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Type 2 diabetes is associated with at least 2-fold elevated risk for all macrovascular complications, coronary heart disease, stroke and peripheral vascular disease. The prevalence and incidence of hemorrhagic stroke is not higher among subjects with type 2 diabetes than in non-diabetic subjects. Therefore, an excess risk of stroke is due to high occurrence of ischemic strokes. High LDL cholesterol, elevated blood pressure, smoking, low HDL cholesterol, high levels of total triglycerides and insulin, central obesity, impaired glucose tolerance and atrial fibrillation have been associated with the risk of stroke. Diabetic patients with stroke should receive effective antihypertensive therapy, lipid-lowering medication, medication to obtain good glycemic control, and anti-platelet therapy. Surgical revascularization is indicated in patients with hemodynamically significant internal carotid artery atherosclerosis independently of symptoms. Patients with atrial fibrillation should be on anticoagulation therapy.

Evidence is accumulating in favour of a link between erectile dysfunction (ED) and coronary artery disease (CAD). Prevalence of common risk factors for atherosclerosis is similar. ED is frequently found in patients with CAD and shares a similar pathogenic involvement of nitric oxide-pathway leading to impairment of endothelium-dependent vasodilatation (early phase) and structural vascular abnormalities (late phase). Moreover, there is room to consider ED as a marker of early sub-clinical CAD. It is therefore crucial to identify asymptomatic patients with ED who may be at risk of occult CAD. Initial screening may adopt risk assessment office-based approaches to score patient into low, intermediate or high risk of future cardiovascular events. Attention should be drawn to patients at intermediate risk. Targets for the assessment of sub-clinical CAD in this subset of patients should include both obstructive and non-obstructive CAD. Although less investigated, non-obstructive CAD is a more important target to assess since acute myocardial infarction is the result of an acute occlusion of a previously non critical coronary vessel. Several non-invasive tests may add important diagnostic and prognostic information in patients at intermediate coronary risk. Some of these directly assess coronary atherosclerosis burden – such as coronary calcium score by electron beam computed tomography – whereas others, such as carotid intima-media thickness by ultrasound are surrogates of coronary involvement.

The impact of visceral obesity epidemic on the incidence of diabetes mellitus and cardiovascular disease is a major concern in the public health management. Even if lifestyle modifications still remain the cornerstone of obesity treatment, the pharmacological approach could help not only to reduce body weight and visceral fat but also their metabolic and cardiovascular complications. It has been shown that endogenous cannabinoid system is overactivated in obese mice and both in subcutaneous and visceral adipose tissue of obese patients. The CB1 antagonist rimonabant is able to antagonize most of the behavioural and metabolic effect of endocannabinoid overactivation. Four double-blind trials compared rimonabant 5 mg or 20 mg daily with placebo in more than 6600 individuals. RIO-Europe, RIO-Lipids, RIO-North America, and RIO-Diabetes have published 1 year results. RIO-North America also included a second year of follow-up. These trials showed that in patients with obesity, including those with cardiovascular risk factors, continued therapy with rimonabant as compared with placebo is associated with a significant reduction in body weight and waist circumference. Such therapy is also associated with other favorable changes in the cardiometabolic risk profile, including an improvement in the lipid profile and in glycaemic control in type 2 diabetics.

Low-density lipoprotein cholesterol (LDL-C) plays a pivotal role in the pathogenesis of coronary heart disease (CHD). A considerable body of evidences supports the clinical benefit of lipid-lowering therapy in term of coronary events and cardiovascular death reduction. Based on these observations, current international guidelines indicate a LDL-C below 100–115 mg/dl as target in subjects with high cardiovascular risk. In the last years, however, new evidences have emerged, suggesting that levels of LDL-C around 50–70 mg/dl are physiologically normal and associated with a significantly lower development of atherosclerosis. For this reason, several large trials involving more than 25,000 patients with stable CHD or presenting an acute coronary syndrome have tested the hypothesis if an aggressive lipid-lowering strategy might result in better cardiovascular outcomes compared to the conventional therapy. Taken together, these studies demonstrated that, when lower levels of LDL-C is attained by high-dose lipid-lowering agents, a significant reduction of coronary events and death, and of any cardiovascular events with a favourable trend toward decreasing cardiovascular mortality can be obtained. Intensive lipid lowering strategy, therefore, provides a significant benefit over standard-dose therapy, supporting a broader use of high-dose lipid-lowering agents for patients with high global cardiovascular risk.

Diabetes mellitus is a pivotal risk factor for cardiovascular disease and a negative prognostic element in cardiovascular patients. The incidence of cardiovascular diseases in diabetics is 3-to-6 times higher than in non-diabetics, and cardiovascular pathology progresses more quickly in the former, thus constituting their major determinant of mortality. In diabetics 65–75% of deaths are caused by cardiovascular factors, and following a major coronary event diabetes increases about 2–3 times the all-cause mortality risk in affected people. Diabetes is also associated with a triple risk of death from coronary heart disease and a 10–12-fold increase in risk of mortality from coronary heart disease if compared with people with neither diabetes mellitus nor coronary heart disease. A healthy lifestyle, including cessation of smoking, suitable exercise, correct diet, appropriate weight loss and stress control, should be recommended to every subject in the perspective of cardiovascular prevention. Additional specific recommendations for diabetics in the primary prevention of cardiovascular events include accurate individually tailored glycemic control (general target: HbA1c < 7%), strict blood pressure treatment (target: < 130/80 mmHg), optimal lipid lowering regimen (target: LDL-C < 100 mg/dl; < 70 mg/dl in very high risk diabetics), antiplatelet therapy with aspirin (dosage: 75–150 mg per day). The current and future objective for health operators and systems is that of harmonically integrating multiple risk factor management not only with stringent treatment goals, but also with selective attention to the specific needs and fundamental values of every diabetic person encountered in daily clinical practice.

