Biomedical subjects

A Benetos

Publications and source records attributed to A Benetos.

At least 55 records · Page 3Linked to original sources

PubMed1999

Pulse pressure and cardiovascular risk.

Numerous studies have shown that increases in diastolic (DBP) and systolic (SBP) blood pressure are positively associated with cardiac events. Since DBP typically varies by smaller amounts, it has historically been the blood pressure value used most often to assess the risk of cardiovascular disease. Further studies have indicated, however, that SBP continues to increase proportionally with age, while DBP levels off. New data have emerged which suggest that DBP can no longer be valued as a reliable predictor of cardiovascular events and may even be diagnostically misleading. Normal levels of DBP can be indicative of a combination of an increase in peripheral vascular resistance (which elevates DBP) with an increase in arterial stiffening (which decreases DBP). These two phenomena 'cancel' each other out; the underlying risk factors are disguised by the apparent normalcy of the DBP reading. DBP is even less of an indicator in older adults, where the prevailing form of hypertension is isolated systolic hypertension and the most common cause is large-artery stiffness. Since arterial stiffening causes SBP to increase and DBP to decrease, the gap between the two, pulse pressure (PP), may be the best predictor of cardiac events for all the blood pressure values. Several studies have confirmed that subjects with the widest PP have the greatest risk of mortality. Pulse pressure has also been observed to be a significant and independent indicator of myocardial infarction. Furthermore, compelling evidence has emerged that PP is a strong indicator of cardiovascular risk even among normotensive individuals.

Antihypertensive Agents↗

PubMed1998

Prevention of arterial structural alterations with verapamil and trandolapril and consequences for mechanical properties in spontaneously hypertensive rats.

We compared the chronic effects in spontaneously hypertensive rats (SHR) of low doses of an angiotensin converting enzyme inhibitor, trandolapril, a Ca2+ channel antagonist, verapamil, and their combination (trandolapril-verapamil), on arterial mechanical properties, arterial wall hypertrophy and extracellular matrix proteins. Four-week-old SHR were randomly allocated to oral treatment with verapamil (50 mg kg(-1) day(-1)), trandolapril (0.3 mg kg(-1) day(-1)), the combination of verapamil (50 mg kg(-1) day(-1)) plus trandolapril (0.3 mg kg(-1) day(-1)), or placebo for 4 months. A group of Wistar Kyoto (WKY) control rats received placebo for the same period of time. At the end of the treatment, mean blood pressure was lower in verapamil-trandolapril than in trandolapril SHR, but remained higher than in WKY. Verapamil had no effects on blood pressure. Equivalent reduction in aortic wall hypertrophy was obtained in all treated SHR. Trandolapril and verapamil-trandolapril combination produced a significant reduction of aortic collagen density compared with placebo SHR. Carotid total fibronectin, EIIIA fibronectin isoform and alpha5beta1 integrin, were higher in the media of placebo SHR than in WKY. EIIIA fibronectin isoform and alpha5beta1 integrin were reduced in verapamil-SHR compared with placebo-SHR and normalized in trandolapril and verapamil-trandolapril-SHR compared with WKY. SHR-placebo and SHR treated with either verapamil or trandolapril as single-drug treatment showed a 4-fold increase in total fibronectin compared to the WKY. Only SHR treated with verapamil-trandolapril combination had total fibronectin not significantly different from that of WKY. Carotid arterial distensibility increased only in verapamil-trandolapril treated rats. Multivariate analysis showed arterial distensibility to be negatively correlated to mean blood pressure (P < 0.0001) and total fibronectin (P < 0.01). In conclusion, chronic treatment with the verapamil-trandolapril combination significantly improved in vivo arterial distensibility in SHR. The most important effects of the combination on arterial mechanics compared to those of verapamil or trandolapril alone may have been the consequence of its stronger action on arterial pressure, arterial wall hypertrophy and total fibronectin density. However we suggest that, in addition to the structural effects, complete normalization of blood pressure is necessary to obtain normal arterial distensibility.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1998

Differential responses of the heart and vasculature to chronic blood pressure reduction in essential hypertension.

