RESUMEN
BACKGROUND AND AIMS: The independent role of serum uric acid (SUA) as a marker of cardio-renal risk is debated. The aim of this study was to assess the relationship between SUA, metabolic syndrome (MS), and other cardiovascular (CV) risk factors in an Italian population of hypertensive patients with a high prevalence of diabetes. METHODS AND RESULTS: A total of 2429 patients (mean age 62 ± 11 years) among those enrolled in the I-DEMAND study were stratified on the basis of SUA gender specific quartiles. MS was defined according to the NCEP-ATP III criteria, chronic kidney disease (CKD) as an estimated GFR (CKD-Epi) <60 ml/min/1.73 m(2) or as the presence of microalbuminuria (albumin-to-creatinine ratio ≥2.5 mg/mmol in men and ≥3.5 mg/mmol in women). The prevalence of MS, CKD, and positive history for CV events was 72%, 43%, and 20%, respectively. SUA levels correlated with the presence of MS, its components, signs of renal damage and worse CV risk profile. Multivariate logistic regression analysis revealed that SUA was associated with a positive history of CV events and high Framingham risk score even after adjusting for MS and its components (OR 1.10, 95% CI 1.03-1.18; P = 0.0060; OR 1.28, 95% CI 1.15-1.42; P < 0.0001). These associations were stronger in patients without diabetes and with normal renal function. CONCLUSIONS: Mild hyperuricemia is a strong, independent marker of MS and high cardio-renal risk profile in hypertensive patients under specialist care. Intervention trials are needed to investigate whether the reduction of SUA levels favorably impacts outcome in patients at high CV risk.
Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Hipertensión/epidemiología , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/epidemiología , Ácido Úrico/sangre , Anciano , Albuminuria/sangre , Albuminuria/epidemiología , Biomarcadores/sangre , Índice de Masa Corporal , Enfermedades Cardiovasculares/sangre , Estudios de Cohortes , Estudios Transversales , Femenino , Tasa de Filtración Glomerular , Humanos , Hipertensión/sangre , Hiperuricemia/sangre , Hiperuricemia/epidemiología , Italia , Modelos Logísticos , Masculino , Síndrome Metabólico/sangre , Persona de Mediana Edad , Análisis Multivariante , Prevalencia , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/epidemiología , Factores de RiesgoRESUMEN
A number of epidemiological studies have reported an association between serum uric acid levels and a wide variety of high-risk conditions including hypertension, insulin resistance, and kidney and cerebro-cardiovascular disease. All things considered, serum uric acid may induce cardiovascular and kidney events both directly and indirectly by promoting other well-known mechanisms of damage. While asymptomatic hyperuricemia is currently not considered to be an indication for urate lowering therapy, there is growing evidence indicating a linear relationship between pharmacological reduction in serum uric acid and incidence of cardiovascular and renal events.
Asunto(s)
Enfermedades Cardiovasculares/sangre , Gota/sangre , Hiperuricemia/sangre , Enfermedades Renales/sangre , Ácido Úrico/sangre , Biomarcadores/sangre , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/epidemiología , Complicaciones de la Diabetes/sangre , Progresión de la Enfermedad , Medicina Basada en la Evidencia , Salud Global , Gota/complicaciones , Gota/epidemiología , Supresores de la Gota/uso terapéutico , Humanos , Hipertensión/complicaciones , Hiperuricemia/complicaciones , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/epidemiología , Resistencia a la Insulina , Enfermedades Renales/complicaciones , Enfermedades Renales/epidemiología , Metaanálisis como Asunto , Síndrome Metabólico/sangre , Enfermedades del Sistema Nervioso/sangre , Pronóstico , Medición de Riesgo , Factores de RiesgoRESUMEN
OBJECTIVE: To develop and validate a model for predicting 5-year eGFR-loss in type 2 diabetes mellitus (T2DM) patients with preserved renal function at baseline. RESEARCH DESIGN AND METHODS: A cohort of 504.532 T2DM outpatients participating to the Medical Associations of Diabetologists (AMD) Annals Initiative was splitted into the Learning and Validation cohorts, in which the predictive model was respectively developed and validated. A multivariate Cox proportional hazard regression model including all baseline characteristics was performed to identify predictors of eGFR-loss. A weight derived from regression coefficients was assigned to each variable and the overall sum of weights determined the 0 to 8-risk score. RESULTS: A set of demographic, clinical and laboratory parameters entered the final model. The eGFR-loss score showed a good performance in the Validation cohort. Increasing score values progressively identified a higher risk of GFR loss: a score ≥ 8 was associated with a HR of 13.48 (12.96-14.01) in the Learning and a HR of 13.45 (12.93-13.99) in the Validation cohort. The 5 years-probability of developing the study outcome was 55.9% higher in subjects with a score ≥ 8. CONCLUSIONS: In the large AMD Annals Initiative cohort, we developed and validated an eGFR-loss prediction model to identify T2DM patients at risk of developing clinically meaningful renal complications within a 5-years time frame.
