Blood pressure control and cardiovascular outcomes in normal-weight, overweight, and obese hypertensive patients treated with three different antihypertensives in ALLHAT.

OBJECTIVE: Epidemiologically, there is a strong relationship between BMI and blood pressure (BP) levels. We prospectively examined randomization to first-step chlorthalidone, a thiazide-type diuretic; amlodipine, a calcium-channel blocker; and lisinopril, an angiotensin-converting enzyme inhibitor, on BP control and cardiovascular outcomes in a hypertensive cohort stratified by baseline BMI [kg/m(2); normal weight (BMI <25), overweight (BMI = 25-29.9), and obese (BMI >30)]. METHODS: In a randomized, double-blind, practice-based Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, 33,357 hypertensive participants, aged at least 55 years, were followed for an average of 4.9 years, for a primary outcome of fatal coronary heart disease or nonfatal myocardial infarction, and secondary outcomes of stroke, heart failure, combined cardiovascular disease, mortality, and renal failure. RESULTS: Of participants, 37.9% were overweight and 42.1% were obese at randomization. For each medication, BP control (<140/90 mmHg) was equivalent in each BMI stratum. At the fifth year, 66.1, 66.5, and 65.1% of normal-weight, overweight, and obese participants, respectively, were controlled. Those randomized to chlorthalidone had highest BP control (67.2, 68.3, and 68.4%, respectively) and to lisinopril the lowest (60.4, 63.2, and 59.6%, respectively) in each BMI stratum. A significant interaction (P = 0.004) suggests a lower coronary heart disease risk in the obese for lisinopril versus chlorthalidone (hazard ratio 0.85, 95% confidence interval 0.74-0.98) and a significant interaction (P = 0.011) suggests a higher risk of end-stage renal disease for amlodipine versus chlorthalidone in obese participants (hazard ratio 1.49, 95% confidence interval 1.06-2.08). However, these results were not consistent among other outcomes. CONCLUSION: BMI status does not modify the effects of antihypertensive medications on BP control or cardiovascular disease outcomes.

Achieved blood pressures in the secondary prevention of small subcortical strokes (SPS3) study: challenges and lessons learned.

BACKGROUND: Lowering blood pressure (BP) after stroke remains a challenge, even in the context of clinical trials. The Secondary Prevention of Small Subcortical Strokes (SPS3) BP protocol, BP management during the study, and achieved BPs are described here. METHODS: Patients with recent symptomatic lacunar stroke were randomized to 1 of 2 levels of systolic BP (SBP) targets: lower: <130mm Hg, or higher: 130-149mm Hg. SBP management over the course of the trial was examined by race/ethnicity and other baseline conditions. RESULTS: Mean SBP decreased for both groups from baseline to the last follow-up, from 142.4 to 126.7mm Hg for the lower SBP target group and from 143.6 to 137.4mm Hg for the higher SBP target group. At baseline, participants in both groups used an average of 1.7±1.2 antihypertensive medications, which increased to a mean of 2.4±1.4 (lower group) and 1.8±1.4 (higher group) by the end-study visit. It took an average of 6 months for patients to reach their SBP target, sustained to the last follow-up. Black participants had the highest proportion of SBP ≥150mm Hg at both study entry (40%) and end-study visit (17%), as compared with whites (9%) and Hispanics (11%). CONCLUSIONS: These results show that it is possible to safely lower BP even to a SBP goal <130mm Hg in a variety of patients and settings, including private and academic centers in multiple countries. This provides further support for protocol-driven care in lowering BP and consequently reducing the burden of stroke.

Predictors of lowering SBP to assigned targets at 12 months in the Secondary Prevention of Small Subcortical Strokes study.

