Association of aortic stiffness with abdominal vascular and coronary calcifications in patients with stage 3 and 4 chronic kidney disease.

RATIONALE AND OBJECTIVES: Increased central (aortic) arterial stiffness has hemodynamic repercussions that affect the incidence of cardiovascular and renal disease. In chronic kidney disease (CKD) there may be an increase in aortic stiffness secondary to multiple metabolic alterations including calcification of the vascular wall (VC). The objective of this study was to analyze the association of central aortic pressures and aortic stiffness with the presence of VC in abdominal aorta (AAC) and coronary arteries(CAC). MATERIALS AND METHODS: We included 87 pacientes with CKD stage 3 and 4. Using applanation tonometry, central aortic pressures and aortic stiffness were studied. We investigated the association of aortic pulse wave velocity (Pvc-f) and Pvc-f adjusted for age, blood pressure, sex and heart rate (Pvc-f index) with AAC obtained on lumbar lateral radiography and CAC assessed by multidetector computed tomography. AAC and CAC were scored according to Kauppila and Agatston methods, respecti-vely. For the study of the association between Pvc-f index, Kauppila score, Agatston score, central aortic pressures, clinical parameters and laboratory data, multiple and logistic regression were used. We investigated the diagnosis performance of the Pvc-f index for prediction of VC using receiver-operating characteristic (ROC). RESULTS: Pvc-f and Pvc-f index were 11.3 ± 2.6 and 10.6 m/s, respectively. The Pvc-f index was higher when CKD coexisted with diabetes mellitus (DM). AAC and CAC were detected in 77% and 87%, respectively. Albuminuria (ß = 0.13, p = 0.005) and Kauppila score (ß = 0.36, p = 0.001) were independently associated with Pvc-f index. In turn, Pvc-f index (ß = 0.39, p = 0.001), DM (ß = 0.46, p = 0.01), and smoking (ß = 0.53; p = 0.006) were associated with Kauppila score, but only Pvc-f index predicted AAC [OR: 3.33 (95% CI: 1.6-6.9; p = 0.001)]. The Kauppila score was independently associated with the Agatston score (ß = 1.53, p = 0.001). The presence of AAC identified patients with CAC with a sensitivity of 73%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 38%. The Vpc-f index predicted the presence of CAC [OR: 3.35 (95% CI: 1.04-10.2, p = 0.04)]. In the ROC curves, using the Vpc-f index, the AUC for AAC and CAC was 0.82 (95%CI: 0.71-0.93, p = 0.001) and 0.81 (95% CI: 0.67-0.96, p = 0.02), respectively. CONCLUSIONS: When stage 3-4 CKD coexists with DM there is an increase in aortic stiffness determined by the Vpc-f index. In stage 3-4 CKD, AAC and CAC are very prevalent and both often coexist. The Vpc-f index is independently associated with AAC and CAC and may be useful in identifying patients with VC in these territories.

Effect of the administration of different forms of vitamin D on central blood pressure and aortic stiffness, and its implication in the reduction of albuminuria in chronic kidney disease. / Efecto de la administración de diferentes formas de vitamina D en la presión arterial y rigidez aórticas, y su implicación en la reducción de la albuminuria en la enfermedad renal crónica.

