Faculty Bibliography

When a forensic DNA sample cannot be associated directly with a previously genotyped reference sample by standard short tandem repeat profiling, the investigation required for identifying perpetrators, victims, or missing persons can be both costly and time consuming. Here, we describe the outcome of a collaborative study using the Identitas Version 1 (v1) Forensic Chip, the first commercially available all-in-one tool dedicated to the concept of developing intelligence leads based on DNA. The chip allows parallel interrogation of 201,173 genome-wide autosomal, X-chromosomal, Y-chromosomal, and mitochondrial single nucleotide polymorphisms for inference of biogeographic ancestry, appearance, relatedness, and sex. The first assessment of the chip's performance was carried out on 3,196 blinded DNA samples of varying quantities and qualities, covering a wide range of biogeographic origin and eye/hair coloration as well as variation in relatedness and sex. Overall, 95 % of the samples (N = 3,034) passed quality checks with an overall genotype call rate >90 % on variable numbers of available recorded trait information. Predictions of sex, direct match, and first to third degree relatedness were highly accurate. Chip-based predictions of biparental continental ancestry were on average ~94 % correct (further support provided by separately inferred patrilineal and matrilineal ancestry). Predictions of eye color were 85 % correct for brown and 70 % correct for blue eyes, and predictions of hair color were 72 % for brown, 63 % for blond, 58 % for black, and 48 % for red hair. From the 5 % of samples (N = 162) with <90 % call rate, 56 % yielded correct continental ancestry predictions while 7 % yielded sufficient genotypes to allow hair and eye color prediction. Our results demonstrate that the Identitas v1 Forensic Chip holds great promise for a wide range of applications including criminal investigations, missing person investigations, and for national security purposes.

BACKGROUND: Clinic-based blood pressure (CBP) has been the default approach for the diagnosis of hypertension, but patients may be misclassified because of masked hypertension (false negative) or 'white coat' hypertension (false positive). The incorporation of other diagnostic modalities, such as home blood pressure monitoring (HBPM) and ambulatory blood pressure monitoring (ABPM), holds promise to improve diagnostic accuracy and subsequent treatment decisions. MATERIALS AND METHODS: We reviewed the literature on the costs and cost-effectiveness of adding HBPM and ABPM to routine blood pressure screening in adults. We excluded letters, editorials, and studies of pregnant and/or pre-eclamptic patients, children, and patients with specific conditions (e.g. diabetes). RESULTS: We identified 14 original, English language studies that included cost outcomes and compared two or more modalities. ABPM was found to be cost saving for diagnostic confirmation following an elevated CBP in six studies. Three of four studies found that adding HBPM to an elevated CBP was also cost-effective. CONCLUSION: Existing evidence supports the cost-effectiveness of incorporating HBPM or ABPM after an initial CBP-based diagnosis of hypertension. Future research should focus on their implementation in clinical practice, long-term economic values, and potential roles in identifying masked hypertension.

Calling 911 during acute coronary syndromes (ACS) decreases time to treatment and may improve prognosis. Women may have more atypical ACS symptoms compared to men, but few data are available on differences in gender and ACS symptoms in calling 911. In this study, patient interviews and structured chart reviews were conducted to determine gender differences in calling 911. Calls to 911 were assessed by self-report and validated by medical chart review. Of the 476 patients studied, 292 (61%) were diagnosed with unstable angina and 184 (39%) with myocardial infarctions (MIs). Overall, only 23% of patients called 911. Similar percentages of women and men with unstable angina called 911 (15% and 13%, respectively, p = 0.59). In contrast, women with MIs were significantly more likely to call 911 than men (57% vs 28%, p <0.001). After adjustment for sociodemographic factors, health insurance status, history of MI, the left ventricular ejection fraction, Global Registry of Acute Coronary Events (GRACE) score, and ACS symptoms, women were 1.79 times more likely to call 911 during an MI than men (prevalence ratio 1.79, 95% confidence interval 1.22 to 2.64, p <0.01). In conclusion, the findings of the present study suggest that initiatives to increase calls to 911 are needed for women and men.

