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Biomedical subjects

M E Safar

Publications and source records attributed to M E Safar.

At least 19 recordsLinked to original sources
PubMed1998

Determination of total effective vascular compliance in patients with sepsis syndrome.

Changes in capacitance vessels have important consequences on cardiac filling pressure and fluid volume distribution in patients with sepsis syndrome. Vascular compliance may be evaluated from the slope of the relationship between changes in total blood volume (deltaTBV) and changes in central venous pressure (deltaCVP) during acute volume expansion (450 ml of gelatin fluid over 6 min), i.e., from the deltaTBV/deltaCVP ratio. The mean ratio (ml x mm Hg-1 x kg-1) was 2.03 +/- 0.21 in control subjects, 1.43 +/- 0.25 in mechanically ventilated patients without sepsis syndrome, and 0.94 +/- 0.24 in mechanically ventilated patients with sepsis syndrome (p < 0.0001 versus the other two groups). Based on echocardiographic determinations, cardiac performance was constantly found within the normal range (cardiac output ranged from 5.6 +/- 1.2 to 6.7 +/- 2.0 L/min in nonseptic patients from 6.8 +/- 1.9 to 7.8 +/- 2.2 in septic patients). Effective compliance of the total vascular bed is therefore reduced in patients with sepsis syndrome, independently of the hemodynamic modifications due to mechanical ventilation.

Adolescent↗
PubMed1997

Systolic blood pressure revisited.

The clinical importance of systolic blood pressure (SBP) needs no emphasis. Its determinants are well known, but recent studies of one of these determinants, arterial distensibility, have led to results that now have clinical relevance. This review summarizes the role of arterial stiffness in ventricular-vascular coupling in the normal circulation and that disordered by aging and hypertension. The discussion defines the unfamiliar terms of compliance, distensibility and modulus and indicates how they are measured. Such measurements have increased our understanding of the parts played by the inhomogeneity of the arterial tree and reflected pressure waves in governing SBP. Elevated SBP is a recognized risk factor for cardiovascular complications among older patients, but when this elevation is due to a stiffened arterial tree, diastolic blood pressure (DBP) is necessarily reduced. Early epidemiologic studies in hypertension required a DBP > or = 90 mm Hg for hospital admission. They therefore excluded persons with high SBP, low DBP and very wide pulse pressure (PP). More recent inclusion of such patients has shown that elevation of SBP and PP is a strong predictor of cardiovascular risk. These considerations point to a possible redefinition of hypertension to include patients with lower DBP and to the inaccuracy but indispensability of the brachial artery pressure as a surrogate for aortic pressure--the pressure the heart sees. Finally, we review the known effects of available antihypertensive drugs on the arterial wall and indicate possible future directions of research stemming from wider understanding of the role of arterial distensibility in hypertension.

Antihypertensive Agents↗
PubMed1997

Association between increased plasma levels of aldosterone and decreased systemic arterial compliance in subjects with essential hypertension.

We previously observed that, in subjects with essential hypertension, acute ouabain constricts the brachial artery diameter in the presence of spironolactone treatment, a finding that is not observed in the absence of aldosterone antagonist and therefore suggests a specific effect of aldosterone on the arterial wall. To evaluate whether aldosterone excess may contribute to modulate arterial function, we investigated 56 patients with sustained essential hypertension in comparison with 36 normotensive controls. Systemic arterial compliance was measured from intraarterial blood pressure and cardiac output measurements using a classical Windkessel model to determine the elasticity of the proximal arterial tree. Radial artery compliance was determined using a previously described echo tracking technique. In hypertensive, but not in normotensive, subjects, systemic arterial compliance was strongly and negatively correlated with plasma aldosterone. The correlation was observed even after adjustment for age and blood pressure. Plasma potassium and renin activity did not interfere in the correlation. Acute administration of diltiazem did not change systemic compliance but significantly decreased plasma aldosterone, suggesting that, in the presence of calcium blockade, the same compliance was achieved for a lower plasma aldosterone level. Taken together, these findings strongly suggest that significant interactions exist between aldosterone and central conduit arteries and that aldosterone might modulate arterial function in subjects with essential hypertension.