BACKGROUND: In subjects with hypertension, converting enzyme inhibitors and calcium entry blockers may decrease arterial stiffness independently of blood pressure changes, but the heterogeneity of response of the arterial tree has never been taken into account. MATERIAL AND METHODS: In 31 subjects with hypertension, we determined through the use of Doppler echographic techniques the compliance and distensibility of the common carotid and femoral arteries and of the abdominal aorta, the radial artery wall thickness, and cardiac mass. In a double-blind randomized study, the converting enzyme inhibitor ramipril and the calcium entry blocker nitrendipine were studied and compared during 12 weeks treatment, then 4 weeks after treatment was stopped. RESULTS: The two drugs caused significantly different plasma levels of active renin, angiotensin I, and norepinephrine but the same effects on blood pressure, cardiac mass, radial artery wall thickness, and stiffness indices. In contrast, the effect of treatment differed substantially according to the site of cardiovascular measurements. Although cardiac mass decreased significantly in parallel with blood pressure reduction, no change in radial artery wall thickness occurred. Carotid compliance and distensibility increased significantly, even after drug treatment was stopped, whereas little or no change was observed for the femoral artery and the abdominal aorta. CONCLUSION: This study provides evidence that the changes in cardiovascular structure and function with ramipril and nitrendipine treatment are poorly influenced by their different mechanisms of action but highly dependent on the site of measurements. The results suggest that local autocrine-paracrine mechanisms act synergistically with blood pressure to produce cardiovascular changes.

Adult↗

PubMed1998

Genetic determination of plasma aldosterone levels in essential hypertension.

The renin-angiotensin-aldosterone system plays an important role in large artery structure and blood pressure homeostasis. Among the genes coding for different components of this system, the aldosterone synthase (CYP11B2) gene could play an important role, but has been less investigated. We examined the role of two variations of the aldosterone synthase gene (CYP11B2), one located in the promoter of the gene, T-344C, the other in the 7th exon, the T4986C (Val/Ala), on plasma levels of renin and aldosterone, blood pressure, and arterial stiffness in subjects with essential hypertension. Subjects of European origin (n = 216) were examined during a 1-day hospitalization. Treatment, if any, was interrupted for at least 21 days before. Arterial stiffness was evaluated by measuring pulse wave velocity. Renin and aldosterone levels were evaluated by using a radioimmunoassay. The two polymorphisms were in complete linkage disequilibrium, as suggested by the presence of only three haplotypes in this population (T-344T4986, T-344C4986, and C-344T4986). The mean age and blood pressure values were similar in the different genotypes. Presence of the -344C allele was associated with elevated levels of plasma aldosterone: 90 +/- 8 pg/mL for TT (n = 67), 110 +/- 6 pg/mL for TC (n = 107), and 129 +/- 10 pg/mL for CC (n = 42) (test of codominant effect, P < .002 after adjustment for age and 24-h Na+ urine excretion). Pulse wave velocity was also increased in the -344C allele carriers: 11.3 +/- 0.4 m/sec, 12.7 +/- 0.3 m/sec, 12.0 +/- 0.5 m/sec in the TT, TC, and CC genotypes, respectively. No association was found between the T4986C polymorphism and the studied variables. In patients with essential hypertension, a variant on the promoter region of the aldosterone synthase gene is associated with significant differences in plasma aldosterone levels and arterial stiffness. These differences are not associated with variations in blood pressure levels.

Age Factors↗

PubMed1998

Nitric oxide synthase gene polymorphisms, blood pressure and aortic stiffness in normotensive and hypertensive subjects.

