Papers by Dulcenombre Gómez-garre
European Journal of Pharmacology, Dec 1, 1992
The mechanisms by which cndolhclin-I (ET-l) acts on polymorphonuclcar Isukocytcs (PMN) arc insuff... more The mechanisms by which cndolhclin-I (ET-l) acts on polymorphonuclcar Isukocytcs (PMN) arc insufficiently known. In this study. WC asscsscd the hypothcscs that ET-l is a PMN-aggregating agent, and that platelet-activating factor (PAF) is the principal mediator of ET-l-induced PMN aggregation. ET-I induced doserclatcd PMN aggregation. which started I min after ET-l exposure. Two diffcrcnt specific PAF rct'cptor antagonists blocked the cffcct of ET-I on PMN aggregation. In addition, FT.1 ifl&cpd I! qjyifirant inrresr in !hc prrr&~!+ nf Ph.!: + PMN nftrr 2 !n 5 mip-f FT-! inr!~h+ir>n FT-1 ;-A.-A ?4F .::ciii Li rclcasc from PMN rather than accumulation. This PAF prodiction was dcpcndcnt on intra-and cxtraccllular Ca'*. In this regard, the PAF rcccptor xntsgonists significantly blunted the ET-I-induced peak in cytosolic free Ca' ' ([Cn" Ii). Our results. thcrcforc, indicate that ET-I is cffcctivc in causing aggregation of human PMN and that its action appears tcr hc mediated by PAF production via a Ca"+=dcpcndcnt mechanism.
PubMed, Feb 1, 1994
In recent years increasing evidence has been accumulated on the role of cytokines in mediating gl... more In recent years increasing evidence has been accumulated on the role of cytokines in mediating glomerular and renal damage. Many such cytokines are released in the inflamed glomeruli by leukocytes and intrinsic glomerular cells. Cytokines not only recruit inflammatory cells into the injured glomeruli, but also induce a variety of responses on glomerular cells that range from a direct toxic effect to shape changes, proliferation, and induction of the release of inflammatory mediators and extracellular matrix, and could promote further glomerular damage. Moreover, exogenous administration of cytokines has induced glomerular injury in healthy animals and has enhanced renal damage in animals with glomerulonephritis. Anti-cytokine strategies have proved to be effective therapeutical alternatives in experimental models of glomerular diseases and may provide a more specific approach to the management of human glomerulonephritis.
PubMed, Apr 1, 1990
Platelet-activating factor (PAF-acether) has been shown to be produced by the kidney and to sharp... more Platelet-activating factor (PAF-acether) has been shown to be produced by the kidney and to sharply reduce glomerular filtration rate (GFR) and renal plasma flow (RPF). Thus, PAF-acether could be a possible mediator of the reduction of GFR and RPF in ischemic-induced acute renal failure (ARF). We have assayed the effect of inhibiting the interaction of PAF-acether with its receptor using two specific PAF-acether antagonists, BN-52021 and alprazolam, on the evolution of the GFR and RPF, in the experimental model of ARF induced in rats by clamping the left artery for 60 min. In addition, we have measured arteriovenous differences in PAF-acether concentration, as well as PAF-acether content in glomeruli from rats with ARF pretreated or not with BN-52021. In metabolic cage studies, plasma creatinine increased more in the untreated than in the BN-52021-treated group, whereas creatinine clearance was higher in treated than in untreated rats. In acute clearance experiments, after renal artery clamping, untreated rats showed a marked oliguria and reduction of the inulin clearance (greater than 99%), which showed no recovery 90 min after clamp release, whereas GFR reached values above 0.1 ml/min in the rats treated with BN-52021 or alprazolam, with clearly significant statistical differences. Results of p-aminohippurate clearance were similar to those of GFR. Glomeruli from rats with ARF had greater amounts of PAF-acether than glomeruli from normal rats, whereas glomeruli from BN-52021-treated rats with ARF produced intermediate amounts. These results provide evidence for a role for PAF-acether in the genesis of this model of experimental ARF.
