Combined effect of obesity and metabolic profile on glomerular dysfunction in hypertensive subjects.

AIM: The aim of this study is to explore the individual and combined effects of obesity and metabolic profile on the impairment of glomerular function among hypertensive subjects. METHODS: This is a cross-sectional study enrolling 499 hypertensive subjects. Based on body mass index values and metabolic profile, they were assigned to one of four metabolic phenotype groups: MHNO: metabolically healthy non-obese, MHO: metabolically healthy but obese, MUHNO: metabolically unhealthy but non-obese, and MUHO: metabolically unhealthy and obese. The effect of the interaction between obesity and metabolic profile was tested on an additive scale, for both microalbuminuria and reduced estimated glomerular filtration rate (eGFR). RESULTS: After adjustment for confounding factors, the highest risk of both microalbuminuria and decreased eGFR was found among patients of the MUHO group (OR = 6.0 [2.13], p < 0.0001, OR = 5.4 [1.26], p = 0.03, respectively). Analysis of the additive interaction indicates that 51% and 53% of the risk of microalbuminuria and its combination with low eGFR respectively is explained by the co-occurrence of obesity and metabolic disorder. The mechanism of this interaction is synergistic (synergy index = 2.6, [1.5.3]). CONCLUSION: The decline of glomerular function in hypertensive subjects is significantly exacerbated by the interaction between obesity and metabolic disorders. The management of such high-risk subjects requires, in addition to the therapeutic regimen, an adequate dietary and physical program in order to preserve glomerular function.

Distance measurement for pulse wave velocity estimation in pediatric age: Comparison with intra-arterial path length.

BACKGROUND AND AIMS: Central pulse wave velocity (PWV) is a marker of arterial stiffness and is calculated by dividing the pulse wave travel distance by the transit time. However, there is no consensus as to the ideal distance measurement in children. The aim of our study was to identify the more reliable method to assess the distance measurement in the pediatric age. METHODS: Carotid-femoral PWV was measured by applanation tonometry in 988 healthy children aged 6.5-19.9 years. Two different surface distances were assessed: the subtraction method, representing the distance from the suprasternal notch to the femoral artery minus the distance from the carotid artery to the suprasternal notch, and the direct method, consisting of 80% of the distance from the carotid artery to the femoral artery. Both these methods were compared with the actual path length determined by magnetic resonance imaging (MRI) in 31 children. RESULTS: Subtraction and direct methods were significantly correlated in patients aged <14 years and the corresponding PWV values showed a good agreement. In children aged ≥14 years, a significant difference between the two methods was found: subtraction - direct distance = -45 ± 28 mm, with a significant difference in the resulting PWV values = -0.57 ± 0.35 m/s (p < 0.0001). This result was confirmed by MRI, showing a 10% overestimation in distance measurement by the direct method in subjects aged ≥14 years, resulting in a significantly higher PWV. CONCLUSIONS: These data suggest a greater reliability of the subtractive method of distance measurement compared to the direct method in children.

Determinants of the aortic pulse wave velocity index in hypertensive and diabetic patients: predictive and therapeutic implications.

OBJECTIVE: Aortic stiffness may provide information to classical risk factors information regarding cardiovascular risk. Aortic pulse wave velocity (PWV) can be measured by applanation tonometry but also theoretical PWV was calculated according to age, blood pressure, heart rate and sex. We aim to highlight biological and hemodynamic determinants of the aortic PWV index, that is the individually calculated [(measured PWV - theoretical PWV)/theoretical PWV] difference, in hypertensive diabetic patients. METHODS: A cross-sectional study was conducted in 514 patients, involving normotensive and hypertensive patients and people with and without diabetes. Biological parameters were measured during day-hospital for cardiovascular screening. Hemodynamic parameters were determined by applanation tonometry. Multivariate regression analyses evaluated the PWV index determinants. RESULTS: Hypertensive and/or diabetic population presents higher PWV index in correlation with the presence of proteinuria (P = 0.0428) and previous cardiovascular events (P = 0.0227). Hypertensive diabetic patients present a higher PWV index than the other patients (P < 0.05). Presence of insulin therapy (P = 0.0101) and the type 1 diabetes (P = 0.0065) were positively and independently modulating PWV index in hypertensive diabetic patients. HDL cholesterol levels (P = 0.0245) and absence of carotid (P = 0.0468) plaques were independently modulating PWV index with a negative correlation in hypertensive without diabetes patients. C reactive protein levels were significantly associated with increased PWV index in hypertensive patients (P = 0.0074) and in hypertensive and/or diabetic population (P = 0.0184). CONCLUSION: PWV index was correlated with numerous cardiovascular risk factors, in addition of being a marker of age and hypertension. Therefore, this index appears as a cardiovascular risk integrator. Its use could be interesting in cardiovascular risk assessment and reduction strategies.