BACKGROUND: Genetic studies may help us to understand the mechanisms underlying the involvement of various neuro-humoral factors in the regulation of the mechanical properties of large arteries. We have shown previously that the angiotensin II type 1 receptor gene polymorphism was a strong determinant of aortic stiffness in hypertensives. OBJECTIVE: To assess the contribution of two polymorphisms of the endothelial nitric oxide synthase gene to aortic stiffness in normotensive and hypertensive subjects in the same cohort. METHODS: We studied 309 untreated hypertensive and 123 normotensive subjects. Aortic stiffness was evaluated by measuring the carotid-femoral pulse-wave velocity non-invasively. The endothelial nitric oxide synthase gene polymorphisms G10-T at intron 23 (GIN23T) and G298-T at exon 7 (Glu298Asp) were determined in each subject. RESULTS: The distributions of genotypes and allele prevalences of the endothelial nitric-oxide synthase G10-T polymorphisms among hypertensive and normotensive subjects were similar. In contrast, the prevalence of the nitric oxide synthase 298G allele was higher in the hypertensive group than it was among normotensive subjects. We found no association of the endothelial nitric oxide synthase genotypes with blood pressure levels or pulse-wave velocity for either population. CONCLUSIONS: The present results do not suggest that two common polymorphisms of the endothelial nitric oxide synthase gene are involved in the regulation of aortic stiffness in hypertensive and normotensive individuals. The higher prevalence of endothelial nitric oxide synthase 298G allele among hypertensives suggests that this gene is involved in essential hypertension but this observation needs further confirmation.

Adolescent↗

PubMed1998

Effects of a chronic high-salt diet on large artery structure: role of endogenous bradykinin.

Bradykinin activity could explain the blood pressure increase during NaCl loading in hypertensive animals, but its contribution on vascular structure was not evaluated. We determined cardiac mass and large artery structure after a chronic, 4-mo, high-salt diet in combination with bradykinin B2-receptor blockade by Hoe-140. Four-week-old rats were divided into eight groups according to strain [spontaneously hypertensive rats (SHR) vs. Wistar-Kyoto (WKY) rats], diet (0.4 vs. 7% NaCl), and treatment (Hoe-140 vs. placebo). In WKY rats, a high-salt diet significantly increased intra-arterial blood pressure with minor changes in arterial structure independently of Hoe-140. In SHR, blood pressure remained stable but 1) the high-salt diet was significantly associated with cardiovascular hypertrophy and increased arterial elastin and collagen, and 2) Hoe-140 alone induced carotid hypertrophy. A high-salt diet plus Hoe-140 acted synergistically on carotid hypertrophy and elastin content in SHR, suggesting that the role of endogenous bradykinin on arterial structure was amplified in the presence of a high-salt diet.

Animals↗

PubMed1998

Pulse pressure and cardiovascular mortality in normotensive and hypertensive subjects.

There is now increasing evidence that high pulse pressure, which is an indicator of large artery stiffness, is an independent risk factor for cardiovascular mortality, especially coronary mortality, in different populations. We have recently shown in a large French population that in male subjects aged 40 to 69 years, increased pulse pressure was a strong predictor of cardiovascular mortality, especially coronary mortality. In the present report, we analyzed the effect of pulse pressure in men and women of the same cohort after classifying them as normotensive (systolic blood pressure [SBP] <140 mm Hg and DBP <90 mm Hg) or hypertensive (SBP >/=160 mm Hg or DBP >/=95 mm Hg). After adjustment for age, mean blood pressure, and other risk factors, the relative risk (95% confidence limits) for cardiovascular mortality for an increase of 10 mm Hg of pulse pressure was 1.20 (1.01 to 1.44) in normotensives and 1.09 (1.03 to 1.14) in hypertensives. Cardiovascular and coronary death rates were similar in the group of normotensive men with a pulse pressure >50 mm Hg and in the group of hypertensive men with a pulse pressure <45 mm Hg. No association between cardiovascular mortality and pulse pressure was observed in either normotensive or hypertensive women (0.85 [0.60 to 1.21] and 1.0 [0. 91 to 1.11], respectively). Low mortality rates could explain this observation in normotensive but not in hypertensive women, in whom cardiovascular mortality rates were relatively high. Because a high pulse pressure in men is an independent predictor of cardiovascular mortality in both hypertensives and in those considered as having normal blood pressure, this parameter could aid in evaluating cardiovascular risk.

Adult↗

PubMed1998

Prevalence of cardiovascular risk factors in a French population.

