Esther Paran

Blood pressure and cognitive functioning among independent elderly

BACKGROUND The morbidity and mortality benefits of blood pressure (BP) control for the elderly is well documented. The cognitive consequences of hypertension control in this population, however, are still under debate. We aim to study the association between BP and cognitive performance in the elderly. Specifically, we explore 1) the possibility that BP is differentially associated with various cognitive domains; and 2) the utility of analyzing both BP and cognitive scores as continuous variables to unravel possible nonlinear associations. METHODS Four hundred ninety-five community living 70 to 85 year olds completed eight cognitive tests that measured memory, concentration, visual retention, verbal fluency, and the mini-mental state examination (MMSE). The performance of each test was analyzed first by comparing four groups (normotensives, normalized hypertensives, untreated hypertensives, and treated but uncontrolled hypertensives). Then, using BP values as continuous variables, linear, U-curve, and J-curve associations were estimated. RESULTS On all cognitive tests, except for verbal fluency, normotensives performed poorest, treated but uncontrolled hypertensives achieved the highest scores. The MMSE scores and the lighter concentration task were linearly related to BP; J-curve association was observed between memory and visual retention; prolonged concentration was related to pulse pressure alone. CONCLUSIONS Low BP, as observed among the normotensive subjects, was associated with poor cognitive performance. Mild hypertension appeared to enhance cognitive functioning among the subjects of this study. Moreover, we found support for the hypothesis that the association between BP and different dimensions of cognition take on different patterns.

Tomato extract and the carotenoids lycopene and lutein improve endothelial function and attenuate inflammatory NF-κB signaling in endothelial cells.

Objectives: In our previous research the antihypertensive properties of lycopene-containing tomato oleoresin have been revealed. The present study was aimed to assess if oleoresin interferes in the inflammatory signalling in endothelial cells, imitating reduction of inflammatory processes in the vessel wall and in this way to propose the mechanism for the reduction of blood pressure by oleoresin. Methods and results: A wide number of functional and inflammatory markers were investigated in two cultured endothelial cell models [EA.hy926 and human umbilical vein endothelial cell (HUVEC)], exposed to oleoresin and carotenoids lycopene and lutein. All the carotenoids significantly improved basic endothelial function as measured by increased nitric oxide and decreased endothelin (ET-1) release. They were effective in attenuation of inflammatory nuclear factor kappa-light-chain-enhancer of activated B cells (NF-&kgr;B) signalling: decrease of tumour necrosis factor-alpha (TNF-&agr;)-induced leukocytes adhesion, expression of adhesion molecules inter-cellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and nuclear translocation of NF-&kgr;B components as well as some revert of inhibitor of kappa B (I&kgr;B) ubiquitination. In addition, the carotenoids were able to inhibit NF-&kgr;B activation in transfected endothelial cells. When combined with lutein, oleoresin exerted synergistic effect on preclusion of leukocytes adhesion. Conclusions: Prevention of over-expression of adhesion molecules through inhibition of NF-&kgr;B signalling may be one of the main mechanisms driving carotenoids to attenuate inflammatory leukocyte adhesion to endothelium. This is the first profound study on the mechanisms involved in the positive action of natural tomato products in endothelial cells.

Stimulation of NADPH oxidase by angiotensin II in human neutrophils is mediated by ERK, p38 MAP-kinase and cytosolic phospholipase A2.

Objective The present research was designed to study the involvement of ERK and p38 MAP-kinase in cytosolic phospholipase A2 (cPLA2) and NADPH-oxidase activation by angiotensin II (Ang II) in human neutrophils. Methods NADPH-oxidase activity was measured by reduction of cytochrome C. cPLA2 activity was measured in cell lysate using sonicated dispersions of 1-stearoyl-2-[14C]arachidonyl phosphatidylcholine. Cells were incubated with MEK inhibitor UO126 or with p38 MAP-kinase inhibitor SB202190 prior to stimulation with Ang II. Translocation of p47phox, p67phox and cPLA2 and phosphorylation of ERK and p38 MAP-kinase were measured by immunoblot analysis. Results Ang II induced a dose-dependent activation of NADPH oxidase in neutrophils and monocytes as well as in differentiated PLB-985 cells towards neutrophil or monocyte lineages, but not in cPLA2-deficient differentiated PLB-985 cells. An immediate activation of both ERK and p38 MAP-kinase and of cPLA2 was induced by Ang II in human neutrophils. In addition, Ang II induced translocation of the cytosolic oxidase components, detected by translocation of p47phox, which preceded the translocation of cPLA2 induced by this agonist. The p38 MAP-kinase inhibitor SB202190 or the MEK–ERK pathway inhibitor UO126 totally inhibited the activation of both NADPH oxidase and cPLA2 as well as the translocation of cytosolic oxidase components and of cPLA2 to the membrane fractions. Conclusions These results suggest that either ERK or p38 MAP-kinase are involved in the activation of both cPLA2 and NADPH oxidase, and that cPLA2 is required for activation of the NADPH oxidase by Ang II in human neutrophils.

Hypertension and cognitive function in the elderly.

