Thomas G. Pickering

Social support in social interaction: a moderator of cardiovascular reactivity.

&NA; This study examines the possibility that social support operates as a moderator of cardiovascular reactivity, which may be a factor in the development of heart disease and hypertension. An experiment was performed in which each of 40 subjects was the object of verbal attack in a discussion of a controversial issue. In each session, one subject and three confederates participated. Two of the confederates argued with the subject; in half the groups, a third confederate defended the subjects position (social support condition); in the other half, the third confederate sat quietly (no support condition). The subjects blood pressure and heart rate were continuously monitored. Subjects in the social support condition showed significantly smaller increases in cardiovascular measures than subjects in the no support condition. The results are discussed in terms of small group dynamics and Social Comparison Theory.

Silent and clinically overt stroke in older Japanese subjects with white-coat and sustained hypertension

OBJECTIVESnWe investigated whether white-coat hypertension is a risk factor for stroke in relation to silent cerebral infarct (SCI) in an older Japanese population.nnnBACKGROUNDnIt remains uncertain whether white-coat hypertension in older subjects is a benign condition or is associated with an increased risk of stroke.nnnMETHODSnWe studied the prognosis for stroke in 958 older Japanese subjects (147 normotensives [NT], 236 white-coat hypertensives [WCHT] and 575 sustained hypertensives [SHT]) in whom ambulatory blood pressure monitoring was performed in the absence of antihypertensive treatment. In 585 subjects (61%), we also assessed SCI using brain magnetic resonance imaging.nnnRESULTSnSilent cerebral infarcts were found in 36% of NT (n = 70), 42% of WCHT (n = 154), and 53% of SHT (n = 361); multiple SCIs (the presence of > or =2 SCIs) were found in 24% of NT, 25% of WCHT and 39% of SHT. During a mean 42-month follow-up period, clinically overt strokes occurred in 62 subjects (NT: three [2.0%]; WCHT: five [2.1%]; SHT: 54 [9.4%]), with 14 fatal cases (NT: one [0.7%]; WCHT: 0 [0%]; SHT: 13 [2.3%]). A Cox regression analysis showed that age (p = 0.0001) and SHT (relative risk, [RR] [95% confidence interval, CI]: 4.3 [1.3-14.2], p = 0.018) were independent stroke predictors, whereas WCHT was not significant. When we added presence/absence of SCI at baseline into this model, the RR (95% CI) for SCI was 4.6 (2.0-10.5) (p = 0.003) and that of SHT was 5.5 (1.8-18.9) versus WCHT (p = 0.004) and 3.8 (0.88-16.7) versus NT (p = 0.07).nnnCONCLUSIONSnIn older subjects the incidence of stroke in WCHT is similar to that of NT and one-fourth the risk in SHT. Although SCI is a strong predictor of stroke, the difference in stroke prognosis between SHT and WCHT was independent of SCI. It is clinically important to distinguish WCHT from SHT even after assessment of target organ damage in the elderly.

When Can the Practicing Physician Suspect White Coat Hypertension? Statement From the Working Group on Blood Pressure Monitoring of the European Society of Hypertension

T he Centers for Medicare and Medicaid Services (CMS) in the United States have recently approved ambulatory blood pressure measurement (ABPM) for reimbursement, but only for “patients with suspected WCH (white coat hypertension)” in whom the CMS believes the information deriving from the technique “is necessary in order to determine the appropriate management of the patient.” This decision, which is likely to change the clinical management of hypertension in the United States, makes white coat hypertension a condition of major importance. The decision by the CMS begs the question as to how the practicing physician can select patients with white coat hypertension. It might indeed be argued that all patients with an elevated clinic blood pressure (BP) are candidates for ABPM. However, the CMS decision carries a few other stipulations. First, white coat hypertension should be defined as “office BP 140/90 mm Hg on at least three separate clinic/office visits with two separate measurements made at each visit.” Second, in addition “there should be at least two BP measurements taken outside the office which are 140/90 mm Hg.” Third, “there should be no evidence of endorgan damage.” Fourth and last, patients selected for ABPM on the foregoing criteria who have” an ambulatory BP 135/85 (presumably average daytime pressure, although this is not stated) with no evidence of end-organ damage” are likely to be at normal risk, whereas those patients whose pressures are above this level “may be at increased cardiovascular risk, and a physician may wish to consider antihypertensive therapies.” In anticipation of a considerable increase in the use of ABPM in clinical practice in the United States, it is timely to examine the CMS recommendations in the light of recent evidence from a number of studies on WCH.