UNLABELLED: STUDY ON THE IDENTIFICATION OF CARDIOVASCULAR RISK FACTORS: Identification of cardiovascular risk factors and the estimation of their prevalence in different populations is an important aim of preventive medicine. We analysed the data from 58,803 volunteers who were subjected to systematic health examinations in the Centre d'Investigations Préventives et Cliniques in Paris during the period January 1991 to December 1993. In this report we present some results concerning the prevalence of the major cardiovascular risk factors and their associations with sex, age and the presence of hypertension. CONCLUSIONS: The present study clearly shows that before the age of 55 years, the prevalence of risk factors is higher in men than in women, whereas in postmenopausal women the risk-profile increases rapidly, reaching the level of men after the age of 65 years. The presence of multiple risk factors is much higher in hypertensive than in normotensive individuals. We also observed that more than two-thirds of the treated hypertensives had systolic/diastolic blood pressure levels of > 140/90 mmHg. These observations could contribute to the debate regarding the evaluation of global risk and therapeutic strategies in cardiovascular disease prevention.

Adult↗

PubMed1998

[Cholesterolemia and total, cardiovascular and cancer mortality. Study of a cohort of 220,000 people].

The distribution of cholesterolemia and their relationship to total mortality, cardiovascular mortality, and cancer mortality were studied in a population of 125,513 men and 96,301 women, aged 16-90. Cholesterolemia in the population increases with age, up to age 50-60 for men and 60-70 for women. Beyond these ages, cholesterolemia decreases very significantly for men and moderately for women. Upon global examination of the entire population, the relationship between cholesterolemia and total mortality is observed as a U-shaped curve. The relationship with cancer mortality is slightly negative in men and appears as a U-shaped curve in women. The relationship with cardiovascular mortality in men is strongly positively correlated when adjusted for body mass index, blood pressure, tobacco consumption, gamma GT, and age. This relationship is not significant in women. There is a significant interaction in the relationship between cholesterolemia and mortality in men for weight, body mass index, vital capacity, maximum expiration volume per second, tobacco consumption, urea, serum albumin, hematocrit, hemoglobin, alkaline phosphatases, gamma GT, red cell volume, and sedimentation rate. Age is a fundamental variable to take into account. Thus, in men under 50 years of age at the time of inclusion, the relationship between cholesterolemia and total mortality shows a positive tendency, and the relationship with cardiovascular mortality is strongly positive. In men over 65 years of age, these relationships are negative. The same tendencies exist for cancer mortality. The reasons for these negative relationships may be related to the decreased cholesterol levels in subjects with malnutrition or diseases (essentially hepatic diseases); this is especially true in older subjects. These data push for additional in-depth analysis of these relationships and interactions, according to age categories and detailed causes of mortality. They also reinforce the idea that, in some patients, low cholesterolemia appears to be a marker for predisposition or the result, but not a cause, of cancer.

Adolescent↗

PubMed1998

[Heart rate and mortality].

Is increased heart rate a marker or a risk factor of cardiovascular morbidity and mortality? Several studies, including the Framingham study, have reported an association. In a large-scale French study, conducted in the Centre d'Investigations Préventives et Cliniques of Paris, based on a cohort of 20,000 male and female patients, heart rate was found to be a marker independent of the other risk factors and its increase was correlated with that of overall mortality in women, and cardiovascular and non-cardiovascular mortality in men. It remains to be seen whether pharmacological reduction of heart rate decreases mortality.

Cardiovascular Diseases↗

PubMed1997

Large artery stiffness in hypertension.

