[Impact of sickle cell trait on arterial stiffness in African subjects]. / Impact du trait drépanocytaire sur la rigidité artérielle des sujets africains.

Sickle cell trait (SCT) is the benign condition of sickle cell disease. Often asymptomatic, the carriers of the sickle cell trait have hemorheological disturbances with increased oxidative stress compared to healthy subjects. These disturbances can lead to structural and functional changes in large vessels. The aim of the study was to measure arterial stiffness, an independent marker of subclinical atherosclerosis, SCT carriers compared to sickle cell anemia (SCA) subjects. Nine SCT carriers aged 32±9 years (7 men) were compared to 14 SCA subjects aged 29±9 years (2 men) and 22 control subjects aged 34±9 years (11 men) recruited by the National blood transfusion center (CNTS) in Dakar (Senegal). Arterial stiffness was assessed by measurement of the finger-toe pulse wave velocity (PWVft) using pOpmètre® (Axelife SAS-France). The cardiovascular risk (CVR) was assessed according to the Framingham Laurier score. The SCT carriers had a higher PWVft (m/s) than SCA subjects (8.2±2.2 vs 6.1±0.9m/s, P=0.004) but not different from that of healthy controls (8.2±2.2 vs 7.4±1.8m/s, P=0.33). Linear regression showed a positive relationship between PWVft and the pulse pressure (PP) (P˂0.001; r2=0.39; F=13.20). The results show that the SCT carriers have stiffer arteries than SCA subjects. Linear regressions adjusted for age, mean arterial pressure (MAP) and PP, showed that only age and PP were independently correlated with arterial stiffness in the entire population.

[Regional and peripheral arterial stiffness measured by pOpmetre® in patients with Cvx risk factor, link with carotid plaques]. / Rigidité artérielle mesurée par pOpmètre® chez les patients à risque cardiovasculaire, lien aux plaques d'athérome carotidien.

PURPOSE: Aortic stiffness is a functional and structural consequence of ageing and arteriosclerosis. Regional arterial stiffness can be easily evaluated using pOpmetre(®) (Axelife SAS, France). This new technique assesses the pulse wave transit time (TT) between the finger (TTf) and the toe (TTt). Based on height chart, regional pulse wave velocity (PWV) between the toe and the finger can be estimated (PWVtf). pOpscore(®) index is also calculated as the ratio between PWVtoe and PWVfinger and can be considered as a peripheral vascular stiffness index. The aim of the study was to evaluate the relationship between pOpmetre(®) indices and the presence of carotid plaques in a population with cardiovascular risk factors. METHODS: In 77 consecutive patients recruited for a vascular screening for atherosclerosis (46 men aged 54 ± 2 years; 31 women aged 49 ± 3 years; ns), the difference between TTt and TTf (called Dt-f), the regional pulse wave velocity between the toe and the finger (PWVtf = constant × height/Dt-fm/s) and pOpscore(®) were measured by pOpmetre(®). Presence of carotid plaques was assessed using ultrasound imaging. The local aortic stiffness (AoStiff) was evaluated by the Physioflow(®) system. RESULTS: No difference was found between patients with or without carotid plaques (n=25 versus 52) for Ankle-Brachial Pressure Index (ABPI: 1.15 ± 0.04 versus 1.12 ± 0.03), nor for diastolic or systolic blood pressure (87 ± 3 versus 82 ± 2; 137 ± 3 versus 132 ± 2 mmHg). The first group was older than the second (59 ± 2 versus 49 ± 2 years, P<0.002) with a larger intimae media thickness (0.69 ± 0.02 versus 0.63 ± 0.01 mm, P<0.004), a higher AoStiff (10.4 ± 0.7 versus 8.2 ± 0.5m/s, P<0.02), and PWVtf (14.3 ± 1.0 versus 10.7 ± 0.7 m/s, P<0.004) and a shorter Dt-f (57.9 ± 5.1 versus 73.5 ± 3.5 ms, P<0.01). PWVtf (r(2)=0.49, P<0.0001) and Dt-f (r(2)=0.54, P<0.0001) correlated with age. A significant difference in pOpscore(®) index was observed between both groups (1.51 ± 0.3 versus 1.41 ± 0.2, P<0.006). CONCLUSION: Our results show a significant arterial stiffness indices measured by pOpmetre(®) in patients with and without carotid plaques.