The renal lesions underlying renal dysfunction differ in type 1 and type 2 diabetes, although the clinical manifestations of diabetic nephropathy, proteinuria, decreased glomerular filtration rate and increasing blood pressure are similar. Indeed, in type 1 diabetes, although also tubular, interstitial and arteriolar lesions are present, the most important structural changes involve the glomerulus, while several type 2 diabetic patients, despite the presence of microalbuminuria or proteinuria, have normal glomerular structure with or without tubulo-interstitial and arteriolar abnormalities. The clinical manifestations of diabetic nephropathy are strongly related with the structural changes, especially with the degree of mesangial expansion in both type 1 and type 2 diabetes. In the last years it has been demonstrated that also changes in the structure and number of podocytes may be involved in the progression of diabetic nephropathy. Previous studies using light and electron microscopic morphometric analysis described the renal structural changes and the renal structural–functional relationships, documenting the contribution of kidney biopsy studies in understanding the pathogenesis of diabetic nephropathy and in identifying the patients with higher risk to progress to end stage renal disease. Finally this review will summarize studies in pancreas transplant recipients demonstrating that the lesions of diabetic nephropathy in humans are reversible, if normoglycemia is achieved and maintained for a long period of time.

The metabolic syndrome (MS) is a disorder characterized by a higher risk of cardiovascular disease (CVD) and by a clustering of cardiovascular risk factors, which per se do not sufficiently explain the excess vascular risk attributed to this syndrome. The core abnormality accounting for most of the features of the MS consists in the resistance to the metabolic and vascular actions of insulin, leading to chronic proinflammatory state, increased oxidative stress, procoagulant/anti-fibrinolytic state, coupled with platelet hyperaggregability.

We have previously provided evidence of persistent thromboxane (TXA₂)-dependent platelet activation in association with features of the MS, including visceral obesity and diabetes. We suggested a cause-and-effect relationship between oxidative stress and platelet activation by showing the linear relationship between the excretion rates of 8-iso-prostaglandin (PG)F_2α and 11-dehydro-TXB₂, markers of in vivo lipid peroxidation and platelet activation, respectively, and their downregulation following improvement of glycemic control in diabetes mellitus or weight loss in obesity. Subsequent observations elucidated the concept that insulin resistance per se is a major determinant of increased platelet activation in obesity, independently of underlying inflammation.

Interventions such as caloric restriction, exercise and insulin sensitizing agents may favourably modulate most of the metabolic abnormalities predisposing to atherothrombosis in the MS.

Obesity and its complications are characterized by elevated circulating levels of inflammation markers like CRP, IL-6 and serum amyloid A.

Although several cells secrete these markers, the adipose tissue seems to play a pivotal role for the proinflammatory state. Obesity with enlarged adipose cells leads to a marked increase in the expression of pro-inflammatory cytokines in the adipose tissue while expression of the anti-inflammatory adipokine, adiponectin, is reduced. The mechanisms for this are currently unknown but a consequence is the recruitment of inflammatory cells into the adipose tissue which, thus, becomes inflamed. Animal experiments have shown that this is associated with a clear accentuation of degree of insulin resistance.

Invasion of inflammatory cells leads to the release of TNFa, which normally is not secreted by the adipose cells. The increased levels of cytokines in the adipose tissue have marked consequences for the normal differentiation of the preadipocytes. These cells become proinflammatory and the normal phenotype, i.e., lipid-accumulating and insulin-sensitive cells, is suppressed.

Although inflammation in the adipose tissue also leads to a reduced insulin sensitivity, recent data have shown that induction of insulin resistance by itself in the adipose tissue also is proinflammatory since insulin can exert an anti-inflammatory effect through its cross-talk with the IL-6 signaling cascade.

It may be expected that new risk factors emerging from research on biomarkers and SNPs will provide more precise and personalized approaches to prevent and treat cardiovascular disease. They will be particularly useful for a better prognosis in first-degree relatives of patients with major implications on preventive medicine. Most importantly, these new risk factors will lead to better understand why more than 60% of all MIs occur in individuals classified as being at low or intermediate risk according to the currently used risk algorithms. Finally, these fascinating developments have the promising potential to provide new insights into molecular mechanisms leading to atherosclerosis and thus may provide important contributions to the development of highly specific new drugs to treat coronary heart disease, myocardial infarction and stroke.

We believe that augmenting or complementing natural functions of the brain can be an effective way to develop the technology for more brain-adequate interfaces. We illustrate this line of approach with examples from our recent work and report briefly on a major research initiative launched recently at Bielefeld University, joining the efforts of computer science groups and linguists towards more brain-adequate human–computer interfaces by studying the topic of interactive alignment in communication.