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BP response of atenolol vs HCTZ
Source: Beitelshees AL, et al. Comparison of office, ambulatory, and home blood pressure antihypertensive response to atenolol and hydrochlorthiazide. J Clin Hypertens 2010;12:14-21.
In untreated subjects with hypertension (HTN), findings on 24-hour ambulatory blood pressure monitoring (ABPM) or home blood pressure monitoring (HBP) have been found to provide better indication of risk than office blood pressure (OBP). On-treatment BP measurement using the same techniques shows similar associations: ABPM is better than HBP, which is better than OBP for risk prediction. Since not all patients can be availed of ABPM, HBP monitoring has received increased advocacy.
HCTZ and atenolol (ATN) are two of the most commonly prescribed antihypertensive agents in the United States. Beitelshees et al performed a randomized controlled trial to assess the relative accuracy of OBP and HBP compared to the gold standard ABPM in subjects (n = 418) treated with HCTZ, atenolol, or the combination.
For both systolic and diastolic BP, correlation with ABPM was significantly better for HBP than OBP. For example, OBP overestimated treatment effects on SBP by 4.6 mm Hg compared with HBP. Recent HTN consensus groups have endorsed routine HBP monitoring; these data support the role of HBP monitoring as a better risk predictor than OBP.
Ipratropium and CV events in COPD
Source: Ogale SS, et al. Cardiovascular events associated with ipratropium bromide in COPD. Chest 2010;137:13-19.
Bronchodilators (i.e., inhaled beta agonists and anticholinergics) are the foundation of symptomatic care for COPD. Metered-dose inhaler administration of ipratropium (IPR) is generally very well tolerated, and associated with few, if any, adverse symptoms. Nonetheless, there remains some conflict about the cardiovascular safety of anticholinergic bronchodilators in COPD. One meta-analysis suggested as much as a 53% increased relative risk for MI in COPD patients treated with IPR; in contrast, a large randomized prospective trial with tiotropium (n = 6000, approximately) did not find any signal for increased cardiovascular events.
Ogale et al performed a cohort study comprised of newly diagnosed COPD patients (n = 82,717) attending an Illinois VA hospital.
Risk for a cardiovascular event was 29% higher in COPD patients treated with IPR than comparators. Risk was time-related: Those with at least a 6-month interval since last exposure to an anticholinergic were not at greater risk. The mechanism by which anticholinergics might increase cardiovascular risk is not clear, although a dose-response relationship between IPR and supraventricular tachyarrhythmia incidence noted in the Lung Health Study intimates a possible connection.
Kidney function, proteinuria, and adverse outcomes
Source: Hemmelgarn BR, et al. Relations between kidney function, proteinuria, and adverse outcomes. JAMA 2010;303:423-429.
Staging of chronic kidney disease (CKD) is based primarily upon estimated GFR. Proteinuria (PRO) is a strong marker for kidney disease, yet its severity is not included in current risk stratification schemes, which are instead driven by GFR. Indeed, the majority (75%) of proteinuric patients do not have a GFR < 60 mg/min. Intuitively, since either PRO or stage of CKD predicts risk, the combination of the two might be an even better risk predictor.
To study the relationship of CKD, PRO, or the combination with outcomes, data from 920,985 Canadian adults was analyzed. Persons with end-stage renal disease at study inception were excluded.
Over 35 months of follow-up, for each decrement in GFR, all-cause mortality, MI, and end-stage renal disease increased. Within each quartile of GFR, progressively increasing levels of proteinuria (normal, mild, heavy) were associated with increased risk. Persons with the very lowest GFR (i.e., most advanced kidney disease), however, experienced less relative impact per degree of proteinuria; in other words, adverse outcomes are more compounded by proteinuria in CKD 2-4 than CKD 5.
The recent adoption of a standardized staging system for CKD is a major step forward. These data suggest that future stratification methods would benefit from inclusion of proteinuria as well as GFR.
