Reduced cerebral blood flow velocity and impaired cerebral autoregulation in patients with Fabry disease.

Hilz MJ, Kolodny EH, Brys M, Stemper B, Haendl T, Marthol H.

New York University School of Medicine, Department of Neurology, 550 First Avenue, NB 7W11, New York, NY, 10016, USA. max.hilz med.nyu.edu

In Fabry disease, there is glycosphingolipid storage in vascular endothelial and smooth muscle cells and neurons of the autonomic nervous system. Vascular or autonomic dysfunction is likely to compromise cerebral blood flow velocities and cerebral autoregulation. This study was performed to evaluate cerebral blood flow velocities and cerebral autoregulation in Fabry patients. In 22 Fabry patients and 24 controls, we monitored resting respiratory frequency, electrocardiographic RR-intervals, blood pressure, and cerebral blood flow velocities (CBFV) in the middle cerebral artery using transcranial Doppler sonography. We assessed the Resistance Index, Pulsatility Index, Cerebrovascular Resistance, and spectral powers of oscillations in RR-intervals, mean blood pressure and mean CBFV in the high (0.15-0.5 Hz) and sympathetically mediated low frequency (0.04-0.15 Hz) ranges using autoregressive analysis. Cerebral autoregulation was determined from the transfer function gain between the low frequency oscillations in mean blood pressure and mean CBFV. Mean CBFV (P < 0.05) and the powers of mean blood pressure (P < 0.01) and mean CBFV oscillations (P < 0.05) in the low frequency range were lower,while RR-intervals, Resistance Index (P < 0.01), Pulsatility Index, Cerebrovascular Resistance (P < 0.05), and the transfer function gain between low frequency oscillations in mean blood pressure and mean CBFV (P < 0.01) were higher in patients than in controls. Mean blood pressure, respiratory frequency and spectral powers of RR-intervals did not differ between the two groups (P > 0.05). The decrease of CBFV might result from downstream stenoses of resistance vessels and dilatation of the insonated segment of the middle cerebral artery due to reduced sympathetic tone and vessel wall pathology with decreased elasticity. The augmented gain between blood pressure and CBFV oscillations indicates inability to dampen blood pressure fluctuations by cerebral autoregulation. Both, reduced CBFV and impaired cerebral autoregulation, are likely to be involved in the increased risk of stroke in patients with Fabry disease.

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Hypertension management and control among English adults aged 65 years and older in 2000 and 2001.

Primatesta P, Poulter NR.

Department of Epidemiology and Public Health, University College London Medical School, London, UK. p.primatesta vcl.ac.uk

OBJECTIVE: To describe blood pressures, and hypertension and its management among older people. DESIGN: Two combined annual cross-sectional surveys. SETTING: England 2000 and 2001. PARTICIPANTS: Nationally-representative sample of 3513 non-institutionalized people aged more than 64 years (elderly). MAIN OUTCOME MEASURES: (1). Use of antihypertensive agents, and hypertension according to two definitions: receiving blood pressure decreasing treatment, or either: systolic blood pressure > or= 160 mmHg or diastolic blood pressure > or= 90 mmHg (old); or systolic blood pressure > or= 140 mmHg or diastolic blood pressure > or=90 mmHg (new). (2). Rates of treatment and control (old: < 160/90 mmHg; new: < 140/85 mmHg). (3). Isolated systolic hypertension stage 1 (systolic blood pressure > or= 140-159 mmHg and diastolic blood pressure < 90 mmHg), or stage 2 (systolic blood pressure > or= 160 mmHg and diastolic blood pressure < 90 mmHg). RESULTS: In 2000/2001, 62 and 81% of elderly adults were hypertensive according to the old and new definitions, respectively. Among those with hypertension (new definition) treatment and control rates were 56 and 19% (control rates among those treated were 36% in men and 30% in women). Of those treated, 54% were receiving one drug, 35% were receiving two, and 10% were receiving three or more drugs. Among untreated hypertensive individuals, 23% had increased systolic and diastolic pressures, 76% had isolated systolic hypertension and 1% had isolated diastolic hypertension. CONCLUSIONS: These data suggest that, according to current guidelines more than 67% of older English adults should receive antihypertensive medication. To pre-empt this situation, population-based strategies to reduce the current rate of increase in blood pressure throughout adult life should be urgently implemented. Only then will the current epidemic of hypertension among the elderly, with the huge cost associated with its management and adverse cardiovascular sequelae, be averted.

