Biomedical subjects

M Safar

Publications and source records attributed to M Safar.

At least 109 records · Page 6Linked to original sources

PubMed1996

Central hypervolemia in the conscious rat: a model of cardiovascular deconditioning.

The aim of the present study as to investigate whether increased central hypervolemia induced by tail suspension (TS) in the rat is an appropriate model of cardiovascular deconditioning (CVD). First, the physiological relationship between central venous pressure (CVP) and extracellular fluid volume (ECFV) was studied. TS (20 degrees) increased CVP (5.8 +/- 0.7 vs. 2.8 +/- 0.8 mmHg; P < 0.01). After 24 h of TS, CVP had returned to control range while ECFV was reduced by 19%. CVP kinetics during 24 h of TS was not affected by either reduction (-20%) or augmentation (/35%) of the ECFV. The normalization of CVP is likely to be a consequence of ECFV reduction, which itself is reduced by increased urinary excretion of water and sodium. Second, recovery from TS was studied. Resumption of the horizontal position was shown to be associated with a significant increase of heart rate (HR) and a slight reduction of blood pressure (BP); there was an apparent delay between increased HR and reduced BP. This imbalance between HR and BP is compatible with CVD. A model of simulated orthostatism (SO) was developed to further investigate the responses of HR and BP. Interestingly, SO (90 degrees rotation) in the normal rat was associated with significant tachycardia and a slight increase of BP. This pattern remained stable for at least 3 h. In rats that were tail suspended for 48 h, episodes of hypotension and bradycardia (5 +/- 1 in 3 h) suggested a defect in adaptation to increased hydrostatic pressure. In conclusion, TS appears to be an appropriate model of CVD. Reduction process. Return to horizontal position in TS rats induced a tachycardia with minimal effects on BP; this pattern is close to that observed in humans assuming upright posture. SO in previously TS rats disclosed episodes of hypotension and bradycardia that deserve further investigation.

Animals↗

PubMed1996

Remodeling of the radial artery in response to a chronic increase in shear stress.

Chronic changes in large artery blood flow rates induce corresponding adjustments in arterial diameter, but little is known about structural adaptations of the vessel wall in humans. We used a high-resolution echo-tracking system to measure radial artery internal diameter, wall thickness, and mean blood flow on both arms of 11 patients with end-stage renal disease. Measurements were performed on the wrist side of the arteriovenous fistula. The contralateral radial artery was investigated as control. Wall cross-sectional area, circumferential wall stress, and mean wall shear stress were calculated. Results indicate a sixfold increase in blood flow on the side of the arteriovenous fistula compared with the control side, with a 1.4-fold increase in internal diameter. The diameter enlargement was sufficient to normalize wall shear stress. Changes in diameter were not associated with arterial wall hypertrophy because wall cross-sectional area was not increased and rather suggest a "remodeling" of the arterial wall. For the same level of blood pressure, circumferential wall stress was increased on the side of the arteriovenous fistula. These results suggest that the structural adaptations of the arterial wall to a chronic increase in blood flow normalize wall shear stress and overcome stretch-induced changes in the particular circumstance of arteriovenous fistula.

Adult↗

PubMed1996

Influence of the angiotensin II type 1 receptor gene polymorphism on the effects of perindopril and nitrendipine on arterial stiffness in hypertensive individuals.

Angiotensin-converting enzyme inhibitors improve arterial stiffness independently of blood pressure reduction. Since we have recently shown that in hypertensive individuals the A1166C polymorphism of the angiotensin II type 1 receptor (AT1-R) is an independent determinant of aortic stiffness, we designed the present study to assess the influence of this polymorphism on the changes of aortic stiffness after chronic treatment with the angiotensin-converting enzyme inhibitor perindopril and the calcium channel blocker nitrendipine. Forty perindopril- and 42 nitrendipine-treated hypertensive individuals were studied. We evaluated aortic stiffness by measuring the carotid-femoral pulse wave velocity. Carriers of the AT1-RC allele showed higher baseline values of pulse wave velocity than AA homozygotes (P < .05). In the perindopril group, a threefold greater reduction in pulse wave velocity was observed in carriers of the C allele than in AA homozygotes (-2.85 +/- 0.62 versus -0.94 +/- 0.32 m/s, respectively; P < .001), whereas in the nitrendipine group, pulse wave velocity decreased only in AA homozygotes and not in AT1-R C carriers (-1.38 +/- 0.35 versus +0.04 +/- 0.60 m/s, respectively; P < .01). These results indicate that according to the AT1-R A1166C genotype, an angiotensin-converting enzyme inhibitor and a calcium channel blocker affect pulse wave velocity in opposite ways. Since some evidence shows that increased pulse wave velocity may enhance cardiovascular risk, it might be useful for physicians to consider the AT1-R genotype when prescribing an angiotensin-converting enzyme inhibitor or calcium channel blocker to a hypertensive individual.