Differential Associations for Salivary Sodium, Potassium, Calcium, and Phosphate Levels with Carotid Intima Media Thickness, Heart Rate, and Arterial Stiffness.

Salivary biomarkers may offer a noninvasive and easy sampling alternative in cardiovascular risk evaluation. The aim of the present study was to establish associations of salivary potassium, sodium, calcium, and phosphate levels with the cardiovascular phenotype determined by carotid ultrasound and carotid-femoral pulse wave velocity and to identify possible covariates for these associations. N = 241 samples of nonstimulated whole buccal saliva were obtained from subjects with (n = 143; 59%) or without (n = 98; 41%) hypertension. The potassium concentrations were 10-fold higher in saliva compared with plasma, whereas sodium concentrations exhibited the reverse relation between saliva and blood. There were no significant correlations between the levels of sodium, potassium, or calcium in saliva and plasma. All salivary electrolytes, except sodium, were significantly associated with age. In age-adjusted analyses, salivary potassium was significantly associated with carotid artery intima media thickness (cIMT) and carotid-femoral pulse wave velocity, and these associations were at the limit of significance in multivariate analyses including prevalent cardiovascular disease and risk factors. Body mass index was a significant confounder for salivary potassium. Salivary phosphate was significantly associated with cIMT in the multivariate analysis. Salivary potassium, calcium, and phosphate levels were significantly associated with heart rate in the univariate age-adjusted as well as in two different multivariate models, whereas no significant associations between sodium and heart rate were observed. In conclusion, the differential association of salivary electrolytes with cardiovascular phenotypes indicates that these electrolytes should be further studied for their predictive value as noninvasive biomarkers for cardiovascular risk evaluation.

Short Telomeres, but Not Telomere Attrition Rates, Are Associated With Carotid Atherosclerosis.

Short telomeres are associated with atherosclerosis. However, the temporal relationship between atherosclerosis and telomere length is unclear. The objective of this work was to examine the temporal formation and progression of carotid atherosclerotic plaques in relation to telomere dynamics. In a longitudinal study, comprising 154 French men and women (aged 31-76 years at baseline), carotid plaques were quantified by echography, and telomere length on leucocytes was measured by Southern blots at baseline and follow-up examinations. Telomere attrition rates during the 9.5-year follow-up period were not different in individuals with plaques at both baseline and follow-up examinations (23.3±2.0 base pairs/y) than in individuals who developed plaques during the follow-up period (26.5±2.0 base pairs/y) and those without plaques at either baseline or follow-up examination (22.5±2.3 base pairs/y; P=0.79). At baseline, telomere length was associated with presence of carotid plaques (P=0.02) and with the number of regions with plaques (P=0.005). An interaction (P=0.03) between age and the presence of plaques was observed, such that the association between plaques and telomere length was more pronounced at a younger age. In conclusion, carotid atherosclerosis is not associated with increased telomere attrition during a 9.5-year follow-up period. Short telomere length is more strongly associated with early-onset than late-onset carotid atherosclerosis. Our results support the thesis that heightened telomere attrition during adult life might not explain the short telomeres observed in subjects with atherosclerotic disease. Rather, short telomeres antecedes the clinical manifestation of the disease.

