Daichi Shimbo

The Relationship Between Visit-to-Visit Variability in Systolic Blood Pressure and All-Cause Mortality in the General Population Findings From NHANES III, 1988 to 1994

Recent data suggest that visit-to-visit variability of blood pressure is associated with stroke incidence. Correlates of increased visit-to-visit variability in blood pressure and the relationship between variability and all-cause mortality were examined using data on US adults ≥20 years of age from the Third National Health and Nutrition Examination Survey (n=956). Three consecutive blood pressure readings were taken during 3 separate study visits from 1988 to 1994. Based on the mean of the second and third measurements from each visit, visit-to-visit blood pressure variability for each participant was defined using the standard deviation and coefficient of variation across visits. Mortality was assessed through December 31, 2006 (median follow-up=14 years; n=240 deaths). The mean of the standard deviation for systolic blood pressure across visits was 7.7 mm Hg. After multivariable adjustment, older age, female gender, history of myocardial infarction, higher mean systolic blood pressure and pulse pressure, and use of angiotensin converting enzyme inhibitors were associated with higher standard deviation in systolic blood pressure. The multivariable adjusted hazard ratios for all-cause mortality associated with a standard deviation of systolic blood pressure of 4.80 to 8.34 mm Hg and ≥8.35 mm Hg, versus <4.80 mm Hg, were 1.57 (95% CI, 1.07 to 2.18) and 1.50 (95% CI, 1.03 to 2.18), respectively. Results were similar when coefficient of variation for systolic blood pressure was evaluated. Visit-to-visit variability for diastolic blood pressure was not associated with mortality. In this population-based study of US adults, higher levels of short-term visit-to-visit variability in systolic blood pressure were associated with increased all-cause mortality.

Enhanced Depression Care for Patients With Acute Coronary Syndrome and Persistent Depressive Symptoms: Coronary Psychosocial Evaluation Studies Randomized Controlled Trial

BACKGROUND Depressive symptoms are an established predictor of mortality and major adverse cardiac events (defined as nonfatal myocardial infarction or hospitalization for unstable angina or urgent/emergency revascularizations) in patients with acute coronary syndrome (ACS). This study was conducted to determine the acceptability and efficacy of enhanced depression treatment in patients with ACS. METHODS A 3-month observation period to identify patients with ACS and persistent depressive symptoms was followed by a 6-month randomized controlled trial. From January 1, 2005, through February 29, 2008, 237 patients with ACS from 5 hospitals were enrolled, including 157 persistently depressed patients randomized to intervention (initial patient preference for problem-solving therapy and/or pharmacotherapy, then a stepped-care approach; 80 patients) or usual care (77 patients) and 80 nondepressed patients who underwent observational evaluation. The primary outcome was patient satisfaction with depression care. Secondary outcomes were depressive symptom changes (assessed with the Beck Depression Inventory), major adverse cardiac events, and death. RESULTS At the end of the trial, the proportion of patients who were satisfied with their depression care was higher in the intervention group (54% of 80) than in the usual care group (19% of 77) (odds ratio, 5.4; 95% confidence interval [CI], 2.2-12.9 [P < .001]). The Beck Depression Inventory score decreased significantly more (t(155) = 2.85 [P = .005]) for intervention patients (change, -5.7; 95% CI, -7.6 to -3.8; df = 155) than for usual care patients (change, -1.9; 95% CI, -3.8 to -0.1; df = 155); the depression effect size was 0.59 of the standard deviation. At the end of the trial, 3 intervention patients and 10 usual care patients had experienced major adverse cardiac events (4% and 13%, respectively; log-rank test, chi(2)(1) = 3.93 [P = .047]), as well as 5 nondepressed patients (6%) (for the intervention vs nondepressed cohort, chi(2)(1) = 0.48 [P = .49]). CONCLUSION Enhanced depression care for patients with ACS was associated with greater satisfaction, a greater reduction in depressive symptoms, and a promising improvement in prognosis. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00158054.

Persistent depression affects adherence to secondary prevention behaviors after acute coronary syndromes.