Considerable excitement and interest have arisen recently concerning the role that acute emotional triggers may play in precipitating a myocardial infarction (MI). Observational studies have found repeatedly that patients report excessive anger, anxiety, sadness, grief, or acute stress immediately prior to onset of MI, and recent meta-analyses summarizing these findings reported strong associations between MI occurrence and many of these acute emotions. However, it is unclear whether and through what mechanisms acute emotional triggers might influence MI, and whether there is any clinical utility in knowing if or how emotions trigger MI. We debate whether emotional triggers matter by reviewing the recent evidence for the association between acute emotional triggers and MI and by describing the potential pathophysiological characteristics and mechanisms underlying this association and the preventive strategies that could be used to mitigate the risk of acute MI. We also examine whether the study of emotional triggers could influence clinical risk management or changes in clinical practice/management. We offer suggestions for research that might shed light on whether emotional triggers could initiate a paradigm shift in preventive cardiology, or whether acute emotional triggers are either intractable catalysts for, or merely an epiphenomenon of, some MIs.

BACKGROUND: Patient demographic characteristics have been associated with longer emergency department (ED) treatment times, but the influence of psychosocial characteristics has not been assessed. We evaluated whether depression was associated with greater ED length of stay (LOS) in non-ST elevation myocardial infarction (NSTEMI) and unstable angina (UA) patients presenting to a large metropolitan academic medical center. METHODS: We calculated ED LOS for NSTEMI or UA patients enrolled an observational cohort study by taking the difference between ED triage time in the medical record and time of transfer to an inpatient bed from standardized transfer documentation forms. Depression status was defined as current, past, or never by clinical interview and also by self-report on the Beck Depression Inventory. RESULTS: Participants were 120 NSTEMI/UA patients [mean age= 62, 36% women, 56% Hispanic, 26% Black/African American, 40% NSTEMI, mean global registry of acute cardiac events (GRACE) score= 93.9]. Mean ED LOS was 11.6 hours, SD= 8.3. A multiple linear regression model that included the above demographic and clinical variables, and time of presentation to ED, explained 11% of the variance in ED LOS, F (11, 108)= 2.35, p= .01, R2 adj.= .11. Currently depressed patients spent 5.4 more hours (95% CI= .40, 10.4 hours) in the ED on average than patients who had never been depressed. CONCLUSIONS: Currently depressed NSTEMI/UA patients are in the ED for an average of 5 hours longer than those who have never been depressed. Further research is needed to identify the reasons for this difference.

Anergia, a commonly occurring syndrome in older adults and patients with cardiovascular diseases, is associated with functional and clinical limitations. To date, the prevalence and clinical-demographic characteristics of anergia in patients with acute coronary syndrome (ACS) have not been elucidated. We examined the prevalence and clinical-demographic characteristics of anergia in a multiethnic sample of patients with ACS. Hospitalized patients with ACS (n = 472), enrolled in the Prescription Usage, Lifestyle, and Stress Evaluation (PULSE) prospective cohort study, completed assessments of demographic, behavioral, and clinical characteristics within 7 days of hospitalization for an ACS event. Current depressive disorder was ascertained using a structured psychiatric interview 3 to 7 days after discharge. Anergia was assessed at baseline and defined using patients' binary responses (yes/no) to 7 items related to energy level. At least 1 complaint of anergia was reported by 79.9% of patients (n = 377) and 32% of patients (n = 153) met criteria for anergia. In a multivariable logistic regression model, anergia was independently associated with being a woman, being white (compared to black), having bodily pain, participating in exercise, having current depressive disorder, and having higher values on the Charlson Co-morbidity Index. In conclusion, anergia is a highly prevalent syndrome in patients with ACS. It is distinct from depression and is associated with modifiable clinical factors such as participation in exercise and bodily pain that may be appropriate targets for intervention.

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 58,228 postmenopausal women enrolled in the Women's 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 participant's mean systolic blood pressure (SBP) across visits (SD) and about the participant's 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.