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

Arterial stiffness in hypertensive subjects with or without end-stage renal disease.

Therapeutic trials have shown that the response to antihypertensive drug treatment is heterogeneous, with substantially higher effects of cardiovascular prevention for the cerebral than for the coronary circulation. This finding suggests that the response of large conduit arteries to elevated blood pressure may vary greatly between the different compartments of the arterial bed. Recent in vivo non-invasive studies in humans suggest that the stiffness of large arteries in subjects with essential hypertension differs greatly according to the vascular territory involved. Operational arterial stiffness, i.e., measured at the mean blood pressure of the hypertensive population by comparison with normotensive subjects, is increased in central arteries (carotid artery, aorta) but normal in peripheral muscular arteries (femoral artery, radial artery). On the other hand, when hypertensive and normotensive subjects are compared for the same blood pressure, arterial stiffness appears to be normal for the radial artery but decreased for the femoral artery and the aorta. In the case of carotid arteries, isobaric arterial stiffness is normal in subjects with uncomplicated essential hypertension but decreased in hypertensive patients with end-stage renal disease. Thus, important differences may be observed according to the territory involved, suggesting that the response to drug treatment of hypertension may be influenced not only by the blood pressure reduction itself but also by the regional properties of each particular vascular bed and the presence of advanced renal disease.

Arteries↗
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

Mechanical stress of the carotid artery at the early phase of spontaneous hypertension in rats.

Common carotid artery (CCA) hypertrophy has long been recognized in the neonatal period of development in spontaneously hypertensive rats (SHR), but the mean circumferential and shear stresses acting on the arterial wall have never been investigated in vivo. We investigated intra-arterial blood pressure in conscious rats, CCA diameter (echotracking techniques), blood flow velocity (pulsed Doppler), wall thickness (histomorphometry), and ganglionic blockade (hexamethonium) in Wistar rats and SHR at 5 and 12 weeks of age. During this interval, weight gain was identical in the strains, whereas the increase in wall thickness and blood pressure was greater in SHR. CCA diameter was identical at week 5 and increased similarly at week 12 in both strains. During ganglionic blockade, a larger diameter was observed in SHR at week 5 for the same BP level, whereas equivalent values were observed at week 12. Blood flow velocity decreased with age but to a significantly greater extent in SHR. Mean circumferential stress and shear stress index were identical in both strains at week 12. However, from weeks 5 to 12, mean circumferential stress increased with age similarly in both strains, whereas the age-related decrease in mean shear stress index was much greater in SHR than Wistar rats. Thus, despite a higher blood pressure, SHR exhibit the same carotid diameter as Wistar rats during early development. Because the kinetics of shear stress are different in both strains, altered flow-dilatation mechanisms, and possibly resulting endothelial dysfunction, may be involved in the diameter changes.

Age Factors↗
PubMed1996

Carotid artery stiffness with applications to cardiovascular pharmacology.

1. Increased carotid stiffness is a characteristic feature of cardiovascular aging, hypertension and, to a lesser extent, atherosclerosis. 2. The pharmacological approach, using nitrates, converting enzyme inhibitors, calcium entry blockers and blockers of the autonomic nervous system, may decrease carotid stiffness through 3 different mechanism: passive decrease in blood pressure, active change in smooth muscle tone, and structural modifications of the carotid arterial wall. 3. In recent years, such changes have been studied in vivo, in both humans and rats, using original in situ carotid preparations and echotracking ultrasound techniques of high resolution, allowing to evaluate both static and dynamic stiffness. 4. This new approach for investigating arterial vessel through changes in both stiffness and thickness should provide a better evaluation of drug effects in cardiovascular pharmacology and new interpretations for cardiovascular events related to morbidity and mortality.