AbstractBACKGROUND: The persistence of depressive symptoms after hospitalization is a strong risk factor for mortality after acute coronary syndromes (ACS). Poor adherence to secondary prevention behaviors may be a mediator of the relationship between depression and increased mortality. OBJECTIVE: To determine whether rates of adherence to risk reducing behaviors were affected by depressive status during hospitalization and 3 months later. DESIGN: Prospective observational cohort study. SETTING: Three university hospitals. PARTICIPANTS: Five hundred and sixty patients were enrolled within 7 days after ACS. Of these, 492 (88%) patients completed 3-month follow-up. MEASUREMENTS: We used the Beck Depression Inventory (BDI) to assess depressive symptoms in the hospital and 3 months after discharge. We assessed adherence to 5 risk-reducing behaviors by patient self-report at 3 months. We used χ2 analysis to compare differences in adherence among 3 groups: persistently nondepressed (BDI<10 at hospitalization and 3 months); remittent depressed (BDI ≥10 at hospitalization; <10 at 3 months); and persistently depressed patients (BDI ≥10 at hospitalization and 3 months). RESULTS: Compared with persistently nondepressed, persistently depressed patients reported lower rates of adherence to quitting smoking (adjusted odds ratio [OR] 0.23, 95% confidence interval [95% CI] 0.05 to 0.97), taking medications (adjusted OR 0.50, 95% CI 0.27 to 0.95), exercising (adjusted OR 0.57, 95% CI 0.34 to 0.95), and attending cardiac rehabilitation (adjusted OR 0.5, 95% CI 0.27 to 0.91). There were no significant differences between remittent depressed and persistently nondepressed patients. CONCLUSIONS: Persistently depressed patients were less likely to adhere to behaviors that reduce the risk of recurrent ACS. Differences in adherence to these behaviors may explain in part why depression predicts mortality after ACS.

Association Between Annual Visit-to-Visit Blood Pressure Variability and Stroke in Postmenopausal Women Data From the Women's Health Initiative

Accumulating evidence suggests that increased visit-to-visit variability (VVV) of blood pressure is associated with stroke. No study has examined the association between VVV of blood pressure and stroke in postmenopausal women, and scarce data exist as to whether this relation is independent of the temporal trend of blood pressure. We examined the association of VVV of blood pressure with stroke in 58228 postmenopausal women enrolled in the Womens Health Initiative. Duplicate blood pressure readings, which were averaged, were taken at baseline and at each annual visit. VVV was defined as the SD for the participants mean systolic blood pressure (SBP) across visits (SD) and about the participants regression line with SBP regressed across visits (SDreg). Over a median follow-up of 5.4 years, 997 strokes occurred. In an adjusted model including mean SBP over time, the hazard ratios (95% CI) of stroke for higher quartiles of SD of SBP compared with the lowest quartile (referent) were 1.39 (1.03–1.89) for quartile 2, 1.52 (1.13–2.03) for quartile 3, and 1.72 (1.28–2.32) for quartile 4 (P trend <0.001). The relation was similar for SDreg of SBP quartiles in a model that additionally adjusted for the temporal trend in SBP (P trend <0.001). The associations did not differ by stroke type (ischemic versus hemorrhagic). There was a significant interaction between mean SBP and SDreg on stroke with the strongest association seen below 120 mmHg. In postmenopausal women, greater VVV of SBP was associated with increased risk of stroke, particularly in the lowest range of mean SBP.

Association of Anhedonia With Recurrent Major Adverse Cardiac Events and Mortality 1 Year After Acute Coronary Syndrome

CONTEXT Depression consistently predicts recurrent events and mortality in patients with acute coronary syndrome (ACS), but it has 2 core diagnostic criteria with distinct biological correlates-depressed mood and anhedonia (loss of pleasure or interest). OBJECTIVE To determine if depressed mood and/or anhedonia predict 1-year medical outcomes for patients with ACS. DESIGN Observational cohort study of post-ACS patients hospitalized between May 2003 and June 2005. Within 1 week of admission, patients underwent a structured psychiatric interview assessing clinically impairing depressed mood, anhedonia, and major depressive episode (MDE). Also assessed were the Global Registry of Acute Coronary Events risk score, Charlson comorbidity index, left ventricular ejection fraction, antidepressant use, and depressive symptom severity using the Beck Depression Inventory. SETTING Cardiac units of 3 university hospitals in New York and Connecticut. PARTICIPANTS Consecutive sample of 453 patients with ACS (age, 25-93 years; 42% women). MAIN OUTCOMES MEASURES All-cause mortality (ACM) and documented major adverse cardiac events (MACEs)-myocardial infarction, hospitalization for unstable angina, or urgent/emergency coronary revascularization)-actively surveyed for 1 year after admission. RESULTS There were 67 events (16 deaths and 51 MACEs; 14.8%): 108 (24%) and 77 (17%) patients had anhedonia and depressed mood, respectively. Controlling for sex, age, and medical covariates, anhedonia (adjusted hazard ratio, 1.58; 95% confidence interval, 1.16-2.14; P < .01) was a significant predictor of combined MACE and ACM, but depressed mood was not. Anhedonia continued to significantly predict outcomes (P < .05) when additionally controlling for MDE diagnosis or depressive symptom severity. Findings were confirmed using depressed mood and anhedonia subscores from the Beck Depression Inventory in place of clinician interview ratings. CONCLUSIONS Anhedonia identifies risk of MACE and ACM beyond that of established medical prognostic indicators, including MDE and depressive symptom severity. Correlates of anhedonia may add to the understanding of the link between depression and heart disease.

