Incidence and prognosis of resistant hypertension in hypertensive patients.

BACKGROUND: Despite a recent American Heart Association (AHA) consensus statement emphasizing the importance of resistant hypertension, the incidence and prognosis of this condition are largely unknown. METHODS AND RESULTS: This retrospective cohort study in 2 integrated health plans included patients with incident hypertension in whom treatment was begun between 2002 and 2006. Patients were followed up for the development of resistant hypertension based on AHA criteria of uncontrolled blood pressure despite use of ≥3 antihypertensive medications, with data collected on prescription filling information and blood pressure measurement. We determined incident cardiovascular events (death or incident myocardial infarction, heart failure, stroke, or chronic kidney disease) in patients with and without resistant hypertension with adjustment for patient and clinical characteristics. Among 205 750 patients with incident hypertension, 1.9% developed resistant hypertension within a median of 1.5 years from initial treatment (0.7 cases per 100 person-years of follow-up). These patients were more often men, were older, and had higher rates of diabetes mellitus than nonresistant patients. Over 3.8 years of median follow-up, cardiovascular event rates were significantly higher in those with resistant hypertension (unadjusted 18.0% versus 13.5%, P<0.001). After adjustment for patient and clinical characteristics, resistant hypertension was associated with a higher risk of cardiovascular events (hazard ratio, 1.47; 95% confidence interval, 1.33-1.62). CONCLUSIONS: Among patients with incident hypertension in whom treatment was begun, 1 in 50 patients developed resistant hypertension. Patients with resistant hypertension had an increased risk of cardiovascular events, which supports the need for greater efforts toward improving hypertension outcomes in this population.

Age-dependent gender differences in hypertension management.

OBJECTIVE: Despite gender-neutral guidelines, prior studies suggest that women have lower rates of hypertension control and these differences may vary with age. Accordingly, we compared rates of hypertension control between women and men as a function of age. METHODS: Within three integrated healthcare systems in the Cardiovascular Research Network, we studied all patients seen from 2001 to 2007 with incident hypertension. Within 1 year of cohort entry, patient's hypertension was categorized as controlled based upon achieving guideline-recommended blood pressure levels, recognized if hypertension was diagnosed or a hypertension medication dispensed, and treated based on hypertension medications dispensed. Multivariable logistic regression models assessed the association between gender and 1-year hypertension outcomes, adjusted for patient characteristics. RESULTS: Among the 152,561 patients with incident hypertension, 55.6% were women. Compared to men, women were older, had more kidney disease and more blood pressure measures during follow-up. Overall, men tended to have lower rates of hypertension control compared to women (41.2 vs. 45.7%, adjusted odds ratio 0.93, 95% confidence interval 0.91-0.95). A significant gender by age interaction was found with men aged 18-49 having 17% lower odds of hypertension control and men aged at least 65 having 12% higher odds of hypertension control compared to women of similar ages (P<0.001). CONCLUSION: In this incident hypertension cohort, younger men and older women had lower rates of hypertension control compared to similarly aged peers. Future studies should investigate why gender differences vary by age in order to plan appropriate means of improving hypertension management regardless of gender or age.

Trends in time to confirmation and recognition of new-onset hypertension, 2002-2006.

Achieving full benefits of blood pressure control in populations requires prompt recognition of previously undetected hypertension. In 2003, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure provided definitions of hypertension and recommended that single elevated readings be confirmed within 1 to 2 months. We sought to determine whether the time required to confirm and recognize (ie, diagnose and/or treat) new-onset hypertension decreased from 2002 to 2006 for adult members of 2 large integrated healthcare delivery systems, Kaiser Permanente Northern California and Colorado. Using electronically stored office blood pressure readings, physician diagnoses, and pharmacy prescriptions, we identified 200 587 patients with new-onset hypertension (2002-2006) marked by 2 consecutive elevated blood pressure readings in previously undiagnosed, untreated members. Mean confirmation intervals (time from the first to second consecutive elevated reading) declined steadily from 103 to 89 days during this period. For persons recognized within 12 months after confirmation, the mean interval to recognition declined from 78 to 61 days. However, only 33% of individuals were recognized within 12 months. One third were never recognized during observed follow-up. For these patients, most subsequent blood pressure recordings were not elevated. Higher initial blood pressure levels, history of previous cardiovascular disease, and older age were associated with shorter times to recognition. Times to confirmation and recognition of new-onset hypertension have become shorter in recent years, especially for patients with higher cardiovascular disease risk. Variability in office-based blood pressure readings suggests that further improvements in recognition and treatment may be achieved with more specific automated approaches to identifying hypertension.

