Vascular Complications Of Hypertension Research Articles

Association of T-cell receptor repertoires and arterial stiffness in patients with essential hypertension.

Abnormal immune responses, particularly T-cell activity, are linked to vascular complications in hypertension, but mechanisms remain unknown. Our study aims to explore the association between arterial stiffness, assessed by brachial-ankle pulse wave velocity (baPWV), and T-cell receptor (TCR) repertoires in essential hypertension patients, focusing on understanding the role of T cells in the development of arterial stiffness in this population. The study included 301 essential hypertension patients and 48 age-matched normotensive controls. Essential hypertension patients were stratified into high (baPWV ≥1400 cm/s, n = 213) and low (baPWV <1400 cm/s, n = 88) baPWV groups. High-throughput sequencing analyzed peripheral TCRβ repertoires. Significant TCRβ repertoire differences were observed between essential hypertension and normotensive groups, as well as between high and low baPWV essential hypertension subgroups. Specifically, patients in the high baPWV group exhibited notable variations in the utilization of specific TCR beta joining (TRBJ) and variable (TRBV) genes compared to the low baPWV group. These alterations were accompanied by reduced TCRβ diversity (represented by diversity 50 s), increased percentages of the largest TCRβ clones, and a higher number of TCRβ clones exceeding 0.1%. The presence of specific TCRβ clones was detected in both groups. Furthermore, reduced diversity 50s and elevated percentages of the largest TCRβ clones were independently correlated with baPWV, emerging as potential risk factors for increased baPWV in essential hypertension patients. TCR repertoires were independently associated with arterial stiffness in patients with essential hypertension, implicating a potential role for dysregulated T-cell responses in the pathogenesis of arterial stiffness in this patient population.Trial registration: ChiCTR2100054414.

Evaluation of YKL-40, C- reactive protein and uric acid levels in hypertensive patients

Hypertension is a major public health problem and leads to severe complications such as cardiovascular disease, stroke, renal and other vascular complications. YKL-40 is a human glycoprotein related to chitinase protein family encoded by chitinase 3‐like 1 (CHI3L1) gene. Recently many studies reported that YKL-40 play a role in the progression of atherosclerosis and other diseases. So, in this view the present study focused to evaluate YKL-40 levels and to find out the association with C- reactive protein (CRP) and uricacid in hypertensive patients.The present study was to assess YKL-40 levels in hypertensive patients compared with healthy volunteers and to correlate these levels with C- Reactive protein and uricacid. Fifty hypertensive patients with 35 to 50 years age group were selected according to JNC-8 for this study and 50 healthy volunteers age matched subjects were selected as controls. Serum YKL-40 and CRP was estimated by ELISA, uric acid and other routine investigations were carried out by ERBA EM-360 fully automated analyzer. YKL-40, CRP, uricacid levels were significantly increased in hypertensive patients compared with healthy volunteers. Serum YKL-40 levels positively correlated with CRP Uricacid, triglycerides, LDL, systolic blood pressure and negative correlation with HDL cholesterol levels. YKL-40 is considered as potential diagnostic marker for the assessment of vascular complications in hypertension. Regular monitoring might be useful for reduction of vascular complications in hypertensive patients. Further longitudinal studies are required for confirm it.

Polymorphisms in the 5’-UTR region of IL-10RA gene are associated with chronic kidney disease

Chronic kidney disease (CKD), characterized by the progressive, irreversible loss of kidney function, has been a significant socioeconomic burden. Thus, identifying potential treatment targets and incipient biological risk indicators for CKD prediction is crucial. Recently several studies revealed that IL-10, IL-10RA, and IL-10RB genes were involved in the development of vascular complications in hypertension and stroke. The purpose of this study was to evaluate the association between CKD and IL-10, IL-10RA, and IL-10RB gene polymorphisms in the Korean population. Ninety-two CKD patients and 312 control subjects participated in the study. Blood samples were drawn for biochemical measurements and genetic polymorphism analysis. To analyze the genotypes of each single nucleotide polymorphism (SNP), PCR products were sequenced by a DNA analyzer. The four SNPs of the IL-10RA gene showed significant associations between CKD and the control group in the codominant1 (rs2228054, rs2228055, and rs9610, OR = 0.48, 95% CI = 0.28–0.82, p = 0.007; rs2256111, OR = 0.49, 95% CI = 0.29–0.83, p = 0.008, respectively), dominant (rs2228054, rs2228055, and rs9610, OR = 0.59, 95% CI = 0.36–0.95, p = 0.028; rs2256111, OR = 0.60, 95% CI = 0.38–0.97, p = 0.037, respectively), and over-dominant model (rs2228054 and rs2228055, OR = 0.47, 95% CI = 0.28–0.79, p = 0.0034; rs9610, OR = 0.48, 95% CI = 0.29–0.80, p = 0.0037; rs2256111, OR = 0.49, 95% CI = 0.29–0.80, p = 0.0039). The four SNPs of IL-10 showed significant associations with the estimated glomerular filtration rate (eGFR) and C-reactive protein (CRP), with the minor homozygote genotype of each SNP associated with lower eGFRs and decreased CRP levels ( p &lt; 0.05, p = 0.001, respectively). The two SNPs of IL-10RA showed significant associations with the CRP levels ( p &lt; 0.05). The two SNPs of IL-10RB were significantly associated with the eGFR, with the minor homozygote genotype of each SNP associated with lower eGFRs ( p &lt; 0.01). Our results show that IL-10RA gene variants are associated with CKD development. Additionally, this study suggests that SNPs of IL-10RA were associated with CRP levels in CKD.