[A new index to evaluate arterial ageing independently of arterial blood pressure: pOpscore(®)]. / Un nouvel index pour évaluer le vieillissement artériel indépendamment de la pression artérielle : pOpscore(®).

AIM: Pulse wave velocity does not correlate to age in the upper limb but in the aorta and lower limb. We studied the link between ageing and pulse wave transit time (PWtt) indexes at the toe and finger. PATIENTS AND METHODS: Measurements were performed in 300 patients in occupational medicine and primary care after 5minutes supine rest using the device studied (pOpmètre(®), Axelife SAS, France). It measures transit time between R-ECG and finger or toe pulse signal (ttf or ttt respectively). We define as follows three indexes: difference between transit times: Dtf=ttt-ttf; pulse wave velocity PWVft=k*subjects height/Dtf (m/s); and the pOpscore(®) as the ratio of toe PWV/fingerPWV. RESULTS: Of the 300 tested patients, 147 were analysed using univariate correlation: age (P<10(-4)), SBP (P<10(-4)), DBP (P<0.02) and BMI (P<0.04) correlated to Dtf, PWVtf and pOpscore(®). Using stepwise regression analysis with Age, BMI, SBP, DBP, MBP: Dtf was dependent with age (P<10(-4)) and SBP (P<0.01); PWVtf with age (P<0.0001), SBP (P<0.01) and DBP (P<0.05); pOpscore(®) was dependent only to age (P<10(-4)). CONCLUSION: In this study, in contrast with the other vascular indexes studied dependent to age and blood pressure, pOpscore(®) was dependent only to ageing. pOpmètre(®) is a promising technique for routine determination of arterial stiffness and pOpscore(®) appears to be appropriate to study the structural vascular ageing in outpatient.

Value of ambulatory blood pressure monitoring in type I (insulin-dependent) diabetic patients with incipient diabetic nephropathy.

Ambulatory blood pressure monitoring (ABPM) is currently proposed for measuring blood pressure in type I, insulin-dependent diabetic subjects with incipient diabetic nephropathy. However, the value of this method, in comparison with conventional ones in detecting blood pressure differences between normotensive type I, insulin-dependent diabetic subjects with or without microalbuminuria, is questionable. We obtained systolic, diastolic, and mean blood pressures (SBP/DBP/MBP) in 10 hospitalized normotensive type I, insulin-dependent diabetic subjects with microalbuminuria, and in 29 others without, using a mercury sphygmomanometer (method 1) and an automatic device (Dinamap; method 2) to obtain morning (9 to 11 AM) measurements, and ABPM (SpaceLabs 90207; method 3) to obtain daytime (7 AM to 10 PM) and nighttime (10 PM to 7 AM) measurements. During the daytime, SBP/DBP/MBP values were higher in microalbuminuric than in normoalbuminuric patients, whatever the blood pressure measurement method used (P = .034/.061/.033, two-factor ANOVA). Analysis of 24-h ABPM also showed higher SBP/DBP/MBP in microalbuminuric than in normoalbuminuric patients (P = .022/.040/.016), and demonstrated a defect in nocturnal SBP decrease in microalbuminuric compared with normoalbuminuric patients (P = .028). Stepwise multiple regression analysis indicated nocturnal SBP as the only independent factor determining for microalbuminuria (F = 6.72). Thus ABPM, in relation to other methods, indicates above all that the most relevant blood pressure change in type I insulin-dependent diabetic subjects with microalbuminuria is a defect in nocturnal SBP decrease.

Relationships between angiotensin I converting enzyme gene polymorphism, plasma levels, and diabetic retinal and renal complications.