Remission of diabetes with bariatric surgery
Source: Wilson JB, Pories WJ. Durable remission of diabetes after bariatric surgery: What is the underlying pathway? Insulin 2010;5:46-55.
The burgeoning population of individuals with type 2 diabetes (DM2) corresponds to a parallel increase in obesity. Although bariatric surgery produces prompt and sustainable weight loss, the post-surgical rapidity with which derangements of diabetes resolve defies explanation by weight loss alone.
Bariatric surgical procedures that eliminate food contact with the duodenum and jejunum as opposed to gastric banding type procedures produce not only substantial weight loss, but also provide remission of DM2 within days. Indeed, as many as 80% of DM2 patients leave the hospital with no diabetes medications, and more than 75% remain DM2-free 5 years later. Similar reversion to normal glucose handling has also been seen in IGT patients who have bypass surgery.
Post-surgical benefits of bariatric surgery include resumption of normal menstrual function, BP and lipid improvements, and reductions in diabetes-related mortality. Studies of gastric banding conclude that weight loss is responsible for these favorable outcomes; in contrast, bariatric bypass surgery, although enjoying benefits attributable to weight loss, has other operant mechanisms: One report of intestinal bypass in lean DM2 individuals found resolution of diabetes without weight loss.
The GI tract has been increasingly recognized as a critical player in glucose dysregulation, as evidenced by evolution of the incretin mimetics and DPP-4 inhibitors. Resolution of dysglycemia within a few days prior to meaningful weight loss is characteristic of bariatric bypass surgery.
Inhaled cortico-steroids and COPD exacerbations
Source: Agarwal R, et al. Inhaled corticosteroids vs placebo for preventing COPD exacerbations: A systematic review and metaregression of randomized controlled trials. Chest 2010;137:318-325.
Acute exacerbations of COPD (AE-COPD) are costly to patients. Not only is the symptomatic deterioration and commonplace requirement for hospitalization burdensome, but an AE-COPD is typically followed by loss of pulmonary function that does not return. Additionally, mortality from hospitalized AE-COPD has been reported to be as high as 10%.
We have no known disease-modifying pharmacotherapy for COPD. Although symptom improvement is considerable from bronchodilators and inhaled corticosteroids (ICS), they do not change disease progression. Short of that outcome, reduction in AE-COPD is a worthy goal to seek.
Agarwal et al reviewed data from 11 placebo-controlled COPD trials (n = 8164) employing ICS to examine the impact upon AE-COPD. Overall, ICS use was associated with an 18% relative risk reduction in AE-COPD; this beneficial effect was driven primarily by persons with an FEV1 < 50%.
Recent meta-analyses have shown an increased risk of pneumonia in COPD patients receiving ICS. Because the risk reduction for AE-COPD is modest, careful consideration to the risk-benefit balance of ICS use is appropriate.
Non-alcoholic fatty liver disease in Japanese patients
Source: Hamaguchi E, et al. Histological course of nonalcoholic fatty liver disease in Japanese patients. Tight glycemic control, rather than weight reduction, ameliorates liver fibrosis. Diabetes Care 2010;33:284-286.
In the United States, diabetes and metabolic syndrome are the disorders most commonly associated with non-alcoholic fatty liver diseases (NAFLD). Because obesity, dyslipidemia, hypertension, and insulin resistance are typical operative components of these disorders, it is difficult to make a clear attribution about which is the primary culprit leading to NAFLD.
Japanese subjects do not demonstrate the same degree of obesity as Americans. Study of NAFLD in this population might provide insight about the primary drivers of pathology.
Serial liver biopsies on two occasions were obtained from 39 Japanese NAFLD patients over a mean follow-up of 2.4 years. During this interval, NAFLD improved in 30.7%, worsened in 28.2%, and was unchanged in 41%.
Improvement in glycemic control, as measured by A1C, was the best predictor of NAFLD improvement. Transforming growth factor-beta and plasminogen activator inhibitor type 1 are known regulators of hepatic fibrosis, both of which are stimulated by high glucose levels.