Impact of A1C screening criterion on the diagnosis of pre-diabetes among U.S. adults.

OBJECTIVE New clinical practice recommendations include A1C as an alternative to fasting glucose as a diagnostic test for identifying pre-diabetes. The impact of these new recommendations on the diagnosis of pre-diabetes is unknown. RESEARCH DESIGN AND METHODS Data from the National Health and Nutrition Examination Survey 1999–2006 (n = 7,029) were analyzed to determine the percentage and number of U.S. adults without diabetes classified as having pre-diabetes by the elevated A1C (5.7–6.4%) and by the impaired fasting glucose (IFG) (fasting glucose 100–125 mg/dl) criterion separately. Test characteristics (sensitivity, specificity, and positive and negative predictive values) using IFG as the reference standard were calculated. RESULTS The prevalence of pre-diabetes among U.S. adults was 12.6% by the A1C criterion and 28.2% by the fasting glucose criterion. Only 7.7% of U.S. adults, reflecting 61 and 27% of those with pre-diabetes by A1C and fasting glucose, respectively, had pre-diabetes according to both definitions. A1C used alone would reclassify 37.6 million Americans with IFG to not having pre-diabetes and 8.9 million without IFG to having pre-diabetes (46.5 million reclassified). Using IFG as the reference standard, pre-diabetes by the A1C criterion has 27% sensitivity, 93% specificity, 61% positive predictive value, and 77% negative predictive value. CONCLUSIONS Using A1C as the pre-diabetes criterion would reclassify the pre-diabetes diagnosis of nearly 50 million Americans. It is imperative that clinicians and health systems understand the differences and similarities in using A1C or IFG in diagnosis of pre-diabetes.

Visit-to-Visit Variability of Blood Pressure and Cardiovascular Disease and All-Cause Mortality A Systematic Review and Meta-Analysis

Visit-to-visit variability of blood pressure (BP) has been associated with cardiovascular disease (CVD) and mortality in some but not all studies. We conducted a systematic review and meta-analysis to examine the association between visit-to-visit variability of BP and CVD and all-cause mortality. Medical databases were searched through June 4, 2014, for studies meeting the following eligibility criteria: adult participants; BP measurements at ≥3 visits; follow-up for CVD, coronary heart disease, stroke, or mortality outcomes; events confirmed via database, death certificate, or event ascertainment committee; and adjustment for confounders. Data were extracted by 2 reviewers and pooled using a random-effects model. Overall, 8870 abstracts were identified of which 37 studies, representing 41 separate cohorts, met inclusion criteria. Across studies, visit-to-visit variability of systolic BP and diastolic BP showed significant associations with outcomes in 181 of 312 (58.0%) and 61 of 188 (32.4%) analyses, respectively. Few studies provided sufficient data for pooling risk estimates. For each 5 mm Hg higher SD of systolic BP, the pooled hazard ratio for stroke across 7 cohorts was 1.17 (95% confidence interval [CI], 1.07–1.28), for coronary heart disease across 4 cohorts was 1.27 (95% CI, 1.07–1.51), for CVD across 5 cohorts was 1.12 (95% CI, 0.98–1.28), for CVD mortality across 5 cohorts was 1.22 (95% CI, 1.09–1.35), and for all-cause mortality across 4 cohorts was 1.20 (95% CI, 1.05–1.36). In summary, modest associations between visit-to-visit variability of BP and CVD and all-cause mortality are present in published studies. However, these findings are limited by the small amount of data available for meta-analysis.