Asunto(s)
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Tasa de Filtración Glomerular , Riñón , Factores de Riesgo , Estudios de CohortesRESUMEN
BACKGROUND: The development of sub-clinical organ damage precedes and predicts the occurrence of cardiovascular (CV) events in hypertensive as well as in obese patients. AIM AND METHODS: We investigated the prevalence and clinical correlates of organ damage (OD), namely carotid atherosclerosis (US scan) and urine albumin to creatinine ratio (three non-consecutive first morning samples) in a group of 164 obese patients and in an age- and gender-matched group of non-obese hypertensive patients. RESULTS: There was a significantly greater prevalence and severity of OD in obese patients as compared to non-obese hypertensive patients. In particular obese patients more frequently had microalbuminuria (16 vs 7%, χ(2) 5.8, P=0.0157) and carotid abnormalities (53 vs 10%, χ(2) 69.5, P<0.0001) as well as higher urinary albumin excretion rate (-0.05 ± 0.52 vs -0.28 ± 0.43log ACR, P<0.0001) and carotid intima-media thickness (0.955 ± 0.224 vs 0.681 ± 0.171, <0.0001). Notably, the coexistence of hypertension and obesity did not entail a greater prevalence and severity of OD. Moreover, after adjusting for potentially confounding factors including blood pressure levels, diagnosis of diabetes, and lipid profile, morbidly obese patients showed a 5-fold, and 22-fold higher risk of having microalbuminuria, and carotid atherosclerosis, respectively. CONCLUSIONS: Sub-clinical OD is highly prevalent in obese patients, even in the absence of high blood pressure. Hypertension and obesity seem to exert an independent, possibly non-additive role on the occurrence of organ damage.
Asunto(s)
Albuminuria/fisiopatología , Hipertensión/epidemiología , Obesidad Mórbida/epidemiología , Obesidad Mórbida/fisiopatología , Adulto , Albuminuria/complicaciones , Presión Sanguínea , Grosor Intima-Media Carotídeo , Creatinina/sangre , Estudios Transversales , Diabetes Mellitus , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/fisiopatología , Lípidos/sangre , Modelos Logísticos , Masculino , Persona de Mediana Edad , Obesidad Mórbida/complicaciones , Prevalencia , Factores de Riesgo , Población BlancaRESUMEN
Tacrolimus is a cornerstone in the immunosuppressive therapy of kidney transplantation. The once-daily formulation of tacrolimus has been shown to improve adherence of patients without affecting short-term efficacy. However, long-term proof of once-daily tacrolimus efficacy and safety is still lacking. From January 2009 to November 2013, 170 clinically stable kidney transplant patients were offered to change from the ongoing twice-daily tacrolimus (TDT) formulation to a once-daily tacrolimus (ODT) regimen. Kidney transplant recipients agreeing to the change to be treated with an ODT regimen (n = 105, estimated glomerular filtration rate [eGFR] 57.1 ± 1.6 mL/min/1.73 m2) and patients continuing on a TDT formulation (n = 65, eGFR 52.0 ± 2.2 mL/min/1.73 m2) were prospectively followed (median follow-up time 10.4 and 12.6 years in the ODT and TDT groups, respectively, P = not significant). At the end of the follow-up, patients in both groups experienced similar eGFR (50.4 ± 2.2 vs 48.0 ± 2.7 mL/min/1.73 m2 in the ODT and TDT groups, respectively, P = not significant). No differences were observed in biopsy-proven acute rejection, overall graft survival, doubling of serum creatinine, and new onset of proteinuria. The 2 groups also had a comparable rate of death, sepsis, and neoplasia. In conclusion, ODT appears safe and effective in stable kidney graft recipients even 10 years after transplantation. These findings support the use of ODT as a primary tacrolimus formulation in patients with kidney transplantation.
Asunto(s)
Rechazo de Injerto/prevención & control , Terapia de Inmunosupresión/métodos , Inmunosupresores/administración & dosificación , Trasplante de Riñón , Tacrolimus/administración & dosificación , Estudios de Cohortes , Esquema de Medicación , Femenino , Supervivencia de Injerto/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
The latest European Guidelines of Arterial Hypertension have officially introduced uric acid evaluation among the cardiovascular risk factors that should be evaluated in order to stratify patient's risk. In fact, it has been extensively evaluated and demonstrated to be an independent predictor not only of all-cause and cardiovascular mortality, but also of myocardial infraction, stroke and heart failure. Despite the large number of studies on this topic, an important open question that still need to be answered is the identification of a cardiovascular uric acid cut-off value. The actual hyperuricemia cut-off (> 6 mg/dL in women and 7 mg/dL in men) is principally based on the saturation point of uric acid but previous evidence suggests that the negative impact of cardiovascular system could occur also at lower levels. In this context, the Working Group on uric acid and CV risk of the Italian Society of Hypertension has designed the Uric acid Right for heArt Health project. The primary objective of this project is to define the level of uricemia above which the independent risk of CV disease may increase in a significantly manner. In this review we will summarize the first results obtained and describe the further planned analysis.
Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Hiperuricemia/epidemiología , Ácido Úrico/sangre , Adulto , Anciano , Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/mortalidad , Femenino , Humanos , Hiperuricemia/sangre , Hiperuricemia/diagnóstico , Hiperuricemia/mortalidad , Italia/epidemiología , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Estudios Observacionales como Asunto , Pronóstico , Proyectos de Investigación , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de TiempoRESUMEN
The glomerular filtration rate is generally accepted as the best overall measure of kidney function and many scientific organizations recommend the use of equations that estimate this parameter to facilitate the diagnosis, evaluation and management of chronic kidney disease. Large-scale epidemiological studies have shown that a mild to moderate reduction in glomerular filtration rate is not an uncommon condition in the general population, and its prevalence further increases in patients at higher cardiovascular risk. Moreover, a large body of evidence has recently established that even minor renal dysfunction is an independent predictor of adverse cardiovascular prognosis. The excess cardiovascular risk related to renal damage is due in part to a higher prevalence of traditional atherosclerotic risk factors, in part to nontraditional, emerging risk factors peculiar to chronic kidney disease which enhance the atherogenic process at the systemic level. Therapeutic approaches in the presence of renal damage are aimed at providing simultaneous cardiovascular and renal protection. Optimal blood pressure control, as indicated by international guidelines, is of the utmost importance both to slow the progression of renal damage and to prevent cardiovascular events. Better outcomes of renal function can be obtained with inhibition of the renin-angiotensin system in both diabetic and nondiabetic renal disease, although the administration of a combination of antihypertensive drugs will be required in almost every patient to achieve the blood pressure target. Aggressive intervention on associated modifiable cardiovascular risk factors is also advisable in order to optimize the global risk profile of patients with chronic kidney disease.
Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Tasa de Filtración Glomerular , Enfermedades Renales/complicaciones , Algoritmos , Aterosclerosis/epidemiología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/terapia , Estudios de Cohortes , Nefropatías Diabéticas/fisiopatología , Nefropatías Diabéticas/terapia , Endotelio Vascular/fisiopatología , Femenino , Humanos , Hiperhomocisteinemia/epidemiología , Hiperhomocisteinemia/fisiopatología , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Hipertensión/fisiopatología , Inflamación/epidemiología , Inflamación/fisiopatología , Enfermedades Renales/diagnóstico , Enfermedades Renales/fisiopatología , Enfermedades Renales/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Sistema Renina-Angiotensina/fisiología , RiesgoRESUMEN
Increased arterial stiffness and the presence of metabolic syndrome (MS) have been shown to predict cardiovascular events in patients with primary hypertension. We investigated the relationship between a recently proposed index of arterial stiffness derived from ambulatory blood pressure (BP) monitoring and MS in 156 untreated, non-diabetic patients with primary hypertension. Ambulatory arterial stiffness index (AASI) was defined as 1 minus the regression slope of diastolic over systolic BP readings obtained from 24-h recordings. A modified National Cholesterol Education Program definition for MS was used, with body mass index replacing waist circumference. The prevalence of MS was 23%. Patients with MS were more frequently male (0.0291) and had increased serum uric acid (P=0.0005), high-sensitivity C-reactive protein (P=0.0259), as well as total and low-density lipoprotein (LDL)-cholesterol (P=0.0374 and P=0.0350, respectively) as compared to those without MS. After adjusting for these confounders, the association between AASI and the presence of MS was statistically significant (P=0.0257). Moreover, the prevalence of increased AASI (upper tertile, that is >or=0.550) was greater in patients with MS (P=0.0156). After adjusting for age and 24-h mean BP, the presence of MS entailed a more than twofold greater risk for increased AASI (0.0280). MS is associated with increased AASI in non-diabetic patients with primary hypertension. These data support the role of this new index of arterial stiffness as a marker of risk and help to explain the high cardiovascular morbidity and mortality that is observed in hypertensive patients with MS.
Asunto(s)
Arterias/fisiopatología , Monitoreo Ambulatorio de la Presión Arterial , Enfermedades Cardiovasculares/fisiopatología , Hipertensión/complicaciones , Hipertensión/fisiopatología , Síndrome Metabólico/complicaciones , Síndrome Metabólico/fisiopatología , Medición de Riesgo/métodos , Albuminuria/epidemiología , Albuminuria/etiología , Proteína C-Reactiva/metabolismo , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Distribución de Chi-Cuadrado , Elasticidad , Femenino , Humanos , Hipertensión/epidemiología , Italia/epidemiología , Lipoproteínas LDL/sangre , Masculino , Síndrome Metabólico/epidemiología , Persona de Mediana Edad , Prevalencia , Análisis de Regresión , Factores de Riesgo , Ácido Úrico/sangreRESUMEN
The cost-effectiveness of antihypertensive treatment increases in parallel with the global burden of risk in the individual patient. Therefore, there has been growing interest in developing sensitive and easy-to-perform clinical tools to accurately and inexpensively identify patients at high cardiovascular risk. Over the past several years a number of studies have provided evidence that microalbuminuria is an integrated marker of hypertensive organ damage and a strong, independent predictor of cardiovascular and cerebrovascular events. Recent data indicate that the risk is linearly related to the degree of urinary albumin excretion, with no identifiable threshold or plateau. Furthermore, changes in urinary albumin excretion parallel changes in risk. We propose the routine search for microalbuminuria in order to optimize cost-effectiveness in the diagnostic approach to patients with primary hypertension.