Comparative effectiveness of angiotensin-converting enzyme inhibitors versus beta-blockers as second-line therapy for hypertension.

BACKGROUND: Trials comparing hypertension monotherapies have found either no difference or modest differences in blood pressure (BP) and cardiovascular events. However, no trial has assessed the comparative effectiveness of 2nd-line therapy in patients whose BP was not controlled with a thiazide diuretic. METHODS AND RESULTS: This was an observational study conducted with a hypertension registry of adults enrolled in 3 large integrated health care delivery systems from 2002 to 2007. Patients newly started on thiazide monotherapy whose BP remained uncontrolled were observed after addition of either an angiotensin-converting enzyme (ACE) inhibitor or ß-blocker for subsequent BP control and cardiovascular events. Patients for whom either add-on drug was indicated or contraindicated were excluded. After adjustment for patient characteristics and study year, BP control during the subsequent 6 to 18 months was comparable for the 2 agents (70.5% ACE, 69.0% ß-blockers; P=0.09). Rates of incident myocardial infarction (hazard ratio, 1.05; 95% confidence interval, 0.69 to 1.58) and stroke (hazard ratio, 1.01; 95% confidence interval, 0.68 to 1.52) were also similar for the ACE inhibitor and ß-blocker groups during an average of 2.3 years of follow-up. There were also no differences in heart failure or renal function. CONCLUSIONS: ACE inhibitors and ß-blockers are equally effective in lowering BP and preventing cardiovascular events for patients whose BP is not controlled with a thiazide diuretic alone and who have no compelling indication for a specific 2nd-line agent.

Prevalence of osteonecrosis of the jaw in patients with oral bisphosphonate exposure.

PURPOSE: Osteonecrosis of the jaw (ONJ) is a serious complication associated with bisphosphonate therapy, but its epidemiology in the setting of oral bisphosphonate therapy is poorly understood. The present study examined the prevalence of ONJ in patients receiving chronic oral bisphosphonate therapy. MATERIALS AND METHODS: We mailed a survey to 13,946 members who had received chronic oral bisphosphonate therapy as of 2006 within a large integrated health care delivery system in Northern California. Respondents who reported ONJ, exposed bone or gingival sores, moderate periodontal disease, persistent symptoms, or complications after dental procedures were invited for examination or to have their dental records reviewed. ONJ was defined as exposed bone (of >8 weeks' duration) in the maxillofacial region in the absence of previous radiotherapy. RESULTS: Of the 8,572 survey respondents (71 +/- 9 years, 93% women), 2,159 (25%) reported pertinent dental symptoms. Of these 2,159 patients, 1,005 were examined and an additional 536 provided dental records. Nine ONJ cases were identified, representing a prevalence of 0.10% (95% confidence interval 0.05% to 0.20%) among the survey respondents. Of the 9 cases, 5 had occurred spontaneously (3 in palatal tori) and 4 occurred in previous extraction sites. An additional 3 patients had mandibular osteomyelitis (2 after extraction and 1 with implant failure) but without exposed bone. Finally, 7 other patients had bone exposure that did not fulfill the criteria for ONJ. CONCLUSIONS: ONJ occurred in 1 of 952 survey respondents with oral bisphosphonate exposure (minimum prevalence of 1 in 1,537 of the entire mailed cohort). A similar number had select features concerning for ONJ that did not meet the criteria. The results of the present study provide important data on the spectrum of jaw complications among patients with oral bisphosphonate exposure.