Alzheimers disease is the most prevalent and common form of cognitive impairment, ie, dementia, in the elderly followed in second place by vascular dementia due to the microangiopathy associated with poorly-controlled hypertension. Besides blood pressure elevation, advancing age is the strongest risk factor for dementia. Deterioration of intellectual function and cognitive skills that leads to the elderly patient becoming more and more dependent in his, her, activities of daily living, ie, bathing, dressing, feeding self, locomotion, and personal hygiene. It has been known and demonstrated for many years that lowering of blood pressure from a previous hypertensive point can result in stroke prevention yet lowering of blood pressure does not prevent the microangiopathy that leads to white matter demyelinization which when combined with the clinical cognitive deterioration is compatible with a diagnosis of vascular dementia. It is known from many large studies, ie, SHEP, SCOPE, and HOPE, that lowering of blood pressure gradually will not and should not worsen the cognitive impairment. However, if the pressure is uncontrolled a stroke which might consequently occur would further worsen their cognitive derangement. So an attempt at slow reduction of blood pressure since cerebral autoregulation is slower as age increases is in the patients best interest. It is also important to stress that control of blood glucose can also be seen as an attempt to prevent vascular dementia from uncontrolled hyperglycemia. Vascular dementia is not considered one of the reversible causes of dementia. Reversible causes of cognitive impairment are over medication with centrally acting drugs such as sedatives, hypnotics, antidepressants, and antipsychotics, electrolyte imbalance such as hyponatremia, azotemia, chronic liver disease, and poor controlled chronic congestive heart failure. Criteria for the clinical diagnosis of vascular dementia include cognitive decline in regards to preceding functionally higher level characterized by alterations in memory and in two or more superior cortical functions that include orientation, attention, verbal linguistic capacities, visual spacial skills, calculation, executive functioning, motor control, abstraction and judgment. Patients with disturbances of consciousness, delirium (acute confusional states), psychosis, serious aphasia, or sensory-motor alterations that preclude proper execution of neuro-psychological testing are also considered to have probably vascular dementia. Furthermore, these are ten of the other essential cerebral or systematic pathologies present that would be able to produce a dementia syndrome.

The effects of replacing β-blockers with an angiotensin converting enzyme inhibitor on the quality of life of hypertensive patients

The aim was to evaluate the effects of a change of treatment from beta-blocker to captopril on the quality of life of hypertensive patients. One hundred forty-nine mild to moderate hypertensive patients who were being treated with beta-blockers were randomly assigned to receive captopril (12.5 to 50 mg twice daily), or to continue on beta-blocker treatment (atenolol: 25 to 100 mg once daily [n = 121], or propranolol, 10 to 80 mg twice daily [n = 12]). When required, 25 mg hydrochlorothiazide was added in each group. The patients were followed over periods ranging from 6 to 12 months. Blood pressure, treatment side effects, and quality of life were monitored. Blood pressure was equally well managed in both groups, though a lower level of treatment was required in the captopril group. The captopril treated patients exhibited favorable changes in several aspects of quality of life: sleep-related, gastrointestinal, and physical activity-related symptoms improved from baseline to end of follow-up. Drowsiness and the ability to concentrate significantly improved in the captopril group only (P <.01). Change in treatment from beta-blocker to captopril resulted in equally well controlled blood pressure on a lower drug dose. Moreover, the change to captopril had a positive impact on the quality of life.

High uric acid level during the first 20 weeks of pregnancy is associated with higher risk for gestational diabetes mellitus and mild preeclampsia.

Objective. To examine the association between uric acid (UA) level during the first 20 weeks of pregnancy and the development of gestational diabetes mellitus (GDM) and preeclampsia in the second half of pregnancy. Methods. The study population included registered births (n = 5507) between 2001 and 2007 in a tertiary medical center. The UA levels during the first 20 weeks of pregnancy were sorted by UA ≤ 2.4 mEq/L; UA = 2.5–4.0 mEq/L, UA = 4.1–5.5 mEq/L, and UA > 5.5 mEq/L. The linear-by-linear chi-square test and ROC curves were used to determine the association between UA level during the first 20 weeks and pregnancy complications. Multivariate analyses were performed to demonstrate whether UA level is an independent factor for the prevalence of preeclampsia and GDM. Results. Significant linear association was documented between UA level in the first 20 weeks and the prevalence of GDM and mild preeclampsia. The lowest and the highest prevalence of GDM were found in the UA ≤ 2.4 mEq/L group (6.3%) and in the UA > 5.5 mEq/L group (10.5%) (p < 0.001), respectively. Mild preeclampsia was diagnosed in 2.1% of the patients from the UA ≤ 2.4 mEq/L group, 3.3% from the UA = 2.5–4.0 mEq/L group, 5.3% from the UA = 4.1–5.5 mEq/L group, and 4.5% from the UA > 5.5 mEq/L group (p < 0.001). Three multiple logistic regression models controlling for maternal age showed that UA level is an independent risk factor for both GDM and mild preeclampsia. Conclusions. UA levels in the highest quartile of the normal range during the first 20 weeks of pregnancy are associated with higher risk for the development of GDM and mild preeclampsia.