Asunto(s)
Albuminuria/complicaciones , Hipertensión/complicaciones , Enfermedades Cardiovasculares/etiología , Humanos , Hipertensión/orina , Medición de Riesgo , Factores de RiesgoRESUMEN
Metabolic syndrome (MS) has been shown to predict cardiovascular events in hypertension. Recently, a new four-group left ventricular (LV) hypertrophy classification based on both LV dilatation and concentricity was proposed. This classification has been shown to provide a more accurate prediction of cardiovascular events, suggesting that the presence of LV dilatation may add prognostic information. We investigated the relationship between MS and the new classification of LV geometry in patients with primary hypertension. A total of 372 untreated hypertensive patients were studied. Four different patterns of LV hypertrophy (eccentric nondilated, eccentric dilated, concentric nondilated and concentric dilated hypertrophy) were identified by echocardiography. A modified National Cholesterol Education Program definition for MS was used, with body mass index replacing waist circumference. The overall prevalence of MS and LV hypertrophy (LVH) was 29% and 61%, respectively. Patients with MS showed a higher prevalence of LVH (P=0.0281) and dilated LV geometries, namely eccentric dilated and concentric dilated hypertrophy (P=0.0075). Moreover, patients with MS showed higher LV end-diastolic volume (P=0.0005) and prevalence of increased LV end-diastolic volume (P=0.0068). The prevalence of LV chamber dilatation increased progressively with the number of components of MS (P=0.0191). Logistic regression analysis showed that the presence of MS entails a three times higher risk of having LV chamber dilatation even after adjusting for several potential confounding factors. MS is associated with LV dilatation in hypertension. These findings may, in part, explain the unfavourable prognosis observed in patients with MS.
Asunto(s)
Hipertensión/complicaciones , Hipertrofia Ventricular Izquierda/complicaciones , Síndrome Metabólico/complicaciones , Adulto , Ecocardiografía , Femenino , Humanos , Hipertensión/diagnóstico por imagen , Hipertensión/fisiopatología , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Masculino , Síndrome Metabólico/diagnóstico por imagen , Síndrome Metabólico/fisiopatología , Persona de Mediana EdadRESUMEN
The prevalence of microalbuminuria and its relationship with several cardiovascular risk factors and target organ damage were evaluated in a cohort of 787 untreated patients with essential hypertension. Albuminuria was measured as the albumin-to-creatinine ratio in three nonconsecutive, first morning urine samples. The prevalence of microalbuminuria was 6.7%. Albuminuric patients were more likely to be men and to be characterized by higher blood pressure, body mass index, and uric acid levels and lower HDL cholesterol and HDL cholesterol-to-LDL cholesterol ratio. Piecewise linear regression analysis demonstrated that uric acid and diastolic blood pressure significantly influence albuminuria and together account for a large part of its variations. K-means cluster analysis performed on the entire cohort of patients confirmed that microalbuminuria is associated with a worse cardiovascular risk profile. Furthermore, microalbuminuria was associated with the presence of target organ damage (eg, electrocardiographic [ECG] abnormalities and retinal vascular changes). Age and the presence of microalbuminuria act as independent risk factors for the development of ECG abnormalities and retinal vascular changes. Cluster analysis allowed us to identify three subgroups of patients who differed in the presence or absence of microalbuminuria, retinopathy, and ECG abnormalities. We conclude that the prevalence of microalbuminuria in essential hypertension is lower than previously reported. Increased urinary albumin excretion is associated with a worse cardiovascular risk profile and is a concomitant indicator of early target organ damage.