BACKGROUND: Masked hypertension (MHT) and prehypertension (PHT) are both associated with an increase in cardiovascular disease (CVD) risk, relative to sustained normotension. This study examined the diagnostic overlap between MHT and PHT, and their interrelationships with left ventricular (LV) mass index (LVMI), a marker of cardiovascular end-organ damage. METHODS: A research nurse performed three manual clinic blood pressure (CBP) measurements on three occasions over a 3-week period (total of nine readings, which were averaged) in 813 participants without treated hypertension from the Masked Hypertension Study, an ongoing worksite-based, population study. Twenty-four-hour ambulatory blood pressure (ABP) was assessed by using a SpaceLabs 90207 monitor. LVMI was determined by echocardiography in 784 (96.4%) participants. RESULTS: Of the 813 participants, 769 (94.6%) had normal CBP levels (<140/90 mm Hg). One hundred and seventeen (15.2%) participants with normal CBP had MHT (normal CBP and mean awake ABP >/=135/85 mm Hg) and 287 (37.3%) had PHT (mean CBP 120-139/80-89 mm Hg). 83.8% of MHT participants had PHT and 34.1% of PHT participants had MHT. MHT was infrequent (3.9%) when CBP was optimal (<120/80 mm Hg). After adjusting for age, gender, body mass index (BMI), race/ethnicity, history of high cholesterol, history of diabetes, current smoking, family history of hypertension, and physical activity, compared with optimal CBP with MHT participants, LVMI was significantly greater in PHT without MHT participants and in PHT with MHT participants. CONCLUSIONS: In this community sample, there was substantial diagnostic overlap between MHT and PHT. The diagnosis of MHT using an ABP monitor may not be warranted for individuals with optimal CBP.

On the surface electrocardiogram, an abnormally wide QRS|T angle reflects changes in the regional action potential duration profiles and in the direction of the repolarization sequence, which is thought to increase the risk of ventricular arrhythmia. We investigated the relation between an abnormal QRS|T angle and mortality in a nationally representative sample of subjects without clinically evident heart disease. We studied 7,052 participants >/=40 years old in the third National Health and Nutrition Examination Survey with 12-lead electrocardiograms. Those with self-reported or electrocardiographic evidence of a previous myocardial infarction, QRS duration of >/=120 ms, or history of heart failure were excluded. Borderline and abnormal spatial QRS|T angles were defined according to gender-specific 75th and 95th percentiles of frequency distributions. All-cause (1,093 women and 1,191 men) and cardiovascular (462 women and 455 men) mortality during the 14-year period was assessed through linkage with the National Death Index. On multivariate analyses, an abnormal spatial QRS|T angle was associated with an increased hazard ratio (HR) for cardiovascular mortality in women (HR 1.82, 95% confidence interval 1.05 to 3.14) and men (HR 2.21, 95% confidence interval 1.32 to 3.68). Also, the multivariate adjusted HR for all-cause mortality associated with an abnormal QRS|T angle was 1.30 (95% confidence interval 0.95 to 1.78) for women and 1.87 (95% confidence interval 1.29 to 2.7) for men. A borderline QRS|T angle was not associated with an increased risk of all-cause or cardiovascular mortality. In conclusion, an abnormal QRS|T angle, as measured on a 12-lead electrocardiogram, was associated with an increased risk of cardiovascular and all-cause mortality in this population-based sample without known heart disease.

OBJECTIVES: The aim of this study was to examine the relation between hostility and incident ischemic heart disease (IHD) and to determine whether observed hostility is superior to patient-reported hostility for the prediction of IHD in a large, prospective observational study. BACKGROUND: Some studies have found that hostile patients have an increased risk of incident IHD. However, no studies have compared methods of hostility assessment or considered important psychosocial and cardiovascular risk factors as confounders. Furthermore, it is unknown whether all expressions of hostility carry equal risk or whether certain manifestations are more cardiotoxic. METHODS: We assessed the independent relationship between baseline observed hostility and 10-year incident IHD in 1,749 adults of the population-based Canadian Nova Scotia Health Survey. RESULTS: There were 149 (8.5%) incident IHD events (140 nonfatal, 9 fatal) during the 15,295 person-years of observation (9.74 events/1,000 person-years). Participants with any observed hostility had a greater risk of incident IHD than those without (p = 0.02); no such relation was found for patient-reported hostility. Those with any observed hostility had a significantly greater risk of incident IHD (hazard ratio: 2.06, 95% confidence interval: 1.04 to 4.08, p = 0.04), after adjusting for cardiovascular (age, sex, Framingham Risk Score) and psychosocial (depression, positive affect, patient-reported hostility, and anger) risk factors. CONCLUSIONS: The presence of any observed hostility at baseline was associated with a 2-fold increased risk of incident IHD over 10 years of follow-up. Compared with patient-reported measures, observed hostility is a superior predictor of IHD.