Influence of angiotensin-converting enzyme inhibition on reversibility of alterations in arterial wall and cognitive performance associated with early hypertension

The importance of optimal blood pressure control for preventing or reducing the impairment of vascular and cognitive functions is well known. However, the reversibility of early alterations in vascular and cognitive functions through antihypertensive agents is under-investigated. In this study, we evaluated the influence of 3 months of angiotensin-converting enzyme (ACE) inhibition treatment on the morphological and functional arterial wall and cognitive performance changes in 30 newly diagnosed primary hypertensive patients. Common carotid intima-media thickness (IMT) and brachial artery flow-mediated dilatation (FMD) were detected by ultrasonography. Arterial stiffness indicated by augmentation index (AIx) and pulse wave velocity (PWV) was assessed by arteriography. Cognitive functions were assessed by neuropsychological examination. The executive function overall score was significantly higher at 3-month follow-up than at baseline (median, 0.233 (IQR, 0.447) vs –0.038 (0.936); P = .001). Three-month ACE inhibition did not produce significant improvement in IMT, FMD, AIx and PWV values. Significant negative associations were revealed between IMT and complex attention (r = –0.598, P = .0008), executive function (r = –0.617, P = .0005), and immediate memory (r = –0.420, P = .026) overall scores at follow-up. AIx had significant negative correlations with complex attention (r = –0.568, P = .001), executive function (r = –0.374, P = .046), and immediate memory (r = –0.507, P = .005). PWV correlated significantly and negatively with complex attention (r = –0.490, P = .007). Timely and effective antihypertensive therapy with ACE inhibitors has significant beneficial effects on cognitive performance in as few as 3 months. Early ACE inhibition may have an important role in the reversal of initial impairments of cognitive function associated with hypertension-induced vascular alterations.L

Uric Acid Control in Advanced Chronic Kidney Disease in a Southeastern US Urban Cohort

Abstract OBJECTIVES: Uric acid (UA) control may be insufficient in chronic kidney disease (CKD) patients in the current era. It is unclear, however, whether this is the result of environmental effects, patient anthropometrics or insufficient dosing of medical therapy (allopurinol). METHODS: We have collected data on multiple clinical and laboratory parameters of 114 CKD clinic patients attending the nephrology clinic of the University of Mississippi Medical Center with an estimated glomerular filtration rate <45 mL · min-1 · 1.73 m2. We assessed the correlates of UA levels and the allopurinol doses along with achieved serum UA and urine pH. RESULTS: The cohort consisted of middle-aged to elderly patients with a mean (± standard deviation) age of 62.1 (11.6) years; 45.6% were female, 68.4% were African American and 47.4% had a history of gout. The mean UA level was 7.7 (2.49) mg/dL (range 3.1-16), allopurinol dose was 192 (99) mg/day (range 50-450) and estimated glomerular filtration rate was 23.8 (11.3) mL · min-1 · 1.73 m2. While the overall serum bicarbonate level was 25 (3.2) mEq/L, urine pH was <6 in 60.5% of the cohort. Significant univariate correlates of the administered doses of allopurinol were weight (r 0.317, P = 0.001), body mass index (BMI; r 0.313, P = 0.001), and female sex (r -0.198; P = 0.035). Achieved UA levels correlated directly with BMI (r 0.201, r = 0.036) but inversely with the allopurinol dose (r -0.196; P = 0.036). During logistic regression analysis with stepwise selection, only weight (β 0.313, P = 0.001) and sex (β -0.190, P = 0.039) proved to be predictive of the allopurinol dose; as for the achieved UA level, only BMI (β 0.271, P = 0.006) and the allopurinol dose (β -0.258; P= 0.009) had a significant effect. CONCLUSIONS: In patients with advanced CKD, conventional dosing recommendations for allopurinol are unlikely to suffice in reaching target serum UA goals. In our cohort, larger-than-usual allopurinol doses were well tolerated

Increased levels of platelet activation markers are positively associated with carotid wall thickness and other atherosclerotic risk factors in obese patients

The role of platelets in the development of atherosclerosis and obesityrelatedprothrombotic state is still under investigation. In this cross-sectionalcohort study, we measured the levels of different platelet activationmarkers and evaluated their relationship with carotid intimamediathickness (IMT) along with other atherosclerotic risk factors inobese patients with or without atherosclerotic co-morbidities. We enrolled154 obese patients, including 98 with either hypertension, type 2diabetes mellitus or dyslipidaemia, 56 without these co-morbiditiesand 62 age- and sex-matched healthy controls. Platelet P-selectin expressionand the number of platelet-derived microparticles (PMPs)were measured by flow cytometry; soluble P-selectin levels were analysedby ELISA and Thr715Pro P-selectin polymorphism was determinedby PCR-RFLP. Carotid IMT was examined by ultrasonography. The levelsof platelet activation parameters were significantly elevated in allobese subjects with increased carotid IMT compared to healthy con-trols. There was no effect of Thr715Pro genotype on soluble P-selectinlevels in obese individuals contrary to normal subjects. Significant andpositive association was revealed between carotid IMT and plateletP-selectin (p<0.0001), soluble P-selectin (p=0.039) and PMP(p=0.0001) levels. After adjusting for multiple variables, independentassociation was found between soluble P-selectin and fibrinogen(p=0.007), PMP levels and body mass index (p<0.0001) as well as plateletP-selectin and carotid IMT (p=0.012) plus plasminogen activatorinhibitor-1 (p=0.009). In conclusion, P-selectin and PMP levels showedpositive associations with abnormal carotid IMT and other risk factorsin obesity suggesting a critical role of enhanced platelet reactivity inatherosclerotic wall alteration