Adult↗

PubMed1996

Repeated measurements of non-invasive ambulatory blood pressure: distinction between reproducibility and the proper effect of placebo.

OBJECTIVE: To determine whether non-invasive ambulatory blood pressure is more reproducible and less affected by the placebo treatment than are clinic blood pressure measurements. METHOD: Thirty-four essential hypertensive outpatients were randomly allocated after a 4-week preselection period in two groups in a cross-over study design. One group received placebo for 4 weeks while the other formed the control group (reproducibility), then the treatments were exchanged for another 4 weeks. Clinic and ambulatory blood pressures were measured at three different times for each patient, namely bnefore the random allocation to groups and at the end of each period, using a mercury sphygmomanometer and 24 h non-invasive ambulatory blood pressure monitoring. RESULTS: Administration of placebo was accompanied by a significant reduction in systolic and diastolic clinic blood pressures (by 3.4+/-13 and 3.6+/-8 mmHg, respectively), but not in 24 h, daytime and night-time blood pressures. Circadian hourly blood pressure and heart rate curves were virtually superimposable. In the 13 placebo responder patients selected on the basis of clinic blood pressure, placebo decreased the clinic blood pressure and also reduced systolic and diastolic ambulatory blood pressures, mainly during the day period (by 5.2+/-6.2 and 4.89+/-7.8 mmHg, respectively). This effect is specific and related to the placebo administration because repetition of the measurements without any treatment showed no significant difference. To characterize at baseline the placebo responder patients, comparison with the non-placebo responders showed lower baseline values of ambulatory systolic blood pressure recorded during 24 h daytime and night-time in the placebo responder group. CONCLUSION: The 24 h ambulatory blood pressure average is not affected by placebo in the present group of patients but that a placebo effect occurs mainly during the daytime in patients who decreased their clinic blood pressure under placebo (placebo responders); the placebo-induced reduction in blood pressure is related to a specific effect of placebo and is independent from any alerting reaction or reproducibility hypothesis. This study clearly indicates the necessity of including placebo and ambulatory blood pressure monitoring in the therapeutic and pharmacological trials of antihypertensive drugs.

Journal Article↗

PubMed1996

Arterial distensibility and circadian blood pressure variability.

OBJECTIVE: To analyse the relationships between arterial distensibility and blood pressure level and its circadian variability assessed by non-invasive ambulatory blood pressure monitoring. DESIGN: One hundred and six patients (69 men, 37 women; aged 20-72 years) without any cardiovascular complication or treatment underwent 24 h ambulatory blood pressure monitoring. Aortic distensibility was evaluated by carotid-femoral artery pulse-wave velocity measurements performed with a validated automatic device (Complior). RESULTS: The pulse-wave velocity correlated significantly with age (P < 0.001), systolic blood pressure (P < 0.01) and heart rate (P < 0.05). Subjects with higher pulse-wave velocities (above the median value) had higher ambulatory blood pressure and heart rate values, mainly during night-time, and present a smaller nocturnal fall both in systolic and in diastolic blood pressure than do those with lower pulse-wave velocities (below the median). The pulse-wave velocity was revealed to be an independent predictor of the nocturnal fall in systolic blood pressure (multiple r = 0.272, P < 0.02) whereas age and, to a lesser extent, mean 24 h diastolic blood pressure were independent predictors of the nocturnal fall in diastolic blood pressure (multiple r = 0.387, P < 0.001). CONCLUSION: Reductions in arterial distensibility are associated with increased blood pressure and heart rate levels whereas perturbations of the circadian blood pressure profile are associated with increased nocturnal values. The increased risk of end-organ damage and vascular events in the presence of higher nocturnal blood pressure values suggests that a study of arterial distensibility in the normal follow-up of hypertensive patients might be of benefit.

Journal Article↗

PubMed1996

Representativeness of peripheral blood pressure values: the pulsatile component of blood pressure in hypertension.