Factors associated with the occurrence and magnitude of earthquake-induced increases in blood pressure

BACKGROUNDnBlood pressure increases transiently after a major earthquake, but the characteristics and the mechanism of this increase are unknown.nnnMETHODSnThe study involved 124 elderly hypertensive outpatients from two clinics near the epicenter of the Hanshin-Awaji earthquake (7.2 on the Richter scale) for whom ambulatory blood pressure monitoring and assessment of end-organ damage had been performed before the earthquake.nnnRESULTSnDuring the 1 to 2 weeks after the earthquake, while major aftershocks persisted, mean (+/- SD) systolic blood pressure was 14 +/- 16 mm Hg greater and mean diastolic blood pressure was 6 +/- 10 mm Hg greater, but these values returned to baseline by 3 to 5 weeks after the earthquake. The earthquake-induced increase in blood pressure correlated significantly with the white coat effect ([clinic systolic blood pressure minus 24-hour systolic blood pressure] r = 0.34, P <0.001), body mass index (r = 0.28, P <0.001), and age (r = 0.24, P <0.01). The earthquake-induced blood pressure increase was prolonged in patients with microalbuminuria for at least 2 months after the earthquake, whereas it was less pronounced in patients who had been treated with an alpha-blocker and in patients with diabetes mellitus.nnnCONCLUSIONSnThese elderly patients with hypertension had a substantial increase in blood pressure after a major earthquake; the increase was usually transient, except in patients who had microalbuminuria. The correlation with white-coat hypertension suggests that both phenomena are related to sympathetic activation.

β-blockers in hypertension—the Emperor has no clothes: an open letter to present and prospective drafters of new guidelines for the treatment of hypertension

Over the past decade, national and international guidelines have proposed beta-blockers to be used on an equal footing with diuretics for initial therapy of hypertension. This preferred status was supposedly based on evidence documenting a reduction in morbidity and mortality with beta-blocker therapy in hypertension. We systematically analyzed all available outcome studies and found no evidence that beta-blocker based therapy, despite lowering blood pressure, reduced the risk of heart attacks or strokes. Despite the inefficacy of beta-blockers, the incidence of adverse effects is substantial. In the MRC study, for every heart attack or stroke prevented, three patients withdrew from atenolol because of impotence, and another seven withdrew because of fatigue. Thus the risk/benefit ratio of beta-blockers is characterized by lack of efficacy and multiple adverse effects. Given that many thorough, prospective, randomized trials attest to efficacy and safety of diuretics, calcium antagonists, ACE inhibitors, and angiotensin receptor inhibitors, the time has come to admit that beta-blockers should no longer be considered appropriate for first-line therapy in uncomplicated hypertension.

The association between daily blood pressure and catecholamine variability in normotensive working women.

&NA; Using ambulatory blood pressure monitors and timed urine collection techniques, blood pressure and the rates of urinary catecholamine excretion were compared across the work, home, and sleep environments of 45 women who perceived their work environment as most stressful (work stressed) and 35 women who perceived their home environment as equally or more stressful (home stressed) on the day of monitoring. The work‐stressed women had higher systolic pressure at work (121 vs. 115; p < 0.05). There were no significant differences in diastolic pressure or the absolute levels of the catecholamines between the groups. However, the percent changes in blood pressure and catecholamines from work or home to sleep were significantly correlated in the work‐stressed but not the home‐stressed women (r values from 0.25 to 0.45, p < 0.05). The work‐stressed and home‐stressed women differed in their proportional make‐up of several demographic characteristics, including having children (percentage of home‐stressed women with children > work‐stressed) (p < 0.05), ethnicity (percent of black home‐stressed > work‐stressed) (p < 0.01), and family history of hypertension (percentage of work‐stressed > home‐stressed) (0.05 < p < 0.10). These differences, in part, may have determined the daily patterns of perceived stress in the two groups of women. Overall, these findings suggest that work stress and/or the sociodemographic characteristics that may influence the perception of work stress may drive a daylong sympathetic response that increases blood pressure in working women.

