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Background: It has been reported that aspirin (ASA) may interfere with the blood pressure (BP)-lowering effect of various antihypertensive agents and attenuate the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in patients with congestive heart failure., Methods and Results: Data from the Hypertension Optimal Treatment (HOT) Study, in which 18 790 intensively treated hypertensive patients were randomized to either ASA 75 mg daily or placebo for 3.8 years (with a 15% reduction in cardiovascular events and a 36% reduction in myocardial infarction in ASA-treated patients), were reanalysed for the whole group of patients and for various subgroups with particular attention to the possible effects of ASA on BP and renal function. In ASA-treated and placebo-treated patients: (1) systolic blood pressure (SBP) and diastolic blood pressure (DBP) values achieved with antihypertensive treatment were superimposable, with clinically irrelevant differences; (2) these superimposable SBP and DBP were achieved with antihypertensive therapies, that were quantitatively and qualitatively similar, and (3) changes in serum creatinine and in estimated creatinine clearance and the number of patients developing renal dysfunction were also similar. Furthermore, the cardiovascular benefits of ASA were of the same magnitude in hypertensive patients receiving or not receiving ACE-inhibitors., Conclusions: Even long-term, low-dose ASA does not interfere with the BP-lowering effect of antihypertensive agents, including combinations with ACE inhibitors, or with renal function. No negative interaction occurs between ACE inhibition and the cardiovascular benefits of small dose of ASA. Our conclusions cannot be extended to larger doses of ASA, or to patients with congestive heart failure.

Objectives: Renal transplant recipients (RTX) show a major impairment of large artery elastic wall properties. Sympathetic overactivity present in patients with renal disease has been shown to alter large artery elasticity; however, in RTX, this issue has not been addressed. The present study therefore investigated a possible relationship between sympathetic activity and large artery distensibility in RTX., Methods: In 32 patients treated with calcineurin inhibitors (RTX-CI, cyclosporine n = 16, tacrolimus n = 16) mean arterial pressure (MAP, automatic sphygmomanometer), muscle sympathetic nerve activity (MSNA, microneurography) and distensibility coefficients of the brachial and carotid arteries (pulsed Doppler) were measured. Sixteen healthy volunteers (CTR), six patients with calcinneurin inhibitor-free immunosuppression (RTX-AZA) and 12 transplant patients after native kidney nephrectomy (RTX-NC) served as control groups., Results: RTX-CI significantly increased MSNA compared to CTR (36 +/- 3 versus 16 +/- 2 bursts/min, P < 0.05, mean +/- SEM). Both brachial and carotid artery distensibility were decreased in RTX-CI compared to CTR (7 +/- 1 versus 13 +/- 1 +/- 10(-3) /kPa and 17 +/- 1 versus 25 +/- 2 x 10(-3) /kPa, respectively, both P < 0.05). In RTX-CI, a significant inverse correlation between brachial, but not carotid artery distensibility and MSNA (r = -0.46, P < 0.01, r = -0.12, not significant, respectively) was found. Correlation between brachial artery distensibility and MSNA remained statistically significant on separate analysis of cyclosporine- or tacrolimus-treated RTX and after correction for arterial diameter, blood pressure, graft function, age and sex by stepwise multiple regression analysis. Results in RTX-AZA were similar to those in RTX-CI. In contrast, in RTX-NC with MSNA not significantly different from CON (16.6 +/- 2.0 bursts/min), brachial artery distensibility was significantly higher compared to RTX-CI and RTX-AZA (14.2 +/- 2.0 x 10(-3) /kPa, P < 0.05, respectively)., Conclusions: Increased sympathetic nerve activity in renal transplant patients is related to decreased distensibility of the muscular type brachial artery, but not the elastic type carotid artery.

