No abstract

Apolipoprotein E (apoE -ε2, ε3, ε4 alleles) plays a role in the regulation of lipid metabolism, with the ε4 considered to be a risk factor for coronary artery disease (CAD). We aimed to evaluate the apoE polymorphisms in Brazilians with CAD and their influence on the lipid profile and other risk factors (hypertension, diabetes mellitus, smoking). Two hundred individuals were examined: 100 patients with atherosclerosis confirmed by coronary angiography and 100 controls. Blood samples were drawn to determine apoE polymorphisms and lipid profile. As expected, the ε3 allele was prevalent in the CAD (0.87) and non-CAD groups (0.81; P = 0.099), followed by the ε4 allele (0.09 and 0.14, respectively; P = 0.158). The ε3/3 (76 and 78%) and ε3/4 (16 and 23%) were the most common genotypes for patients and controls, respectively. The lipid profile was altered in patients compared to controls (P < 0.05), independently of the ε4 allele. However, in the controls this allele was prevalent in individuals with elevated LDL-cholesterol levels only (odds ratio = 2.531; 95% CI = 1.028-6.232). The frequency of risk factors was higher in the CAD group (P < 0.05), but their association with the lipid profile was not demonstrable in ε4 carriers. In conclusion, the ε4 allele is not associated with CAD or lipid profile in patients with atherosclerosis. However, its frequency in the non-CAD group is associated with increased levels of LDL-cholesterol, suggesting an independent effect of the ε4 allele on lipid profile when the low frequency of other risk factors in this group is taken into account.

Objective: This study aimed at assessing the endothelial function in patients with Type 1 diabetes (T1DM) using flow-mediated dilation (FMD) response and carotid artery intima-media thickness (CIMT). Materials and methods: This study enrolled 32 T1DM patients (mean disease duration 4.1 years) and 28 age-matched controls (CTL Group). Endothelial function and CIMT were assessed with high-resolution ultrasound using standardized offline measurements. Results: FMD was significantly lower in patients in the T1DM Group (8.9 ± 3.2%) compared with those in the CTL Group (13.3 ± 4.3%; P-value < 0.0001). Similarly, CIMT differed significantly between T1DM patients (0.525 ± 0.03 mm) and controls (0.508 ± 0.03 mm; P-value = 0.041). Even though, the values are within the normal range for age. Conclusions: Patients with T1DM have impaired endothelial function characterized by reduced FMD when compared to controls. However, vascular remodeling as seen by increases in CIMT was not found in this study. Arch Endocrinol Metab. 2017;61(6):542-9

he vascular endothelial surface has an intrinsic capacity to prevent cardiovascular disease through modulation of arterial tone, thrombosis, inflammation and structural changes by releasing vasoactive agents, in particular, nitric oxide (NO). [1][2][3] Endothelial cells in hypertensive disease are the target of blood pressure increases, which impair endothelial function and precede cardiovascular structural changes such as vascular and myocardial remodeling and hypertrophy. [4][5][6] Abnormal endotheliumdependent vascular relaxation in patients with primary hypertension has been described 7 and is associated with abnormalities of the NO system. 8,9 Low-renin (volume-dependent 10 hypertension (VDH)) is an important subset of primary hypertension (25-30% of patients), and is characterized by specific biological and pathophysiological clinical features such as salt-sensitivity and increased diuretic response, as well as heterogeneous blood pressure increments in response to high dietary salt intake. [11][12][13] Animal studies have demonstrated that reduced NO production favors the development of salt-sensitive hypertension. 14 Studies in salt-sensitive hypertensive patients have reported defective endothelium-dependent vasodilation in the forearm assessed using strain-gauge plethysmography, suggesting that abnormalities of the NO system are implicated in the development of salt-sensitive hypertension. [15][16][17] However, the association between the low-renin state and endothelial dysfunction has not been adequately investigated and the pathophysiological mechanisms involved remain unclear. Carotid arterial wall thickness assessed by intima-media thickness (IMT) has been shown to have an association with cardiovascular risk factors of atherosclerosis such as hypertension, hypercholesterolemia, diabetes and smoking. [18][19][20] Recent evidence has shown that an increased carotid IMT is a strong predictor of coronary heart disease and strokes. 21 Vascular reactivity evaluated by flow-mediated dilation (FMD) 22,23 and the vascular remodeling reflected by carotid IMT measurements are adequately assessed by highresolution ultrasound examinations. 19 The aim of this study was to evaluate the FMD in the brachial artery and vascular remodeling of the distal common carotid artery by measuring the IMT using highresolution ultrasound in hypertensive subjects subdivided according to plasma renin activity (PRA) as either volume dependent (VDH; low-renin, PRA <0.6 ng· ml -1 · h -1 ) or renin dependent (RDH; PRA >0.6 ng·ml -1 ·h -1 ) after balanced urinary sodium excretion. 11,12 (VDH) is not yet known. To evaluate this, flow-mediated dilation (FMD) of the brachial artery and the carotid intima-media thickness in the distal common carotid artery were measured and compared between renin-dependent mild-hypertensive patients (RDH) and controls. Method and ResultsThe study group comprised 40 mild-hypertensive patients and 25 controls. Plasma renin activity (PRA), plasma aldosterone concentration, angiotensin II and nitrite/nitrate...

BackgroundResistant hypertension is characterized when the blood pressure (BP) remains above the recommended goal after taking three antihypertensive drugs with synergistic actions at their maximum recommended tolerated doses, preferably including a diuretic. Identifying the contribution of intravascular volume and serum renin in maintaining BP levels could help tailor more effective hypertension treatment, whether acting on the control of intravascular volume or sodium balance, or acting on the effects of the renin-angiotensin-aldosterone system (RAAS) on the kidney.Methods/designThis is a randomized, open-label, clinical trial is designed to compare sequential nephron blockade and its contribution to the intravascular volume component with dual blockade of the RAAS plus bisoprolol and the importance of serum renin in maintaining BP levels. The trial has two arms: sequential nephron blockade versus dual blockade of the RAAS (with an angiotensin converting enzyme (ACE) inhibitor plus a beta-blocker) both added-on to a thiazide diuretic, a calcium-channel blocker and an angiotensin receptor-1 blocker (ARB). Sequential nephron blockade consists in a progressive increase in sodium depletion using a thiazide diuretic, an aldosterone-receptor blocker, furosemide and, finally, amiloride.On the other hand, the dual blockade of the RAAS consists of the progressive addition of an ACE inhibitor until the maximum dose and then the administration of a beta-blocker until the maximum dose. The primary outcomes will be reductions in the systolic BP, diastolic BP, mean BP and pulse pressure (PP) after 20 weeks of treatment. The secondary outcomes will evaluate treatment safety and tolerability, biochemical changes, evaluation of renal function and recognition of hypotension (ambulatory BP monitoring (ABPM)). The sample size was calculated assuming an alpha error of 5% to reject the null hypothesis with a statistical power of 80% giving a total of 40 individuals per group.DiscussionIn recent years, the cost of resistant hypertension (RH) treatment has increased. Thus, identifying the contribution of intravascular volume and serum renin in maintaining BP levels could help tailor more effective hypertension treatment, whether by acting on the control of intravascular volume or sodium balance, or by acting on the effects of the RAAS on the kidney.Trial registrationSequential Nephron Blockade vs. Dual Blockade Renin-angiotensin System + Bisoprolol in Resistant Arterial Hypertension (ResHypOT). ClinicalTrials.gov, ID: NCT02832973. Registered on 14 July 2016. First received: 12 June 2016. Last updated: 18 July 2016.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-2343-3) contains supplementary material, which is available to authorized users.