Evaluating the response of mild hypertensives to biofeedback-assisted relaxation using a mental stress test

The objective of this study was to evaluate the long term effect of a program of biofeedback-assisted relaxation on hypertensive patients by mental stress test reactivity. Twenty mild hypertensive patients were subjected to a mental arithmetic stress test before and six months after completing biofeedback-assisted relaxation therapy. The therapy consisted of 10 sessions of biofeedback-assisted relaxation instruction and continuous home practise. The study group was compared to a control group. The biofeedback-assisted relaxation treatment produced a mild improvement in blood pressure control and decreased the dose of drugs used as well as a decrease in state-anxiety (p < 0.05). The stress-induced increases in systolic blood pressure, diastolic blood pressure, heart rate, galvanic skin response and skin temperature were all significantly attenuated six months after completion of biofeedback-assisted relaxation treatment.

Pheochromocytoma: cyclic attacks of hypertension alternating with hypotension

Background A 52-year-old woman was admitted to hospital with recurrent episodes of chest and abdominal pain, dyspnea, palpitations and diaphoresis. Continuous blood pressure recordings revealed rhythmic alternation between episodes of severe hypertension and episodes of hypotension. This cyclic hemodynamic crisis continued for 2 hours, with each cycle lasting around 15 min.Investigations Physical examination, electrocardiography, chest radiography, continuous intra-arterial pressure monitoring, blood and urine analysis, echocardiography, abdominal CT and 131I miodobenzylguanidine scanning.Diagnosis Pheochromocytoma—a catecholamine secreting tumor.Management Intravenous phentolamine and fluids, oral doxazosin and surgical removal of the tumor.

Can carotenoids attenuate vascular aging

One of the main manifestations of vascular aging is the development of atherosclerotic lesions. These lesions become unstable and prone to rupture due to the formation of reactive oxygen species (ROS) that are produced by the inflammatory milieu in the atherosclerotic plaque. The carotenoids are a group of red, orange, or yellow pigmented polyisoprenoid hydrocarbons synthesized by prokaryotes and higher plants. Lycopene, lutein, and other carotenoids have anti-oxidant activity that attenuates the inflammatory atherosclerotic process and delays vascular aging. This ability improves endothelial function due to the increase in bioavailability of NO. Carotenoid consumption also improves the metabolic profile, decreasing the incidence of diabetes, lowering LDL levels, and improving blood pressure control. The beneficial metabolic effect is translated to improvement in atherosclerosis, which is characterized by a decrease in carotid intima-media thickness. The favorable anti-atherosclerotic effect of carotenoids was also demonstrated in cross-sectional population studies showing a positive correlation between low carotenoid levels and adverse cardiovascular outcome. However, carotenoid utilization failed to decrease major cardiovascular and cerebrovascular events in randomized control double blind trials. The main still unanswered question is: What is the therapeutic role of carotenoids in atherosclerotic disease? Is their anti-atherosclerotic effect restricted to primary prevention or can it alter the prognosis of existing cardiovascular and cerebrovascular diseases?

N-Terminal Rather Than Full-Length Osteopontin or Its C-Terminal Fragment Is Associated With Carotid-Plaque Inflammation in Hypertensive Patients

BACKGROUND Hypertensive patients develop carotid atherosclerotic plaques with enhanced inflammation. Full-length osteopontin (OPN-FL), a multifunctional protein whose levels are elevated in association with atherosclerosis, is cleaved by thrombin and matrix metalloproteinases to form a C-terminal and a putatively biologically active N-terminal fragment (OPN-C, OPN-N, respectively). We conducted a study to examine whether plaque inflammation in hypertensive patients corresponds to the expression of OPN or of its cleaved forms or both. METHODS We collected 42 carotid plaques from 41 consecutive hypertensive patients during carotid endarterectomy. Plaque tissue was used to measure matrix metalloproteinase-12 (MMP-12) and OPN proteins, and for the classification of plaques as showing low- or high-degree inflammation through histological and immunohistochemical evaluation. RESULTS Fifteen highly inflamed plaques and 27 plaques with characteristics of low-grade inflammation were collected. Moderate to heavy staining for OPN characterized 87% of the plaques with high-degree inflammation but only 44% of those with low-degree inflammation, corresponding to the percentages of plaques that were heavily stained for the macrophage marker CD68 (93% versus 26%, respectively, P < 0.01). Western blot analysis showed that the abundance of OPN-FL and OPN-C was comparable in the two groups. However, the abundance of OPN-N was significantly greater in the highly inflamed plaques (median, 3.8 (range, 0.8-7.3) vs. median, 0.9 (range, 0.2-1.5); P = 0.017, respectively). The abundance of MMP-12 was significantly greater in the high- than in the low-degree plaque inflammation group (4.8 (range 1.9-8.8) vs. 1.1 (range 0.3-1.4), respectively; P = 0.03). CONCLUSIONS The N-terminal fragment of osteopontin, rather than OPN-FL or OPN-C, is associated with carotid plaque inflammation in hypertensive patients. Future studies should assess whether targeting OPN cleavage could present a new approach to preventing high-risk carotid plaques.