Insulin-dependent diabetes mellitus (IDDM), cardiovascular morbidity, and vital prognosis are linked to diabetic nephropathy, which is probably determined by renal hemodynamic abnormalities and by a genetic predisposition. Angiotensin I converting enzyme (ACE) regulates systemic and renal circulations through angiotensin II formation and kinins metabolism. Plasma and cellular ACE levels are genetically determined; an insertion/deletion polymorphism of the ACE gene is strongly associated with ACE levels, subjects homozygote for insertion (genotype II) having the lowest plasma values. We studied the relationship between the ACE gene polymorphism or plasma levels and microcirculatory disorders of IDDM through two independent studies: one involved 57 subjects with or without diabetic retinopathy, and the other compared 62 IDDM subjects with diabetic nephropathy to 62 diabetic control subjects with the same characteristics (including retinopathy severity) but with normal kidney function. The ACE genotype distribution was not different in diabetic subjects with or without retinopathy and in a healthy population. Conversely, an imbalance of ACE genotype distribution, with a low proportion of II subjects, was observed in IDDM subjects with diabetic nephropathy compared with their control subjects (P = 0.006). Plasma ACE levels were mildly elevated in all diabetic groups, independently of retinopathy, but they were higher in subjects with nephropathy than in those without nephropathy (P = 0.0022). The II genotype of ACE gene is a marker for reduced risk for diabetic nephropathy.

Comparison of reduction in microalbuminuria by enalapril and hydrochlorothiazide in normotensive patients with insulin dependent diabetes.

OBJECTIVE: To compare the effects of sodium depletion and of angiotensin I converting enzyme inhibition on microalbuminuria in insulin dependent diabetes. DESIGN: Randomised, double blind, double dummy parallel study of normotensive diabetic patients with persistent microalbuminuria (30-300 mg/24 h) treated with enalapril or hydrochlorothiazide for one year after a three month, single blind placebo period. SETTING: Diabetic clinic in a tertiary referral centre. PATIENTS: 10 diabetic patients with low microalbuminuria (30-99 mg/24 h) and 11 with high microalbuminuria (100-300 mg/24 h). INTERVENTIONS: 11 subjects (six with low microalbuminuria, five with high microalbuminuria) were given enalapril 20 mg plus placebo hydrochlorothiazide once daily and 10 (four with low microalbuminuria, six with high microalbuminuria) hydrochlorothiazide 25 mg plus placebo enalapril once daily. MAIN OUTCOME MEASURES: Monthly assessment of urinary albumin excretion and mean arterial pressure; plasma active renin and aldosterone concentrations and renal function studies at 0, 6, and 12 months. RESULTS: Median urinary albumin excretion decreased from 59 (range 37-260) to 38 (14-146) mg/24 h with enalapril and from 111 (33-282) to 109 (33-262) mg/24 h with hydrochlorothiazide (analysis of variance, p = 0.0436). During the last three months of treatment with enalapril five patients had persistent normoalbuminuria (2-3 times below 30 mg/24 h), five low microalbuminuria, and one high microalbuminuria; in the hydrochlorothiazide group one had normoalbuminuria, three low microalbuminuria, and six high microalbuminuria (chi 2 test = 6.7; p = 0.03). Mean arterial pressure did not differ before (98 (SD 7) with enalapril v 97 (9) mm Hg with hydrochlorothiazide) or during treatment (88 (7) with enalapril v 90 (7) mm Hg with hydrochlorothiazide (analysis of variance, p = 0.5263)). Glomerular filtration rate did not vary. The aldosterone to active renin ratio was decreased by angiotensin I converting enzyme inhibition and increased by sodium depletion, showing treatment efficacy. CONCLUSION: Angiotensin I converting enzyme inhibition by enalapril effectively reduces microalbuminuria in normotensive diabetic patients whereas hydrochlorothiazide is not effective. Changes in blood pressure and activity of the renin-angiotensin-aldosterone system may contribute to these different effects.

[Comparison of 3 methods of measurement of blood pressure in insulin-dependent diabetic patients with or without incipient diabetic nephropathy]. / Comparaison de trois méthodes de mesure de la pression artérielle chez des diabétiques insulino-dépendants avec ou sans néphropathie diabétique débutante.