EFFECTS OF HYPERTENSION ON LARGE ARTERIES: The mechanical properties of large arteries make a major contribution to cardiovascular haemodynamics through the buffering of stroke volume and by propagation of the pressure pulse. A sustained increase in blood pressure often leads to stiffness of the large arteries, especially when other risk factors are present. The increased stiffness, in turn, aggravates hypertension by increasing systolic blood pressure and can induce cardiac hypertrophy and arterial lesions. Epidemiological studies strongly suggest that subjects with stiffer arteries have a high pulse pressure, and that stiffening of large arteries is associated with excess morbidity and mortality independently of other cardiovascular risk factors. ENVIRONMENTAL AND GENETIC FACTORS: Apart from high blood pressure and ageing, various environmental and genetic factors that influence the composition of the extracellular matrix of the arterial wall can increase arterial stiffness. Clinical studies suggest that the presence of some genotypes may be a particularly important risk marker for arterial stiffness, and may modulate the effects of hypertension, ageing and lipids on large arteries. EFFECTS OF ANTIHYPERTENSIVE DRUGS: The development of accurate, non-invasive methods has now made it possible to detect alterations of the large arteries. Among antihypertensive drugs, angiotensin converting enzyme inhibitors and calcium channel blockers have proved to be highly effective in improving large artery compliance, and have shown no adverse effects on metabolic factors that can alter arterial structure and function such as lipids, plasma glucose and insulin tolerance. Therefore these drugs may be particularly suitable for treating patients with increased arterial stiffness. Finally, a determination of genotypes may be helpful in the future in choosing antihypertensive therapy.

Adult↗

PubMed1997

Non-invasive evaluation of arterial abnormalities in hypertensive patients.

ARTERIAL ABNORMALITIES IN HYPERTENSION: Morbidity and mortality in hypertension are mainly determined by arterial lesions which may occur in different regional circulations (e.g. kidney, cerebral, coronary circulations, causing nephro-angiosclerosis, stroke or myocardial infarction, respectively). Despite arterial heterogeneity, structural and functional abnormalities are usually observed at an early stage of hypertension in both large and small arteries. These alterations modify physiological and mechanical properties of the arterial wall, which may become clinically evident by increasing arterial pulsatility or pulse pressure; the alterations facilitate the establishment and progression of atherosclerosis and arteriosclerosis. METHODS OF ASSESSING ARTERIAL ABNORMALITIES: Several non-invasive techniques can be used to assess haemodynamic properties of arteries: (1) casual and ambulatory blood pressure measurements can be used to evaluate pulse pressure; (2) pulse pressure can be measured directly in different sites of the arterial tree using the Tonometer device; (3) ultrasound techniques can be applied, including Doppler signals to assess the arterial flow, video-echo signals to analyse the arterial structure such as the intimal-medial thickness and echo-tracking systems for direct measurements of arterial wall distension and thickness; (4) pulse wave velocity is widely used as index of arterial distensibility; this parameter, assessed by the Complior device, has shown that hypertensive patients have decreased arterial distensibility and that antihypertensive treatment does not always reverse this abnormality. TREATMENT: It is important to evaluate the effect of cardiovascular risk-reduction measures on the arterial wall. Large therapeutic trials are necessary to show whether an evaluation of arterial abnormalities can identify patients with a high cardiovascular risk and contribute to their treatment and prognostic improvement.

Arteries↗

PubMed1997

Association between high heart rate and high arterial rigidity in normotensive and hypertensive subjects.

BACKGROUND: The dynamic elastic modulus of central arteries is very frequency-dependent Although resting heart rate is a potent independent risk factor for morbidity and mortality both from cardiovascular and from noncardiovascular disease, no link between tachycardia and arterial stiffness has ever been established. OBJECTIVE: To relate arterial stiffness to heart rate in a population with relatively low cardiovascular risk. METHODS: Pulse-wave velocity measurements and high-resolution echo-tracking techniques were used to determine the degree of arterial distension (of carotid and femoral arteries, and terminal aorta) and the velocity of the pulse wave (aorta and upper and lower limbs) at the same time as heart rate, in members of a large population of normotensive and hypertensive subjects in a multicenter study in Paris, Fleury-Merogis and Grenoble (France). RESULTS: A high heart rate was strongly associated with reduced distension and elevated pulse-wave velocity, even after adjustment for age and blood pressure. A high aortic pulse-wave velocity was also negatively associated with a low baroreflex sensitivity. The most significant associations between high heart rate and high arterial rigidity were found for the carotid artery, the thoracic aorta, and the lower limbs, but there was no significant result for the terminal aorta and the arm arteries. CONCLUSION: This study demonstrates that there is a statistically significant positive link between high heart rate and high arterial stiffness measured at the site of central and lower limb arteries. Since an elevated heart rate has been shown to be associated with cardiovascular risk, such findings may be relevant for future cardiovascular studies in epidemiology.