Whereas mean arterial pressure remains practically unmodified along the arterial tree, pulse pressure increases markedly from central to peripheral arteries, principally due to an increase in systolic blood pressure and a small lowering of diastolic blood pressure. This hemodynamic pattern, due to the progressive increase in arterial stiffness and to the summation between the incident and the backward pressure wave along the arterial tree, has several implications, in that: i) the pulse pressure amplification increases with the effective length of the arterial tree (and therefore with the body height of subjects), but decreases with aging, due to a significant age-induced increase in aortic wave reflections and pulse pressure, ii) the magnitude of the pulse pressure amplification is strongly influenced by the status of the autonomic nervous system, so that carotid pulse pressure decreases more than brachial pulse pressure following sympathetic stimulation using lower body negative pressure, and iii) the pulse pressure amplification may be restored following administration of pharmacological agents as converting enzyme inhibitors and calcium entry-blockers but not dihydralazine. These particularities of pressure wave transmission may have fundamental consequences for: the diagnosis of hypertension, whether in humans or in animal; the evaluation of cardiac afterload and the effectiveness of antihypertensive agents; and finally, the interpretation of cardiovascular epidemiology. Indeed increased brachial pulse pressure is known to be an independent cardiovascular risk factor, particularly for myocardial infarction, but not for cerebrovascular complications.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1996

Arterial stiffening: opposing effects of age- and hypertension-associated structural changes.

This article reviews the effects of aging and hypertension on geometrical (lumen and arterial wall thickness) and functional (distensibility) properties of large and medium-sized arteries in humans. Several clinical and animal studies show that arterial wall hypertrophy does not increase the elastic modulus of the arterial wall material during sustained essential hypertension. The structural changes associated with either hypertension or aging have opposing effects on arterial distensibility, under similar transmural conditions: the former increasing it, the latter decreasing it. Thus, hypertension cannot be assimilated to aging. The structural and functional changes of the arterial wall material that are associated with the hypertension-induced hypertrophy could be a means by which medium-sized arteries maintain their distensibility characteristics despite increased distending pressure, and large arteries compensate for the age-induced decrease in arterial compliance.

Aging↗

PubMed1996

[Two strains of genetically hypertensive rats, LH and SRH, have distinct profiles of postnatal expression of tropoelastin and type III collagen in the aortic wall].

Experimental pharmacology and studies on hypertension frequently use genetically hypertensive animal models like the SHR or the Lyon hypertensive rat LH. In order to further characterize these two models we measured the expression levels of three major extracellular matrix components in the aortic wall, tropoelastin (TE) and type I and type III collagen, during postnatal development. The type I collagen expression decreases progressively during the first twelve weeks of postnatal development without significant differences between SHR and LH, or their normotensive controls, WKY or LN respectively. No differences were detected either for the expression levels of TE and type III collagen between the hypertensive strains and their respective controls. However, direct comparison of the two hypertensive strains SHR and LH, revealed a specific, strong increase of TE and type III expression for the LH at 5 and 12 weeks (p < 0.001 and 0.005 respectively). The evolution of the ratios of expression levels between the two collagens (type III/type I) on one side and of TE and collagen type I (TE/type I) on the other side were similar for the hypertensive strains and their respective controls, but diverged significantly for LH and SHR animals (up to p < 0.001 depending on the age group). Both indicators, III/I and TE/I, are considerably higher in LH compared to SHR from 5 weeks of postnatal development onwards. Our results indicate that the genes for TE and type I and III collagen are regulated during postnatal development of LH and SHR. It is however not possible at this point to establish a link between mRNA levels and hypertension in these animals. Nevertheless, the ratios III/I and TE/I seem to be good phenotypic markers for the characterisation of LH and SHR strains.

Animals↗

PubMed1996

[Family physicians and scientific information. Survey on hypertension and diuretics].

In order to analyse the quality of scientific communication in the field of hypertension, we have conducted a survey among French physicians. The topics of the questions were partly related to hypertension and partly to diuretics; 3,600 questions forms have been mailed: 610 answers were returned (17%). The results show that most of physicians are unsufficiently informed about primary prevention therapeutical trials and recommendations. Moreover, whereas all physicians questionned (97%) consider that diuretics constitute a current therapeutic approach, this class remains largely unknown concerning its mechanisms, efficacy and tolerance dose relationships. As 80% of general practitioners having participated to this survey wish to be more informed on recent data in this field, these results emphasize the necessity of adapting information to the need of practitioners, raise questions concerning the information supports, the role of scientific committees in the medical information and the necessity to complete clinical research by studies which results may be rapidly applicable in clinical practice.