Aging↗
PubMed1996

Antihypertensive therapy and wave reflections.

Studies of pulsatile arterial hemodynamics have emphasized that the pulsatile component of pulse pressure has two important characteristics: (i) it increases from central to peripheral arteries for a similar value of mean arterial pressure, and (ii) it is dominantly influenced by the amplitude and timing of the backward pressure wave. Although these important aspects of wave reflections have been poorly investigated in the field of hypertension, they may be easily studied noninvasively in humans on the basis of the analysis of the pulse wave contour of carotid and aortic blood pressure. Increased wave reflections returning toward the thoracic aorta during systole may have deleterious consequences on the structure and function of the heart. Some (but not all) antihypertensive drugs may contribute to decrease and/or to delay wave reflections in association with blood pressure reduction.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Cardiac and arterial interactions in end-stage renal disease.

Although cardiac hypertrophy is a frequent complication of end-stage renal disease (ESRD), relatively little is known about large arterial geometry and function in vivo in these patients, and the relationship between arterial changes and cardiac hypertrophy is unknown. Common carotid artery (CCA) intima-media thickness and internal diameter and left ventricular geometry and function were determined by ultrasound imaging in 70 uncomplicated ESRD patients and in 50 age-, sex-, and blood pressure-matched controls. Arterial distensibility and compliance were determined from simultaneously recorded CCA diameter and stroke changes in diameter and CCA pressure waveforms, obtained by applanation tonometry, and also by the measurement of carotid-femoral pulse wave velocity. Compared with control subjects, ESRD patients had greater left ventricular diameter (P < 0.01), wall thicknesses and mass (P < 0.001), increased CCA diameter (6.25 +/- 0.87 vs. 5.55 +/- 0.65 mm; P < 0.001), larger CCA intima-media thickness (777 +/- 115 vs. 678 +/- 105 microns; P < 0.001) and intima-media cross-sectional area (17.5 +/- 4.5 vs. 13.4 +/- 3.3 mm2; P < 0.001). In uremic patients, arterial hypertrophy was associated with decreased CCA distensibility (17.8 +/- 8.8 vs. 24.0 +/- 12.7 kPa-1.10(-3); P < 0.001) and compliance (5.15 +/- 2 vs. 6.0 +/- 2.5 m2.kPa-1.10(-7); P < 0.05), accelerated carotid-femoral pulse wave velocity (1055 +/- 290 vs. 957 +/- 180 cm/seconds; P < 0.001), early return and increased effect of arterial wave reflections (20.5 +/- 15.4 vs. 9.2 +/- 18.4%; P < 0.001). The latter phenomenons were responsible for increased pulsatile pressure load in CCA (58.3 +/- 21 vs. 48 +/- 17 mm Hg; P < 0.01) and were associated with a decreased subendocardial viability index (157 +/- 31 vs. 173 +/- 30%; P < 0.001). The CCA diameter was correlated with the left ventricular diameter (P < 0.01), and a significant correlations existed between CCA wall thickness or CCA intima-media cross-sectional area and left ventricular wall thicknesses and/or left ventricular mass (P < 0.01). In multivariate analysis, these relationships were independent regarding age, sex, blood pressure and body surface area. The present study documents parallel cardiac and vascular adaptation in ESRD, and demonstrates the potential contribution of structural and functional large artery alterations to the pathogenesis of left ventricular hypertrophy and functional alterations.

Adult↗
PubMed1996

Structural changes of large conduit arteries in hypertension.

