Power to identify a genetic predictor of antihypertensive drug response using different methods to measure blood pressure response

<p>Abstract</p> <p>Background</p> <p>To determine whether office, home, ambulatory daytime and nighttime blood pressure (BP) responses to antihypertensive drug therapy measure the same signal and which method provides greatest power to identify genetic predictors of BP response.</p> <p>Methods</p> <p>We analyzed office, home, ambulatory daytime and nighttime BP responses in hypertensive adults randomized to atenolol (N = 242) or hydrochlorothiazide (N = 257) in the Pharmacogenomic Evaluation of Antihypertensive Responses Study. Since different measured BP responses may have different predictors, we tested the "same signal" model by using linear regression methods to determine whether known predictors of BP response depend on the method of BP measurement. We estimated signal-to-noise ratios and compared power to identify a genetic polymorphism predicting BP response measured by each method separately and by weighted averages of multiple methods.</p> <p>Results</p> <p>After adjustment for pretreatment BP level, known predictors of BP response including plasma renin activity, race, and sex were independent of the method of BP measurement. Signal-to-noise ratios were more than 2-fold greater for home and ambulatory daytime BP responses than for office and ambulatory nighttime BP responses and up to 11-fold greater for weighted averages of all four methods. Power to identify a genetic polymorphism predicting BP response was directly related to the signal-to-noise ratio and, therefore, greatest with the weighted averages.</p> <p>Conclusion</p> <p>Since different methods of measuring BP response to antihypertensive drug therapy measure the same signal, weighted averages of the BP responses measured by multiple methods minimize measurement error and optimize power to identify genetic predictors of BP response.</p

Beyond the Evidence of the New Hypertension Guidelines. Blood pressure measurement – is it good enough for accurate diagnosis of hypertension? Time might be in, for a paradigm shift (I)

Despite widespread availability of a large body of evidence in the area of hypertension, the translation of that evidence into viable recommendations aimed at improving the quality of health care is very difficult, sometimes to the point of questionable acceptability and overall credibility of the guidelines advocating those recommendations. The scientific community world-wide and especially professionals interested in the topic of hypertension are witnessing currently an unprecedented debate over the issue of appropriateness of using different drugs/drug classes for the treatment of hypertension. An endless supply of recent and less recent "drug-news", some in support of, others against the current guidelines, justifying the use of selected types of drug treatment or criticising other, are coming out in the scientific literature on an almost weekly basis. The latest of such debate (at the time of writing this paper) pertains the safety profile of ARBs vs ACE inhibitors. To great extent, the factual situation has been fuelled by the new hypertension guidelines (different for USA, Europe, New Zeeland and UK) through, apparently small inconsistencies and conflicting messages, that might have generated substantial and perpetuating confusion among both prescribing physicians and their patients, regardless of their country of origin. The overwhelming message conveyed by most guidelines and opinion leaders is the widespread use of diuretics as first-line agents in all patients with blood pressure above a certain cut-off level and the increasingly aggressive approach towards diagnosis and treatment of hypertension. This, apparently well-justified, logical and easily comprehensible message is unfortunately miss-obeyed by most physicians, on both parts of the Atlantic. Amazingly, the message assumes a universal simplicity of both diagnosis and treatment of hypertension, while ignoring several hypertension-specific variables, commonly known to have high level of complexity, such as: - accuracy of recorded blood pressure and the great inter-observer variability, - diversity in the competency and training of diagnosing physician, - individual patient/disease profile with highly subjective preferences, - difficulty in reaching consensus among opinion leaders, - pharmaceutical industry's influence, and, nonetheless, - the large variability in the efficacy and safety of the antihypertensive drugs. The present 2-series article attempts to identify and review possible causes that might have, at least in part, generated the current healthcare anachronism (I); to highlight the current trend to account for the uncertainties related to the fixed blood pressure cut-off point and the possible solutions to improve accuracy of diagnosis and treatment of hypertension (II)

Prevention of hemodialysis-related muscle cramps by intradialytic use of sequential compression devices: A report of four cases

Background: Hemodialysis (HD)-related lower extremity (LE) muscle cramps are a common cause of morbidity in end-stage renal disease patients on maintenance HD. Numerous pharmacologic and physical measures have been tried with variable success rates. Methods: Sequential compression devices (SCD) improve venous return (VR) and are commonly used to prevent LE deep venous thrombosis in hospitals. We hypothesized that LE cramps are triggered by stagnant venous flow during HD and are preventable by improving VR. We prospectively studied four adult patients (mean age 61 ± 14 years) on thrice-weekly HD who experienced two or more episodes of LE cramping weekly in the month before the study. SCD were applied before each HD on both legs and compressions were intermittently applied at 40 mmHg during treatment. Results: All four patients reported complete resolution of cramping during the study period that lasted 1 month or 12 consecutive dialysis treatments. Conclusion: Application of SCD to LE may prevent the generation of LE HD-related cramping in a select group of patients. Larger, controlled studies are needed to establish the utility of this noninvasive alternative for the prevention of LE HD-related cramps. © 2004 International Society for Hemodialysis