Objective: Arterial distensibility is reduced in end-stage renal failure and also after renal transplantation. The aim of the present study was to test the hypothesis that reduced carotid artery distensibility is a predictor of cardiovascular disease in patients after renal transplantation., Subjects and Methods: Sixty-eight asymptomatic renal transplant recipients were studied between March 1990 and December 1992, 3-6 months after transplantation. The mean duration of follow-up was 95 +/- 2 months (mean +/- SEM). At entry, vessel wall movements of the common carotid artery were recorded using a pulsed multigate Doppler system; blood pressure was measured by sphygmomanometry., Results: Nineteen cardiovascular events (CVE) occurred during follow-up, leading to death in six cases. The distensibility coefficient of the common carotid artery was significantly lower in patients with CVE than in those without CVE (12.2 +/- 1.0 10-3/kPa versus 16.8 +/- 0.7 10-3/kPa, P < 0.005). Logistic regression analysis showed that the occurrence of cardiovascular disease during follow-up was related to carotid artery distensibility (P < 0.05), independent of sex, age, smoking habits, carotid artery end-diastolic diameter, systolic and diastolic blood pressure levels, heart rate, serum creatinine, cholesterol and haemoglobin levels. Patients with a distensibility coefficient above the age-adjusted mean had a significantly longer interval free of cardiovascular disease than patients with a distensibility coefficient below the age-adjusted mean (P < 0.01)., Conclusions: The distensibility of the common carotid artery is an independent predictor of cardiovascular disease in renal transplant recipients.

Background: The Hypertension Optimal Treatment (HOT) Study provided information about cardiovascular events in 18,790 hypertensives, subjected to pronounced blood pressure lowering for a mean of 3.8 years., Methods and Results: The HOT Study data have been further analysed after risk stratification of the patients (1999 World Health Organization and International Society of Hypertension guidelines criteria): (i) no patients of the HOT Study were classified as low risk, 50% were classified as medium risk, 20.2% as high risk and 29.8% as very high risk; (ii) incidence of cardiovascular events in these patients with excellent blood pressure control [92% had diastolic blood pressure (DBP) < or = 90 mmHg] remained proportional to pretreatment risk. The relative risk of very high- versus medium-risk strata was between two and three both when HOT Study patients were considered independently of, or within the DBP target group they had been randomized to; and (iii) event rates in all risk strata were calculated to be much lower (possibly 60% lower) than rates expected from baseline risk calculated approximately by the Framingham equation., Conclusions: The low event rate in HOT Study patients is likely to result from pronounced blood pressure lowering, and is not explained by a lower risk profile than in previous controlled trials of antihypertensive treatment. The persistence of a risk gradient despite intensive blood pressure lowering suggests a combination of blood pressure control with other strategies of risk correction and the need to initiate antihypertensive therapy before complications develop.

Objective: Diadenosine polyphosphates (APnAs, n = 3-6) are a family of endogenous vasoactive purine dinucleotides which have been isolated from thrombocytes. Diadenosine pentaphosphate (AP5A) and diadenosine hexaphosphate (AP6A) are more potent than diadenosine tetraphosphate (AP4A) and diadenosine triphosphate (AP3A) and cause skeletal muscle vasoconstriction in rats. Little is known about their physiological and pathophysiological significance in humans. The aims of the present study were to compare thrombocyte APnA concentrations in patients with essential hypertension (HYP) and in healthy normotensive humans (CON) using a novel quantitative assay and to assess a possible relationship between thrombocyte APnA concentrations and skeletal muscle vascular resistance., Design and Methods: We describe a novel assay for quantification of APnAs in human platelets, involving platelet isolation from human blood, a solid-phase extracting procedure with a derivatized resin, desalting and quantitative determination of the substances with an ion-pair reversed-phase high-performance liquid chromatography (HPLC) system. The structural integrity of the isolated APnAs was confirmed by mixed assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) measurements and co-elution with added standards. The detection threshold for all four APnAs was 1 pmol/l and the inter-assay coefficients of variation were < 11% (n = 12). After venous blood sampling, mean arterial blood pressure (MAP) and forearm blood flow (FBF, using venous occlusion plethysmography) were measured in HYP and CON. Forearm vascular resistance (FVR) was calculated as MAP/FBF. significantly differ in platelet AP3A and AP4A content, but HYP had significantly higher thrombocyte concentrations of AP5A (56 +/- 7 versus 32 +/- 3 ng/microg beta-thromboglobulin, P = 0.003) and AP6A (10 +/- 1 versus 6 +/- 1 ng/microg beta-thromboglobulin, P = 0.015) than CON. HYP had significantly elevated FVR (50 +/- 6 versus 33 +/- 2 arbitrary units, P = 0.01) compared to CON. Significant correlations were found between AP5A and FVR (p = 0.38, P = 0.04) as well as between AP6A and FVR (p = 0.42, P = 0.02). In contrast, there were no significant correlations between APnAs and MAP., Conclusions: The study shows that thrombocyte concentrations of AP5A and AP6A are elevated in patients with essential hypertension. Vasoconstriction caused by release of AP5A and AP6A from thrombocytes may contribute to the increase of vascular resistance in hypertensive patients.