Incomplete benefit of antihypertensive therapy on stroke reduction in older hypertensives with abnormal nocturnal blood pressure dipping (extreme-dippers and reverse-dippers)

To determine whether the benefits of antihypertensive treatment vary according to dipper status, 811 asymptomatic elderly Japanese hypertensives underwent 24-h ambulatory blood pressure monitoring. During a mean follow-up period of 41 months, 32 stroke events were observed in patients who remained nonmedicated (n = 385), and in 27 patients in the medicated group (n = 426), indicating a 24% lower rate of stroke as a result of antihypertensive therapy. Patients were divided into a white-coat hypertensive (WCHT) group (ambulatory blood pressure <130/80 mm Hg; n = 236) and a sustained hypertensive (SHT) group (n = 575). Sixty-one percent of SHT and 32% of WCHT patients were being medicated. In the SHT group, the stroke rates were 12.4% in nonmedicated and 7.4% in medicated group (P =.04), whereas in the WCHT group the stroke rates were 2.5% in nonmedicated and 1.3% in medicated group (P = not significant). The SHT were further classified according to their nocturnal systolic blood pressure (BP) decrease, as follows: 97 extreme-dippers with >20% nocturnal systolic BP decrease; 230 dippers with >10% but <20% decrease; 185 nondippers with >0% but <10% decrease; 63 reverse-dippers with <0% decrease. In the dipping groups of SHT, the stroke rates were similar according to medication versus no-medication in extreme-dippers (12% v 13%), and reverse-dippers (23% v 22%), but in nondippers there was a significantly lower rate (by 65%, P =.038) in the medicated (4.4%) than the nonmedicated (13%) groups. In dippers, the stroke rate was also lower in the medicated than the nonmedicated patients (4.7% v 8.8%), a decrease of 47% (P =.217), although the difference was not significant. In conclusion, in older SHT subjects, antihypertensive therapy using clinic BP may be less effective for the groups with extremely abnormal diurnal BP patterns (extreme-dippers and reverse-dippers) than those with relatively normal patterns (dippers and nondippers). Patients with WCHT also showed no benefit.

The effect of work environments on blood pressure : evidence from seven New York organizations

The prevalence of hypertension defined according to National Health and Nutrition Examination Survey II (NHANES II) criteria (140/90 mmHg and/or taking antihypertensive medication) was analyzed cross-sectionally at seven worksites in New York City (n = 4274; 2616 men and 1648 women), in order to assess whether exposure to different work environments and occupations contributes to blood pressure variation. The prevalence of hypertension across worksites was 26% among men and 12% among women. Blood pressure was significantly different across worksites even after controlling for known risk factors using analysis of covariance. Of the variation in systolic pressure, 34% was predicted significantly by eight variables; after adjusting for upper-arm circumference, age and body mass index, higher pressures were associated with worksite differences (9.0 mmHg), being male (7.2 mmHg), lacking a high-school education (4.3 mmHg), having a clerical occupation (2.9 mmHg) and being unmarried (1.8 mmHg). Similar results for diastolic pressure suggest that researchers should consider worksite and job characteristics as important predictors of blood pressure differences in working populations.

Heightened psychobiological reactivity to laboratory stressors in healthy women at familial risk for breast cancer.

