Angiotensin converting enzyme (ACE) gene polymorphism and silent cerebral white matter lesions in middle-aged essential hypertensive patients

Angiotensin converting enzyme (ACE) gene polymorphism and silent cerebral white matter lesions in middle-aged essential hypertensive patients

54A POSTERS: Cerebrovascular Disease/Stroke P-74 ANGIOTENSIN CONVERTING ENZYME (ACE) GENE POLYMORPHISM AND SILENT CEREBRAL WHITE MATTER LESIONS IN M...

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54A

POSTERS: Cerebrovascular Disease/Stroke

P-74 ANGIOTENSIN CONVERTING ENZYME (ACE) GENE POLYMORPHISM AND SILENT CEREBRAL WHITE MATTER LESIONS IN MIDDLE-AGED ESSENTIAL HYPERTENSIVE PATIENTS Cristina Sierra, Alejandro de la Sierra, Elisenda Gomez-Angelats, Esteban Poch, Josep Oriola, Antonio Coca. 1Hypertension Unit, Hospital Clinic, Barcelona, Spain It has been reported that the presence of the DD genotype of the angiotensin converting enzyme (ACE) gene is a risk factor for stroke in hypertensive patients. Likewise, the presence of cerebral white matter lesions (WML) may also represent a risk factor for the development of stroke. The aim of the present study was to evaluate the possible association between the DD genotype of the ACE gene and the presence of silent cerebral WML in asymptomatic middle-aged untreated essential hypertensive patients. Fifty-six never treated essential hypertensive patients (34 men, 22 women), aged 50-60 years (mean age 54.4 ⫾ 4.1 years) without clinical evidence of target organ damage were studied. Patients with diabetes mellitus, carotid stenosis ⬎50% or daily alcohol intake ⬎30g were excluded. All patients underwent 24-hour ambulatory blood pressure monitoring and brain-magnetic resonance imaging in order to establish the presence or absence of cerebral white matter lesions, using the Rotterdam scale. All patients were also genotyped by polymerase chain reaction for the I/D polymorphism of the ACE gene. The distribution of genotypes in the whole group of essential hypertensive patients studied was DD: 24 (43%), ID: 20 (36%), and II: 12 (21%). These frequencies did not deviate from Hardy-Weinberg equilibrium. Twenty-four hypertensive patients (43%) were found to have WML on brain resonance. We found a significant association between both the ACE genotype (P⫽0.033) and allele distribution (P⬍0.001) and the presence of WML. The proportion of DD genotype in patients with WML (15 patients; 62.5%) was higher than observed in patients without WML (9 patients; 28.1%). The relative risk of the DD genotype for the presence of WML was 4.26 (CI 95%: 1.38-13.2). Likewise, the proportion of D allele in patients with WML (73%) was higher than in patients without WML (52%). The relative risk of the D allele for the presence of WML was 2.53 (CI 95%: 1.13-5.65). Age, gender distribution, body mass index, cholesterol and smoking habit did not differ among hypertensives classified by ACE genotype. We conclude that the presence of the DD genotype and/or the D allele of the ACE gene may be a risk factor for developing WML in essential hypertensive patients. Key Words: Genetics, Cerebral white matter lesions, Angiotensin converting enzyme gene

P-75 HYPERTENSION: THE MOST PREVALENT RISK FACTOR FOR STROKE IN RENAL TRANSPLANT RECIPIENTS A. Oliveras, J. Roquer, J. M. Puig, A. Orfila, S. Hurtado, J. Masramon, J. Lloveras. 1Hypertension Unit, Departments of Nephrology and Neurology, Hospital del Mar., Barcelona, Spain Cerebrovascular pathology, in comparison with cardiovascular diseases, has not been widely studied in renal transplant recipients (RTR). We here analize the etiopathogenic and clinical aspects as well as the outcome of stroke (S) in this special population. We evaluated the clinical features and risk factors of 19 out of 404 RTR who suffered S after renal grafting, taking into account the following data: age, gender, time after renal transplantation, original nephropathy, previous stroke and also the well-known cardiovascular risk factors: tobacco smoking, dislipemia, hypertension (HT) and diabetes mellitus (DM). We also describe the nature of S, their localization, clinical outcome and time to death if it occurred. 0895-7061/01/$20.00