Low salivary resolvin D1 to leukotriene B4 ratio predicts carotid intima media thickness: A novel biomarker of non-resolving vascular inflammation.

Background Different lipid mediators may have opposing effects on vascular inflammation. For example, whereas leukotriene B4 (LTB4) transduces inflammation, resolvin D1 (RvD1), which is synthesized from the omega-3 fatty acid docosahexaenoic acid, facilitates the resolution of inflammation. The aim of this study was to determine the association of the RvD1/LTB4 ratio with subclinical atherosclerosis. Methods Saliva samples and ultrasound measurements of the intima media thickness of the carotid artery was obtained for 254 participants. The lipid mediators RvD1 and LTB4 were measured by enzyme-linked immunosorbent assay. Results Participants with a salivary RvD1/LTB4 ratio >1 had a significantly lower intima media thickness than those in whom LTB4 prevailed. The salivary RvD1/LTB4 ratio independently predicted carotid intima media thickness. Conclusions The ratio between the proresolving and proinflammatory salivary lipid mediators RvD1 and LTB4 may serve as a biomarker of non-resolving inflammation and its relation to intima media thickness in cardiovascular disease.

The Addition of Vascular Calcification Scores to Traditional Risk Factors Improves Cardiovascular Risk Assessment in Patients with Chronic Kidney Disease.

BACKGROUND: Although a variety of non-invasive methods for measuring cardiovascular (CV) risk (such as carotid intima media thickness, pulse wave velocity (PWV), coronary artery and aortic calcification scores (measured either by CT scan or X-ray) and the ankle brachial index (ABI)) have been evaluated separately in chronic kidney disease (CKD) cohorts, few studies have evaluated these methods simultaneously. Here, we looked at whether the addition of non-invasive methods to traditional risk factors (TRFs) improves prediction of the CV risk in patients at different CKD stages. METHODS: We performed a prospective, observational study of the relationship between the outputs of non-invasive measurement methods on one hand and mortality and CV outcomes in 143 patients at different CKD stages on the other. During the follow-up period, 44 patients died and 30 CV events were recorded. We used Cox models to calculate the relative risk for outcomes. To assess the putative clinical value of each method, we also determined the categorical net reclassification improvement (NRI) and the integrated discrimination improvement. RESULTS: Vascular calcification, PWV and ABI predicted all-cause mortality and CV events in univariate analyses. However, after adjustment for TRFs, only aortic and coronary artery calcification scores were found to be significant, independent variables. Moreover, the addition of coronary artery calcification scores to TRFs improved the specificity of prediction by 20%. CONCLUSION: The addition of vascular calcification scores (especially the coronary artery calcification score) to TRFs appears to improve CV risk assessment in a CKD population.

Influence of the AGTR1 A1166C genotype on the progression of arterial stiffness: A 16-year longitudinal study.

BACKGROUND: We examined the influence of the AGTR1 A1166C genotype on the 16-year evolution of pulse wave velocity (PWV) in a middle-aged population. In a cross-sectional study, we reported that the presence of the AGTR1 1166C allele was associated with higher aortic stiffness compared with the AGTR1 1166AA genotype. METHODS: The study was conducted in 259 subjects who underwent 3 health check-ups over 16 years at the Centre IPC-Paris: an initial visit in 1992-1993, an intermediate visit in 1998-1999, and a final visit in 2007-2008. Aortic stiffness was assessed during the 3 visits by measuring carotid-femoral PWV. AGTR1 A1166C polymorphism was assayed by allele-specific oligonucleotide hybridization. RESULTS: AGTR1 1166C allele carriers (AC + CC genotypes) had a 35% more pronounced increase in PWV over this 16-year period when compared with the AGTR1 1166AA subjects (3.01 ± 0.32 vs. 1.92 ± 0.23 m/s; P < 0.001). This increase remained significant after adjustment for age, sex, initial PWV values, and changes in blood pressure (+37%; P < 0.05). The genotype-related differences in PWV were only observed at the last visit (i.e., later in life, after the age of 55 years). The effects of this genotype on PWV were not related to the presence of antihypertensive treatment. CONCLUSIONS: This is the first long-term longitudinal study indicating that AT1 1166C carriers are at increased risk of pronounced arterial stiffening during aging especially after the age of 55.