This study examined the possibility that reactivity to acute stressors may be altered among women facing the chronic stress of being at familial risk for breast cancer. Sixteen healthy women with histories of breast cancer in their families (Risk Group) and 32 women at normal risk (Comparison Group) were exposed to 15 min of classic laboratory stressors. Seventeen women at normal risk were randomly assigned to nonstressful tasks (manipulation check). Self-reported distress, natural killer cell activity (NKCA), and NK cell numbers (percentage of CD3-CD16/56+ lymphocytes) were assessed before and after the tasks. Cardiovascular activity was assessed throughout the session. The tasks elicited increases in distress, heart rate, NKCA, and NK cells numbers in both experimental groups. Supporting study hypotheses, the Risk Group had larger increases in distress, heart rate, NKCA, and NK cell numbers. These findings raise the possibility that the chronic stress associated with familial cancer risk may have negative health consequences through changes in psychobiological reactivity.

The Rise and Fall of Omapatrilat

THE JOURNAL OF CLINICAL HYPERTENSION 371 This column does not usually deal with antihypertensive drug issues, but I happened to be a participant in the recent review by the Food and Drug Administration (FDA) Cardiorenal Advisory Committee of the application for omapatrilat as an antihypertensive agent by Bristol-Myers Squibb (BMS), and it makes an interesting story. This was its second FDA review, and when it was first reviewed in March, 2000 it was hailed as the first of an entirely new class of antihypertensive agents, the vasopeptidase inhibitors. These agents are essentially “super ACE inhibitors,” and have a dual action, combining inhibition of both the angiotensin-converting enzyme (ACE) and neutral endopeptidase. The latter enzyme is responsible for the breakdown of the three natriuretic peptides—atrial natriuretic peptide, brain-derived natriuretic peptide, and Ctype natriuretic peptide—and bradykinin. The natriuretic peptides have actions that might be considered beneficial for hypertensive patients—vasodilation, natriuresis, and inhibition of the sympathetic nervous system and the renin-angiotensin-aldosterone system. Neutral endopeptidase inhibition was tested as a possible means of lowering blood pressure, but on its own was found to be ineffective.1 However, numerous studies of omapatrilat (not all of which appear to have been published as full papers) have shown that it is a highly potent antihypertensive agent, and when compared with some of the leading antihypertensives such as losartan, amlodipine,2 lisinopril,3 and enalapril, it beat them all. Somewhat surprisingly, this extra potency cannot be attributed to a diuretic effect, which appears to be weak. Furthermore, when omapatrilat is added to a thiazide, there is an additional antihypertensive effect.4 One factor that may give vasopeptidase the edge over ACE inhibitors as antihypertensives may be their greater potentiation of bradykinin,5 but as we shall see below, this may also be their Achilles heel. These encouraging results in the treatment of hypertension were bolstered by equally exciting initial results in heart failure. The Inhibition of Metallo Protease by BMS-186716 in a Randomized Exercise and Symptoms Study in Subjects With Heart Failure (IMPRESS) trial6 randomized patients with congestive heart failure to either omapatrilat (289 patients) or lisinopril (284). At the end of 7 months there were significantly fewer end points (hospitalizations for heart failure or mortality) in the omapatrilat group. In 2000, confident that they had a blockbuster antihypertensive in the wings, BMS took out one page nonpromotional advertisements in the national press titled “an open letter to healthcare providers nationwide,” which pointed out that hypertension control in the United States was abysmal, and exhorting health care providers to make a commitment to improve the situation. It was signed by 35 hypertension experts (including Dr. Marvin Moser and myself and many members of the editorial board of this journal). No drugs were mentioned. As a result of these findings, two large and more definitive outcome studies were planned. The first was OVERTURE (Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events), which enrolled 5770 heart failure patients randomized to enalapril or omapatrilat. The results, which were announced at the American College of Cardiology in 2002,7 were disappointing, since there was no effect on the major end points, which included death and hospitalization for heart failure. The second was OPERA (Omapatrilat in Persons With Enhanced Risk of Atherosclerotic Events).8 This was The Rise and Fall of Omapatrilat