PubMed, 1993
1. Kidney Int Suppl. 1993 Jan;39:S59-64. Role of tumor necrosis factor-alpha in the pathogenesis ... more 1. Kidney Int Suppl. 1993 Jan;39:S59-64. Role of tumor necrosis factor-alpha in the pathogenesis of glomerular diseases. Egido J, Gómez-Chiarri M, Ortíz A, Bustos C, Alonso J, Gómez-Guerrero C, Gómez-Garre D, López-Armada ...
Kidney International, Apr 1, 1991
Renal effects and mesangial cell contraction induced by endothelin are mediated by PAF. The recen... more Renal effects and mesangial cell contraction induced by endothelin are mediated by PAF. The recently discovered vasoactive peptide endotheun and platelet activating factor (PAF) share similar renal effects. The purpose of the present series of experiments has been to analyze the functional relations between the effect of endothelin on renal function and glomerular and mesangial cell contraction and the production and actions of PAF in kidney. Endothelin I nmol/kg body wt induced a transient decrease of glomerular filtration rate (from 1.99 0. 17 to 0.56 0.18 mI/mm) and renal blood flow (from 10.8 1.3 to 2.7 0.3 mi/mm). Endothelin also induced a marked reduction of planar cell surface area of cultured mesangial cells (30 5%) and of cross sectional area of isolated glomeruli (from 1.51 0.02 to 1.31 0.02 m2 x l08). BN-52021 or WEB-2 170, two potent specific inhibitors of PAF receptor binding, blocked the effects of endothelin on renal function and on the contraction of isolated glomeruli and mesangial cells. In addition, endothelin induced a significant increase in the production of PAF by isolated glomeruli (Basal, 81 10 pg/mg protein; endothelin, l0 M, 140 18 pg/mg protein). Endothelin also stimulated the incorporation of [3H]acetate into PAF, both in glomeruli (264.27 27.7%) and mesangial cells (251 4 1%). These effects were blocked by EGTA and by verapamil. Our results suggest that PAF may be a mediator of the effects of endothelin on renal function and glomerular and mesangial cell contraction. The potent vasoconstrictor peptide, endothelin, has been isolated and purified from the supernatant of cultured porcine aortic endothelial cells [11. On the other hand, platelet activating factor (PAF) is a phospholipid with a wide range of biological activities [2, 31. Both endothelin and PAF share some physiological properties: a) both decrease glomerular filtration rate (GFR) and renal blood flow (RBF) when infused into the kidney [4-71. b) Both increase packed cell volume when injected intravenously, by increasing vascular permeability [2, 4, 8]. c) Both are released during ischemia [1, 91. d) Both induce glomerular and mesangial cell contraction [10-121. e) Both increase intracellular calcium in mesangial cells [13, 14]. The purpose of the present study was to analyze whether a functional relationship exists between the effects of endothelin on renal function and glomerular and mesangial cell contraction and the production of PAF by the kidney.
Hypertension, Apr 1, 2001
The mechanisms by which persistent proteinuria induces interstitial inflammation and fibrosis are... more The mechanisms by which persistent proteinuria induces interstitial inflammation and fibrosis are not well known, although nuclear factor-B (NF-B), which regulates the transcription of many genes involved in renal injury, could be implicated. In rats with intense proteinuria, we studied the renal activation of NF-B as well as the potential involvement of the vasoactive hormones angiotensin II (Ang II) and endothelin-1 (ET-1). Uninephrectomized Wistar-Kyoto rats receiving 1 g/d of BSA had proteinuria but no renal morphological lesions at day 1. By contrast, tubular atrophy and/or dilation and mononuclear cell infiltration were observed after 8 or 28 days of BSA administration, coinciding with maximal proteinuria. In relation to control uninephrectomized rats, the renal cortex of nephritic rats showed an increment in the activation of NF-B at all time periods studied. By in situ Southwestern histochemistry, NF-B activity was mainly localized in proximal tubules, interstitial mononuclear cells, and, to a lesser extent, the glomeruli. The administration of the ACE inhibitor quinapril plus the ET A /ET B receptor antagonist bosentan during 28 days to BSA-overloaded animals diminished proteinuria, renal lesions, and NF-B activity more markedly than single drugs. Cultured tubular epithelial cells exposed to BSA revealed an intense NF-B activation in a time-and dose-dependent manner. Incubation of cells with receptor antagonists of Ang II (AT 1 : losartan and AT 2 : PD-123,319) or ET-1 (ET A : BQ123 and ET B : IRL1038) inhibited significantly the BSA-induced NF-B activity (90%, 75%, 90%, and 60% of inhibition versus basal, respectively). Our results show that overload proteinuria causes NF-B activation in tubular epithelial cells both in vivo and in vitro. The vasoactive peptides Ang II and ET-1 appear to be implicated in this effect. The results reveal a novel mechanism of perpetuation of renal damage induced by persistent proteinuria.