Adult↗

PubMed1997

Role of angiotensin II and bradykinin on aortic collagen following converting enzyme inhibition in spontaneously hypertensive rats.

We previously showed that chronic angiotensin-converting enzyme (ACE) inhibition prevented the increase in aortic collagen in spontaneously hypertensive rats (SHRs) independently of blood pressure reduction. The aim of the present study was to determine whether the effects of ACE inhibition on aortic fibrosis were due to inhibition of angiotensin II formation, preservation of bradykinin, or a combination of both. Four week-old SHRs were treated for 4 months with the ACE inhibitor quinapril, quinapril with the bradykinin B2 receptor antagonist Hoe 140, or the angiotensin II AT1 receptor antagonist CI996. Control SHR and Wistar-Kyoto (WKY) rats received a placebo for the same period of time. At the end of the treatment, as compared to conscious SHR and WKY controls, quinapril completely prevented the development of hypertension, whereas quinapril-Hoe 140 and the AT1 receptor antagonist produced only a partial reduction of blood pressure. In relation with blood pressure changes, aortic hypertrophy was significantly prevented by quinapril but not by quinapril-Hoe 140 or CI996. In contrast, aortic collagen accumulation was completely prevented by all three treatments. The study provides evidence that in young live SHRs, the prevention of aortic collagen accumulation is independent of blood pressure changes and bradykinin preservation and involves exclusively angiotensin II inhibition through AT1 receptors.

Angiotensin II↗

PubMed1997

Prevention of aortic fibrosis by spironolactone in spontaneously hypertensive rats.

We have previously shown that long-term angiotensin-converting enzyme (ACE) inhibition prevents the increase in aortic collagen in spontaneously hypertensive rats (SHRs), independent of blood pressure reduction. More recently, we reported that the effects of ACE inhibition in the prevention of aortic collagen accumulation were related to the inhibition of angiotensin II actions on angiotensin II type 1 receptors. Aldosterone, the synthesis of which is mainly modulated by angiotensin II through type 1 receptor stimulation, is known to promote cardiac fibrosis in different experimental models. The aim of the present study was to determine whether inhibition of aldosterone formation was able to prevent aortic fibrosis in SHRs. For this purpose, we compared the effects of a 4-month treatment with the aldosterone antagonist spironolactone with the ACE inhibitor quinapril in 4-week-old SHRs. Control SHRs and Wistar-Kyoto (WKY) rats received placebo for the same period of time. At the end of treatment, in conscious SHRs vs WKY controls, quinapril completely prevented the development of hypertension, whereas spironolactone produced only a slight but significant reduction in blood pressure. Aortic hypertrophy was significantly prevented by ACE inhibition but not by spironolactone. On the contrary, aortic collagen accumulation was completely prevented by both quinapril and spironolactone. In the latter case, collagen density was significantly below that of WKY controls. These results show that in SHRs, spironolactone can markedly prevent aortic fibrosis in the presence of a very slight antihypertensive effect. It is suggested that ACE inhibition or type 1 receptor antagonist-induced prevention of aortic collagen accumulation is at least partially related to aldosterone inhibition.

Animals↗

PubMed1997

In vivo/in vitro comparison of rat abdominal aorta wall viscosity. Influence of endothelial function.

