Advances in Cardiology最新文献

The relationship between metabolic disorders and obstructive sleep apnea (OSA) is multidirectional. Obesity is recognized as the strongest risk factor for OSA. It is unknown whether metabolic syndrome and insulin resistance/type 2 diabetes mellitus contribute to the development or aggravation of OSA, although this is likely. Conversely, OSA may be a risk factor for metabolic disorders. Strong evidence suggests that OSA may increase the risk of developing insulin resistance, glucose intolerance and type 2 diabetes mellitus. OSA has also been associated with the development and/or aggravation of obesity, dyslipidemia, metabolic syndrome and nonalcoholic fatty liver disease - a liver manifestation of metabolic syndrome. In addition, metabolic disorders are confounding factors in OSA. Metabolic disorders and OSA share common intermediate pathogenic pathways, including alterations in autonomic nervous system regulation, increased inflammatory activity, and alterations in adipokine levels and endothelial dysfunction, which may be involved in the interplay between these conditions. Overall, this complexity makes it especially difficult to reveal and understand the links between OSA and metabolic and cardiovascular disorders. The International Diabetes Federation has recently published clinical practice recommendations suggesting that OSA patients should be routinely screened for markers of metabolic disturbance and cardiovascular risk, such as waist circumference, blood pressure, and fasting lipid and glucose levels. It also recommends that the possibility of OSA should be considered in the assessment of all patients with type 2 diabetes mellitus and metabolic syndrome.

The endothelium is the common target of all cardiovascular risk factors, and functional impairment of the vascular endothelium in response to injury occurs long before the development of visible atherosclerosis. The endothelial cell behaves as a receptor-effector structure which senses different physical or chemical stimuli that occur inside the vessel and, therefore, modifies the vessel shape or releases the necessary products to counteract the effect of the stimulus and maintain homeostasis. The endothelium is capable of producing a large variety of different molecules which act as agonists and antagonists, therefore balancing their effects in opposite directions. When endothelial cells lose their ability to maintain this delicate balance, the conditions are given for the endothelium to be invaded by lipids and leukocytes (monocytes and T lymphocytes). The inflammatory response is incited and fatty streaks appear, the first step in the formation of the atheromatous plaque. If the situation persists, fatty streaks progress and the resultant plaques are exposed to rupture and set the conditions for thrombogenesis and vascular occlusion. Oxidant products are produced as a consequence of normal aerobic metabolism. These molecules are highly reactive with other biological molecules and are referred as reactive oxygen species (ROS). Under normal physiological conditions, ROS production is balanced by an efficient system of antioxidants, molecules that are capable of neutralizing them and thereby preventing oxidant damage. In pathological states, ROS may be present in relative excess. This shift of balance in favor of oxidation, termed 'oxidative stress', may have detrimental effects on cellular and tissue function, and cardiovascular risk factors generate oxidative stress. Both type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetic patients have mostly been described under enhanced oxidative stress, and both conditions are known to be powerful and independent risk factors for coronary heart disease, stroke, and peripheral arterial disease. Hyperglycemia causes glycosylation of proteins and phospholipids, thus increasing intracellular oxidative stress. Nonenzymatic reactive products, glucose-derived Schiff base, and Amadori products form chemically reversible early glycosylation products which subsequently rearrange to form more stable products, some of them long-lived proteins (collagen) which continue undergoing complex series of chemical rearrangements to form advanced glycosylation end products (AGEs). Once formed, AGEs are stable and virtually irreversible. AGEs generate ROS with consequent increased vessel oxidative damage and atherogenesis. The impressive correlation between coronary artery disease and alterations in glucose metabolism has raised the hypothesis that atherosclerosis and diabetes may share common antecedents. Large-vessel atherosclerosis can precede the development of diabetes, suggesting that rather than at