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How many times should blood pressure be measured at home for better prediction of stroke risk? Ten-year follow-up results from the Ohasama study.

Ohkubo T, Asayama K, Kikuya M, Metoki H, Hoshi H, Hashimoto J, Totsune K, Satoh H, Imai Y; Ohasama Study.

Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Science and Medicine, Sendai, Japan and Ohasama Hospital, Iwate, Japan. tohkubo mail.tains.tohoku.ac.jp

OBJECTIVE: To determine the optimum number of blood pressure self-measurements taken at home (home blood pressure) in relation to their predictive value for stroke risk. METHODS: We obtained more than 14 measurements of home blood pressure from 1491 people aged >or=40 years without a history of stroke in the general population in Japan, and followed them up after a mean period of 10.6 years. The prognostic significance of blood pressure for stroke risk was examined using the Cox proportional hazards regression model, which was adjusted for possible confounding factors. RESULTS: The predictive value of home blood pressure increased progressively with the number of measurements, showing the highest predictive value with the average of whole measurements (mean = 25 measurements, 35% increase in the risk of stroke per 10 mmHg elevation in blood pressure). The initial home blood pressure values (one measurement) showed a significantly greater relation with stroke risk than conventional blood pressure values (mean of two measurements) (19/8% increase in the risk of stroke per 10 mmHg elevation in initial home/conventional systolic blood pressure values, respectively). CONCLUSIONS: There was no threshold for the number of home blood pressure measurements within the range of 1-14 measurements for increasing the predictive power of stroke risk, suggesting that as many measurements as possible, preferably more than 14 measurements, is recommended for better prediction of stroke risk. It should be emphasized that home blood pressure has a stronger predictive power than does conventional blood pressure, even for a lower number of measurements.

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Sex-dependent association of blood pressure with oestrogen receptor genes ERalpha and ERbeta.

Ellis JA, Infantino T, Harrap SB.

Department of Physiology, The University of Melbourne, Victoria 3010, Australia. justine unimelb.edu.au

BACKGROUND: There is mounting physiological evidence for an important role of the oestrogen receptors, ERalpha and ERbeta, in vasodilatation and the response to vascular injury. In addition, genetic studies have suggested that the genes encoding these receptors may be involved in the genetic regulation of blood pressure. The existence of such sex steroid-related genes may help to explain the observed sex differences in blood pressure. OBJECTIVE: To investigate the role of the oestrogen receptor genes (ERalpha and ERbeta) in blood pressure variation in women and in men. DESIGN: We performed a genetic association study of the oestrogen receptor genes in 718 unrelated healthy white individuals (386 men and 332 women) from the parental generation of the Victorian Family Heart Study, a general population survey of cardiovascular risk. METHODS: Participants were genotyped for single nucleotide polymorphisms (SNPs) in ERalpha and ERbeta, and blood pressure phenotypes were compared between genotype groups by analysis of variance. RESULTS: When genotype groups were compared, men inheriting the 'a' allele of the ERalpha SNP had significantly higher systolic blood pressure than men with other genotypes [127.7 +/-14.3 mmHg (mean +/- SD) compared with 132.4 +/- 16.1 mmHg; P = 0.014)]. In addition, men inheriting the 'b' allele of the ERbeta SNP had significantly higher diastolic blood pressure than men with other genotypes (81.4 +/-8.1 mmHg compared with 84.4 +/- 9.6 mmHg; P = 0.004). No significant associations between the oestrogen receptor genes and blood pressure were detected in women. DISCUSSION: These results suggest that ERalpha and ERbeta may be involved in the genetic regulation of blood pressure in men, that the two genes may have different roles, and that these genes may contribute to the differences in blood pressures between the sexes.