Glycemic response to newly initiated diabetes therapies.

OBJECTIVE: The glycemic response to antihyperglycemic therapies for type 2 diabetes has been thoroughly evaluated in randomized controlled trials, but inadequately studied in real-world settings. STUDY DESIGN: We studied glycemic response among 15 126 type 2 diabetic patients who initiated any single new antihyperglycemic agent (metformin, sulfonylureas, thiazolidinediones, or insulin added to medical nutrition therapy or to existing diabetes therapies) during 1999-2000 within Kaiser Permanente of Northern California, an integrated healthcare delivery system. METHODS: Pre-post (3-12 months after initiation) change in glycosylated hemoglobin (A1C) was analyzed using ANCOVA (analysis of covariance) models adjusted for baseline A1C, concurrent (ongoing) antihyperglycemic therapy, demographics, health behaviors, medication adherence, clinical factors, and processes of care. RESULTS: Mean A1C was 9.01% (95% confidence interval [CI] 8.98%-9.04%) before therapy initiation and 7.87% (95% CI 7.85%-7.90%) 3 to 12 months after initiation (mean A1C reduction 1.14 percentage points; 95% CI 1.11-1.17). Overall, 30.2% (95% CI 29.2%-31.1%) of patients achieved glycemic target (A1C < 7%). Although baseline disease severity and concurrent therapies differed greatly across therapeutic classes, after adjustment for these baseline clinical characteristics, no significant differences were noted in glucose-lowering effect across therapeutic classes. Treatment effects did not differ by age, race, diabetes duration, obesity, or level of renal function. CONCLUSIONS: Metformin, sulfonylures, thiazolidinediones, and insulin were equally effective in improving glucose control. Nonetheless, most patients failed to achieve the glycemic target. Findings suggest that, to keep up with progressive worsening of glycemic control, patients and providers must commit to earlier, more aggressive therapy intensification, triggered promptly after A1C exceeds the recommended glycemic target.

Longitudinal study of new and prevalent use of self-monitoring of blood glucose.

OBJECTIVE: We sought to assess longitudinal association between self-monitoring of blood glucose (SMBG) and glycemic control in diabetic patients from an integrated health plan (Kaiser Permanente Northern California). RESEARCH DESIGN AND METHODS: Longitudinal analyses of glycemic control among 1) 16,091 patients initiating SMBG (new-user cohort) and 2) 15,347 ongoing users of SMBG (prevalent-user cohort). SMBG frequency was based on pharmacy use (number of blood glucose test strips dispensed), and glycemic control was based on HbA(1c) (A1C). In the new-user cohort, ANCOVA models (pre- and posttest design) were used to assess the effect of initiating SMBG. In the prevalent-user cohort, repeated-measure, mixed-effects models with random-intercept and time-dependent covariates were used to assess changes in SMBG and A1C. All models were stratified by therapy (no medications, oral agents only, or insulin) and adjusted for baseline A1C, sociodemographics, insulin injection frequency, comorbidity index, medication adherence, smoking status, health care use, and provider specialty. RESULTS: Greater SMBG practice frequency among new users was associated with a graded decrease in A1C (relative to nonusers) regardless of diabetes therapy (P < 0.0001). Changes in SMBG frequency among prevalent users were associated with an inverse graded change in A1C only among pharmacologically treated patients (P < 0.0001). CONCLUSIONS: These observational findings are consistent with short-term benefits of initiating SMBG practice for all patients but continuing benefits only for pharmacologically treated patients. Differences in effectiveness between new versus prevalent users of SMBG have implications for guideline development and interpretation of observational outcomes data.

Epidemiology and adverse cardiovascular risk profile of diagnosed polycystic ovary syndrome.