OBJECTIVE: Lowering blood pressure for secondary stroke prevention remains a challenge. These analyses were conducted to identify factors predicting achievement of SBP targets in the Secondary Prevention of Small Subcortical Strokes (SPS3) study. METHODS: SPS3 is a randomized trial assigning patients with lacunar stroke to two targets of SBP control (130-149 mmHg or <130 mmHg). Logistic regression models were used to identify patient and SPS3 site characteristics predictive of lowering SBP to target at the 12-month study visit. RESULTS: Of those above target at baseline (n = 1041), 69% were within their assigned target at 12 months. In the model with baseline characteristics only, those receiving treatment for hypertension at baseline were 68% less likely to achieve target [odds ratio (OR) = 0.32; 95% confidence interval (CI) = 0.17-0.60], whereas those of Hispanic ethnicity were 1.49 times more likely (95% CI = 1.09-2.03) to achieve SBP target. When clinical site characteristics were added to the model, only treated hypertension at baseline remained significant. In addition, management at a larger site (OR = 1.51; 95% CI = 1.03-2.20), SBP in target at 6 months (OR = 2.39; 95% CI = 1.79-3.19), and medication adherence (OR = 2.73; 95% CI = 1.51-4.95) were positively associated with achieving target SBP. Missed appointments (OR = 0.55; 95% CI = 0.41-0.73) were negatively associated with lowering SBP to target at 12 months. CONCLUSION: These results demonstrate that it is feasible to achieve targets of SBP control in this multiethnic stroke cohort across multiple sites and countries. The results highlight the important variables reflecting clinical site management.

Discarding the first of three nurse-auscultatory or oscillometric blood pressure measurements does not improve the association of office blood pressure with ABPM.

OBJECTIVE: Guidelines for office blood pressure (BP) measurements recommend two or more readings at each visit. It has been suggested that discarding the first reading may improve the diagnostic utility of office readings. We compare two methods of office BP measurement to determine whether discarding the first BP affects their association with ambulatory blood pressure monitoring (ABPM) readings. METHODS: We studied measurements in 313 mildly hypertensive patients (181 men, median age 51 years) at the end of the washout phase of a hypertension treatment trial. All patients had three auscultatory readings by a trained nurse using a mercury manometer before a 24-h ABPM and three automated readings (Omron 705 CP) to American Heart Association standards after ABPM. Daytime ABPM (09:00-21:00) of systolic BP and diastolic BP were compared with office methods using first only, second and third only, and all three readings. Associations were assessed using Bland-Altman plots and Pearson's correlations. RESULTS: Bland-Altman plots revealed no differences between office methods and daytime ABPM regardless of whether the first reading was included or discarded. Results were similar for both systolic BP and diastolic BP. The Pearson correlations of office method readings with ABPM readings were lowest using the first measurement alone; however, discarding the first measurement did not improve the correlation compared with using all three readings. CONCLUSION: Discarding the first office BP reading does not change the association of office BP with ABPM or improve the correlation with ABPM values in hypertensive patients.

Diagnosis and management of chronic kidney disease.

As the US population has continued to age, the number of patients with chronic kidney disease (CKD) has dramatically increased. Faced with this increase, clinicians need a better understanding of what an elevated serum creatinine level represents and a simple codified approach to evaluating renal failure. Creatinine, a muscle waste product, has an imperfect but predictable association with the glomerular filtration rate (GFR). Although other markers of GFR exist, including cystatin C, urea, inulin, and radioisotopic methods, their role in estimating GFR remains a matter for debate, especially that of cystatin C. Diagnosis and management of CKD are challenges for the nonspecialist. We describe a systematic approach that can be used by the nonspecialist to identify most but not all causes of renal insufficiency. Although this approach should allow for earlier recognition of treatable causes of CKD, it does not eliminate the involvement of a nephrologist in the care and management of the conditions causing the renal insufficiency. The nonspecialist should also be able to recognize the 9 therapies that are helpful in preservation of renal function in all patients with CKD.

Novel use of Kaplan-Meier methods to explain age and gender differences in hypertension control rates.