Asunto(s)
Albuminuria/epidemiología , Albuminuria/fisiopatología , Hipertensión/orina , Adolescente , Adulto , Anciano , Albuminuria/etiología , Análisis por Conglomerados , Creatinina/sangre , Creatinina/orina , Femenino , Cardiopatías/etiología , Humanos , Hipertensión/genética , Hipertensión/fisiopatología , Masculino , Registros Médicos , Persona de Mediana Edad , Prevalencia , Enfermedades de la Retina/etiologíaRESUMEN
BACKGROUND: Microalbuminuria has recently emerged as a strong, independent predictor of cardiovascular mortality in patients with essential hypertension, yet the pathophysiological mechanisms underlying this association remain to be elucidated. OBJECTIVE: To study the relationship between microalbuminuria and left ventricular geometry and function and extra-cardiac vascular changes in a group of 211 untreated hypertensive patients. METHODS: Albuminuria was evaluated as albumin-to-creatinine ratio in three non-consecutive first morning urine samples. Left ventricular mass index and function were assessed by M-B mode echocardiography and carotid wall thickness by high-resolution ultrasound scan. RESULTS: The prevalences of microalbuminuria and left ventricular hypertrophy were 14 and 47% respectively. Patients in the top quartile of albuminuria showed a higher left ventricular mass index (57 +/- 1.8, 55 +/- 2, 47 +/- 1.4 and 48 +/- 1.6 g/m2.7, respectively; P< 0.0001) as well as a higher prevalence of left ventricular hypertrophy (72, 65, 26 and 25%, respectively; P< 0.001) and especially concentric hypertrophy (56, 47, 17 and 21%, respectively; P< 0.0001) in the four quartiles of albuminuria. Microalbuminuric patients showed depressed left ventricular performance as indicated by a reduced midwall fractional shortening (15.7 +/- 0.3, 15.9 +/- 0.3, 16.7 +/- 0.4 and 16.8 +/- 0.3%, respectively; P< 0.02). Furthermore patients in the top quartile of albuminuria showed increased carotid wall thickness as compared to normoalbuminuric patients (0.78 +/- 0.03, 0.7 +/- 0.04, 0.65 +/- 0.03 and 0.6 +/- 0.03 mm, respectively; P < 0.001). CONCLUSIONS: Hypertensive patients with microalbuminuria show a higher prevalence of unfavourable left ventricular geometric patterns, depressed left ventricular function and early signs of extra-cardiac vascular damage. These findings strengthen the role of microalbuminuria as an indicator of subclinical cardiovascular disease and may account for the worse outcome that is usually associated with increased urinary albumin excretion in essential hypertension.
Asunto(s)
Albuminuria/fisiopatología , Ventrículos Cardíacos/patología , Hipertensión/fisiopatología , Hipertrofia Ventricular Izquierda/fisiopatología , Función Ventricular Izquierda , Adulto , Anciano , Ecocardiografía , Femenino , Ventrículos Cardíacos/fisiopatología , Humanos , Hipertensión/patología , Hipertensión/orina , Masculino , Persona de Mediana EdadRESUMEN
Hyperhomocyst(e)inemia is a known risk factor for the development of atherosclerotic vascular damage. Plasma homocyst(e)ine levels are influenced by nutritional and hereditary factors. A point mutation (cytosine to thymidine substitution; C677T) in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR) makes the enzyme thermolabile and has been associated with elevated homocyst(e)ine levels in homozygous carriers (TT genotypes). We evaluated the relationship between the T allele encoding for the thermolabile variant of MTHFR and several biochemical risk factors and early signs of hypertensive and atherosclerotic organ damage in 206 untreated patients with primary hypertension. The MTHFR genotype was evaluated by polymerase chain reaction. Albuminuria was measured as albumin-to-creatinine ratio in three nonconsecutive first morning urine samples (negative urine culture). Persistent Mi (Alb+) was defined as an average albumin-to-creatinine ratio between 2.38 and 19 (men) and 2.96 and 20 (women). Left ventricular (LV) mass index (LVMI) was assessed by M-B mode echocardiography (LV hypertrophy, LVH = LVMI > or = 125 g/m2), carotid geometry by high-resolution ultrasound scan, and retinal vascular changes by direct ophthalmoscopy (Keith-Wagener classification). The prevalence of Mi, LVH, and retinopathy was 14%, 45%, and 42%, respectively. The prevalence of carotid plaque was 25%. Allele frequencies for C (wild-type allele) and T allele (mutant allele) were 56% and 44%, respectively. Genotype frequencies were CC 29%, CT 54%, TT 17% according to Hardy Weinberg equilibrium. There were no differences as for age, sex, body mass index, blood pressure levels, lipid profile, smoking habits, and alcohol intake, and LVMI and urinary albumin excretion on the basis of MTHFR genotype. Patients with TT polymorphism showed a higher prevalence of retinal vascular changes (TT, 61% v CT + CC, 38%; P < .02) and carotid plaque (TT, 42% v CT + CC, 21%; P < .05) compared to patients with CC and CT polymorphism. Moreover, patients with T allele showed increased carotid artery size as demonstrated by intima plus media thickness (IT, 0.79 +/- 0.05 mm v CT + CC, 0.67 +/- 0.02 mm; P < .02), relative wall thickness (TT, 0.23 +/- 0.01 mm v CT + CC, 0.20 +/- 0.005 mm; P < .02), and surface area (TT, 19 +/- 1.9 mm2 v CT + CC, 15 +/- 0.55 mm2; P < .05). Multiple linear regression analysis demonstrated that MTHFR genotype and systolic blood pressure independently influence intima-media thickness and together account for about 11% of its variations (r2 = 0.11, F = 9.7, dF = 1-205, P < .0001). Homozygosity for the T allele of the MTHFR gene is an independent risk factor for the development of early atherosclerotic organ damage in hypertensive patients.