Elderly Algerian women lose their sex-advantage in terms of arterial stiffness and cardiovascular profile.

OBJECTIVES: Several studies have shown lower carotid-femoral pulse wave velocity (cfPWV) levels in women compared to men, a difference that could partially explain the increased longevity in women. However, these studies have been performed in industrial countries while few data are available in emerging populations. We studied arterial stiffness, as evaluated by cfPWV, in elderly Algerian men and women. METHODS: cfPWV was studied in 321 Algerian men (81.2 ±â€Š5.3 years) and women (81.1 ±â€Š4.4 years). An age-matched and sex-matched cohort of European individuals (n = 321) was used as a control group. RESULTS: Comparatively to men, Algerian women exhibited higher BMI and heart rate (HR), higher prevalence of hypertension, and were more frequently treated for hypertension. cfPWV was not different between Algerian men (14.8 ±â€Š3.3 m/s) and women (14.9 ±â€Š3.4 m/s). By contrast, in Europeans, women had lower cfPWV (12.7 ±â€Š2.7 m/s) than men (14.0 ±â€Š3.3 m/s; P <0.001). Comparatively to European women, Algerian women had a higher cfPWV (P <0.01). In both ethnic groups, multivariate analyses revealed that age, mean blood pressure (BP), HR, and diabetes were positively associated with cfPWV, whereas female sex was associated with lower cfPWV only in Europeans. CONCLUSION: Elderly Algerian women exhibit arterial stiffness similar to men, whereas European women display lower arterial stiffness than men. This loss of 'arterial sex advantage' in Algerians may be explained by higher BP, HR, and a worse metabolic profile in Algerian women. Interventions in emerging populations, especially in women, should be a priority in order to address these risk factors by acting on current lifestyle.

Inflammatory mediators in saliva associated with arterial stiffness and subclinical atherosclerosis.

OBJECTIVE: Whereas circulating levels of C-reactive protein (CRP) have been associated with, for example, arterial stiffness, subclinical atherosclerosis and metabolic syndrome, other inflammatory biomarkers with potential interest for these conditions may not be measurable systemically. The predictive value of salivary biomarkers in these contexts has remained largely unexplored. The aim of the present study was to establish the association of different salivary biomarkers of inflammation with subclinical cardiovascular disease. METHODS: Two hundred and fifty-nine individuals were included in the study. Saliva and plasma samples were collected, and each individual underwent carotid ultrasound and measures of pulse wave velocity and blood pressure. Medical history of previous cardiovascular disease, current medications and smoking were collected by questionnaire. RESULTS: Salivary levels of CRP, leukotriene B4 (LTB4), prostaglandin E2 (PGE2), matrix metalloproteinase 9 (MMP-9), creatinine and lysozyme were measured. Salivary levels of CRP were significantly correlated with plasma levels (r = 0.73, P < 0.0001). In an age-adjusted and sex-adjusted analysis, salivary CRP was significantly and positively correlated with mean arterial blood pressure, pulse pressure, pulse wave velocity, BMI, metabolic syndrome, waist-to-hip ratio and intima-media thickness. Increasing age and sex-adjusted salivary CRP tertiles were in addition associated with carotid plaques. In a multivariate analysis, CRP and MMP-9 were associated with intima-media thickness, LTB4 and PGE2 with arterial stiffness, and lysozyme with hypertension. CONCLUSION: Saliva may represent an alternative mean for evaluation of cardiovascular risk.

Role of birth weight and postnatal growth on pulse wave velocity in teenagers.

