Gregory A. Harshfield

Value of Echocardiographic Measurement of Left Ventricular Mass in Predicting Cardiovascular Morbid Events in Hypertensive Men

To assess whether echocardiographic and electrocardiographic detection of left ventricular hypertrophy could predict cardiovascular morbid events in patients with uncomplicated essential hypertension, we followed 140 men for a mean of 4.8 years. Initial echocardiographic measurements of left ventricular mass were normal (less than 125 g/m2 body surface area) in 111 patients and revealed hypertrophy in 29 patients. Morbid events occurred in more patients with hypertrophy on echocardiography (7 of 29, 4.6/100 patient-years) than with normal ventricular mass (7 of 111, 1.4/100 patient-years; p less than 0.01). Electrocardiography showed hypertrophy in too few patients to be of predictive value. Multiple logistic regression analysis showed that left ventricular mass index had the highest independent relative risk for future events and that systolic and diastolic pressures and age had slightly lower relative risks. In men with mild uncomplicated hypertension, left ventricular hypertrophy detected by echocardiography identifies patients at high risk for cardiovascular morbid events and is a significant risk factor for future morbid events independent of age, blood pressure, or resting ventricular function.

What is the value of home blood pressure measurement in patients with mild hypertension

To investigate the value of home blood pressure (BP) measurements, the BP was recorded daily by the patient at home and compared with recordings in the physicians office and with a 24-hour BP recording taken with a noninvasive ambulatory BP recorder in a group of 93 patients with mild untreated hypertension. Office BPs (mean 148/94 mm Hg) were higher than either home (138/89 mm Hg) or average 24-hour BPs (131/89 mm Hg). For systolic BP, home and office measurements gave similar correlations with 24-hour BP (0.67 and 0.55). For diastolic BP, however, home readings were lower and more accurate (0.76 vs 0.36). Thus, our findings indicate that home readings reflect the overall level of BP more reliably than office readings, and if due consideration is given to the fact that they are usually lower than office readings, they may be used as an alternative and cost-effective means of evaluating patients with mild hypertension.

The reproducibility of average ambulatory, home, and clinic pressures.

The reproducibility of ambulatory, home, and clinic blood pressures was compared in 13 untreated mildly hypertensive and 14 normotensive subjects. Each subject had two sets of daily ambulatory recordings, home self-measured readings (over 6 days), and clinic measurements taken 2 weeks apart. Comparisons over the 2 weeks within and among the methods of measurements were made using a repeated-measures analysis of variance. The results showed that there was no consistent average change in the ambulatory or home pressures and no change in clinic diastolic pressures, but the clinic systolic pressure of the hypertensive subjects dropped 6 mm Hg (p less than 0.05), while that of the normotensive subjects showed no significant change. Test-retest correlations of each of the three methods were similar in magnitude, indicating a similar level of reliability. Test-retest correlations of the ambulatory standard deviations, however, were low, indicating a low reliability of this measure of daily pressure variability. These results suggest that the reproducibility of ambulatory pressures may be as good or better than that of home or clinic measurements. They also suggest that the average ambulatory pressure may be preferable as the measurement in clinical trials, since it may be less influenced by measurement anxiety, particularly in hypertensive subjects.

What is the role of ambulatory blood pressure monitoring in the management of hypertensive patients

Noninvasive ambulatory blood pressure (BP) recording is now clinically available for the evaluation of hypertensive patients. It is well known that pressures measured in the office or clinic are unreliable and that repeated measurements are better at predicting outcome than are single measurements. Several studies have compared the correlation between target organ damage and different measures of BP, and in every instance ambulatory BP measurements have given better correlations than clinic readings. In one prospective study the ambulatory BP readings were more predictive of BP-related morbidity than were clinic readings. Data are now being obtained that will establish normal ranges of BP during ambulatory monitoring, against which values from patients being evaluated for hypertension can be compared. It is concluded that ambulatory BP monitoring is of clinical value for the evaluation of patients with mild hypertension.