Contributions To Nephrology, Apr 20, 2015
... by grants from Fondo de Investigaciones Sanitarias (FIS, 91/162, 94/370), Ministerio de Educa... more ... by grants from Fondo de Investigaciones Sanitarias (FIS, 91/162, 94/370), Ministerio de Education y Ciencia (PM 89/65; 92/42), Fundacion Conchita Rabago and ... 11 Mathews N. Neale ML: Cytotoxicity assays for tumor necrosis factor and lymphotoxin: in Clemens MJ, Moris AG. ...
Journal of The American Society of Nephrology, May 1, 1997
Angiotensin-converting enzyme (ACE) inhibitors diminish proteinuria and the progression to renal ... more Angiotensin-converting enzyme (ACE) inhibitors diminish proteinuria and the progression to renal failure in several experimental models of renal injury. Endothelin-1 (ET-1) possesses potent biological actions on renal vessels and has been considered as a potential mediator of renal damage. Because angiotensin II (Ang II) induces ET-1 synthesis in endothelial and mesangial cells, we hypothesized that some of the beneficial effects of the ACE inhibitors could result from the blockade of ET-1 synthesis. In a normotensive model of immune-complex nephritis, in which there exists an increase in renal ACE activity, the effect of the ACE inhibitor quinapril on preproET-1 and ETA receptor mRNA expression, as well as on ET-1 protein levels, was examined in this study. In relation to controls, nephritic rats showed an increase in preproET-1 and ETA receptor gene expression in renal cortex and medulla, coinciding with the maximal renal ACE activity. PreproET-1 mRNA (in situ hybridization) and ET-1 protein (immunohistochemistry) were localized in glomerular capillary walls, mesangial and glomerular epithelial cells, as well as in the brush border of some proximal tubules, and in small vessels. In nephritic rats, there was an increase in preproET-1 mRNA levels and ET-1 protein in all of these areas, without modification of their distribution. The administration of the ACE inhibitor quinapril decreased proteinuria and morphological lesions, preproET-1 gene transcription, and ET-1 protein levels, as well as the ETA receptor mRNA. The results from this study show that in a normotensive model of immune-complex nephritis, there was an overexpression of ET-1 in several structures of the kidney that was downregulated by quinapril administration. The beneficial effect of ACE inhibitors could be a result of the modulation of local production of Ang II and ET-1.
Kidney International, Apr 1, 2006
Although structural and functional changes of resistance arteries have been proposed to participa... more Although structural and functional changes of resistance arteries have been proposed to participate in arterial hypertension (HTA) outcome, not all therapies may correct these alterations, even if they normalize the blood pressure (BP). The aim of this study was to investigate the mechanisms of the protection afforded by the angiotensin receptor antagonist losartan in resistance arteries from patients with essential HTA. In all, 22 untreated hypertensive patients were randomized to receive losartan or amlodipine for 1 year and the morphological characteristics of resistance vessels from subcutaneous biopsies were evaluated. Protein expression of connective tissue growth factor (CTGF), transforming growth factor b (TGF-b), and collagens III and IV was detected by immunohistochemistry. In comparison with normotensive subjects, resistance arteries from hypertensive patients showed a significant media:lumen (M/L) ratio increment and a higher protein expression of CTGF, TGF-b, and collagens. After 1 year of treatment, both losartan and amlodipine similarly controlled BP. However, M/L only decreased in patients under losartan treatment, whereas in the amlodipine-treated group this ratio continued to increase significantly. The administration of losartan prevented significant increments in CTGF, TGF-b, and collagens in resistance arteries. By contrast, amlodipine-treated patients showed a higher vascular CTGF, TGF-b, and collagen IV staining than before treatment. Our results show that the administration of losartan, but not amlodipine, to hypertensive patients improves structural abnormalities and prevents the production of CTGF and TGF-b in small arteries, despite similar BP lowering. These data may explain the molecular mechanisms of the better vascular protection afforded by drugs interfering with the renin-angiotensin system.