PURPOSE: Low birth weight and accelerated postnatal growth appear to play a significant role in the pathogenesis of hypertension and cardiovascular disease in adulthood. The aim of the present study was to characterize the factors determining pulse wave velocity (PWV) in teenagers and, in particular, to verify the relationship with birth weight, postnatal growth, timing of adiposity rebound, lifestyle, and hemodynamic parameters. METHODS: Carotid-femoral and carotid-radial pulse wave velocities of 558 healthy teenagers (age range: 16.2-19.9 years) were determined by means of a PulsePen tonometer. Birth weight and gestational age were obtained from obstetrical records, and data regarding postnatal growth were obtained from pediatric clinical records. RESULTS: No change in aortic PWV was found in association with birth weight, postnatal growth, and timing of adiposity rebound. However, the study showed a strong association between accelerated growth from 0 to 12 months and carotid-radial PWV (trend: p = .02). Subjects with birth weight values <2,500 g showed higher values of upper limb PWV (p < .05) and higher values of diastolic and mean arterial pressure (p < .05). Stepwise regression analysis revealed that mean arterial pressure, age, and height were the main independent factors determining aortic PWV in this young population. CONCLUSIONS: These results suggest that there is no linear correlation between birth weight and hemodynamic parameters in teenagers; however, subjects characterized by very low birth weight and accelerated postnatal weight gain appear to demonstrate increased upper limb PWV and diastolic and mean arterial pressure values.

Markers of vascular disease in plasma from patients with chronic kidney disease identified by proteomic analysis.

OBJECTIVES: Chronic kidney disease (CKD) patients belong to the group of patients with a high prevalence of cardiovascular disease (CVD). Arterial calcification and aortic stiffness are currently used as surrogates for vascular alterations. However, still little is known about prediction and the patho-physiologic mechanisms leading to CVD. METHODS: We applied capillary electrophoresis coupled mass spectrometry profiling to blood specimens collected from 34 CKD stage 5D patients suffering from vascular alterations to allow insights into the molecular pathology of the disease. RESULTS: Statistical comparison of plasma profiles from mild and severe CVD cases according to either arterial calcification or aortic stiffness unveiled 13 novel biomarkers for vascular disease. Tandem mass spectrometry identified four of these as fragments of collagen alpha-1 type I and III and one as fragment of apolipoprotein CIII. Integrated in a distinct pattern the candidates were validated using the moderate CVD cases among the 34 CKD patients (N=11) and an additional independent blinded cohort of CKD stage 4-5 patients (N=21), who all had not been considered during biomarker discovery. The panel distinguished mild and severe CVD with sensitivity of 89% and specificity of 67% in this independent cohort. CONCLUSION: This diagnostic phase I/II study supports the notion that vascular alterations are reflected by distinct changes in plasma profiles of CKD patients.

Reference values of pulse wave velocity in healthy children and teenagers.

Carotid-femoral pulse wave velocity is an established method for characterizing aortic stiffness, an individual predictor of cardiovascular mortality in adults. Normal pulse wave velocity values for the pediatric population derived from a large data collection have yet to be available. The aim of this study was to create a reference database and to characterize the factors determining pulse wave velocity in children and teenagers. Carotid-femoral pulse wave velocity was measured by applanation tonometry. Reference tables from pulse wave velocities obtained in 1008 healthy subjects (aged between 6 and 20 years; 495 males) were generated using a maximum-likelihood curve-fitting technique for calculating SD scores in accordance with the skewed distribution of the raw data. Effects of sex, age, height, weight, blood pressure, and heart rate on pulse wave velocity were assessed. Sex-specific reference tables and curves for age and height are presented. Pulse wave velocity correlated positively (P<0.001) with age, height, weight, and blood pressure while correlating negatively with heart rate. After multiple regression analysis, age, height, and blood pressure remained major predictors of pulse wave velocity. This study, involving >1000 children, is the first to provide reference values for pulse wave velocity in children and teenagers, thereby constituting a suitable tool for longitudinal clinical studies assessing subgroups of children who are at long-term risk of cardiovascular disease.

Association of current weight and birth weight with blood pressure levels in Saharan and European teenager populations.