Despite 40 years of research demonstrating the efficacy of antihypertensive medications for lowering blood pressure and decreasing cardiovascular disease, hypertension control rates worldwide remain low. We explored here how both medication efficacy rates and patient/physician decision-making (discontinuation rates) affect overall hypertension control rates. To do this we introduced the use of Kaplan-Meier methodology to predict hypertension control rates separately within age strata. An important aspect of our analysis is the use of a "treatment intensity score," including both the number of agent(s) and the percentage of maximal dose of agent(s). We investigated how blood pressure control rates vary with age, gender, and treatment intensity. Our analysis found that both efficacy and discontinuation rates at different treatment intensities vary with age and gender, so that for each increase in age by 1 decade, the log hazard of achieving controlled blood pressure at any given intensity decreases by 0.10 in men and 0.20 in women. Overall hypertension control rates ranged from 80.8% for persons age 15 to 39 years to only 42.1% for persons age >/=80 years. Our analysis more accurately represents achievable hypertension control rates, with differences by gender, than previous work, because we investigated the contributions of efficacy and treatment aggressiveness in the control of hypertension.

What is adequate hypertension control? Having your dinner and dessert too.

Now that many options for treating hypertension are available and the studies of their use have proliferated, selecting a specific antihypertensive agent for a specific condition often receives an inordinate amount of attention from physicians. Controlling the blood pressure per se should be our primary concern ("dinner"), while choosing agents that may have added benefit in specific situations is secondary ("dessert").

Reliability and validity of blood pressure measurement in the Secondary Prevention of Small Subcortical Strokes study.

RATIONALE: The Secondary Prevention of Small Subcortical Strokes study is a multicenter, international trial funded by the National Institutes of Health testing the role of lowering systolic blood pressure to <130 mmHg in the prevention of stroke recurrence and cognitive decline in patients with recent symptomatic small subcortical stroke. Reliable and unbiased blood pressure measurement is critical to successful completion of the trial. METHODS: We looked at the reliability and validity of both the device used for blood pressure measurement and observer performance during measurement to assess the quality of blood pressure determination in the study. The Colin 8800C blood pressure device was tested for performance to Association for the Advancement of Medical Instrumentation standards and for presence of skipped digits. Observer performance was tested by examining adherence to the Secondary Prevention of Small Subcortical Strokes protocol. RESULTS: The mean difference (in mmHg) between the Colin device and the average of the two observers was 3.9 (SD 6.7) and -2.1 (SD 6.1) for systolic and diastolic pressures respectively, thereby meeting Association for the Advancement of Medical Instrumentation requirements. No skipped digits were found between 82-230 and 40-120 mmHg for systolic and diastolic pressures, respectively. Observer performance was excellent with greater than 90% of patients having blood pressure measured consistently according to the protocol. CONCLUSIONS: Device and observer performance in Secondary Prevention of Small Subcortical Strokes is excellent. Interpretation of the Secondary Prevention of Small Subcortical Strokes data for the effect of lowering systolic blood pressure on patient outcomes will not likely be adversely affected by these factors. Accuracy will be monitored throughout the remainder of the trial to ensure that this high quality is maintained.

The occurrence of the alerting response is independent of the method of blood pressure measurement in hypertensive patients.

OBJECTIVE: Current guidelines stress the need for more than one measurement of blood pressure in the hypertensive patient. The frequency with which the first blood pressure significantly exceeds subsequent blood pressures (alerting response) is unknown. Participants in a hypertension treatment trial before initiation of therapy were included in post-hoc analyses to investigate the alerting response separately for trained nurse blood pressure measurements with mercury sphygmomanometer and measurements taken by an Omron 705 CP automated device. BASIC METHODS: A total of 313 participants were included. Each participant had three nurse blood pressure readings before a 24-h automated blood pressure monitoring device was attached, and three Omron measurements at the time the automated blood pressure monitoring device was removed. Alerting response was defined separately for systolic and diastolic measures as a decrease of > or =8 or > or =6 mmHg, respectively, from first measure to the average of the second and third measures. MAIN RESULTS: An alerting response was observed in 20.4% of nurse-performed blood pressure measurements and 28.4% of Omron measurements. A large range of variation between first blood pressure and average second and third measures was observed, with changes of up to 30 mmHg systolic and 20 mmHg diastolic. The only demographic factor associated with the alerting response was body mass index, with obese patients more likely to exhibit an alerting response (P=0.004) in nurse-measured blood pressure. CONCLUSIONS: We found the alerting response with both methods of blood pressure measurement; however, it was not consistently observed in the same individuals. This confirms that hypertensive patients require multiple blood pressure measurements.