Atherosclerosis Supplements, Apr 1, 2004
In 134 type 2 diabetic patients (61 males, 73 females, mean age 61-4-9.8 yrs, mean diabetes durat... more In 134 type 2 diabetic patients (61 males, 73 females, mean age 61-4-9.8 yrs, mean diabetes duration, DD, 12.5-4-10.2 yrs) were checked: blood pressure (BP), smoking, BMI, total-, HDL-, LDL cholesterol; Lp (a), A1 and B apolipoproteins, plasma uric acid, fibrinogen, CRP, tHcy, urinary-AER, fasting glucose, HbAlc, mean pie-and post-prandial glycemic sticks (MPPsticks), GFR together with letinopathy and neuropathy. Cat'otid vessel B-mode ultrasonography, aortic and peripheral vessel xray to seat'ch calcific plaques were performed. IMT was taken on-line bilaterally on fi'ozen images of the distal common carotid posterior wall; right + left measurements were averaged to give mean-IMT. Twenty healthy sex-age-matched controls were studied. In diabetics, the mean IMT was 0.926-4-0.231 ram, in controls 0.552-4-0.021 ram. IMT con'elated with age, smoking, BP, lipids and macrovascular complications, not with metabolic control or microvasculat" involvement. An internal SCOle including mean-IMT, presence or not of ultrasonographic cat'otid plaques, aortic and/or peripheral vessel calcific plaques significantly COla'elated with HbAlc, MPPsticks, DD, retinopathy, neuropathy, not with lipids. Conclusions: in type 2 diabetics mean-IMT is higher than in controls and significantly related to cat'diovasculat" risk factors. While metabolic control and diabetes duration are closely COla'elated with generalized atherosclerosis, they don't seem influence IMT which appeat's a more localized and/or eat'ly ATS index.
Hypertension, Apr 1, 1996
Mesangial cell growth and accumulation of extracellular matrix proteins constitute key features o... more Mesangial cell growth and accumulation of extracellular matrix proteins constitute key features of progressive glomerular injury. Endothelin-1 (ET-1) and angiotensin II (Ang II), two potent vasoconstrictor agents, evoke a number of similar responses in mesangial cells. In rat mesangial cells, we compared ET-1 and Ang II effects on matrix protein production and cell proliferation as well as the potential interaction between the two hormones. When cells in 0.5% fetal calf serum were incubated for 24 hours with various concentrations of ET-1 or Ang II, both peptides stimulated, in a dose-dependent manner, fibronectin and type IV collagen mRNA expression, fibronectin synthesis, and mitogenesis. Incubation with specific receptor antagonists of both hormones demonstrated that endothelin subtype A (ETA) and angiotensin type 1 (AT1) receptors were involved. Preincubation of cells with two different protein kinase C inhibitors or with a neutralizing anti–transforming growth factor-β antibody, but not an unrelated IgG, diminished the peptide-induced fibronectin synthesis. A dual interrelation seems to exist between ET-1 and Ang II. Thus, the AT1receptor antagonist losartan and the angiotensin-converting enzyme inhibitors quinaprilat and captopril diminished the ET-1–mediated effects, whereas the ETAreceptor antagonist BQ-123 diminished the Ang II–induced fibronectin synthesis and mesangial cell proliferation. Our results suggest that ET-1 and Ang II stimulate matrix protein synthesis and mesangial cell mitogenesis through ETAand AT1receptors, respectively, by complicated mechanisms, implicating protein kinase C activation, synthesis of transforming growth factor-β, and release of one peptide by the other. These data could be important for a better understanding of the participation of vasoactive substances in the pathogenesis of glomerulosclerosis.