BACKGROUND: The Saharan adult population is characterized by a high prevalence of hypertension. The aim of the present study was to compare blood pressure (BP) levels in Saharan Arab-origin teenagers, in relationship with Europeans of the same age, and to assess the association with birth weight, body weight, and other anthropometric measurements. METHODS: BP values, heart rate (HR), clinical parameters, and anthropometric measurements were determined in 2,057 teenagers ages 15-19, 1,122 Algerians (388 boys) and 935 Italians (407 boys). Birth weight was obtained from obstetrical records in 568 Algerians and 735 Italians. RESULTS: The European teenagers were significantly taller and heavier than their Algerian counterparts. In the Algerian population, systolic BP (SBP) was higher in boys (P < 0.01) and lower in girls (P < 0.0001) compared to the Italians, whereas diastolic BP (DBP) was higher in Italians (P < 0.001). Both SBP and DBP were higher in boys than in girls independently of geographic origin (P < 0.001). In all four gender and ethnic groups, both SBP and DBP were strongly correlated with weight or body mass index (BMI). Influence of body weight was stronger on SBP than on DBP; in all four groups, those with the highest weight or BMI quartiles had higher SBP levels by 6-12 mm Hg as compared to those individuals in the lowest quartiles. No correlation was found between birth weight, and SBP or DBP. CONCLUSIONS: In Algerian and Italian teenagers, both male and female, current weight but not birth weight was found to be a strong determinant of BP levels.

Intraaortic pulse pressure amplification in subjects at high coronary risk.

Peripheral (brachial) pulse pressure normally exceeds central (aortic) pulse pressure but is a less powerful predictor of cardiovascular risk. The difference between the 2 variables, called pulse pressure amplification, has never been specifically studied between the proximal and distal aorta in coronary patients. Our goal was to determine aortic pulse pressure amplification in subjects at high coronary risk, with emphasis on associated renal and inflammatory factors. Blood pressure was measured invasively in the ascending aorta, abdominal aorta (at the level of kidneys), and iliac artery in 101 subjects (mean age, 63+/-11 years; 61 men) undergoing coronary angiography. Independently of age, sex, and the presence of coronary stenosis, the increase of pulse pressure between the ascending and terminal aorta was over 10 mm Hg (P<0.001), whereas mean blood pressure remained unchanged. Pulse pressure amplification did not differ significantly between patients with and without coronary artery stenosis. Irrespective of confounding variables, high pulse pressure measured in the ascending aorta and at the level of renal arteries (but not in the iliac artery) was independently related to proteinuria. The increase in pulse pressure from the ascending aorta to the renal level was negatively associated with leukocyte count, even after multivariate adjustment (beta coefficient, -0.19; 95% CI, -0.39 to 0.0; P<0.05). Increased plasma creatinine and aortic pulse wave velocity were independently and positively correlated (beta coefficient, 0.36; CI, 0.18 to 0.54; P<0.001). Independently of coronary atherosclerosis, aortic pulse pressure integrates the predictive value of aortic, inflammatory, and renal factors.

Pulse wave velocity and vascular calcification at different stages of chronic kidney disease.

BACKGROUND: Increased arterial stiffness and vascular calcification have been recognized as important predictors of cardiovascular mortality in patients with chronic kidney disease. METHOD: In order to examine the precise temporal link between aortic stiffness and cardiovascular risk at the earliest stages of chronic kidney disease, we studied a cohort of 150 patients with chronic kidney disease (52 stage 2/3 patients, 51 stage 4/5 patients and 47 stage 5D patients). Each patient underwent a plain, lateral lumbar radiograph and an abdominal and thoracic multislice spiral computer tomography scan in order to identify and quantify aortic and coronary calcifications. Pulse wave velocity was used as a measure of arterial stiffness. RESULTS: Regardless of the disease stage, patients with chronic kidney disease had higher adjusted pulse wave velocity than controls with preserved renal function (14.6 +/- 3.8 vs. 10.7 +/- 1.7 m/s, respectively; P < 0.0001). Regarding aortic calcification, there was a gradual but significant rise in later chronic kidney disease stages. A similar trend was found for coronary calcification. In a multivariate analysis only age, mean arterial pressure, diabetes and the aortic calcification score were independent determinants of higher pulse wave velocity. CONCLUSION: We found that both vascular stiffness and vascular calcification appear early in patients with chronic kidney disease, but only vascular calcification worsens as the disease progresses. The increase of vascular stiffness in adult patients with chronic kidney disease seems to be more related to age, systolic blood pressure, diabetes and vascular calcification than to uremic toxicity.