CONTEXT: Polycystic ovary syndrome (PCOS) is associated with menstrual and reproductive abnormalities, insulin resistance, and obesity. OBJECTIVE: The objective of this study was to determine the prevalence of diagnosed PCOS and its association with cardiovascular risk factors. SETTING: The study is set in an integrated health care delivery system in northern California. PATIENTS: A total of 11,035 women with PCOS were identified by one or more outpatient diagnoses of PCOS using health plan databases. An age-matched sample of women without PCOS was also selected. OUTCOME MEASURES: Prevalence of PCOS and targeted cardiovascular risk factors [hypertension, dyslipidemia, diabetes mellitus, and body mass index (BMI)] were measured. RESULTS: During 2002-2004, the prevalence of diagnosed PCOS among female members aged 25-34 yr was 2.6% (95% confidence interval 1.6-1.7%). Women with diagnosed PCOS were more likely than those without PCOS to be obese [BMI > or = 30 mg/m(2); odds ratio (OR) 4.21, 3.96-4.47]. Furthermore, PCOS was associated with diabetes (OR 2.45, confidence interval 2.16-2.79), hypertension (OR 1.41, 1.31-1.51) and known dyslipidemia (OR 1.53, 1.39-1.68), even after adjusting for BMI and known confounders. Among women with PCOS, compared with whites, Blacks and Hispanics were more likely and Asians less likely to be obese; Asians and Hispanics were more likely to have diabetes; and Blacks were more likely and Hispanics less likely to have hypertension. CONCLUSIONS: Within a large, community-based population receiving health care, diagnosed PCOS was highly prevalent and associated with a much higher frequency of cardiovascular risk factors that varied by race/ethnicity. Our prevalence estimates likely underestimate the true prevalence of PCOS. Further studies are needed to explore racial/ethnic differences and the extent to which PCOS contributes to future cardiovascular risk.

Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do randomized trials translate into clinical practice?

CONTEXT: Warfarin has been shown to be highly efficacious for preventing thromboembolism in atrial fibrillation in randomized trials, but its effectiveness and safety in clinical practice is less clear. OBJECTIVE: To evaluate the effect of warfarin on risk of thromboembolism, hemorrhage, and death in atrial fibrillation within a usual care setting. DESIGN: Cohort study assembled between July 1, 1996, and December 31, 1997, and followed up through August 31, 1999. SETTING: Large integrated health care system in Northern California. PATIENTS: Of 13,559 adults with nonvalvular atrial fibrillation, 11,526 were studied, 43% of whom were women, mean age 71 years, with no known contraindications to anticoagulation at baseline. MAIN OUTCOMES: Ischemic stroke, peripheral embolism, hemorrhage, and death according to warfarin use and comorbidity status, as determined by automated databases, review of medical records, and state mortality files. RESULTS: Among 11,526 patients, 397 incident thromboembolic events (372 ischemic strokes, 25 peripheral embolism) occurred during 25,341 person-years of follow-up, and warfarin therapy was associated with a 51% (95% confidence interval [CI], 39%-60%) lower risk of thromboembolism compared with no warfarin therapy (either no antithrombotic therapy or aspirin) after adjusting for potential confounders and likelihood of receiving warfarin. Warfarin was effective in reducing thromboembolic risk in the presence or absence of risk factors for stroke. A nested case-control analysis estimated a 64% reduction in odds of thromboembolism with warfarin compared with no antithrombotic therapy. Warfarin was also associated with a reduced risk of all-cause mortality (adjusted hazard ratio, 0.69; 95% CI, 0.61-0.77). Intracranial hemorrhage was uncommon, but the rate was moderately higher among those taking vs those not taking warfarin (0.46 vs 0.23 per 100 person-years, respectively; P =.003, adjusted hazard ratio, 1.97; 95% CI, 1.24-3.13). However, warfarin therapy was not associated with an increased adjusted risk of nonintracranial major hemorrhage. The effects of warfarin were similar when patients with contraindications at baseline were analyzed separately or combined with those without contraindications (total cohort of 13,559). CONCLUSIONS: Warfarin is very effective for preventing ischemic stroke in patients with atrial fibrillation in clinical practice while the absolute increase in the risk of intracranial hemorrhage is small. Results of randomized trials of anticoagulation translate well into clinical care for patients with atrial fibrillation.