Adult↗

PubMed1996

[Arterial hypertension, aging and cardiac decompensation].

Cardiac function of hypertensive patients is normal, or even better than normal, despite the presence of cardiac hypertrophy. It is therefore difficult to explain the mechanism of decompensation phenomena, especially as clinicians are rarely able to observe the passage from the compensated phase to the phase of decompensated hypertensive heart failure. Various arguments suggest that cardiovascular ageing, independently of hypertension, exerts specific haemodynamic effects which can be responsible for decompensation. In the heart, extension of fibrosis can be responsible for a defect of diastolic expansion and the development of arrhythmias. In the vessels, increased aortic rigidity is responsible for a dissociation between cardiac and vascular functions, especially as the pressure reflection wave returns during the systolic phase rather than the diastolic phase of the pressure curve. These data suggest that Cardiac failure phenomena now justify thorough evaluation of arterial function, which can currently be investigated by noninvasive techniques.

Aging↗

PubMed1996

[Treatment of hypertension with indapamide 1.5 mg sustained-release form: synthesis of results].

In accordance with international recommendations on the need to decrease doses of antihypertensive drugs, a low-dose (1.5 mg) sustained-release form of indapamide was developed so as to optimize the safety/efficacy ratio, while maintaining a once-daily administration. The new formulation ensures that the active ingredient release occurs in a sustained manner over 24 hours, with mean concentrations close to the maximal concentration over a prolonged period, while avoiding peak plasma concentrations. Clinical data were obtained mainly through two European multicenter, randomized, double-blind trials, totalling 690 patients. Firstly, the antihypertensive efficacy' of the new indapamide 1.5 mg form was demonstrated by measuring blood pressure 24 hours after the last drug intake, using a mercury sphygmomanometer; the equivalence of its antihypertensive efficacy with the immediate-release form of indapamide 2.5 mg was then verified. Biochemical safety data showed better acceptability with indapamide 1.5 mg with in particular a reduction of more than 50% of the number of patients with kalemia < 3.4 mmol/l; clinical safety data confirmed the good acceptability observed with the 2.5 mg immediate-release form of indapamide since many years, especially regarding glucose and lipid neutrality. In conclusion, the 1.5 mg sustained-release form of indapamide has an improved antihypertensive efficacy/safety ratio which is in accordance with international recommendations for the usage of low doses of antihypertensive drugs and diuretics in the first-line treatment of hypertension.

Adolescent↗

PubMed1996

[Evaluation of trough/peak ratio of indapamide 1.5 mg sustained-release form assessed by ambulatory blood pressure monitoring].

Because of the high variability of casual blood pressure measurements. ABPM has become a complementary clinical tool for evaluating antihypertensive treatment. Nevertheless, there is still a lack of practical guidelines to interpret the data. A review of the literature shows that ABPM efficacy data are analyzed differently, especially the trough-to-peak ratio proposed by the Food and Drug Administration. Published trough-to-peak ratios are widely disparate due to the diversity of the calculation methods which are most often not justified. Thus inappropriate comparisons of these results can easily produce incorrect conclusions. The aim of this review is to select, through the literature, basic methodological requirements commonly agreed on for accurate assessment of trough-to-peak ratio, and to apply them to the ABPM data on indapamide, a diuretic related to the thiazides. Six methodological requirements commonly agreed on at this time are the following: 1. study design: placebo-controlled study with a placebo run-in period; 2. patients selection: compliance with the study protocol, record obtained before and after treatment for each patient; 3. population analysis: whole and responder population: 4. quality control of the records: 5. placebo effect subtraction; 6. global and individual calculation with the indication of median values. Given that, no T/P ratio, especially for a diuretic, has yet been calculated according to these requirements, the above methodological points were taken into account for the T/P calculation of indapamide, from a placebo-controlled dose-finding study involving 285 patients.

Adult↗

PubMed1995

Vascular wall thickness in hypertension: the Perindopril Regression of Vascular Thickening European Community Trial: PROTECT.

