Beta-blockers and diabetes: the bad guys come good

Type 2 diabetes is becoming very common and is closely linked to physical inactivity and obesity. It is associated with clustering of coronary risk factors and 60–80% of cases have hypertension.The first therapeutic action is appropriate adjustment of life style. Anti-hypertensive therapies such as diuretics, ACE inhibitors and calcium antagonists have been effective in reducing cardiovascular events in type 2 diabetes, though calcium antagonists may be less effective than older therapies and ACE-inhibitors in reducing the risk of heart attacks and heart failure (but possibly more effective in stroke reduction).Beta-blockers (BBs) have a poor image as a potential therapy due to apparent adverse effects on surrogate end-points such as insulin-resistance. However large, controlled trials have shown BBs to be highly effective in reducing the risk of cardiovascular events and death in post myocardial infarction patients with diabetes. The UKPDS study in type 2 diabetics with hypertension showed first-line beta-blockade to be at least as effective as ACE-inhibition in preventing all primary macrovascular and microvascular end-points. The active ingredient appears to be beta-1 blockade, acting not only to lower blood pressure but also to prevent sudden death and cardiovascular damage stemming from chronic beta-1 stimulation associated with raised noradrenaline activity.By contrast, in the LIFE study atenolol was less effective than the angiotensin receptor antagonist losartan in reducing cardiovascular events and all-cause mortality in mainly elderly hypertensives with diabetes. Thus the best beta-blocker results in reducing hard cardiovascular end-points occur in hypertension studies (including the UKPDS study) involving younger/middle aged (say less than 60–65 years) patients, with relatively high sympathetic activity, relatively compliant/elastic arteries (narrow pulse-pressure) and normally functioning beta-1 receptors. In elderly hypertensive patients beta-blockers may be given as second-line therapy on the back of a low-dose diuretic (but possibly as first line agent in elderly hypertensives with prior myocardial infarction).Thus inappropriate attention to surrogate end-points can lead to faulty prescribing habits. Beta-blockers, currently severely underprescribed, should be considered as a first line therapeutic option for all diabetics with ischaemic heart disease or younger/middle aged diabetics with hypertension (but co-prescribed with low dose diuretic therapy in the elderly). The active ingredient for cardiovascular protection appears to be beta-1 blockade; optimal efficacy in lowering blood pressure and safety e.g. reducing risk of bronchoconstriction, is achieved by choosing an agent with high beta-1 selectivity.     

Employment interviews: making the right choice.

Respiratory therapists who become supervisors may not be experienced in or comfortable with the interviewing process. The author presents guidelines for making the right choice when it is time to hire.     

Hepato-pancreato-biliary fat: the good, the bad and the ugly

Obesity has become epidemic in the United States, in Europe, and in many urban areas in the developing world. The globalization of certain 'fast foods' and 'soft drinks' may, in part, be contributing to this epidemic. Diets high in saturated fatty acids and trans fats as well as drinks that have high fructose corn syrup levels may be particularly harmful. Recent research suggests that fat is a dynamic endocrine organ and that visceral fat is associated with the metabolic syndrome. Central obesity leads to organ steatosis and altered serum adipokines including reduced adiponectin and markedly elevated leptin. This abnormal adipokine milieu results in increased tissue infiltration of monocytes and macrophages which produce proinflammatory cytokines that alter organ function. Over many years, the combination of steatosis and local inflammation leads to fibrosis and eventually to cancer. Nonalcoholic fatty liver disease (NAFLD) is a precursor for nonalcoholic steatohepatitis (NASH). NAFLD and NASH (1) lead to cirrhosis and hepatocellular carcinoma, (2) increase the risk of liver resection, and (3) compromise the outcome of liver transplantation. Similarly, in the pancreas nonalcoholic fatty pancreas disease (NAFPD) may lead to nonalcoholic steatopancreatitis (NASP). NAFPD and NASP may (1) promote the development of chronic pancreatitis and pancreatic cancer, (2) exacerbate the severity of acute pancreatitis, and (3) increase the risk of pancreatic surgery. In the gallbladder nonalcoholic fatty gallbladder disease (NAFGBD, cholecystosteatosis) may lead to steatocholecystitis. Cholecystosteatosis may be an explanation for (1) the increased incidence of chronic acalculous cholecystitis and (2) the increased number of cholecystectomies.     

Substance P in heart failure: The good and the bad

The tachykinin, substance P, is found primarily in sensory nerves. In the heart, substance P-containing nerve fibers are often found surrounding coronary vessels, making them ideally situated to sense changes in the myocardial environment. Recent studies in rodents have identified substance P as having dual roles in the heart, depending on disease etiology and/or timing. Thus far, these studies indicate that substance P may be protective acutely following ischemia-reperfusion, but damaging long-term in non-ischemic induced remodeling and heart failure. Sensory nerves may be at the apex of the cascade of events leading to heart failure, therefore, they make a promising potential therapeutic target that warrants increased investigation.     

Coronary calcium: the good, the bad, and the uncertain

BACKGROUND: Coronary calcium deposits have been widely regarded to result from a passive process of encrustation or adsorption of mineral onto advanced, complex atherosclerotic lesions. Increasing interest has focused on noninvasive radiologic detection of these calcium deposits as a diagnostic and prognostic adjunct to clinical evaluation of coronary artery disease, particularly with the use of newer, high-resolution imaging techniques such as electron beam computed tomography. METHODS AND RESULTS: We reviewed the literature on coronary calcium and its relation to pathologic atherosclerosis, angiographic stenoses,and clinical events. Clinical calcium detection studies have demonstrated an association between coronary calcium and both extent of coronary artery disease and risk of adverse events. These studies have in the past tended to reinforce the perception that calcific deposits result from a passive mineralization process, signify advanced coronary artery disease, and foreshadow future coronary events. CONCLUSIONS: Recent pathologic, genetic, clinical, and biochemical evidence reviewed in this article suggests that coronary calcium deposits are a manifestation of a complex, organized, and regulated process similar in many respects to new bone formation and may not be a reliable indicator of either the extent of coronary disease or the risk of a future event. These studies also suggest that atherosclerosis and calcific deposits may be distinct pathologic entities that frequently occur together and are related to each other in ways that are poorly understood.