Incipient diabetic nephropathy is characterized by a urinary albumin excretion (UAE) between 30-300 mg/24 h and a slightly elevated blood pressure. We measured blood pressure in 14 insulin-dependent diabetic subjects (IDDs) with persistent microalbuminuria (group A) and 50 IDDs with persistent normoalbuminuria (group B) using 3 different methods: 1) Sphygmomanometer, by a nurse, on supine position since 10 min, on the third day of hospitalization; 2) automatic device (Dinamap), on supine position, every 5 min, during 30 min; 3) ambulatory blood pressure (Spacelab 90202 every 15 min between 8 a.m. and 8 p.m.; values obtained with this last method were compared to the mean values of healthy subjects of same age. Recorded UAE was the median value of 3 twenty-four-hours urines. Blood pressure was not different among the two groups with any of the three methods: 1) SBP/DBP A: 136 +/- 14/81 +/- 9 vs B: 131 +/- 13/78 +/- 8 mmHg; ns; 2) SBP/MBP/DBP A: 134 +/- 17/96 +/- 12/79 +/- 10 vs B: 127 +/- 13/90 +/- 10/74 +/- 10 mmHg; ns; 3) A: 132 +/- 12/97 +/- 11/84 +/- 9 vs B: 127 +/- 11/91 +/- 9/82 +/- 12 mmHg; ns. There were no concordance between microalbuminuria/normoalbuminuria and systolic or diastolic blood pressure higher/lower than the mean of the healthy subjects (X2 = 1.6; ns). However, UAE was significantly related to MBP measured with 1): r = 0.29; p = 0.027, but not with 2): r = 0.24; ns, nor with 3): r = 0.26; ns. These results suggest that: 1-blood pressure of IDDs should be measured in standardized conditions; 2-diurnal ambulatory blood pressure recording does not predict incipient nephropathy in these subjects.

[Increase of activity of angiotensin-converting enzyme in insulin-dependent diabetic patients with permanent microalbuminuria]. / Elévation de l'activité de l'enzyme de conversion chez des diabétiques insulino-dépendants présentant une microalbuminurie permanente.

Angiotensin I Converting Enzyme (ACE), which is synthesized by vascular endothelial cells, can be elevated in some diabetic subjects. To study if serum ACE can be elevated in subjects with high risk for malignant microangiopathy, 34 normotensive type I, insulin-dependent diabetic subjects with persistent microalbuminuria (30-300 mg/24 h) were compared for serum ACE activity (Liebermann's method) with 30 normotensive, normoalbuminuric type I, insulin-dependent diabetic subjects of same age (33 +/- 15 (M +/- SD) vs 39 +/- 14 years), sex (13 F/21 M vs 15 F/15 M), stage of retinopathy (14 vs 16 nil/11 vs 7 background/6 vs 4 preproliferative/3 vs 3 proliferative), HbA1c (7.7 +/- .9 vs 8.2 +/- 1.0%). Serum ACE activity of diabetic subjects were also compared with 120 age and sex related healthy controls. Serum ACE activity was higher in type I, insulin-dependent diabetic subjects with microalbuminuria than in those with normoalbuminuria (406 +/- 114 vs 359 +/- 97 IU/l; p = 0.05), or in controls (307 +/- 95 IU/l; p = 0.0001). Normoalbuminuric subjects also had higher ACE activity than controls (p = 0.02). In diabetic subjects, serum ACE activity was not related to diabetes duration (r = 0.1; ns), stage of retinopathy (r = 0.06; ns), HbA1c (r = 0.02; ns), or to blood pressure (r = 0.03; ns), but was related to urinary albumin excretion (r = 0.28; p = 0.03) in diabetic subjects. However, stage of retinopathy was related to diabetes duration (r = 0.74; p = 0.0004) and to age (r = 0.42; p = 0.003) in these subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

[Increase of angiotensin converting enzyme activity during oral load of glucose]. / Augmentation de l'activité de l'enzyme de conversion au cours d'une charge en glucose par voie orale.

Elevated serum angiotensin I-converting enzyme activity may occur in diabetic subjects. This may signal alteration of vascular endothelium. To study the effect of acute glucose change on serum Angiotensin Converting Enzyme (ACE), we performed an oral glucose tolerance test in 17 obese subjects (7M/10F), (Body Mass Index, (BMI): 31 +/- 1 kg/m2), aged 48 +/- 3 years. We measured serum ACE activity (Lieberman's method), active renin (RIA Pasteur kit), and aldosterone (RIA, Cis-International kit), before and 2 hours after oral glucose intake (75 g), and plasma glucose and insulin every 30 min. After oral glucose tolerance test, subjects were classified as 6 Non Insulin-Dependent Diabetic (NIDD), 8 Glucose intolerant (GI), and 3 NormoGlycaemic (NG) subjects. Active renin did not vary after glucose loading (14 +/- 2 vs 15 +/- 2 pg/ml) nor aldosterone (104 +/- 14 vs 133 +/- 18 pg/ml), while ACE activity rose significantly (229 +/- 25 vs 277 +/- 28 IU/l; p = 0.02). Serum ACE activity were different in the 3 groups before glucose loading (NIDD: 266 +/- 37, GI: 252 +/- 32, NG: 90 +/- 21 IU/l; Kruskal-Wallis H = 7.03; p = 0.03), but not after 2 hours (NIDD: 297 +/- 42, GI: 275 +/- 36, NG: 204 +/- 113 IU/l; ns).(ABSTRACT TRUNCATED AT 250 WORDS)

