cardiovascular events. Quantitative calcification evaluation using electron beam tomography indicated a correlation between artery calcification and well-known cardiovascular risk factors, i.e. smoking, obesity, and hyperlipidemia. Elevated calcium scores are especially observed in diabetic patients, which may even explain the higher mortality in this group. Calcification leads to increased blood vessel rigidity and, consequently, elevated arterial vascular resistance and left ventricular hypertrophy. An increased risk of plaque rupture in relation to calcium-rich atherosclerotic lesions was not proved. Plaque rupture and thromboembolitic complications are probably higher in the case of lipid-rich lesions. Atherosclerotic calcification is an active process in which many cells (monocytes/macrophages, vascular smooth muscle cells, and endothelial cells) participate. Many substances and transcription factors normally participating in the bone remodeling process are found in calcified atherosclerotic lesions (e.g. Cbfa-1, osteocalcin, alkaline phosphatase, BMP-2, osteopontin, osteoprotegrin, and RANKL). On monocytes, cells playing an important role in atherosclerosis progression, the presence of a calcium-sensing receptor (CaR) has been demonstrated. Increase in monocyte chemotaxis and increased interleukin 6 secretion in response to extracellular calcium were observed. Monocytes also directly and indirectly enhance vascular calcification. Immune cells and cytokines participating in vascular calcification are connected in one pathogenetic mechanism, i.e. atherosclerosis as an inflammatory disease and calcification.
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PMID:[The role of calcium ions in the pathomechanism of the artery calcification accompanying atherosclerosis]. 1576 85

Primary hypertension is well known to occur in children, but the characteristics of such children are changing due to the influence of the obesity epidemic. In view of this, we conducted a cross-sectional study of 70 children [age 13.3+/-4 years (mean +/- SD)] with primary hypertension referred to a specialized pediatric hypertension clinic. Secondary hypertension had been excluded after a standardized diagnostic evaluation. Isolated systolic hypertension was present in 62.9% of subjects. Family history of hypertension was present in 86.2%, and 52.9% were obese (BMI > or =95th percentile). BMI was weakly correlated with systolic BP (r =0.28,P =0.10) and was significantly correlated with total cholesterol (r =0.36,P =0.005) and triglycerides (r =0.42,P =0.01). Mean plasma renin activity (PRA) was 3.1+/-2.7 ng/ml/h. PRA was correlated with diastolic but not systolic BP. Patients with high PRA had higher diastolic BP and lower BMI compared to those with low PRA. Left ventricular hypertrophy was present in 24%. Mean 24-h systolic BP load by ambulatory BP monitoring was 52+/-24%; mean 24-h diastolic BP load was 18+/-16%; BP loads were greater in patients with high PRA. These data suggest that primary hypertension in children is characterized by systolic BP elevation, positive family history and obesity. Hyperlipidemia accompanies primary hypertension in obese children, and left ventricular hypertrophy is common. Patients with high PRA have more severe BP elevation. Future studies should focus on further defining the pathophysiology of primary hypertension in children, including the roles of renin and insulin resistance, so that improved methods of prevention and treatment can be developed.
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PMID:Characteristics of children with primary hypertension seen at a referral center. 1586 53


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