Utility of ambulatory blood pressure monitoring in children and adolescents.

Diagnosis of hypertension is critically dependent on accurate blood pressure measurement. "Accurate" refers to carefully following the guidelines for blood pressure measurement laid out for children and adults to minimize observer and subject errors that commonly occur in clinical blood pressure measurement. Accurate blood pressure measurement is more important in children and adolescents as the misdiagnosis of hypertension may have a life-long adverse impact on insurability and employment. Automated blood pressure measurement offers multiple advantages in achieving high-quality blood pressure determinations by reducing observer errors. The most commonly used form of automated blood pressure measurement is 24-h ambulatory blood pressure measurement (ABPM). Information on ABPM in children has grown exponentially over the last decade. Normative data exists for diagnosis of hypertension in children using ABPM including a novel method for determining normal values with the LMS method. There is further information about the utility of different determinants of 24-h blood pressure such as dipping status, morning surge and blood pressure load. ABPM has been able to detect significant differences in blood pressure in many disease states in children including chronic renal failure, polycystic kidney disease, solitary functioning kidney, and after renal transplantation. Increasingly nonambulatory automated blood pressure determinations have been used in management of hypertension in children. Although nonambulatory automated readings lack information about nocturnal blood pressure or blood pressure during daily activity, studies have suggested that home automated blood pressure measurements are a helpful adjunct to the usual office blood pressure reading.

The impact of observer and patient factors on the occurrence of digit preference for zero in blood pressure measurement in a hypertension specialty clinic: evidence for the need of continued observation.

BACKGROUND: Many investigators have reported unconscious over-reporting of the terminal digit zero but little literature exists on observer or patient-related factors that may predict the occurrence. This study analyzes the occurrence of zero preference in 52,827 blood pressure (BP) measurements in 8513 patients by 11 hypertension nurse specialists in the Hypertension Division at Mayo Clinic, Rochester, Minnesota. METHODS: Data from the electronic database of the Hypertension Division from April 1997 to September 2001 were analyzed for the occurrence of zero preference. Nurse-specific zero preference was stratified on four variables: number of BPs performed, years as hypertension nurse specialist, time of day BP performed (fatigue), and nursing degree. Three patient-specific factors were analyzed: age at visit (stratified by decade), type of care (continuing versus short-term), and hypertension status. RESULTS: We found significantly increased frequency of zero preference for all BPs with mean frequency of 31% v 20% expected (P < .0001). Individual nurse zero preference varied widely, 22.0% to 53.6% for systolic BP and 22.2% to 40.8% for diastolic BP). Continuing care patients had a higher zero preference than did short-term care patients for both systolic BP (34.5% v 30.2%; P < .0001) and diastolic BP (34.7% v 33.3%; P = .006). Zero preference was also more common at higher categories of hypertension (P < .001). Time of day, nursing degree, patient age, the number of BPs performed, years of service did not affect the occurrence of digit preference. CONCLUSIONS: Digit preference was demonstrated and varied significantly among well-trained hypertension nurse specialists. Further studies in a larger number of observers are required.

The trained observer better predicts daytime ABPM diastolic blood pressure in hypertensive patients than does an automated (Omron) device.