Asunto(s)
Arteriosclerosis/etiología , Hipertensión/complicaciones , Hipertensión/genética , Oxidorreductasas/genética , Polimorfismo Genético , 5,10-Metilenotetrahidrofolato Reductasa (FADH2) , Adulto , Arteriosclerosis/diagnóstico por imagen , Arteriosclerosis/patología , Arteria Carótida Común/diagnóstico por imagen , Ecocardiografía , Femenino , Fondo de Ojo , Humanos , Hipertensión/diagnóstico por imagen , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2) , Persona de Mediana Edad , Retina/patología , Enfermedades de la Retina/etiología , Enfermedades de la Retina/patologíaRESUMEN
Microalbuminuria has been associated with a cluster of metabolic and nonmetabolic risk factors, suggesting that it might indicate the presence of generalized microvascular damage in patients with essential hypertension. To explore whether microalbuminuria is associated with early target organ damage, two groups of essential hypertensive patients, with (n = 17) (HtAlb+) and without (n = 16) (HtAlb-) microalbuminuria, and a control group (C) of healthy normotensive subjects (n = 20) were studied. The study groups, selected among participants of a large epidemiologic trial, were carefully matched for several potentially confounding variables such as gender, age, duration of hypertension, and body mass index. Albumin excretion rate was evaluated by radioimmunoassay in three nonconsecutive timed overnight collections after 3 weeks of pharmacologic wash-out. Left ventricular mass was assessed by M-B-mode echocardiography, carotid wall thickness by a high resolution ultrasound scan, and renal vascular impedance by Doppler scan. Office as well as 24-h ambulatory pressure monitoring (Takeda TM-2420) were also evaluated. There was no difference between the two hypertensive groups for office and 24-h blood pressure levels except for a lower daytime/nighttime systolic blood pressure ratio in the group with microalbuminuria. Microalbuminuric patients showed signs of early organ damage as compared to normoalbuminuric patients and normal subjects, namely greater left ventricular mass indices (LVMI 167+/-7 g/m2 in HtAlb+; 139+/-9 g/m2 in HtAlb-; 118+/-5 g/m2 in C, P < .001) and increased wall thickness of common carotid arteries (intima plus media thickness 12.5+/-0.2 mm in HtAlb+; 11.7+/-0.3 mm in HtAlb-; 11.2+/-0.2 mm in C, P < .001) as well as higher intrarenal vascular resistance (mean resistive index 0.62+/-0.01 in HtAlb+; 0.59+/-0.01 in HtAlb-; 0.59+/-0.01 in C, P < .05). In conclusion, microalbuminuria is an early marker of diffuse target organ damage in essential hypertension and therefore can be useful to identify patients for whom more aggressive preventive strategies or additional treatment measures are advisable.
Asunto(s)
Albuminuria/orina , Hipertensión/orina , Biomarcadores , Arterias Carótidas/diagnóstico por imagen , Ecocardiografía , Femenino , Humanos , Hipertensión/diagnóstico por imagen , Riñón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Valores de Referencia , Análisis de Regresión , Circulación Renal/fisiología , Resistencia Vascular/fisiologíaRESUMEN
Microalbuminuria (Mi) is thought to reflect diffuse vascular damage and to predict cardiovascular morbidity and mortality in essential hypertension, although its pathogenesis remains to be fully elucidated. The relationship between microalbuminuria and several cardiovascular risk factors and target organ damage was evaluated in a large cohort of untreated essential hypertensive patients. Albuminuria was measured as the albumin to creatinine ratio in three non consecutive first morning urine samples. Cardiac damage was evaluated by ECG and retinal vascular changes by direct ophtalmoscopy. In a subgroup of 23 patients with Mi and in a control group of 22 normoalbuminurics, selected from the entire cohort of patients and carefully matched for age, gender, body mass index (BMI) and duration of disease, we also measured left ventricular mass index by M-B mode echocardiography, common carotid wall thickness by high resolution US-scan, and renal vascular resistances by US-doppler of interlobar arteries. K-means cluster analysis performed on the entire cohort of patients showed that microalbuminuria is associated with the presence of an unfavorable risk profile and target organ damage. Furthermore, microalbuminuric hypertensive patients have a larger left ventricular mass index, increased intima media thickness of carotid arteries and higher intrarenal vascular resistances as compared to a well matched group of normoalbuminuric patients. We conclude that in essential hypertension increased urinary albumin excretion can be useful to identify patients for whom more aggressive preventive strategies and/or additional treatment measures are advisable.