BACKGROUND AND OBJECTIVES: Vitamin D(vitD) participates in phospho-calcium metabolism and exerts multiple pleiotropic effects. There is tissue 1-α (OH)ase that converts 25-OH cholecalciferol (25 (OH) D) in calcitriol that exerts autocrine and paracrine effects. 25 (OH)D deficiency could limit these tissue effects of vitD. The administration of nutritional vitD and the activator of the vitD receptor, paricalcitol, may promote beneficial effects on vascular and renal function. The objective of this work was to study in subjects with chronic kidney disease (CKD) the effect that the administration of different forms of vitD has on arterial function and albuminuria, and the possible relationship between the modifications of these variables. PATIENTS AND METHODS: We studied in 97 patients with CKD stages 3-4 the effect of the administration of cholecalciferol (group 2; n: 35) and paricalcitol (n: 31; group 3) on parameters derived from brachial blood pressure, aortic blood pressure and on aortic stiffness studied using carotid-femoral pulse velocity (Vpc-f), and on albuminuria. A group of patients with stages 3-4 CKD who did not receive vitD therapy served as a control group (n: 31; group 1). All parameters were studied at baseline and after the follow-up period which was 7 ± 2 months. RESULTS: In the baseline phase, no differences were observed between the groups in brachial systolic blood pressure (bSBP), central systolic blood pressure (SBP), brachial pulse pressure (bPP), and central pulse pressure (pCP) or in aortic stiffness that was increased in all groups with a baseline Vpc-f value of 10.5 (9.2-12.1) m/sec. The baseline albuminuria value in the grouped patients was 229 (43-876) mg / g (median (interquartile range)), with no differences between the groups. Serum calcium and phosphorus increased significantly in those treated with cholecal-ciferol (native vitD) and paricalcitol (active vitD). Parathormone (PTH) values decreased in those treated with paricalcitol.bPP and cPP decreased in all groups treated with native and active vitD. No significant changes in bPP and cPP were observed in the control group. Vpc-f did not change significantly in any of the groups, although the variation was quantitatively greater in group 3 (11.2±2 vs. 10.7±1.6 (P=.06)). No differences were observed in the changes in Vpc-f between the groups when adjusted to the baseline values of estimated glomerular filtration rate (eGFR), albuminuria, PTH, vitD, brachial and central blood pressure parameters, and their changes with treatment.Those who received treatment with native and active vitD presented a significant decrease in albuminuria of 17% (group 2) and 21% (group 3) compared to a 16% increase in the untreated group (group 1) (P=.01). A decrease in albuminuria ≥30% was observed more frequently in the groups treated with some form of vitD (group 2: 23%; group 3: 45%) than in the control group (13%) (P=.03). The decrease in albuminuria observed in the groups treated with any of the forms of vitD did not vary when the baseline values of the biochemical parameters of phosphorus-calcium metabolism, those of arterial function (PPb, PPc, Vpc-f) or its modifications were introduced as covariates. There was no significant correlation between changes in Vpc-f and albuminuria. In logistic regression, changes in arterial function parameters were also not explanatory for the ≥30% decrease in albuminuria. CONCLUSIONS: In patients with CKD stages 3-4, treated with RAS blockers and with residual albuminuria, the administration of or paricalcitol reduces brachial and aortic pulse pressures, and albuminuria. The decrease in albuminuria does not seem to be mediated, at least not decisively, by changes in central hemodynamics or aortic stiffness.

Role of increased central arterial stiffness in macro and microvascular damage in patients with coronary artery disease. / Papel del aumento de la rigidez arterial central en el daño macro y microvascular en pacientes con enfermedad coronaria.

BACKGROUND: Patients with heart disease frequently have renal dysfunction manifested by a decrease in glomerular filtration rate (GFR) and / or increase of albuminuria. OBJECTIVES: The objective was to study the possible role of increased aortic stiffness in the presence and extent of coronary artery disease (CAD) and kidney dysfunction in a group of patients with suspected CAD. PATIENTS AND METHODS: We studied forty-eight patients undergoing coronariography for suspected coronary disease (CAD). Using applanation tonometry on the radial artery and applying a transfer function, central blood pressure values were calculated. The study of aortic stiffness was done by determining the carotid-femoral pulse velocity (Pvc-f). RESULTS: Of the 48 patients, 11 had no significant coronary lesions, 24 showed significant lesions in 1 or 2 coronary arteries and 13 in ≥ 3 arteries. The group with a higher degree of CD had significantly higher cPP values than the group without CD. The Pvc-f increased progressively and significantly with the degree of CD. The logistic regression showed that Pvc-f independently predicted the presence of CD. The relative risk of CD increased 2.5 times for each meter of increase in Pvc-f. The GFR was negatively and significantly correlated with age and Pvc-f was associated with albuminuria. CONCLUSIONS: In patients with stable CD, Pvc-f, expression of aortic stiffness, is independently associated with the existence of CD and its degree of extension. The increase in arterial stiffness also participates in the decrease in GFR and in the increase in albuminuria.

Oral anticoagulation in chronic kidney disease with atrial fibrillation.