OBJECTIVES: Accurate blood pressure measurement is critical to successful clinical trials. Concerns about observer errors have led to the use of automated oscillometric devices without evidence that their performance is similar to that of trained observers. This study compares blood pressures obtained by trained observers and with an oscillometric device (Omron 705CP) to 24-h ambulatory blood pressure monitoring. METHODS: We performed a post-hoc analysis of 313 untreated hypertensive patients at the end of the washout phase of a Novartis hypertension trial. Patients had three seated trained observer mercury auscultatory blood pressure measurements followed by 24-h ambulatory blood pressure monitoring. The next day, the ambulatory blood pressure monitoring was removed and three seated readings were obtained with an Omron 705CP. Correlations for systolic blood pressure and diastolic blood pressure were obtained between daytime ambulatory blood pressure monitoring (0900 and 2100) and the two office methods. In addition, we investigated the degree of difference of trained observer and Omron measurements from ambulatory blood pressure monitoring. RESULTS: For systolic blood pressure, the correlation with ambulatory blood pressure monitoring of the trained observer was significantly better than with that of the Omron 705CP (0.641 vs. 0.555, P=0.01). For diastolic blood pressure values, even greater disparity between the two office method correlations with ambulatory blood pressure monitoring was observed (trained observer=0.593 vs. Omron=0.319, P<0.0001). Both trained observer and Omron readings were consistently higher than ambulatory blood pressure monitoring for systolic blood pressure (P<0.0001) and diastolic blood pressure (P<0.0001). Omron measurements, however, deviated from ambulatory blood pressure monitoring more than those of the trained observer (P<0.0001 for systolic blood pressure and diastolic blood pressure). CONCLUSIONS: For clinical trials using diastolic blood pressure targets, the Omron 705CP cannot replace the auscultatory blood pressure measurements of a trained observer. For systolic blood pressure, the Omron device and the trained observer had similar correlations with ambulatory blood pressure monitoring; however, both methods gave consistently higher systolic blood pressure values. Further study of oscillometric devices should be conducted before universally replacing auscultatory blood pressure determinations by trained observers in clinical trials.

Limited (6-h) ambulatory blood pressure monitoring is a valid replacement for the office blood pressure by trained nurse clinician in the diagnosis of hypertension.

OBJECTIVE: To assess the ability of limited ambulatory blood pressure monitoring as a valid replacement for office blood pressure measurement done to American Heart Association criteria in diagnosing hypertension. METHODS: In all, 105 adults, who had been referred for limited ambulatory blood pressure monitoring, participated in the study. Limited ambulatory blood pressure monitoring consisted of 6 h of blood pressure measurement while ambulatory at the Mayo Clinic, using a SpaceLabs 90207 (SpaceLabs Medical, Issaquah, Washington, USA) collecting six readings per hour for the period of observation. The study participants gave consent for three additional consecutive office blood pressure measurements, using a validated aneroid device, done to American Heart Association criteria, by a single hypertension nurse specialist. RESULTS: Mean systolic blood pressure by limited ambulatory blood pressure monitoring was 137.9+/-14.2 mmHg and for the nurse, 137.9+/-20.1 mmHg. Mean diastolic blood pressure by limited ambulatory blood pressure monitoring was 81.5+/-9.7 mmHg and for the nurse, 74.3+/-11.9 mmHg. The intermethod difference for systolic blood pressure was 0.03+/-12.5 mmHg and diastolic blood pressure, -7.2+/-8.0 mmHg. Using <140/90 as criteria factor, limited ambulatory blood pressure monitoring and the trained nurse agreed 77% of the time on whether the patient was hypertensive. This agreement increased to 81% if the participant's referral blood pressure was >or=140/90. CONCLUSIONS: Limited ambulatory blood pressure monitoring is an excellent replacement for office blood pressure, done to American Heart Association criteria, in diagnosing hypertension. This avoids issues of variability introduced by the observers, such as digit preference and bias, and increases reproducibility of blood pressure measurements. The appropriate normal value for limited ambulatory blood pressure monitoring is <140/90 mmHg compared with <135/85 mmHg used in 24-h ambulatory blood pressure monitoring.

A survey of validated automated home blood pressure monitors available for the Internet shopper.