Journal of nephrology
Even with optimal blood pressure control, organ protection may also depend on the selected therap... more Even with optimal blood pressure control, organ protection may also depend on the selected therapeutic regime. Angiotensin-converting enzyme inhibitors have been shown to provide excellent organ protection in hypertension, and may show dose-dependent protective effects. Adrenergic alpha blockers have been associated with an increased rate of heart failure in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) and Vasodilator-Heart Failure Trial (V-HeFT). This has been related to a proapoptotic effect of this drug in cardiomyocytes. Our purpose is to compare the heart and renal protection of a high quinapril dose, with a combined low quinapril dose plus doxazosin, in an animal model of chronic hypertension. Uninephrectomized spontaneously hypertensive 12-week-old rats were treated for 36 weeks with either quinapril or a combination of doxazosin plus a low quinapril dose. Tight blood pressure control was achieved with both treatments. Renal and car...
British Journal of Pharmacology, Apr 6, 2009
Background and purpose: Ezetimibe, a selective inhibitor of intestinal cholesterol absorption, mi... more Background and purpose: Ezetimibe, a selective inhibitor of intestinal cholesterol absorption, might also suppress inflammatory components of atherogenesis. We have studied the effects of ezetimibe on two characteristics of atherosclerotic plaques (infiltrate and fibrosis) and on expression of inflammatory genes in a rabbit model of accelerated atherosclerosis. Experimental approach: Femoral atherosclerosis was induced by a combination of endothelial desiccation and atherogenic diet. Animals were randomized to ezetimibe (0.6 mg•kg-1 •day-1), simvastatin (5 mg•kg-1 •day-1), ezetimibe plus simvastatin or no treatment, still on atherogenic diet. A control group of rabbits received normolipidemic diet. Key results: Rabbits fed the normolipidemic diet showed normal plasma lipid levels. Either the normolipidemic diet or drug treatment reduced the intima/media ratio (normolipidemic diet: 22%, ezetimibe: 13%, simvastatin: 27%, ezetimibe + simvastatin: 28%), compared with rabbits with atherosclerosis. Ezetimibe also decreased macrophage content and monocyte chemoattractant protein-1 expression in atherosclerotic lesions. Furthermore, ezetimibe reduced the increased activity of nuclear factor kB in peripheral blood leucocytes and plasma C-reactive protein levels in rabbits with atherosclerosis. In THP-1 cells, ezetimibe decreased monocyte chemoattractant protein-1-induced monocyte migration. Importantly, the combination of ezetimibe with simvastatin was associated with a more significant reduction in plaque monocyte/macrophage content and some proinflammatory markers than observed with each drug alone. Conclusions and implications: Ezetimibe had beneficial effects both on atherosclerosis progression and plaque stabilization and showed additional anti-atherogenic benefits when combined with simvastatin. Its effect on monocyte migration provides a potentially beneficial action, in addition to its effects on lipids.
Heart Rhythm, May 1, 2022
Atherosclerosis Supplements, Jun 1, 2011
Atherosclerosis Supplements 12, no. 1 (2011) 13-184 Poster presentations aortas of both studied m... more Atherosclerosis Supplements 12, no. 1 (2011) 13-184 Poster presentations aortas of both studied mouse strains, suggesting that these pathways are not related to distinct predisposition to atherosclerosis.