AJH–April 2001–VOL. 14, NO. 4, PART 2

There were 11 males and 8 females, average 49.8yr age, with an interval from RT to S of 52.1months in average (min: 3.41m- max: 87.82m; sd⫽25.55m). Eight out of the 19 RTR (42.1%) had suffered S previously to RT. Regarding to the classic cardiovascular risk factors, HT was prevalent in 100% of the cases, dislipemia in 68.4%, smoker condition in 26.3% and DM in 31.6% (interval: 23-63yr) of the patients. There were 7 cerebral hemorrhages and 12 ischemic S (7 of them were atherothrombotic). Localization was deep/basal ganglia in 10, superficial/ lobar in 8, and the other one was placed in the brainstem. Nine out of 19 patients (47.36%) died within the 3 months following S, and S was the cause of death in seven out of these 9 patients (77.78%). We conclude that: 1) HT was the most prevalent risk factor for S in the RTR 2) cerebral hemorrhage was more prevalent (36.84% of S) in RTR than in general population. 3) mortality after S is high in RTR (~50%). According to these conclusions, we think that we must do a great effort to optimize the control of HT in those patients (RTR) in order to prevent them from such disease paying an special attention to patients with diabetes and to patients with other manifestations of cardiovascular disease. Key Words: Stroke, Renal transplantation, Hypertension

P-76 HYPERTENSION AND OTHER PREDICTIVE RISK FACTORS FOR STROKE IN RENAL TRANSPLANT RECIPIENTS A. Oliveras, J. M. Puig, J. Roquer, J. Vila, M. Mir, J. Masramon, J. Lloveras. 1Hypertension Unit, Departments of Nephrology and Neurology, Hospital del Mar., Barcelona, Spain Cardiovascular diseases are the most important causes of morbidity and mortality in renal transplant recipients (RTR). However, there are very few reports about cerebrovascular pathology in these patients. We study the predictive value of hypertension (HT) and other risk factors for stroke (S) in renal transplanted patients. A cohort of 404 RTR of one or more grafts was analyzed. For each of them the following data were evaluated: age, gender, body mass index, smoking status, primary nephropathy, pre-existing diabetes mellitus (DM), HT, hyperlipemia, hypertensive and/or ischemic cardiopathy, peripheral vascular disease (PVD), and donor HT, as well as the following diseases appeared after renal transplantation (RT): heart disease and cytomegalovirus infection. Moreover, laboratory analysis (serum creatinine, uric acid, cholesterol, tryglicerides, hemoglobin, hematocrit and proteinuria) were evaluated. Kaplan-Meier method was used in order to establish cumulative survival comparison between group A (RTR with S) and grup B (RTR without S). We found Group A⫽19 RTR and group B⫽385 RTR Prevalence of S ⫽ 7.97% at 10yr. (confidence interval:4.3-11.6%). Time elapsed from RT to S ⫽ 49.33m (min.3.41m-max:87.82m; sd⫽25.55m). Predictive risk factors were: Age⬎40yr HT prior to RT DM prior to RT PVD prior to RT ADPKD Diabetic nephropaty Cardiac disease

GroupA

GroupB

“p” (Log Rank)

13 16 5 5 4 5 16

195 237 15 12 33 12 237

0,0166 0,0399 0,0015 0,000 0,0343 0,000 0,0310

We conclude that 1) prevalence of S was 7.97% in our RTR population 2) diabetic nephropathy and PVD were the most important predictors of S in RTR 3)HT as well as age, DM, autosomal dominant policystic kidney disease (ADPKD) and cardiac disease were also significative risk factors 4) none of the 57 RTR due to interstitial nephropathy suffered S. Key Words: Stroke, Hypertension, Renal transplantation © 2001 by the American Journal of Hypertension, Ltd. Published by Elsevier Science Inc.