A quantitative analysis of the effects of activity and time of day on the diurnal variations of blood pressure

The effects of activity and time of day on blood pressure (BP) were analyzed in 461 patients with untreated hypertension who wore a noninvasive portable BP recorder which took readings every 15 minutes for 24 hours. Patients recorded activity and location in a diary. The data were analyzed separately for two groups of patients: the 190 who stayed at home and the 271 who went to work. The effects of 16 different activities on BP were estimated by relating the BP to the associated activity and to the individuals clinic BP. Blood pressure was higher at work than at home, but the increment of BP for individual activities was similar in the two locations. The overall effect of activities on BP variability was computed using a one-way analysis of covariance model. For the patients who went to work this model accounted for 40% of the observed variation (R2) for systolic and 39% for diastolic BP. A similar model using time of day instead of activity accounted for 33% of variability in both systolic and diastolic BP. Combining activity and time of day was little better than activity alone (41% for both). After allowing for the effects of activity on BP, where sleep is one of the activities, there was no significant diurnal variation of BP. We conclude that there is no important circadian rhythm of BP which is independent of activity.

Obesity related methylation changes in DNA of peripheral blood leukocytes

BackgroundDespite evidence linking obesity to impaired immune function, little is known about the specific mechanisms. Because of emerging evidence that immune responses are epigenetically regulated, we hypothesized that DNA methylation changes are involved in obesity induced immune dysfunction and aimed to identify these changes.MethodWe conducted a genome wide methylation analysis on seven obese cases and seven lean controls aged 14 to 18 years from extreme ends of the obesity distribution and performed further validation of six CpG sites from six genes in 46 obese cases and 46 lean controls aged 14 to 30 years.ResultsIn comparison with the lean controls, we observed one CpG site in the UBASH3A gene showing higher methylation levels and one CpG site in the TRIM3 gene showing lower methylation levels in the obese cases in both the genome wide step (P = 5 × 10-6 and P = 2 × 10-5 for the UBASH3A and the TRIM3 gene respectively) and the validation step (P = 0.008 and P = 0.001 for the UBASH3A and the TRIM3 gene respectively).ConclusionsOur results provide evidence that obesity is associated with methylation changes in blood leukocyte DNA. Further studies are warranted to determine the causal direction of this relationship as well as whether such methylation changes can lead to immune dysfunction.See commentary: http://www.biomedcentral.com/1741-7015/8/88/abstract

Ethnic and Gender Differences in Ambulatory Blood Pressure Trajectories Results From a 15-Year Longitudinal Study in Youth and Young Adults

Background— Cross-sectional studies demonstrated ethnic and gender differences in ambulatory blood pressure patterns, but little is known about the longitudinal development of these differences. Methods and Results— Twenty-four-hour ambulatory blood pressure was measured up to 12 times (5 times on average) over a 15-year period in 312 African Americans (AAs) and 351 European Americans aged 7 to 30 years. Multivariate individual growth curves across age were created for daytime and nighttime blood pressure jointly. For both daytime and nighttime systolic blood pressure (SBP), AAs and males had higher levels (P<0.001) than European Americans and females. Males also showed a greater increase with age (P<0.001) than females. For nighttime SBP, a faster increase of SBP with age (P<0.01) in AAs was additionally observed. The ethnic difference in nighttime SBP levels and its increase with age were significantly larger than in daytime SBP. For daytime and nighttime diastolic blood pressure, AAs had higher levels than European Americans (P<0.001), and this difference was significantly larger at night. From late adolescence onward, males showed a greater increase in diastolic blood pressure with age than females. Ethnic and gender differences persisted after adjustment for height, body mass index, socioeconomic status, and stress-related coping styles. Family history of essential hypertension explained ethnic differences in daytime SBP. Conclusions— We observed significant ethnic and gender differences in longitudinal trajectories of ambulatory blood pressure in youth and young adults. The blunted nocturnal decline and its exacerbation with age in AAs corroborate and extend findings of cross-sectional studies.