Exaggerated serotonin-mediated platelet reactivity as a possible link in depression and acute coronary syndromes

In conclusion, this study demonstrates that platelet reactivity to serotonin is significantly increased in depressed patients compared with non-depressed matched controls. Further, depressed patients did not have excess platelet reactivity to adenosine diphosphate. These data suggest that serotonin-mediated platelet reactivity may play a role in the depression-ACS link.

Refractory Hypertension: Determination of Prevalence, Risk Factors, and Comorbidities in a Large, Population-Based Cohort

Refractory hypertension is an extreme phenotype of antihypertensive treatment failure. Participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study, a large (n=30 239), population-based cohort were evaluated to determine the prevalence of refractory hypertension and associated cardiovascular risk factors and comorbidities. Refractory hypertension was defined as uncontrolled blood pressure (systolic/diastolic, ≥140/90 mm Hg) on ≥5 antihypertensive drug classes. Participants with resistant hypertension (systolic/diastolic, ≥140/90 mm Hg on ≥3 or <140/90 mm Hg on ≥4 antihypertensive classes) and all participants treated for hypertension served as comparator groups. Of 14 809 REGARDS participants receiving antihypertensive treatment, 78 (0.5%) had refractory hypertension. The prevalence of refractory hypertension was 3.6% among participants with resistant hypertension (n=2144) and 41.7% among participants on ≥5 antihypertensive drug classes. Among all participants with hypertension, black race, male sex, living in the stroke belt or buckle, higher body mass index, lower heart rate, reduced estimated glomerular filtration rate, albuminuria, diabetes mellitus, and history of stroke and coronary heart disease were associated with refractory hypertension. Compared with resistant hypertension, prevalence ratios for refractory hypertension were increased for blacks (3.00; 95% confidence interval, 1.68–5.37) and those with albuminuria (2.22; 95% confidence interval, 1.40–3.52) and diabetes mellitus (2.09; 95% confidence interval, 1.32–3.31). The median 10-year Framingham risk for coronary heart disease and stroke was higher among participants with refractory hypertension when compared with those with either comparator group. These data indicate that although resistant hypertension is relatively common among treated patients with hypertension, true antihypertensive treatment failure is rare.

Generalizability of SPRINT Results to the U.S. Adult Population

BACKGROUND In SPRINT (Systolic Blood Pressure Intervention Trial), a systolic blood pressure (SBP) goal of <120 mm Hg resulted in lower cardiovascular disease (CVD) risk compared with an SBP goal of <140 mm Hg. OBJECTIVES The purpose of this study was to estimate the prevalence, number, and characteristics of U.S. adults meeting SPRINT eligibility criteria and determine the broader population to whom SPRINT could be generalized. METHODS We conducted a cross-sectional, population-based study using data from the National Health and Nutrition Examination Survey, 2007 to 2012. The SPRINT inclusion criteria were age ≥50 years, SBP 130 to 180 mm Hg depending on the number of antihypertensive medication classes being taken, and high CVD risk (history of coronary heart disease, estimated glomerular filtration rate of 20 to 59 ml/min/1.73 m(2), 10-year CVD risk ≥15%, or age ≥75 years). Exclusion criteria were diabetes, history of stroke, >1 g in 24 h of proteinuria daily, heart failure, estimated glomerular filtration rate <20 ml/min/1.73 m(2), or receiving dialysis. Treated hypertension was defined by self-reported use of medication to lower blood pressure with ≥1 class of antihypertensive medication identified through a pill bottle review. RESULTS Overall, 7.6% (95% confidence interval [CI]: 7.0% to 8.3%) or 16.8 million (95% CI: 15.7 to 17.8 million) U.S. adults, and 16.7% (95% CI: 15.2% to 18.3%) or 8.2 million (95% CI: 7.6 to 8.8 million) adults with treated hypertension met the SPRINT eligibility criteria. Among both the overall U.S. population and adults with treated hypertension, the percentage meeting SPRINT eligibility criteria increased with older age, was higher among males than females, and was higher among non-Hispanic whites compared with non-Hispanic blacks or Hispanics. Of U.S. adults eligible for SPRINT, 51.0% (95% CI: 47.8% to 54.1%) or 8.6 million (95% CI: 8.0 to 9.1 million) were not treated for hypertension. CONCLUSIONS A substantial percentage of U.S. adults meet the eligibility criteria for SPRINT.