Chronic kidney disease (CKD) and atrial fibrillation (AF) frequently coexist, amplifying the risk of cardiovascular events and mortality. In patients with CKD stage 3 and non-valvular AF, direct oral anticoagulants (DOACs) have shown, compared to vitamin K antagonists (VKA), equal or greater efficacy in the prevention of stroke and systemic embolism, and greater safety. There are no randomizedtrials of the efficacy and safety of DOACs and VKA in advanced CKD. On the other hand, observational studies suggest that DOACs, compared to warfarin, are associated with a lower risk of acute kidney damage and generation/progression of CKD. This paper reviews the epidemiological and pathophysiological aspects of the CKD and AF association, the evidence of the efficacy and safety of warfarin and ACODs in various stages of CKD with AF as well as the comparison between warfarin and ACODs in efficacy and anticoagulant safety, and in its renal effects.

Mineralcorticoid receptor blockers in chronic kidney disease.

There are many experimental data supporting the involvement of aldosterone and mineralcorticoid receptor (MR) activation in the genesis and progression of chronic kidney disease (CKD) and cardiovascular damage. Many studies have shown that in diabetic and non-diabetic CKD, blocking the renin-angiotensin-aldosterone (RAAS) system with conversion enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs) decreases proteinuria, progression of CKD and mortality, but there is still a significant residual risk of developing these events. In subjects treated with ACEi or ARBs there may be an aldosterone breakthrough whose prevalence in subjects with CKD can reach 50%. Several studies have shown that in CKD, the aldosterone antagonists (spironolactone, eplerenone) added to ACEi or ARBs, reduce proteinuria, but increase the risk of hyperkalemia. Other studies in subjects treated with dialysis suggest a possible beneficial effect of antialdosteronic drugs on CV events and mortality. Newer potassium binders drugs can prevent/decrease hyperkalemia induced by RAAS blockade, and may reduce the high discontinuation rates or dose reduction of RAAS-blockers. The nonsteroidal MR blockers, with more potency and selectivity than the classic ones, reduce proteinuria and have a lower risk of hyperkalemia. Several clinical trials, currently underway, will determine the effect of classic MR blockers on CV events and mortality in subjects with stage 3b CKD and in dialysis patients, and whether in patients with type 2 diabetes mellitus and CKD, optimally treated and with high risk of CV and kidney events, the addition of finerenone to their treatment produces cardiorenal benefits. Large randomized trials have shown that sodium glucose type 2 cotransporter inhibitors (SGLT2i) reduce mortality and the development and progression of diabetic and nondiabetic CKD. There are pathophysiological arguments, which raise the possibility that the triple combination ACEi or ARBs, SGLT2i and aldosterone antagonist provide additional renal and cardiovascular protection.

Oral anticoagulation in chronic kidney disease with atrial fibrillation. / Anticoagulación oral en la enfermedad renal crónica con fibrilación auricular.

Chronic kidney disease (CKD) and atrial fibrillation (AF) frequently coexist, amplifying the risk of cardiovascular events and mortality. In patients with CKD stage3 and non-valvular AF, direct oral anticoagulants (DOACs) have shown, compared to vitaminK antagonists (VKA), equal or greater efficacy in the prevention of stroke and systemic embolism, and greater safety. There are no randomized trials of the efficacy and safety of DOACs and VKA in advanced CKD. On the other hand, observational studies suggest that DOACs, compared to warfarin, are associated with a lower risk of acute kidney damage and generation/progression of CKD. This paper reviews the epidemiological and pathophysiological aspects of the CKD and AF association, the evidence of the efficacy and safety of warfarin and ACODs in various stages of CKD with AF as well as the comparison between warfarin and ACODs in efficacy and anticoagulant safety, and in its renal effects.

[Mineralcorticoid receptor blockers in chronic kidney disease]. / Bloqueantes del receptor mineralcorticoide en la enfermedad renal crónica.