Heritability of Blood Pressure and Hemodynamics in African- and European-American Youth

Abstract— Hypertension prevalence is much higher in African‐Americans (AAs) than in European‐Americans (EAs). It is unknown whether this difference is related to potential ethnic differences in the relative contribution of genes and environment to population variation in blood pressure and underlying hemodynamics. We studied 308 EA and 226 AA twin pairs, including monozygotic and dizygotic twins, of the same as well as the opposite sex (mean±SD age, 14.7±3.1 years). Supine resting systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure, and heart rate (HR) were measured by a Dinamap instrument and hemodynamics (stroke volume, cardiac index, and total peripheral resistance [TPR] index) by impedance cardiography. Ethnic and sex effects on genetic and environmental contributions to resting blood pressure and hemodynamics were estimated by genetic model fitting. For most measures, the best‐fitting model showed no differences in heritability between AAs and EAs or between males and females, with heritabilities of 0.50 for cardiac index, of 0.64 for HR, and of SBP, pulse pressure, and stroke volume in between. Heritability of DBP was 0.45 in EAs and 0.58 in AAs with no effect of sex. For TPR index in EAs, 46% of the variance could be attributed to familial effects, but no significant distinction could be made between shared environmental and genetic factors. Heritability of TPR index in AAs was 0.51. Adjustment for obesity yielded virtually identical heritabilities. In summary, relative influences of genetic and environmental factors on blood pressure and hemodynamics in AA and EA youth are similar and independent of (genes for) obesity.

The influence of happiness, anger, and anxiety on the blood pressure of borderline hypertensives.

&NA; Differences in blood pressure associated with reported happiness, anger, and anxiety are examined among 90 borderline hypertensives during 24‐hr blood pressure monitoring. There were 1152 individual ambulatory blood pressure readings for which subjects classified their emotional state as happy (n = 628), angry (n = 67), or anxious (n = 457) on scales from one (low) to ten (high). Pressures were transformed to z‐scores using the subjects 24‐hr mean and standard deviation to assess relative elevation during reported emotional arousal. The results show that emotional arousal significantly increases systolic and diastolic pressure (p less than 0.00001), an effect independent of posture and location of subject during measurement (at work, home, or elsewhere). On average, pressures during reported angry or anxious states were higher than those during a happy state (p less than 0.01). Examination of arousal intensity showed that scores on the happiness scale were inversely related to systolic pressure (p less than 0.01) whereas the degree of anxiety was positively associated with diastolic pressure (p less than 0.02). Emotional effects were also related to the degree of individual daily pressure variation such that the greater the variability, the larger the blood pressure change associated with the emotions. The results suggest that happiness, anger, and anxiety increase blood pressure to differing degrees and that emotional effects may be greater in individuals with more labile blood pressure.

Race and gender influence ambulatory blood pressure patterns of adolescents.

&NA; The purpose of this study was to examine ambulatory blood pressure and heart rate patterns in healthy, normotensive adolescents and to determine the influence of race and gender on these patterns. Ambulatory blood pressure recordings were performed on 199 adolescents; 42 were black males, 55 were white males, 65 were black females, and 37 were white females. The mean age (±SD) was 13±2 years. Blood pressure readings were obtained with an automatic, noninvasive recorder. Black adolescents and white adolescents had similar blood pressures while awake (116/69 vs. 116/69 mm Hg), with boys having higher levels of systolic blood pressure (118 vs. 114 mm Hg) and comparable levels of diastolic blood pressure (69 vs. 69 mm Hg) relative to girls. The patterns while the adolescents were asleep, however, were different. White boys (106 mm Hg), white girls (105 mm Hg), and black girls (105 mm Hg) had similar systolic blood pressures during sleep. Black boys (112 mm Hg), however, had significantly higher systolic blood pressures while asleep. Black adolescents, as a group, had significantly higher diastolic blood pressures than white adolescents while asleep (64 vs. 61 mm Hg). Changes in blood pressure from awake to asleep were not related to changes in heart rate. Results of this study indicate that both race and gender are important determinants of the diurnal pattern of blood pressure and heart rate in adolescents. (Hypertension 1989;14:598‐603)