Arterial wall viscosity (AWV) is a potential source of energy dissipation in circulation. That arteries, which are known to be markedly viscous in vitro, have lower viscosity in vivo has been suggested but not demonstrated under similar pressure conditions. Endothelium, which may modulate AWV through smooth muscle tone, could contribute to the low level of viscosity in vivo. Our objectives were first to compare AWV of the rat abdominal aorta, in vivo and in vitro, with similar pulse-pressure waves, and second, to determine whether endothelial function influences AWV in vivo and in vitro. The diameter of the abdominal aorta and distending pressure were measured in vivo and in vitro with a high-resolution echotracking system and a micromanometer, respectively. AWV was calculated as the area of the pressure-volume curve hysteresis. After in vivo examination, the arterial segments were isolated in vitro and submitted to resynthesized pressure waves identical to those recorded in vivo. Deendothelialization was performed in vivo by balloon rubbing; then arteries were examined either in vivo or in vitro. AWV was markedly lower in vivo than in vitro (6.6 +/- 0.7 versus 22.7 +/- 3.7 J.m-1.10(-5), respectively; P < .001). After deendothelialization, a sustained 40% increased AWV was observed during a 15-minute follow-up (P < .01). In vitro, deendothelialized arteries have a 64% higher AWV than segments with endothelium (P < .01). Our results indicate that the physiological effective viscosity, measured in vivo in intact animals, is threefold lower than the intrinsic viscosity of the arterial wall, measured in vitro. Endothelium removal determines a sustained increase in AWV, either in vivo or in vitro. These results suggest that active mechanisms compensate for intrinsic viscosity under physiological conditions. One of these energy-saving mechanisms might be dependent on normal endothelial function.

Animals↗

PubMed1997

Pulse pressure: a predictor of long-term cardiovascular mortality in a French male population.

Studies on the usefulness of blood pressure as a prognostic factor in cardiovascular disease have more often involved investigations of the levels of diastolic or systolic blood pressure. However, blood pressure may be divided into two other components: steady (mean pressure) and pulsatile (pulse pressure). In this study, the relationship of pulse pressure to cardiovascular mortality was investigated in 19 083 men 40 to 69 years old who were undergoing a routine systematic health examination and were being followed up after a mean period of 19.5 years. Subjects were divided into four groups according to age (40 to 54 and 55 to 69 years) and mean arterial pressure (<107 and > or =107 mm Hg). Each group was further divided into four subgroups according to the pulse pressure level. A wide pulse pressure (evaluated according to the quartile group or as a continuous quantitative variable) was an independent and significant predictor of all-cause, total cardiovascular, and, especially, coronary mortality in all age and mean pressure groups. No significant association between pulse pressure and cerebrovascular mortality was observed. In conclusion, in a large population of men with a relatively low cardiovascular risk, a wide pulse pressure is a significant independent predictor of all-cause, cardiovascular, and, especially, coronary mortality.

Adult↗

PubMed1996

Influence of angiotensin-converting enzyme and angiotensin II type 1 receptor gene polymorphisms on aortic stiffness in normotensive and hypertensive patients.

BACKGROUND: Clinical and experimental studies have demonstrated a major role of the renin-angiotensin system in the functional and structural changes of the large arteries in hypertension. Because genetic studies may help us to understand the mechanisms underlying the involvement of this system in arterial regulation, the present study was designed to assess the contribution of polymorphisms of the ACE insertion/deletion (I/D) and angiotensin II type 1 receptor (AGTR1 A 1166C) genes on aortic stiffness regulation. METHODS AND RESULTS: This study included 311 untreated hypertensive and 128 normotensive subjects. Aortic stiffness was evaluated by measurement of the carotid-femoral pulse-wave velocity (PWV). In normotensive subjects, the two polymorphisms did not influence any of the studied parameters. In hypertensive subjects, there was a decreasing trend of mean PWV with the number of ACE D alleles, but this association became significant only after adjustment for blood pressure (P < .05). Conversely, the AGTR1 A 1166C polymorphism was independently associated with aortic stiffness. Mean values of PWV were 11.6 +/- 2.7 m/s in AGTR1 AA homozygotes, 13.3 +/- 3.3 m/s in AC heterozygotes, and 15.3 +/- 4.3 m/s in CC homozygotes (P < .0001 and P < .00001 after adjustment for age and mean blood pressure, respectively). The percentage of variance of PWV explained by AGTR1 A 1166C polymorphism (11.6%) was much larger than that of ACE I/D polymorphism (1.7%). CONCLUSIONS: These results suggest that in hypertensive but not normotensive subjects, the AGTR1 and ACE genotypes are involved in the regulation of aortic rigidity. The presence of the AGTR1 C allele is a strong independent determinant of aortic stiffness, whereas presence of the ACE 1 allele is weakly associated with increased stiffness.

Adolescent↗