Asunto(s)
Albuminuria/sangre , Enfermedades Cardiovasculares/sangre , Hipertensión/sangre , Biomarcadores , Enfermedades Cardiovasculares/epidemiología , Análisis por Conglomerados , Electrocardiografía , Femenino , Hemodinámica/fisiología , Humanos , Hipertensión/epidemiología , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Increased urine albumin excretion is associated with an unfavourable cardiovascular risk profile and prognosis in primary hypertension, even though its pathogenesis is currently unknown. Microalbuminuria (Mi) has been proposed as an integrated marker to identify patients with subclinical organ damage, but its routine use is still too often neglected in clinical practice. The aim of our study was to evaluate the relationship between urinary albumin excretion and early signs of subclinical target organ damage (TOD), namely left ventricular hypertrophy and carotid atherosclerosis in a large group of non diabetic hypertensive patients. A group of 346 never treated patients with primary hypertension (212 men, 134 women, mean age 47 +/- 9 years) referred to our clinic were included in the study. They underwent the following procedures: (1) family and personal medical history and physical examination; (2) clinical blood pressure measurement; (3) routine blood chemistry and urine analysis including determination of urinary albumin excretion (ACR); (4) electrocardiogram; (5) ultrasound evaluation of left ventricular mass (LVMI) and carotid artery thickness (IMT). The overall prevalence of Mi, left ventricular hypertrophy, and carotid plaque was 13, 51, and 24% respectively. Mi was significantly correlated with LVMI (P < 0.0001), IMT (P < 0.0001) and several metabolic and non-metabolic risk factors (blood pressure, body mass index, serum lipids). Cluster analysis identified three subgroups of patients who differ significantly with regards to TOD and albuminuria (P < or = 0.001 for each of the examined variables). Patients with higher IMT and LVMI values also showed increased ACR levels. Furthermore, patients with microalbuminuria were more likely to have both LVH and IMT values above the median for the study population (OR 21, C.I. 4.6-99.97, P < 0.0001). Mi is an integrated marker of subclinical organ damage in patients with primary hypertension. Evaluation of urinary albumin excretion is a specific, cost-effective way to identify patients at higher risk for whom additional preventive and therapeutic measures are advisable.
Asunto(s)
Albuminuria/orina , Enfermedades de las Arterias Carótidas/orina , Hipertensión/orina , Hipertrofia Ventricular Izquierda/orina , Análisis de Varianza , Biomarcadores/orina , Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/etiología , Análisis por Conglomerados , Ecocardiografía , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/etiología , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
A reduction in renal function is associated with high cardiovascular morbidity and mortality in hypertension. The aim of the present study was to investigate the relationship between creatinine clearance and subclinical organ damage in 957 never previously treated, middle-aged patients with primary hypertension. Renal function was estimated by means of the serum creatinine level using the Cockcroft-Gault formula; left ventricular hypertrophy (LVH) was determined according to electrocardiographic criteria; and retinal vascular changes were evaluated by direct ophthalmoscopy. Creatinine clearance was, on the average, 83+/-21.2 ml/min, and the prevalence of LVH and retinopathy was 13 and 49%, respectively. Creatinine clearance was inversely related to the duration of disease (r=-0.132, P<0.0001), systolic blood pressure (r=-0.110, P=0.001), serum glucose (r=-0.090, P=0.007), total cholesterol (r=-0.196, P<0.0001), and LDL-cholesterol (r=-0.196, P<0.0001). Patients in the lower quintile of creatinine clearance showed a higher prevalence of electrocardiogram (ECG) determined LVH (P=0.04), as well as retinal changes (P=0.02). The risk of having LVH or retinal vascular changes increases significantly with each s.d. decrease in creatinine clearance, regardless of traditional cardiovascular risk factors. Moreover, patients with ECG-determined LVH and retinal changes showed lower creatinine clearance as compared to those with lesser degrees of target organ involvement (P<0.01). In conclusion, a mild reduction in creatinine clearance is associated with preclinical end-organ damage in patients with normal creatinine and primary hypertension. These data may help explain the high cardiovascular mortality observed in patients with renal dysfunction. Routine evaluation of creatinine clearance could be useful for identifying patients at higher cardiovascular risk.