European Journal of Heart Failure, Feb 20, 2006
Peroxisome proliferator-activated receptors (PPARs), key transcriptional regulators of lipid and ... more Peroxisome proliferator-activated receptors (PPARs), key transcriptional regulators of lipid and energy metabolism in cardiomyocytes, have recently been proposed to modulate cardiovascular pathophysiological responses in experimental models. However, there is little information about the functional activity of PPARs in human heart failure. To investigate PPAR-alpha and -gamma expression and activity, and the association with ET-1 production and fibrosis, in cardiac biopsies from patients with end-stage heart failure due to ischemic cardiomyopathy (ICM) in comparison and from non-failing donor hearts. All samples were obtained during cardiac transplantation. Morphological analysis (by Masson trichrome and image analysis) did not detect fibrosis in the left atrium from non-failing donors (NFLA) or from ICM patients (FLA). However, left ventricles from failing hearts (FLV) contained a greater number of fibrotic areas (NFLA: 3.21+/-1.15, FLA: 1.63+/-0.83, FLV: 14.5+/-3.45%; n = 9, P<0.05). By RT-PCR, preproET-1 expression was similar in the non-failing and failing atrium but was significantly higher in the ventricles from failing hearts (NFLA: 1.00+/-0.06, FLA: 1.08+/-0.11, FLV: 1.74+/-0.19; n = 9, P<0.05). PPAR-alpha and PPAP-gamma mRNA (by RT-PCR) and protein (by Western blot) levels were higher in the ventricles from failing hearts compared with the atrium from failing and non-failing hearts. Electrophoretic mobility shift assays showed that PPAR-alpha and PPAP-gamma were not activated in the ventricles (NFLA: 1.00+/-0.11, FLA: 1.89+/-0.24, FLV: 0.95+/-0.07; n = 9, P<0.05). These data suggest that PPAR-alpha and PPAP-gamma are selectively activated in the atria from ICM patients and might be functionally important in the maintenance of atrial morphology.
Antioxidants, Jul 21, 2020
Background: The objective of this study is to determine the role of mitochondrial oxidative stres... more Background: The objective of this study is to determine the role of mitochondrial oxidative stress in the dysbiosis associated with a high fat diet in rats. In addition, the impact of gut microbiota (GM) in the cardiometabolic consequences of diet-induced obesity in rats has been evaluated. Methods: Male Wistar rats were fed either a high fat diet (HFD) or a control (CT) one for 6 weeks. At the third week, one-half of the animals of each group were treated with the mitochondrial antioxidant MitoTempo (MT; 0.7 mgKg −1 day −1 i.p). Results: Animals fed an HFD showed a lower microbiota evenness and diversity in comparison to CT rats. This dysbiosis is characterized by a decrease in Firmicutes/Bacteroidetes ratio and relevant changes at family and genera compared with the CT group. This was accompanied by a reduction in colonic mucin-secreting goblet cells. These changes were reversed by MT treatment. The abundance of certain genera could also be relevant in the metabolic consequences of obesity, as well as in the occurrence of cardiac fibrosis associated with obesity. Conclusions: These results support an interaction between GM and mitochondrial oxidative stress and its relation with development of cardiac fibrosis, suggesting new approaches in the management of obesity-related cardiometabolic consequences.
Clínica e Investigación en Arteriosclerosis, Jul 1, 2011
Ezetimibe suppresses adhesion and chemotaxis of human monocytes through the p44/p42 ERK1/2-depend... more Ezetimibe suppresses adhesion and chemotaxis of human monocytes through the p44/p42 ERK1/2-dependent pathway Abstract Introduction: Recently, our group has demonstrated that ezetimibe, a specific inhibitor of intestinal absorption, is able to inhibit vascular inflammation in a rabbit model of atherosclerosis. In this study, we investigated the effect of ezetimibe on the adhesion and migration of human THP-1 monocytes in vitro. We also studied the involvement of the MAP kinase signalling pathway, p44/p42 ERK1/2 , as a potential mechanism responsible for the observed effect. Material and methods: Adhesion of THP-1 monocytes was measured as the ability of cells to bind to plates. Migration was studied using two-compartment chambers. The expression of adhesion molecules was assessed by flow cytometry. Activation of p44/p42 ERK1/2 was measured by Western Blot. Results: Preincubation of THP-1 monocytes with ezetimibe prevented PMA-induced adhesion and MCP-1-induced migration in a dose-dependent manner. Preincubation of THP-1 monocytes with ezetimibe also inhibited the expression of the integrins CD11a and CD11b, as well as phosphorylation of p-p44/p42 ERK1/2 (the active form) induced by MCP-1. More than 90% of cells (evaluated through trypan blue) were viable 1 or 2 days after exposure to ezetimibe. Conclusions: Our results indicate that, in addition to its lipid lowering activity, ezetimibe is able to inhibit the process of adhesion and migration of monocytes in vitro. Blocking of the p44/p42 ERK1/2 MAPK signalling pathway seems to play a role in this anti-inflammatory effect.