Prevention of dementia by antihypertensive drugs: how AT1-receptor-blockers and dihydropyridines better prevent dementia in hypertensive patients than thiazides and ACE-inhibitors.

Our review of cohort studies and clinical trials evaluating antihypertensive drugs in the prevention of cognition decline and all dementia in patients with hypertension indicates that two antihypertensive drug classes have greater protective effects, independent of blood pressure decrease: dihydropyridine calcium-channel blockers as shown in the Syst-Eur trial and angiotensin-AT1 receptor blockers as found in the MOSES and ONTARGET trials. By contrast, diuretics and angiotensin-converting enzyme-inhibitors (ACEIs) prevent dementia only in patients with a stroke history, provided they are combined, and prevent stroke recurrence. A Japanese cohort study and a small trial in patients already suffering from Alzheimer's disease (AD) suggest, however, that the BBB-penetrating ACEI may slow down cognitive decline. Only cohort studies support the hypothesis that diuretics, (especially potassium-sparing diuretics), may decrease the risk of AD. beta-blockers worsen cognition decline, or are neutral, according to whether or not they cross the BBB. Centrally-acting sympatholytic agent have a negative impact on cognition as BBB-penetrating beta-blockers, probably by blunting the adrenergic pathways. The AD protective effect of DHP appears related to the blockade of neuronal calcium channels. The ambiguous effect of ACEI on cognitive decline and dementia prevention may be explained by the fact that brain ACE is not specific for angiotensin-I. Brain ACE also catabolizes cognition-enhancing brain peptides, amyloid peptides and converts toxic Abeta(42) into less toxic Abeta(40). Therefore, ACEIs may have short-term cognition-enhancing properties and may increase in the long term Abeta(42) brain burden and cognitive decline. The clinical relevance of this scenario, mainly observed in animals, cannot be excluded in man, since the ACE gene has been associated with AD via the human whole genome analysis. To support the hypothesized deleterious effect of ACEI on human AD, confirmation that the ACE gene polymorphism DD is associated with protection against AD is necessary, since this polymorphism increases ACE activity. Independently of their preventive impact on beta-amyloid degenerative neuropathological process by overexpressing insulin degrading enzyme which catabolyses amyloid, the angiotensin AT1-receptor-blockers may have greater cognition protective effects than ACEI (observed in the ONTARGET trial), as they share with ACEI cognition-enhancing effects directly linked with a common AT1-blunting effect. In addition, they increase angiotensin II and IV formation and therefore stimulate non-opposed AT2 and AT4 receptors, whose activation in cognitive processes is well established.

Prevalence and determinants of hypertension in the Algerian Sahara.

BACKGROUND: In-Salah is a city-oasis located in the middle of the Algerian Sahara, a desert area whose drinking water has a high sodium content. No cardiovascular epidemiological studies have ever been conducted in this region. METHODS: A randomized sample of 635 men and 711 women, aged 40-99 years, was studied. Blood pressure measurements, combined with a clinical questionnaire that included educational and socio-economic data, and standard blood samples for the detection of dyslipidemia and diabetes mellitus, were collected. RESULTS: The mean age was 55 +/- 12 years. The prevalence of hypertension was 44% and was highly influenced by age, sex, skin colour, educational status, obesity and metabolic parameters. The higher prevalence of hypertension among black individuals was independent of socio-economic and educational levels, and of metabolic parameters. The presence of antihypertensive treatment was three times more frequent in women than in men, and there was no difference according to skin colour. Among treated subjects, 25% were well controlled, and this percentage was similar among both black and white individuals. CONCLUSION: Epidemiological studies in such an emergent population indicate that hypertension is a major public health problem. The high sodium content in drinking water in this region could play a major role in the development of hypertension.