BACKGROUND: Structural alterations of large conduit arteries are a common pathway for any complication of hypertensive vascular disease. Whether increased arterial wall thickness occurs at an early phase in uncomplicated hypertension has remained largely ignored until recent years. METHODS: Sophisticated echo-Doppler techniques with a high degree of resolution and reproducibility have been developed to obtain reliable non-invasive determinations of intima-media thickness of superficial arteries such as the radial and the common carotid arteries. RESULTS: In uncomplicated hypertension, a significant increase in intima-media thickness is observed at the sites both of the radial and of the carotid arteries. The former is known to be constantly undamaged by atheroscierosis and is composed almost exclusively of arterial smooth muscle; operational arterial stiffness is found to be normal. The latter is strongly affected by atheroscierosis and predominantly composed of elastin and collagen fibres; operational arterial stiffness is found to be increased. In old subjects with systolic hypertension, radial artery hypertrophy is significantly reversed by drug therapy involving diuretics, converting enzyme inhibitors or both. This change occurs in parallel with the reduction in blood pressure. CONCLUSION: In sustained essential hypertension, arterial wall hypertrophy can be demonstrated in the absence of organ damage. Operational arterial elasticity is maintained in peripheral but not in central arteries. Structural changes of the large conduit arteries are substantially reversed by drug therapy together with a reduction in blood pressure.

Animals↗
PubMed1996

Antihypertensive effects and arterial haemodynamic alterations during angiotensin converting enzyme inhibition.

OBJECTIVE: To assess the respective roles of the anti-hypertensive and blood pressure-independent effects of angiotensin converting enzyme (ACE) inhibition in the changed arterial haemodynamics observed in hypertensive patients with end-stage renal disease (ESRD) treated by haemodialysis. DESIGN AND METHODS: Twelve hypertensive patients with ESRD were included in a double-blind, cross-over study comparing a single 20 mg dose of the ACE inhibitor quinapril versus placebo. Two study periods each of 172 h duration were separated by a 2-week placebo period. Repeated measurements of the following parameters were performed: brachial artery systolic blood pressure (SBP); diastolic blood pressure and mean blood pressure (using a mercury sphygmomanometer); carotid artery SBP and pulse pressure (by applanation tonometry); aortic stiffness (by pulse wave velocity); and the effect of arterial wave reflections in the common carotid artery (the augmentation index, by applanation tonometry). A radioimmunoassay was used to determine plasma angiotensin II levels. Quinaprilat pharmacokinetics were studied using a specific assay. Two-way (time-treatment) analysis of variance for repeated measures, analysis of covariance for two within-factors and a covariate changing with the level of the factor time (pressures measured at each time) and baseline values of the studied parameter as a second covariate were used for statistical analysis. RESULTS: Quinapril treatment induced a long-lasting decrease in arterial wave reflections, which was still observable 172 h after quinapril administration and still present after removing the effect of the decrease in blood pressure. The effect on wave reflections was associated with a more pronounced and sustained decrease in carotid SBP and pulse pressure than that in brachial SBP and pulse pressure. Quinapril administration also induced a long-lasting decrease in aortic pulse wave velocity, but this effect was entirely dependent on parallel changes in blood pressure. Arterial haemodynamic changes were not related to plasma angiotensin II or quinaprilat levels. CONCLUSIONS: The results of this controlled study indicate that, in ESRD patients, ACE inhibition results in a long-lasting, blood pressure-independent decrease in arterial wave reflections. The consequence of this was a decrease in pulsatile pressure load in the central arteries with increased aortic distensibility. The increased aortic distensibility resulted from the decrease in blood pressure. The observed arterial haemodynamic alterations suggest that ACE inhibition induced alterations in arterial wave reflections in the distal parts of the arterial tree.

Adult↗
PubMed1996

Arterial alterations in hypertension with a disproportionate increase in systolic over diastolic blood pressure.