There are many experimental data supporting the involvement of aldosterone and mineralcorticoid receptor (MR) activation in the genesis and progression of chronic kidney disease (CKD) and cardiovascular damage. Many studies have shown that in diabetic and non-diabetic CKD, blocking the renin- angiotensin-aldosterone (RAAS) system with conversion enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs) decreases proteinuria, progression of CKD and mortality, but there is still a significant residual risk of developing these events. In subjects treated with ACEi or ARBs there may be an aldosterone breakthrough whose prevalence in subjects with CKD can reach 50%. Several studies have shown that in CKD, the aldosterone antagonists (spironolactone, eplerenone) added to ACEi or ARBs, reduce proteinuria, but increase the risk of hyperkalemia. Other studies in subjects treated with dialysis suggest a possible beneficial effect of antialdosteronic drugs on CV events and mortality. Newer potassium binders drugs can prevent / decrease hyperkalemia induced by RAAS blockade, and may reduce the high discontinuation rates or dose reduction of RAAS-blockers. The nonsteroidal MR blockers, with more potency and selectivity than the classic ones, reduce proteinuria and have a lower risk of hyperkalemia. Several clinical trials, currently underway, will determine the effect of classic MR blockers on CV events and mortality in subjects with stage 3b CKD and in dialysis patients, and whether in patients with type 2 diabetes mellitus and CKD, optimally treated and with high risk of CV and kidney events, the addition of finerenone to their treatment produces cardiorenal benefits. Large randomized trials have shown that sodium glucose type 2 cotransporter inhibitors (SGLT2i) reduce mortality and the development and progression of diabetic and nondiabetic CKD. There are pathophysiological arguments, which raise the possibility that the triple combination ACEi or ARBs, SGLT2i and aldosterone antagonist provide additional renal and cardiovascular protection.

Effect of dapagliflozin on arterial stiffness in patients with type 2 diabetes mellitus. / Efecto de dapagliflozina sobre la rigidez arterial en pacientes con diabetes mellitus tipo 2.

INTRODUCTION: Oral antidiabetic inhibitors of the sodium-glucose cotransporter (SGLT2i) reduce cardiovascular morbidity and mortality in DM2. The increase in arterial stiffness can participate in this morbidity and mortality. The aim of this study was to analyse the effect of the administration of dapagliflozin on arterial stiffness. PATIENTS AND METHODS: Prospective observational study that included 32 patients with DM2. Before starting dapagliflozin, and at 6 and 12 months, biochemical parameters in blood and urine were analysed. Before starting dapagliflozin and at 12 months the velocity of the carotid-femoral pulse (VPc-f) was determined by tonometry. Changes in the variables and their interrelation was analysed by repeated data ANOVA, Wilcoxon's test and multiple regression. RESULTS: A significant decrease in the VPc-f was observed. There was no association between decreased VPc-f and changes in blood glucose, uric acid, blood pressure or weight. CONCLUSIONS: Dapagliflozin, in subjects with DM2, produces a medium to long-term decrease in arterial stiffness.

Renal safety profile of sodium-glucose cotransporter-2 inhibitors and other safety data. / Perfil de seguridad renal de los inhibidores del cotransportador sodio-glucosa tipo 2 y otros datos de seguridad.

The main effect of SGLT2 inhibitors is their glycosuric action. These drugs reverse the deleterious effect of increased glucose reabsorption by the renal tubule in persons with DM2. In terms of efficacy, SGLT2 inhibitors produce a mean HbA1c reduction of 0.8%, although higher initial HbA1c levels can show a larger decrease. In addition to these glycaemic effects, this drug class also favours weight loss and blood pressure control, without increasing hypoglycaemic episodes. Due to their insulin-independent mechanism of action, SGLT2 inhibitors can be used in monotherapy, in patients with metformin intolerance, or in combination with other glucose-lowering drugs, including insulin. These drugs have few secondary effects and most are related to their mechanism of action. The most frequent adverse effects are genitourinary infections, usually mycotic infections. SGLT2 inhibitors have an adequate cardiovascular safety profile. The development of ketoacidosis remains to be elucidated, and may be related to use in patients with insulinopenia. A randomised clinical trial of an SGLT2 inhibitor in patients with DM2 and underlying cardiovascular disease showed that its use in association with standard therapy slowed the progression of renal damage and reduced significant renal events such as doubling of serum creatinine values and initiation of dialysis. These effects are probably due to the favourable effects of SGLT2 inhibition on glomerular haemodynamics, by reducing hyperfiltration, to the reduction of glucose-induced tubular toxicity, as well as its beneficial effects on glycaemia, blood pressure, weight, and uricaemia.

[Measurement of blood pressure in consultation and automated mesurement (BPTru(®)) to evaluate the white coat effect]. / Medida de la presión arterial en consulta y automatizada (BPTru®) para evaluar el efecto de bata blanca.