A high prevalence of increased intima/media thickness of the arterial wall has been documented in hypertension. These alterations in vascular wall structure may be potent determinants for the promotion of the development of atherosclerosis. Direct histologic data from animal models of hypertension, and indirect data from hypertensive patients, have demonstrated a marked regression of increased intima/media thickness by angiotensin-converting enzyme (ACE) inhibition. Long-term effects of ACE inhibition on structural wall changes in humans have not been examined. Therefore, a multicenter, randomized, double-blind European trial was designed to compare the effects of the ACE inhibitor perindopril and the diuretic hydrochlorothiazide in slowing or reversing progression of increased intima/media thickness of carotid and femoral arteries in hypertensive patients. A total of 800 patients at 17 clinical centers in 7 European countries, aged 35-65 years, with hypertension and ultrasonographically proven intima/media thickness > or = 0.8 mm of the common carotid artery will be randomly assigned to receive in a double-blind fashion either perindopril or hydrochlorothiazide and will be followed for 24 months. High resolution duplex sonography will be used to quantify intima/media thickness at baseline and twice a year during follow-up. A change of 0.1 mm of intima/media thickness from baseline is considered to be detectable, and the standard deviations of the changes from baseline are expected not to be higher than 0.2 mm. The primary endpoint of the study is the comparison of changes in intima/media thickness of the common carotid artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Neuronal metabolism of catecholamines in pithed and electrically stimulated rats.

The aim of the present study was to investigate a possible physiological equilibrium, assessed by statistically significant correlations, between pre-junctional mechanisms that regulate both release and reuptake of norepinephrine (NE) and post-junctional mechanisms that participate in the regulation of the smooth muscle cell and thus in the regulation of blood pressure. This study was carried out in pithed and electrically stimulated (2.5 Hz) rats to obtain an experimentally controlled release of NE. A radio-enzymatic assay was used to measure plasma concentrations of NE, index of NE release and levels of its deaminated metabolites 3,4-dihydroxyphenyl glycol (DHPG) and 3,4-dihydroxymandelic acid (DOMA). DHPG is known to be an index of NE reuptake and deamination while the physiological significance of DOMA remains unclear. Our results demonstrate a statistically significant correlation between plasma NE concentration and blood pressure on one hand, and between plasma NE and DHPG concentrations on the other. These correlations support our working hypothesis and suggest a physiological equilibrium between pre- and post-junctional phenomena in the control of blood pressure. During 2.5-Hz stimulation, plasma DHPG concentration was increased while plasma DOMA remained unchanged. This is consistent with activation of the reduction pathway and the consequent formation of DHPG by aldehyde reduction, while the oxidation pathway mediated by aldehyde dehydrogenase does not appear to play a major role in the presynaptic metabolism of reuptaken NE in the present experimental conditions. Further investigations are needed to investigate the apparent dissociation between the two enzymatic pathways involved in the second step of the deamination process.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1995

Nosocomial acquisition of multiresistant Acinetobacter baumannii: risk factors and prognosis.

To identify risk factors for and prognostic indicators of the nosocomial acquisition of multiresistant Acinetobacter baumannii in an intensive care unit, we prospectively studied 40 patients: 13 who were infected with this organism and 27 who were colonized. Isolates were identified by pulsed-field gel electrophoresis; the infected/colonized patients were compared with 348 noninfected, noncolonized patients by logistic regression analysis and with matched historical controls in a cohort study. The severity of illness (evaluated by the APACHE II score; P < .05) and previous infection (P < .001) were retained as independent risk factors for acquiring A. baumannii. Logistic regression analysis selected a high APACHE II score (P < .01) and the acquisition of A. baumannii (P < .01) as factors independently associated with death. The acquisition of A. baumannii was associated not only with high mortality but also with a length of stay on the intensive care unit in excess of that due to the underlying disease alone; specifically, the attributable mortality was 25%, with a risk ratio for death of 2.0 (95% confidence interval, 1.11-3.62), and the duration of stay for infected/colonized patients was 10.3 days longer than that for controls (P < .001).

APACHE↗

PubMed1995

Structural changes and in situ aortic pressure-diameter relationship in long-term chemical-sympathectomized rats.