Objective: To investigate the different effects of hypertension, hyperlipidaemia and atherosclerosis on the visco-elastic properties of large arteries., Design: Vessel wall properties were determined in patients who had been subjected for the first time to coronary arteriography. Normotensive patients with no coronary disease (n = 15), one-vessel disease (n = 15) or two- or three-vessel disease (n = 15), 15 treated hypertensive patients (mean +/- SEM duration of hypertension 9.6 +/- 1.7 years) with no coronary disease and normocholesterolaemia and 15 healthy controls were matched for blood pressure, age and sex., Methods: Arterial distension of the common carotid artery was determined by using a multigate Doppler system. The blood pressure curve was recorded by finger plethysmography., Results: The end-diastolic diameter was significantly higher in the hypertensives (P<0.05) but not significantly different in the normotensives compared with the controls. Arterial distensibility was significantly lower in the hypertensive group [(13.3 +/- 0.8) x 10(-3)/kPa] than in the controls [(19.1 +/- 1.5) x 10(-3)/kP; P<0.01), in the group with no coronary disease [(18.8 +/- 1.3) x 10(-3)/kPa; P<0.01] and in those with one-vessel disease [(17.7 +/- 1.4) x 10(-3)/kPa; P<0.05]. Arterial distensibility was not significantly lower in the hypertensives than in the group with two- or three-vessel disease [(15.0 +/- 1.0) x 10(-3)/kPa; NS). No significant correlation was found between cholesterol or lipoprotein(a) levels and arterial distensibility in the normotensive patients., Conclusions: Hypertension is the predominant factor affecting the visco-elastic properties of large arteries. Arterial compliance is significantly altered only in extensive atherosclerosis.

The effects of shifted working and sleeping phases on the diurnal blood pressure rhythm were investigated in 15 physically working industrial shift workers at a slowly rotated three-shift system. Ambulatory 24-h blood pressure monitoring was performed during the morning and night shifts. In the two shifts the mean 24-h blood pressure was identical. There were no differences in the blood pressure levels in the sleeping phases or in the working periods between the two 24-h cycles. Diurnal blood pressure fluctuations had equal amplitudes. Corresponding to the lag between the working period there was a phase difference of 8 h between the 24-h blood pressure curves. At this lag, there was a high correlation between the mean hourly blood pressure values (r = 0.683). Twenty-four-hour blood pressure curves during the first and last day of a night shift were nearly equal. Thus the effects of shift rotation on the 24-h blood pressure profile were fully expressed within the first 24 hours. The immediate and complete adaptation of the 24-h blood pressure curve to shifted activity and sleeping phases indicates that activity determines the diurnal blood pressure profile. The blood pressure is largely independent of internal circadian rhythm.

Blood pressure and plasma catecholamine levels were followed up for a total of 7 years in 26 subjects with borderline hypertension and in 24 normotensive subjects. During the observation period, five subjects from the borderline hypertensive group became definitely hypertensive, 10 remained in the borderline hypertensive range and in 10, blood pressure fell below borderline hypertensive levels. Of the original 24 normotensive subjects, 15 remained in the normotensive range. In seven, blood pressure rose, but did not reach borderline hypertensive levels. Three subjects were lost to follow-up. In contrast with the subjects who remained normotensive and borderline hypertensive, those who became definitely hypertensive had consistently high plasma noradrenaline concentrations at rest. Plasma adrenaline levels and plasma noradrenaline concentrations during exercise did not differ, however. The study suggests that borderline hypertensive subjects who develop definite hypertension within a few years have consistently enhanced sympathetic activity.