BACKGROUND AND OBJECTIVE: White coat effect (WCE) is one of the main bias that can affect office blood pressure (BP) measurement. Therefore, it is a factor must be considered in hypertensives to avoid mistakes in diagnosis and/or treatment. Employment of automated office BP (AOBP) devices could diminish that effect. METHODS: Two studies were designed with the objective of evaluating differences between routinely office and AOBP measurements. WCE was also assessed. First, the TRUE-ESP study included normotensive and hypertensive patients attending specialized consultations at Cardiology, Nephrology, Internal Medicine, Endocrinology and Family Practice. Second, the TRUE-HTA study included hypertensives attending a protocoled Hypertension Unit, with a trained staff. RESULTS: TRUE-ESP study included 300 patients, 76% being hypertensives. A significant difference between office BP and AOBP measurement (SBP/DBP 9.8±11.6/3.4±7.9 mmHg, P<.001) was observed. Percentage of patients gathering WCE criteria was 27.7%. TRUE-HTA study included 101 hypertensive patients. A significant difference between office BP and AOBP measurement (SBP/DBP 5.7±9.3/2.1±5.3 mmHg, P<.001) and activity period-ABPM (SBP/DBP 8.5±6.7/3.5±2.5 mmHg, P<.001) was observed. Percentage of WCE patients was 32.1%. CONCLUSIONS: Use of AOBP devices can contribute to decrease WCE and to improve accuracy of office BP measurement.

Comparison of the MDRD and the CKD-EPI equations to estimate the glomerular filtration rate in the general population.

BACKGROUND AND OBJECTIVE: The Chronic Kidney Disease Epidemiology Collaboration (CDK-EPI) equation has been proposed as a replacement for the Modification of Diet in Renal Disease (MDRD) equation to estimate the glomerular filtration rate, but this equation has not yet been evaluated in the general population. PATIENTS AND METHODS: Cross-sectional analysis of a random sample of 858 participants from the general population aged 50-75 years without known kidney disease. The prevalence of low eGFR (< 60 mL/min/1.73 m(2)) was assessed with the MDRD and the CKD-EPI equations in the overall sample and in normoalbuminuric individuals. RESULTS: With the MDRD equation the median eGFRs (interquartile range) in men/women were 63.3(12.2)/56.7(9.4)mL/min/1.73 m(2), and with the CKD-EPI equation 66.6(14.2)/61.3(11.6) mL/min/1.73 m(2). The prevalence of low eGFR in men/women was 35.2%/68.5% and 25.1%/45.7% with the MDRD and the CKD-EPI equations, respectively. Normoalbuminuric women without risk factors for CKD experienced the most pronounced reduction in the number of cases with low eGFR with the CKD-EPI equation. The prevalence of renal impairment in this subgroup still remained even greater than that in men with diabetes, hypertension, or cardiovascular disease. CONCLUSIONS: Compared with the MDRD, the CKD-EPI equation generates a substantial reduction in the prevalence of renal impairment in subjects with diabetes, hypertension, cardiovascular disease, and in subjects without risk factors. The prevalence of renal impairment in normoalbuminuric females may be still overestimated with the CKD-EPI equation.

Target organ damage and cardiovascular complications in patients with hypertension and type 2 diabetes in Spain: a cross-sectional study.

BACKGROUND: Target organ damage (mainly cardiac and renal damage) is easy to evaluate in outpatient clinics and offers valuable information about patient's cardiovascular risk. The purpose of this study was to evaluate, using simple methods, the prevalence of cardiac and renal damage and its relationship to the presence of established cardiovascular disease (CVD), in patients with hypertension (HT) and type 2 diabetes mellitus (DM). METHODS: The RICARHD study is a multicentre, cross-sectional study made by 293 investigators in Nephrology and Internal Medicine Spanish outpatient clinics, and included patients aged 55 years or more with HT and type 2 DM with more than six months of diagnosis. Demographic, clinical and biochemical data, and CVD were collected from the clinical records. Cardiac damage was defined by the presence of electrocardiographic left ventricular hypertrophy (ECG-LVH), and renal damage by a calculated glomerular filtration rate (GFR) of <60 ml/min/1.73 m2, and/or the presence of an albumin/creatinine ratio > or = 30 mg/g; or an urinary albumin excretion (UAE) > or = 30 mg/24 hours. RESULTS: 2339 patients (mean age 68.9 years, 48.2% females, 51.3% with established CVD) were included. ECG-LVH was present in 22.9% of the sample, GFR <60 ml/min/1.73 m2 in 45.1%, and abnormal UAE in 58.7%. Compared with the reference patients (those without neither cardiac nor renal damage), patients with ECG-LVH alone (OR 2.20, [95%CI 1.43-3.38]), or kidney damage alone (OR 1.41, [1.13-1.75]) showed an increased prevalence of CVD. The presence of both ECG-LVH and renal damage was associated with the higher prevalence (OR 3.12, [2.33-4.19]). After stratifying by gender, this relationship was present for both, men and women. CONCLUSION: In patients with HT and type 2 DM, ECG-LVH or renal damage, evaluated using simple methods, are associated with an increased prevalence of established CVD. The simultaneous presence of both cardiac and renal damage was associated to the higher prevalence of CVD, affording complementary information. A systematic assessment of cardiac and renal damage complements the risk assessment of these patients with HT and type 2 DM.