[Microalbuminuria and left ventricular hypertrophy in essential arterial hypertension. A study in non-diabetic patients]. / Microalbuminurie et hypertrophie ventriculaire gauche au cours de l'hypertension artérielle essentielle. Etude chez des sujets non diabétiques.

To evaluate the relationship between urinary albumin excretion and left ventricular hypertrophy in essential hypertension, we studied, cross-sectionally, 64 subjects with essential hypertension and no diabetes. Urinary albumin excretion and Sokolow index correlated significantly (r = 0.483; P = 0.0001). Five subjects were positive for microalbuminuria (> 30 mg/24 h) and Sokolow index (> 35 mm); 43 were negative for both, with a concordance rate of 77 percent (chi-squared test 11.1; P = 0.0009). Stepwise multivariate regression analysis indicated two independent determinants for urinary albumin excretion: Sokolow index (F = 18.29), and diastolic blood pressure (F = 12.23). The relationships between urinary albumin excretion, Sokolow index, and blood pressure were not different in the 18 subjects taking angiotensin I-converting enzyme inhibitors and in the 46 others. The close relationship between urinary albumin excretion and Sokolow index observed in this study suggests that left ventricular hypertrophy due to hypertension may account for the increased cardiovascular mortality observed in non diabetic subjects with microalbuminuria.

Glomerular hyperfiltration in type I, type II, and secondary diabetes.

Glomerular hyperfiltration, a risk factor for diabetic nephropathy, has been reported in type I insulin-dependent diabetics, but it is not clear if it occurs in other types of diabetes. To ascertain the prevalence of glomerular hyperfiltration in various types of diabetes, we measured glomerular filtration rate (GFR) in 158 diabetics (91 type I, 36 type II without insulin treatment, 20 type II with insulin treatment, and 11 subjects with diabetes secondary to chronic pancreatitis), and classified them as hyper-, normo-, or hypofiltration according to values measured in 36 age-match controls. After elimination of subjects with overt renal disease or hypertension, glomerular hyperfiltration was detected in 35% of the type I diabetics, 32% of the type II diabetics without insulin treatment, one subject with chronic pancreatitis, and one type II diabetics with insulin treatment. Glomerular hyperfiltration was associated with high blood glucose in type I, insulin-dependent diabetics, and with a high apolipoprotein B/A1 ratio in type II, non-insulin-dependent diabetics without insulin treatment. In all subjects with glomerular hyperfiltration, GFR values and urinary albumin excretion were positively related (r = 0.33; n = 34; p = 0.05). Glomerular hyperfiltration is detectable among all types of diabetics.

[Dissociation of hypotensive and renal hemodynamic effects of an angiotensin converting enzyme inhibitor in insulin-dependent diabetic patients with incipient nephropathy]. / Dissociation des effets hypotenseurs et hémodynamiques rénaux d'un inhibiteur de l'enzyme de conversion chez des diabétiques insulinodépendants avec néphropathie débutante.