Journal of Acquired Immune Deficiency Syndromes, Feb 1, 2012
HIV-infected patients present increased incidence of cardiovascular disease (CVD). Although incip... more HIV-infected patients present increased incidence of cardiovascular disease (CVD). Although incipient kidney function impairment has been associated with CVD in the general population, this association has not been properly addressed in HIV-infected patients. We assessed the relationship between incipient renal impairment (IRI) and subclinical atherosclerosis in HIV-infected patients. Estimated glomerular filtration rate (eGFR), carotid intima-media thickness (cIMT), and cardiovascular biomarkers were measured in 145 HIV-infected patients. IRI was defined as a composite variable: eGFR <90 mL/min, rate of eGFR decrease >3% annually over a period of 3 years, and albumin/creatinine urine ratio above the median (≥5 mg/g). Individuals with a cIMT ≥75th percentile or plaque were classified as having subclinical atherosclerosis. Ninety-five patients (64.1%) met the criteria for IRI. As for HIV-related factors, patients with IRI more frequently had lipodystrophy (41.3% vs. 21.6%; P = 0.017), a lower CD4 lymphocyte nadir [210 (125-343) vs. 302 (178-408) cells/mL; P = 0.046], and longer exposure to nucleoside reverse transcriptase inhibitors [187 (84-259) vs. 104 (34-170) months; P = 0.001], to nonnucleoside reverse transcriptase inhibitors [32 (7-77) vs. 20 0-40) months; P = 0.043], and to protease inhibitors [42 (0-115] vs. 2.5 (0-59) months; P = 0.007]. Patients with IRI more frequently had subclinical atherosclerosis (40.7% vs. 13.7%; odds ratio: 4.3; 95% confidence interval: 1.8 to 10.6; P = 0.001), even after adjustment for cardiovascular and HIV-related parameters (odds ratio: 3.8; 95% confidence interval: 1.3 to 11; P = 0.012). The presence of IRI is an independent predictor of increased cIMT in HIV-infected patients and may help to identify patients with subclinical atherosclerosis and, therefore, increased risk of CVD.
European Journal of Preventive Cardiology, Jun 20, 2012
While the detection of subclinical atherosclerosis may provide an opportunity for the prevention ... more While the detection of subclinical atherosclerosis may provide an opportunity for the prevention of cardiovascular disease (CVD), which currently is a leading cause of death in HIV-infected subjects, its diagnosis is a clinical challenge. We aimed to compare the agreement and diagnostic performance of Framingham, SCORE and D:A:D equations for the recognition of subclinical atherosclerosis in HIV patients and to adjust the D:A:D equation using HIV and CVD variables. Atherosclerosis was evaluated in 203 HIV-infected individuals by measuring the carotid intima-media thickness (IMT). The CVD risk was calculated using the Framingham, SCORE and D:A:D risk equations. Framingham, SCORE and D:A:D equations showed a low agreement with the IMT (Kappa: 0.219, 0.298, 0.244, respectively; p = 0.743) and a moderate predictive performance, (area under the curve [AUC] = 0.686, 0.665 and 0.716, respectively; p = 0.048), with the D:A:D equation being the most accurate. Atherosclerosis was demonstrated in a significant proportion of subjects with low predicted CVD risk by all three algorithms (16.3%, 17.2%, 17.2%, respectively; p = 0.743). In patients with an estimated low CVD risk atherosclerosis was associated with older age (p = 0.012) and low CD4 counts (p = 0.021). A model was developed to adjust the D:A:D equation; a significant increase in accuracy was obtained when CD4 counts and low-grade albuminuria were included (AUC = 0.772; p < 0.001). The D:A:D equation overperforms Framingham and SCORE in HIV patients. However, all three equations underestimate the presence of subclinical atherosclerosis in this population. The accuracy of the D:A:D equation improves when CD4 counts and low-grade albuminuria are incorporated into the equation.
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Papers by Dulcenombre Gómez-garre