Doxazosin GITS versus standard doxazosin in mild to moderate hypertension.

BACKGROUND: The selective alpha 1-adrenoceptor antagonist doxazosin in both standard formulation and gastrointestinal therapeutic system (GITS) controlled-release formulation is effective for hypertension without having a negative impact on serum lipids. This study was designed to compare the relative efficacy of these two formulations of doxazosin on clinic and ambulatory blood pressure and serum lipids in patients with mild to moderate hypertension. METHODS: Hypertensive patients aged 18-70 years (n = 335) were evaluated in a multi-center prospective randomized study. Following a 2-week placebo run-in phase, patients were randomized to receive doxazosin 2 or 4 mg, with dose titration, or doxazosin GITS 4 mg, no dose titration, for 9 weeks. RESULTS: Both doxazosin formulations reduced clinic diastolic and systolic blood pressure from baseline (P < 0.0001). Doxazosin GITS and doxazosin 4 mg had similar blood pressure-lowering effects. Doxazosin GITS reduced sitting diastolic and systolic blood pressure compared with doxazosin 2 mg (P < 0.01 for both). A greater proportion of the doxazosin GITS group reached goal blood pressure (< or = 140/90 mm Hg) after 9 weeks compared with the doxazosin 2-mg group. All doses of doxazosin reduced 24-h and daytime (7:00 am to 10:00 pm) ambulatory blood pressure from baseline (all P < 0.01). Doxazosin GITS significantly reduced nighttime (10:00 pm to 7:00 am) ambulatory blood pressure from baseline. A neutral effect on serum lipids was observed with doxazosin. CONCLUSIONS: Doxazosin GITS and doxazosin were effective in reducing clinic and ambulatory blood pressure. The GITS formulation reduced the need for dose titration. Both doxazosin formulations were well tolerated.

[Biomarkers of vascular inflammation and subclinical atherosclerosis in the metabolic syndrome]. / Marcadores biológicos de inflamación vascular y aterosclerosis subclínica en el síndrome metabólico.

BACKGROUND AND OBJECTIVE: The metabolic syndrome (MS) is linked to an increase of cardiovascular mortality and morbidity, the pathological substrate of cardiovascular events being atherosclerosis. Inflammatory phenomena play a role in the genesis of atherosclerosis. The aim of this study was to analyze the vascular (adhesins) and systemic [interleukins, amyloid A serum protein (AAS), C reactive protein (PCR)] inflammation markers as well as hemodynamic parameters and the presence or absence of subclinical atherosclerosis measured by intima-media thickness (TIM) determination in MS. PATIENTS AND METHOD: In this transversal study we enrolled 29 patients (18 men,11 women) with a diagnosis of MS. We assessed interleukins (IL-1beta, IL-6, TNF-alpha, TGF-beta, MCP-1), intercellular and intervascular adhesions molecules (sICAM-1, sVCAM-1), systemic inflammation markers (PCR, AAS), microalbuminuria and, as a lipidic oxidation marker, urinary F2 isoprostanes (F2I). TIM was measured by ultrasounds. Ten healthy people with a similar age were included as a control group. RESULTS: Patients with MS, when compared with the control group, showed higher levels of homocysteine (10 [0.5] vs 7.9 [0.5] micromol/l; p < 0.05), sICAM1 (263 [13] vs 203 [14] ng/ml; p < 0.01), IL-6 (7.1 [0.5] vs 4.6 [0.6] pg/ml; p < 0.05), TGF-beta (34 [1.7] vs 26 [1.4] ng/ml; p < 0.01), PCR (0.69 [0.07] vs 0.23 [0.03] mg/dl; p < 0.001), AAS (9.7 [0.7] vs 6.7 [0.7] microg/ml; p < 0.01), microalbuminuria (32 [13] vs 3.2 [0.14] mg/g creatinine; p < 0.05), and F2I (22.4 [2.5] vs 9.1 [0.69] pg/mg creatinine; p < 0.001). TIM in the MS group was greater than in the control group (1.14 [0.14] vs 0.79 [0.02] mm; p < 0.05). F2I values were directly correlated with TIM, systolic arterial pressure and pulse pressure. CONCLUSIONS: Our results show that in MS there is an increase of vascular inflammation and lipooxidation markers and a higher prevalence of subclinical atherosclerosis.