The mechanism of action of angiotensin converting enzyme (ACE) inhibitors on urinary albumin excretion (UAE) in diabetics is controversial. In order to dissociate the hypotensive and intrarenal effects, 16 insulin-dependant diabetics with permanent microalbuminuria (30-300 mg/24 h) without hypertension were given Ramipril, a long acting ACE inhibitor, at hypotensive (treatment A 5 mg/day; N = 8) and at sub-hypotensive doses (treatment B, 1.25 mg/day; N = 8) over a 6 week period in parallel double-blind study. Blood pressure, UAE, glomerular filtration renal blood flow (continuous 125I-Iodothalamate + 131I-Hippurate infusion) and converting enzyme activity (Liebermann's method), before and after treatment. In treatment group A, the blood pressure fell from 133 +/- 5/79 +/- 4 (mean +/- SE) to 125 +/- 4/77 +/- 2 mmHg (p less than 0.05 for systolic blood pressure) whereas it remained stable in treatment group B (132 +/- 7/79 +/- 4 to 128 +/- 5/80 +/- 4 mmHg). The UAE decreased in both groups: group A from an average of 74 (40-198) to 47 (5-202) mg/24 h (p = 0.07; group B, from an average of 77 (50-136) to 19 (15-120) mg/24 h (p less than 0.005), as did ACE activity: group A from 332 +/- 44 to 163 +/- 33 iu/l (p less than 0.004), group B from 423 +/- 39 to 191 +/- 28 iu/l (p less than 10-4).(ABSTRACT TRUNCATED AT 250 WORDS)

Small doses of ramipril to reduce microalbuminuria in diabetic patients with incipient nephropathy independently of blood pressure changes.

The mechanism of action of angiotensin-converting enzyme (ACE) inhibitors on urinary albumin excretion (UAE) in diabetic patients remains controversial. Sixteen type 1, insulin-dependent diabetics with incipient nephropathy received ramipril, a long-acting ACE inhibitor, at hypotensive doses (treatment A: 5 mg/day, n = 8) or at nonhypotensive doses (treatment B: 1.25 mg/day, n = 8) during a 6-week, double-blind, parallel study to establish whether its antihypertensive effects could be dissociated from its local renal effects. Blood pressure, UAE, glomerular filtration rate (GFR), effective renal plasma flow (ERPF, constant [125I]iodothalamate + [131I]hippurate infusion), and ACE activity were measured before and after treatment. Blood pressure was lowered with treatment A but not with treatment B. UAE and ACE activity were reduced with both treatments. Baseline GFR and ERPF were not altered by either treatment. In the patient population as a whole, ACE inhibition correlated with a rise in ERPF and with a reduction in filtration fraction (GFR/ERPF), but not with the changes in blood pressure. Changes in UAE correlated with the changes in filtration fraction. It is concluded that renal hemodynamics may be modified by ramipril independently of blood pressure changes.

[Urinary excretion of albumin and lipid abnormalities in hypertensive insulin-dependent diabetics]. / Excrétion urinaire d'albumine et anomalies lipidiques chez les diabétiques insulinodépendants hypertendus.

Patients with insulin dependent diabetes mellitus (IDDM) often suffer from cardiovascular diseases as renal failure occurs. Elevated albumin excretion rate (AER) is a predictive value of this event. Relations between AER, blood pressure, serum lipids and apoproteins concentrations in 100 patients with IDDM have been surveyed. Twenty one hypertensive patients (HT group) were compared to 21 patients without hypertension (n HT group), matched for sex, age, diabetes duration, and metabolic control, assessed by glycosylated haemoglobin. Comparison of both groups showed HT group had elevated systolic blood pressure (137 +/- 12 vs 126 +/- 20 mmHg; p less than .05), elevated diastolic blood pressure (80 +/- 7 vs 71 +/- 8 mmHg; p less than .001), increase in AER (27 range 3-4023 vs 6 range 2-51 mg/day; p less than .001), slightly elevated serum creatinine (95 +/- 32 vs 78 +/- 15 mumol/l; p less than .05). In HT group, serum lipid composition showed: raise in total cholesterol (251 +/- 43 vs 221 +/- 41 mg/dl; p less than 0.5), elevated apoprotein B (130 +/- 30 vs 99 +/- 21 mg/dl; p less than .001) elevated apoprotein B/apoprotein A1 ratio (.91 +/- .32 vs .66 +/- .27; p less than .001), elevated triglycerides (157 +/- 53 vs 98 +/- 43 mg/dl; p less than .005) and elevated LDL-cholesterol (170 +/- 42 vs 143 +/- 33 mg/dl; p less than .05). Levels of apoprotein A1 and HDL-cholesterol were not significantly different. Body mass index, daily insulin requirement and tobacco usage were similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)