Evidence of the effectiveness of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) within continuum of atherothrombotic conditions and particularly in the treatment and prevention of coronary heart disease (CHD) is well established. Large-scale, randomized, prospective trials involving patients with CHD have shown that statins reduce the clinical consequences of atherosclerosis, including cardiovascular deaths, nonfatal myocardial infarction and stroke, hospitalization for acute coronary syndrome and heart failure, as well as the need for coronary revascularization. Direct testing of varying degrees of low-density lipoprotein (LDL)- cholesterol lowering has now been carried out in 4 large outcomes trials: PROVE IT-TIMI 22, A to Z, TNT and IDEAL. However, the question whether more aggressive LDL-cholesterol lowering by high-dose statins monotherapy is an appropriate strategy is still open: higher doses of statins are more effective mainly for the prevention of the nonfatal cardiovascular events but such doses are associated with an increase in hepatotoxicity, myopathy and concerns regarding noncardiovascular death. Moreover, despite the increasing use of statins, a significant number of coronary events still occur and many such events take place in patients presenting with type 2 diabetes and metabolic syndrome. More and more attention is now being paid to combined atherogenic dyslipidemia which typically presented in patients with type 2 diabetes and metabolic syndrome. This mixed dyslipidemia (or 'lipid quartet') - hypertriglyceridemia, low high-density lipoprotein (HDL)-cholesterol levels, a preponderance of small, dense LDL particles and an accumulation of cholesterol-rich remnant particles - emerged as the greatest 'competitor' of LDL-cholesterol among lipid risk factors for cardiovascular disease. Most recent extensions of the fibrates trials (BIP, HHS, VAHIT and FIELD) give further support to the hypothesis that patients with insulin-resistant syndromes such as diabetes and/or metabolic syndrome might be the ones to derive the most benefit from therapy with fibrates. However, different fibrates may have a somewhat different spectrum of effects. Other lipid-modifying strategies included using of niacin, ezetimibe, bile acid sequestrants, CETP inhibitors and omega-3 fatty acids. Particularly, ezetimibe/statins combinations provide superior lipid-modifying benefits compared Tenenbaum/Fisman/Motro/Adler 128 with any statins monotherapy in patients with atherogenic dyslipidemia. Atherogenic dyslipidemia is associated with increased levels of chylomicrons and their remnants containing 3 main components: apolipoprotein B-48, triglycerides and cholesterol ester of intestinal origin. Reduction in accessibility for one of them (specifically cholesteryl ester lessening due to ezetimibe administration) could lead to a decrease of the entire production of chylomicrons and result in a decrease of the hepatic body triglycerides po

The impressive correlation between cardiovascular disease and alterations in glucose metabolism has raised the likelihood that atherosclerosis and type 2 diabetes may share common antecedents. Inflammation is emerging as a conceivable etiologic mechanism for both. Interleukins are regulatory proteins with ability to accelerate or inhibit inflammatory processes, and matrixins are prepro enzymes responsible for the timely breakdown of extracellular matrix. Interleukins (ILs) are classified based on their role in diabetes and atherosclerosis, hypothesizing that each interleukin acts on both diseases in the same direction - regardless if harmful, favorable or neutral. They are clustered into three groups: noxious (the 'bad', 8 members), comprising IL-1, IL-2, IL-6, IL-7, IL-8, IL-15, IL-17 and IL-18; protective (the 'good', 5 members), comprising IL-4, IL-10, IL-11, IL-12 and IL-13; and 'aloof' , comprising IL-5, IL-9, IL-14, IL-16 and IL-19 through IL-29 (15 members). Each group presented converging effects on both diseases. IL-3 was reluctant to clustering and IL-30 through 33 were not included due to the scarce available data. It may be seen that (1) favorable effects of a given interleukin on either diabetes or atherosclerosis predicts similar effects on the other; (2) equally, harmful interleukin effects on one disease can be extrapolated to the other, and (3) absence of influence of a given interleukin on one of these diseases forecasts lack of effects on the other. Matrixins seem to present a similar pathophysiological pattern. These facts further support the unifying etiologic theory of diabetes and heart disease, emphasizing the importance of a cardiovascular diabetologic approach to these cytokines for future research. A pharmacologic simultaneous targeting of interleukins and matrixins might provide an effective means to concurrently control both atherosclerosis and diabetes.

Both essential hypertension and diabetes mellitus affect the same major target organs. The common denominator of hypertensive/diabetic target organ-disease is the vascular tree. Left ventricular hypertrophy and coronary artery disease are much more common in diabetic hypertensive patients than in patients suffering from hypertension or diabetes alone. The combined presence of hypertension and diabetes concomitantly accelerates the decrease in renal function, the development of diabetic retinopathy and the development of cerebral diseases. Lowering blood pressure to less than 130/80 mm Hg is the primary goal in the management of the hypertensive diabetic patients. Beta-blockers have been reported to adversely affect the overall risk factor profile in the diabetic patient. In contrast, calcium antagonists, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have been reported to be either neutral or beneficial with regard to the overall metabolic risk factor profile. Combination therapy is usually required to achieve blood pressure goal in diabetic patients. The addition of aldosterone antagonists may be beneficial in patients with resistant hypertension and low levels of serum potassium. Aggressive control of blood pressure, cholesterol and glucose levels should be attempted to reduce the cardiovascular risk of diabetic hypertensive patients.