Asunto(s)
Creatinina/sangre , Hipertensión/sangre , Hipertensión/complicaciones , Hipertrofia Ventricular Izquierda/etiología , Enfermedades Renales/etiología , Enfermedades de la Retina/etiología , Adulto , Ecocardiografía , Femenino , Humanos , Hipertensión/diagnóstico por imagen , Hipertensión/patología , Hipertrofia Ventricular Izquierda/epidemiología , Enfermedades Renales/sangre , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oftalmoscopía , Prevalencia , Vasos Retinianos/patologíaRESUMEN
BACKGROUND: Preventing subclinical organ damage is currently a major issue in the management of patients with essential hypertension. Antihypertensive drugs which act through different pathophysiological mechanisms might confer specific target organ protection beyond what is already provided by their blood pressure lowering effect. METHODS: Thirty-one patients with essential hypertension were randomized to receive long-term treatment with either a calcium channel blocker (nifedipine GITS, 90 mg/day) or an ACE-inhibitor (lisinopril, 20 mg/day). Blood pressure, left ventricular mass, carotid wall thickness and timed urinary albumin excretion were measured at baseline and over the course of 24 months of treatment. RESULTS: Both regimens significantly lowered mean blood pressure over the 24 months (from 124+/-2 to 103+/-2 mmHg in the lisinopril group and from 122+/-2 to 104+/-1 in the nifedipine group). Overall, end-organ damage improved with persistent blood pressure control. However, the two treatments had different specific effects. Lisinopril induced a more pronounced reduction of the left ventricular mass index (from 56+/-3 to 52+/-2 g/m2.7, P< 0.05) and urinary albumin excretion (from 34+/-15 to 9+/-2 microg/min, P< 0.01), while nifedipine achieved a greater reduction of carotid intima plus media thickness (from 0.8+/-0.06 to 0.6+/-0.06 mm, P< 0.01). CONCLUSIONS: Blood pressure control does help reduce the severity of organ damage in patients with essential hypertension. Different antihypertensive treatments may confer additional specific cardiorenal and vascular protection regardless of blood pressure control. These data could be useful when devising individualized therapeutic strategies in high-risk hypertensive patients.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Hipertensión/tratamiento farmacológico , Lisinopril/uso terapéutico , Nifedipino/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
The increased atherothrombotic risk in patients with metabolic syndrome (MetS) has been classically explained by the multiplicative effect of systemic concomitant pro-atherosclerotic factors. In particular, centripetal obesity, dyslipidaemia, glucose intolerance, hypertension (differently combined in the diagnosis of the disease) would be expected to act as classical cardiovascular risk conditions underlying accelerated atherogenesis. In order to better understand specific atherosclerotic pathophysiology in MetS, emerging evidence focused on the alterations in different organs that could serve as both pathophysiological targets and active players in the disease. Abnormalities in adipose tissue, heart and arteries have been widely investigated in a variety of basic research and clinical studies in MetS. In this narrative review, we focus on pathophysiological activities of the liver and kidney. Considering its key role in metabolism and production of soluble inflammatory mediators (such as C-reactive protein [CRP]), the liver in MetS has been shown to be altered both in its structure and function. In particular, a relevant amount of the fat accumulated within this organ has been shown to be associated with different degrees of inflammation and potential insulin resistance. In humans, non-alcoholic fatty liver disease (NAFLD) has been described as the hepatic manifestation of MetS. In an analogous manner, epidemiological evidence strongly suggested a "guilty" association between MetS and chronic kidney disease (CKD). Some biomarkers of hepatic (such as C-reactive protein, TNF-alpha or other cytokines) and renal diseases (such as uric acid) associated with MetS might be particularly useful to better manage and prevent the atherothrombotic risk.
Asunto(s)
Aterosclerosis/epidemiología , Hígado Graso/epidemiología , Riñón/metabolismo , Hígado/metabolismo , Síndrome Metabólico/epidemiología , Insuficiencia Renal Crónica/epidemiología , Trombosis/epidemiología , Animales , Aterosclerosis/inmunología , Biomarcadores/metabolismo , Citocinas/metabolismo , Humanos , Mediadores de Inflamación/metabolismo , Resistencia a la Insulina , Riñón/patología , Hígado/patología , Síndrome Metabólico/inmunología , Enfermedad del Hígado Graso no Alcohólico , Riesgo , Trombosis/inmunologíaRESUMEN
Organ damage (OD) is an indicator of increased cardiovascular risk. Blood pressure variability (BPV) is related to greater incidence of events, regardless of the severity of hypertension. We investigated the relationship between ambulatory blood pressure monitoring (ABPM)-derived indices of BPV and the presence of multiple OD in primary hypertension (PH). One hundred and sixty-nine untreated patients with PH were evaluated. Systolic (SBP) and diastolic blood pressure (DBP) variability were assessed as the crude and weighted (w.) standard deviation (s.d.), and average real variability (ARV) of the mean value of 24-h, awake and asleep ABPM recordings. Left ventricular mass index, intima-media thickness, estimated-glomerular filtration rate and urinary albumin excretion were assessed as indices of cardiac, vascular and renal damage, respectively. Risk profile progressively increased starting from patients without OD to patients with only one sign of OD, and then to those with multiple OD. In addition to greater severity of the organ involvement, the only variables that were found to significantly differ between subjects with multiple and single OD were office SBP (160 ± 14 vs 154 ± 11 mm Hg, P=0.0423) and DBP (101 ± 7 vs 97 ± 8 mm Hg, P=0.0291), ambulatory arterial stiffness index (AASI) (0.60 ± 0.10 vs 0.50 ± 0.17, P=0.0158) and indices of BPV (24-h SBP s.d., 23 ± 5 vs 20 ± 6 mm Hg, P=0.0300; awake SBP s.d., 22 ± 6 vs 19 ± 6 mm Hg, P=0.0366; 24-h SBP w.s.d., 20 ± 5 vs 17 ± 5 mm Hg, P=0.0385; and 24-h SBP ARV, 18 ± 4 vs 15 ± 5 mm Hg, P=0.0420). All the above mentioned BPV parameters turned out to be determinants of multiple OD, regardless of several confounding variables, including BP levels. Therefore, in hypertensive patients increased SBP variability is associated with multiple signs of OD, regardless of BP values.