This study determined the effects of long-term chemical sympathectomy with guanethidine (GN) on the mechanical properties and composition of the distal abdominal aorta in Wistar rats. GN was daily administered for 3 mo (3M-GN, from 1 to 12 wk), 5 wk (5W-GN, from 7 to 12 wk), and 8 days (8D-GN, from 11 to 12 wk). All experiments were performed at 12 wk of age to avoid age differences at examination. We used a high-resolution echo-tracking system to determine in situ, in the systolic-diastolic range, the aortic diameter-, compliance-, and distensibility-pressure curves in anesthetized rats. We observed an equivalent significant fall in the tyramine pressor response in all conscious GN-treated rats. Blood pressure was not affected by sympathectomy after 8 days and 5 wk of treatment but was significantly reduced in 3M-GN rats. Chronic sympathetic denervation increased aortic diameter and compliance in 8D-GN rats, compared with those obtained at the same distending pressure in control rats, suggesting vascular smooth muscle relaxation. In contrast, in 5W-GN and 3M-GN rats, the distensibility pressure-curves were significantly shifted toward lower levels of distensibility and pressure, indicating a decreased aortic distensibility at the same level of arterial pressure. Sympathectomy produced a significant reduction in the content of elastin, one of the most distensible components of the arterial wall in 5W-GN and 3M-GN rats. These results suggest that intact sympathetic nerves are necessary to maintain normal functional and structural properties of large arteries in rat. The reduction in aortic distensibility, in long-term sympathectomized rats, could have resulted from complex interactions between local aortic denervation, change in the set point of distending pressure, and changes in aortic smooth muscle tone and/or wall composition.

Animals↗

PubMed1995

Common carotid artery stiffness and patterns of left ventricular hypertrophy in hypertensive patients.

The aim of this study was to determine the relationship between the lumen diameter and function of the common carotid artery, a vessel representative of the capacitance portion of the circulation, and the different patterns of left ventricular hypertrophy in uncomplicated essential hypertensive patients. Carotid luminal diastolic cross-sectional area, distensibility, and compliance were derived from measurements by a high-definition echotracking system. Left ventricular dimensions were from echocardiography. The 86 hypertensive patients included 31 who had never been treated (group 1), 31 in whom treatment had been stopped for at least 2 weeks (group 2), and 24 treated patients (group 3). In multivariate analysis of the population as a whole, the following relations were statistically independent of age, blood pressure, gender, and group: Left ventricular end-diastolic volume index was positively correlated to carotid luminal cross-sectional area (r = .46, P < .0001) and compliance (r = .47, P < .0001); left ventricular mean wall thickness and mass-volume ratio were negatively correlated to distensibility (r = -.68, P < .0001; r = -.46, P < .0001, respectively) and compliance (r = -.40, P < .0001; r = -.37; P < .001, respectively); and left ventricular mass index was positively correlated to luminal cross-sectional area (r = .23, P < .02) and negatively to distensibility (r = -.26, P < .01). These results indicate that geometric and functional changes in the common carotid artery accompany geometric changes in the left ventricle. More specifically, they suggest that a reduction in distensibility paralleled cardiac concentric hypertrophy and remodeling, whereas an increase in arterial volume paralleled increased left ventricular cavity size.

Adult↗

PubMed1995

Influence of angiotensin II type 1 receptor polymorphism on aortic stiffness in never-treated hypertensive patients.

Several clinical and experimental studies have suggested a significant role of angiotensin II in the development of alterations of small and large arteries. The present study was designed to assess the contribution of polymorphism (corresponding to an A1166-->C transversion) of the angiotensin II type 1 receptor (AT1) gene to aortic stiffness. One hundred thirty-four never-treated hypertensive patients were included in the study. Aortic distensibility was evaluated by measuring carotid-femoral pulse wave velocity. Age, systolic and diastolic pressure, and metabolic parameters were similar in the three genotypes. Pulse wave velocity was 11.4 +/- 2.5 m/s in AT1 AA homozygotes, 12.5 +/- 3.2 m/s in AC heterozygotes, and 14.7 +/- 4.0 m/s in CC homozygotes (P = .003, P < .001 after adjustment for age, blood pressure, and body mass index). Moreover, an interaction was found between AT1 genotype and the ratio of total to high-density lipoprotein cholesterol in terms of the development of aortic stiffness. Thus, a positive correlation was observed between the ratio of total to high-density lipoprotein cholesterol and pulse wave velocity in AC and CC (r = .42, P < .001) but not AA patients. These results suggest that the AT1 gene is involved in the development of aortic stiffness in hypertensive patients and could modulate the effects of lipids on large arteries.

Adult↗