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Blood pressure destabilization and edema among 8538 users of celecoxib, rofecoxib, and nonselective nonsteroidal antiinflammatory drugs (NSAID) and nonusers of NSAID receiving ordinary clinical care.

Wolfe F, Zhao S, Pettitt D.

National Data Bank for Rheumatic Diseases, Arthritis Research Center Foundation, Wichita, KS 67214, USA. fwolfe arthritis-research.org

OBJECTIVE: To investigate the relationship between nonselective nonsteroidal antiinflammatory drugs (NS NSAID), rofecoxib, celecoxib, and risk of edema and blood pressure destabilization in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) receiving ordinary clinic care. METHODS: Patients participating in a longterm outcome study reported drug use, as well as the presence of edema and blood pressure increases occurring during the previous 6 months. To measure pure drug effect, analyses were restricted to 8538 patients who exclusively used a NS NSAID, rofecoxib, or celecoxib, and compared to nonusers of NS NSAID, rofecoxib, or celecoxib. We evaluated blood pressure destabilization using patient-reported increases in blood pressure and/or difficulty in controlling blood pressure. RESULTS: Compared with nonusers, after adjusting for age, sex, presence of RA, and history of heart disease and hypertension, patients using rofecoxib, but not celecoxib or NS NSAID, had an increased rate of edema (23.3% vs 18.0%), while the rates for celecoxib and NS NSAID were 17.5% and 18.2%, respectively. The adjusted risk of edema was significantly increased for rofecoxib compared to celecoxib (OR 1.33, 95% CI 1.08-1.64). For blood pressure increases, among patients who did not report having hypertension, no significant increase was noted for NS NSAID and celecoxib compared with nonusers. However a significant increased risk of blood pressure increase was seen for rofecoxib (OR 2.08, 95% CI 1.41-3.06). Among patients who reported having hypertension, patients taking rofecoxib had a significant increased risk of blood pressure increase compared to nonusers (OR 1.55, 95% CI 1.23-1.96), while the risks of blood pressure increase for users of celecoxib and NS NSAID were not significantly different than among nonusers. After controlling for age, sex, RA, and new starts on NSAID, the risk of blood pressure increase was significantly higher for users of rofecoxib than celecoxib (OR 1.21, 95% CI 1.03-1.61) among patients with hypertension, and numerically higher for nonhypertensives (OR 1.42, 95% CI 0.96-2.22). The increased risk for hypertension and edema of rofecoxib compared to celecoxib users was further confirmed by analysis of specific reported side effects during 2 separate 6-month periods (July 1 to December 31, 1999, and January 1 to June 30, 2000). During these 2 periods, rofecoxib-treated patients were 2.16 to 3.82 times more likely to report edema or blood pressure increase side effects compared to celecoxib-treated patients. CONCLUSION: Rofecoxib, but not celecoxib and NS NSAID, is associated with an increased risk of edema and blood pressure increase compared to nonusers of NSAID.

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Hypertension was the major risk factor leading to development of cardiovascular diseases among men with hyperuricemia.

Lin KC, Tsao HM, Chen CH, Chou P.

Community Medicine Research Center and Institute of Public Health, National Yang-Ming University, Taipei, Taiwan.