Comparison of the blood pressure-lowering effects and tolerability of Losartan- and Amlodipine-based regimens in patients with isolated systolic hypertension.

BACKGROUND: Elevated systolic blood pressure is a more important risk factor for cardiovascular and renal disease than elevated diastolic blood pressure. Isolated systolic hypertension (ISH) is the predominant form of hypertension in the elderly. Effects of angiotensin II on the vascular wall and endothelium may contribute to development of ISH. OBJECTIVE: The primary objective of this study was to compare the effects on trough sitting systolic blood pressure (SiSBP) of a regimen of losartan, a selective angiotensin II-receptor antagonist, and an amlodipine-based regimen in patients with ISH. METHODS: This multicenter, prospective, randomized, double-blind, parallel-group study consisted of a 4-week placebo phase and an 18-week active-treatment phase. The losartan-based regimen consisted of losartan 50 mg, increased as needed to losartan 50 mg/hydrochlorothiazide (HCTZ) 12.5 mg at week 6 and to losartan 100 mg/HCTZ 25 mg at week 12 to achieve a target SiSBP <140 mm Hg. the amlodipine-based regimen consisted of amlodipine 5 mg, increased as needed to amlodipine 10 mg at week 6 and to amlodipine 10 mg/HCTZ 25 mg at week 12. The primary efficacy measure was change in trough SiSBP from baseline to week 18. Information on the tolerability of study treatments was collected at each visit, including the investigator's and patient's observations of clinical adverse experiences (CAEs), laboratory adverse experiences, and responses to a symptom questionnaire. RESULTS: Eight hundred fifty-seven patients (65.6% female) were randomized to treatment, 432 in the losartan group and 425 in the amlodipine group. Their mean age was 67.6 years, and they had a mean duration of hypertension of 6.7 years at baseline. The losartan and amlodipine groups (intent-to-treat population) had baseline mean SiSBP values of 171.2 and 171.9 mm Hg, respectively. At week 18 (the primary end point), the mean change from baseline in SiSBP was -27.4 mm Hg for 426 patients who received losartan and -28.1 mm Hg for 419 patients who received amlodipine (estimated least-square mean difference, 0.3 mm Hg; 95% CI, -1.4 to 2.0), indicating that losartan's effect on systolic blood pressure was noninferior to that of amlodipine. The proportion of patients who responded (SiSBP <140 mm Hg or a > or =20-mm Hg decrease in SiSBP from baseline) was comparable between groups (73.9% losartan, 75.4% amlodipine). The incidence of CAEs and drug-related CAEs was significantly greater in the amlodipine group (amlodipine, 79.8% and 43.8%, respectively; losartan, 67.8% and 25.5%; P < or = 0.001). In addition, more patients in the amlodipine group discontinued therapy due to a drug-related CAE compared with patients in the losartan group (12.9% vs 4.4%, respectively; P < or = 0.001). Lower-extremity edema was the most common drug-related CAE in the amlodipine group (24.0% amlodipine, 2.5% losartan; P < or = 0.001); dizziness was the most common drug-related CAE in the losartan group (6.0% losartan, 4.0% amlodipine). CONCLUSIONS: In these patients with ISH, losartan and amlodipine produced comparable clinically relevant reductions in SiSBP; however, losartan was better tolerated, as evidenced by fewer CAEs and discontinuations compared with amlodipine. Losartan may be considered for the initial treatment of ISH.