OBJECTIVE: Self-measurement of blood pressure using an automated home blood pressure monitoring (AHBPM) is increasingly used in hypertension management. Internet commerce increases dramatically each year. This study looked to identify the availability of validity of AHBPM and the correct cuff size to go with the AHBPM. METHODS AND RESULTS: Using the search engine 'Google.com', the author identified 124 consecutive unique sites offering at least one AHBPM. Validated AHBPM were those devices that had published studies showing that they had passed a recognized validation protocol. Each site was evaluated for all forms of sphygmomanometer, number of AHBPM, manual blood pressure devices, all cuff sizes available, additional cost of large adult cuff, number of validated AHBPM offered, and whether the site mentioned device validation. Of the 124 sites, 109 (81%) offered arm AHBPM and 66 (53%) offered one or more (range, 1-11) validated AHBPM. Only six of the 66 (9%) offering a validated AHBPM mentioned that fact; 58 of the 109 (53%) sites offering arm AHBPM offered more than one size of cuff; and 46 of the 58 (80%) charged extra for a large adult cuff (average US dollars 23.75, range, US dollars 4.80-98). CONCLUSIONS: Validated AHBPMs are readily available on the Internet. Currently, these sites do little to aid the consumer in purchasing a validated AHBPM. Large adult cuffs, commonly needed by hypertensive patients, are not always available for purchase. Charging extra for large adult cuffs is a potential hindrance to consumers purchasing the correct cuff size for accurate blood pressure measurement and should be eliminated.

Does evidence-based medicine suggest that physicians should not be measuring blood pressure in the hypertensive patient?

The most common reason for an outpatient physician visit is for the diagnosis and treatment of hypertension. The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC) VII, which is increasingly evidence-based, advises the clinician to use studies of the mean response and benefit derived from reduction in blood pressure (BP) from antihypertensive therapy and to translate this data into recommendations for the individual hypertensive patient. We believe that the increasingly aggressive approach to hypertension mandated by JNC VII calls into question the use of physician-measured BP. Ample evidence has shown that phycisians have not been adequately trained to measure BP and, therefore, rarely measure BP to the standards asked for by JNC VII or the American Heart Association (AHA) guidelines. In addition, the white coat effect dilutes the validity and usefulness of physician-measured BPs. Finally, in the evidenced-based studies used to derive the JNC VII guidelines, BPs were measured by nurses, other "trained observers," or automated devices, not physicians. Accurate BP measurement is critical to diagnosis and management of hypertension. We recommend, therefore, that for this purpose physicians should not measure BP themselves but should rely on BPs from well-trained and monitored observers or validated automated devices to improve the quality of care of the hypertensive patient.

The Accoson Greenlight 300, the first non-automated mercury-free blood pressure measurement device to pass the International Protocol for blood pressure measuring devices in adults.

BACKGROUND: Accurate blood pressure measurement is critical to successful care of the hypertensive patient. The mercury manometer is rapidly being removed from clinical practice due to concerns about environmental contamination. The Accoson Greenlight 300 device is the first non-automated mercury-free device for auscultatory blood pressure measurement to pass the International Protocol for validation of blood pressure measuring devices in adults. METHODS: Fifty-one patients were enrolled to obtain the 33 patients required to fill the three systolic blood pressure (SBP) ranges (low 90-129 mmHg, medium 130-160 mmHg, high 161-180 mmHg) and diastolic blood pressure (DBP) ranges (low 40-79 mmHg, medium 80-100 mmHg, high 101-130 mmHg). Nine sequential blood pressure measurements by two observers with the mercury manometer and the supervisor with the Greenlight 300 were taken. The first two observer blood pressures were used to classify the SBP and DBP range. The readings were then analyzed in two phases to determine whether the device passed the International Protocol. RESULTS: The device passed Phase 1 using 15 subjects. In Phase 2.1 (n=33) for the 99 readings of SBP, 84 of 99 were within 5 mmHg, 95 of 99 were within 10 mmHg, and 98 of 99 were within 15 mmHg. For the 99 readings of DBP, 74 of 99 were within 5 mmHg, 90 of 99 were within 10 mmHg, and 96 of 99 were within 15 mmHg. In Phase 2.2 (n=33) for SBP, 33 of 33 had 2 of 3 SBP within 5 mmHg and none had all three readings >or=5 mmHg. For DBP, 27 of 33 had 2 of 3 of their DBP within 5 mmHg and only three had all three readings > or =5 mmHg. CONCLUSIONS: The Accoson Greenlight 300 is the first electronic non-automated blood pressure measurement device to pass the International Protocol.