OBJECTIVE: A 7-year followup study among men with hyperuricemia was conducted to study the longterm relationships between serum uric acid concentrations and cardiovascular diseases. Any interaction between uric acid levels and other risk factors (e.g., obesity, hypertension) on the development of cardiovascular diseases was also examined. METHODS: A total of 391 men with hyperuricemia aged 30 and over screened from the community-based Kinmen study in 1991-92 (the baseline study) were followed in 1997-98, with a 75% followup rate. Demographic, clinical, and biochemical data were collected in both baseline and followup periods. RESULTS: After followup for 7 years, the significant risk factors of coronary heart disease were age, increase of uric acid level at followup, baseline systolic blood pressure, and increase of systolic blood pressure at followup. Factors independently associated with left ventricular hypertrophy included baseline systolic blood pressure and increase of systolic blood pressure at followup. Gouty syndrome, age, baseline fasting plasma glucose level, and increase of systolic blood pressure followup were significantly related to cardiac arrhythmia. After adjusting for baseline serum uric acid level, we found that hyperuricemic men with hypertension, especially overt hypertension stage 2 and stage 3, would predict cardiovascular disease incidence synergistically with uric acid level. CONCLUSION: There is a positive and statistically significant relationship between gout and subsequent cardiac arrhythmia. Moreover, hypertension was the major risk factor leading to aggravation of development of atherosclerosis among hyperuricemic subjects. Gout and elevated uric acid level seemed not to be an independent risk factor for most cardiovascular diseases. Nevertheless, blood pressure level was predictive for cardiovascular disease incidence synergistically with serum uric acid level.

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ATP-sensitive potassium channels are involved in adenosine-induced reduction of blood pressure variability in spontaneously hypertensive rats.

Shen FM, Zhu GM, Miao CY, Guan YF, Su DF.

Department of Pharmacology, Second Military Medical University, Shanghai, China.

With a computerized analysis system, blood pressure was recorded continuously in conscious unrestrained spontaneously hypertensive rats. The effects of different adenosine receptor agonists and ATP-sensitive potassium channel opener and blocker on blood pressure variability in spontaneously hypertensive rats were studied. It was found that adenosine, 5'-N-cyclopropyl-carboxamidoadenosine (CPCA, a selective adenosine A2-receptor agonist) and pinacidil (a nonselective ATP-sensitive potassium channel opener) decreased blood pressure variability when one of them was used alone, whereas N -cyclopentyladenosine (CPA, a selective adenosine A1-receptor agonist) had no significant effects on blood pressure variability. When pretreated with glibenclamide (a nonselective ATP-sensitive potassium channel blocker), the inhibitory effects of adenosine and CPCA on blood pressure variability were significantly prevented. By itself, however, glibenclamide had no influence on blood pressure variability. These results suggest that the effect of adenosine on blood pressure variability in spontaneously hypertensive rats is due to activation of ATP-sensitive potassium channels mediated by adenosine A2-receptor.

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Moderating effects of perceived racism on John Henryism and blood pressure reactivity in Black female college students.

Clark R, Adams JH.

Department of Psychology, Wayne State University, Detroit, MI 48202, USA. rclark sun.science.wayne.edu

BACKGROUND: Relative to other ethnic groups in the United States Blacks have disproportionately higher rates of hypertension. Research suggest that perceived racism might moderate the relation between such Pearson variables as John Henryism and cardiac/vascular functioning. PURPOSE: This study examined the possible moderating influence of perceived racism on the John Henryism reactivity relation in a sample of 117 Black female college students (M age = 26.10 years, SD = 8.83). METHODS: Blood pressure was measured before and during a speaking task. John Henryism and perceived racism were assessed via self-report. RESULTS: Hierarchial regression analyses revealed that John Henryism was inversely related to systolic blood pressure reactivity (p = .007). These analyses also indicated that John Henryism and perceived racism interacted to predict both systolic (p = .007) and diastolic blood pressure reactivity (p = .0005). Follow-up regression analyses indicated that John Henryism was unrelated to systolic and diastolic blood pressure reactivity for women high in perceived racism (ps > .62) and was inversely associated with systolic and diastolic blood pressure reactivity for women low in perceived racism (ps < .01). CONCLUSIONS: The findings highlight the importance of examining the potential moderating effects of ethnically relevant situation factors when exploring the relation of John Henryism to blood pressure reactivity.

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