BACKGROUND: Although systolic and diastolic blood pressure and cardiovascular risk are directly related in epidemiologic studies, the results of large therapeutic trials in mild to moderate hypertension have indicated that the prevention of cerebrovascular accidents was much more effective than that of coronary ischemic accidents. Actually, a significant decrease in coronary events was observed only in aged populations in which systolic (and not diastolic) blood pressure was chosen as criterion of entry. Whether the choice of the mechanical factor (systolic or diastolic blood pressure or both) used to define hypertension might have created a bias in the studied populations remains an important question. FINDINGS: Above 50 years of age, most hypertensive populations are characterized by a disproportionate increase in systolic over diastolic blood pressure, so that the pulsatile component of blood pressure is strikingly augmented. This pattern is commonly observed in old people with essential hypertension, in hypertensive subjects with advanced renal failure undergoing hemodialysis and in atherosclerotic subjects with hypertension, particularly those with atherosclerosis of the lower limbs and cerebral vessels. In all these populations, the disturbed pulse pressure is associated with significant alterations in large conduit arteries involving hypertrophy of central and peripheral large vessels and increased values of operational stiffness and altered wave reflections which return during the systolic (and not the diastolic) component of the aortic blood pressure curve. Sodium sensitivity is commonly observed in these patients, so that low doses of diuretics correct the increased pulse pressure, particularly in those with normal or low plasma renin activity. CONCLUSIONS: Although strong interactions may be observed between the pulsatile component of blood pressure and the arterial changes in hypertension, much more research is required before a clear-cut cause-effect relationship can be established between these two variables. With the exception of diuretic therapy in the elderly, there are at present no treatments that can selectively reduce pulse pressure or reverse the arterial changes or both in patients with essential hypertension and a disproportionate increase in systolic blood pressure.

Arteries↗
PubMed1996

Arterial wall remodelling and stiffness in hypertension: heterogeneous aspects.

1. Hypertension is associated with hypertrophy and decreased operating distensibility of the large artery wall. Because similar pathological and functional changes are observed with ageing, hypertension is often looked upon as an accelerated form of aging. 2. Considering the decrease in arterial distensibility observed with both ageing and hypertension, whether the change is due to age, an increase in distending pressure or to hypertension-induced changes in large artery structural properties may be much debated. 3. The purpose of the present review is to study the effects of aging and hypertension on structural (lumen diameter and arterial wall thickness) and functional (distensibility) properties of large central and medium-sized arteries in humans. 4. From clinical studies in subjects with hypertension with or without advanced renal disease, it is suggested that age- and hypertension-induced structural arterial changes are quite heterogeneous, depending on the topography of the vessel and on the severity of the underlying disease.

Aging↗
PubMed1996

The effect of metformin on the metabolic abnormalities associated with upper-body fat distribution. BIGPRO Study Group.

OBJECTIVE: The constellation of anomalies associated with insulin resistance is a plausible additional cause of ischemic cardiovascular disease and of NIDDM. To test this hypothesis in a primary prevention trial, the effects of metformin as a potential candidate for intervention in the insulin resistance syndrome (IRS) were evaluated in 324 middle-aged subjects with upper-body obesity. RESEARCH DESIGN AND METHODS: Trial patients were selected on the basis of a high waist-to-hip ratio. They were randomly allocated to receive either metformin or placebo, following a double-blind procedure. After 1 year of treatment, the main clinical and biological parameters of the IRS were assessed and their evolution compared between treatment groups. RESULTS: Compared with placebo, metformin induced a significant weight loss, a better maintenance of fasting blood glucose, total and LDL cholesterol levels, and a greater decrease of fasting plasma insulin concentration. Moreover, tissue-type plasminogen activator antigen, a marker of fibrinolytic impairment, showed a significant decrease under metformin. By contrast, metformin treatment had no significant effect on blood pressure or serum triglyceride and HDL cholesterol concentrations. The main side effect of metformin was diarrhea. CONCLUSIONS: The BIGuanides and Prevention of Risks in Obesity (BIGPRO1) results suggest that metformin would be a suitable candidate for long-term intervention for the prevention of diabetes but that its use in a trial of primary prevention of cardiovascular diseases requires either a reevaluation of its properties toward the most potentially atherogenic anomalies of the IRS or a better definition of the target population.

Adipose Tissue↗