Target Organ Damage in Hypertension

Target Organ Damage in Hypertension

Blockade of Sympathetic Nervous System Activity by Rilmenidine Increases Plasma Adiponectin Concentration in Patients With Essential Hypertension

Adiponectin is an adipose tissue-specific protein with antiatherogenic and insulin-sensitizing properties. In patients with essential hypertension plasma adiponectin levels are lower than in healthy subjects. It is hypothetized that low plasma adiponectin concentration may be involved in the pathogenesis of vascular complications in hypertension. The aim of the study was to evaluate the effect of 6 months of antihypertensive therapy with rilmenidine on plasma adiponectin concentration in patients with essential hypertension. In 20 patients with essential hypertension (mean age 39 +/- 14 years; 11 F, 9 M; mean duration of hypertension 8 +/- 9 years) plasma adiponectin concentration (ELISA; B-Bridge International, San Jose, CA), insulin sensitivity (metabolic clearance of glucose-M value and M/plasma insulin ratio) by the euglycemic-hyperinsulinemic glucose clamp technique, and body fat content (DEXA) were estimated twice, before and after 6 months of antihypertensive monotherapy with rilmenidine (daily dose 1 to 2 mg). The 6 months of treatment with rilmenidine resulted in a significant decrease of systolic (P = .007), diastolic (P = .002), and mean arterial blood pressure (P = .002), no significant change of body mass index (27.7 +/- 4.7 and 27.6 +/- 4.4 kg/m(2)), total body fat content (25.4 +/- 7.3 and 24.9 +/- 6.8 kg), and insulin sensitivity parameters (M value 6.0 +/- 2.5 and 5.8 +/- 4.3 mg/kg/min and M/plasma insulin ratio 7.4 +/- 5.0 and 6.9 +/- 4.3 mg/kg/min/mU/L). However after 6 months of treatment with rilmenidine a significant increase in plasma adiponectin concentration (from 12.5 +/- 6.1 to 16.9 +/- 11.1; P = .0002) was observed. Antihypertensive therapy with rilmenidine correlates with an increase of plasma adiponectin concentration without any significant changes of insulin sensitivity and body fat content in patients with essential hypertension.

Opinion: What Clinical Insights from the Early Days of Dialysis Are Being Overlooked Today?

problem of extracellular fluid hydration was recog­ nized in early papers published on It was recognized that blood pressure was largely influenced by fluid accumulation and that increased treatment fre­ quency improved control. In Scribner et al.'s (1) remarks on hypertension in an American Society for Artificial Internal Organs (ASAIO) Transactions paper in 1960, he mentions the combination of dietary sodium restriction and ultrafiltration during dialysis permits regulation of extracellular fluid volume. In time, it may be possible to clarify importance of size of extracellular space in etiology of hypertension and effect its size may have on modifying response to antihyper­ tensive therapy. Eberhard Ritz wrote a guest commen­ tary when this paper was reprinted in Milestones of series in Journal of American Soci­ ety of Nephrology in 1998 (2). He remarked that The genesis of hypertension in dialyzed patient is cer­ tainly multifactorial and complex, but in this very first article Scribner immediately grasped importance of hypervolemia. It is almost amusing to note that very recently, authors still felt it necessary to point to importance of hypervolemia in increasingly confused discussion on hypertension and optimal long-term blood pressure management on dialysis. How well proven is Scribner's prediction that vascular complications of hypertension will become a major problem, if these patients live very long. Now, some 40 years later, hypertension is very common, most dialysis patients are overhydrated, and left ventricular mass is increased. Dialysis is usually without incidents since plasma refilling is easy and hypovolemia is not a problem. Dry weight is a much abused term since, routinely, no serious attempt is made to achieve it (I am generalizing) and, as a result, continuing cardiac damage is inexorable. paradoxical nature of relationship of blood pressure level to outcome has added to relative lack of will to decrease extracellular fluid to normal and therefore treat hypertension. As demonstrated by Zager et al. (3) and others, both very low and very high blood pressures are associated with increased mortality, with

Ramipril improves hemodynamic recovery but not microvascular response to ischemia in spontaneously hypertensive rats

Background Angiotensin converting enzyme (ACE) inhibition exerts positive effects on the microvasculature of normotensive animals, although this concept is not universally accepted. Recently, ACE inhibitors have been suggested to be useful for rescue in peripheral ischemia. Methods We investigated whether chronic treatment with the ACE inhibitor ramipril may have a positive impact on the defective healing response to ischemia that is typical of spontaneously hypertensive rats (SHR). Unilateral limb ischemia was induced in 20-week-old SHR by surgically removing the left femoral artery. Rats were allowed to regain consciousness and then were randomly allocated to treatment with ramipril (1 mg/kg body weight in drinking water) or vehicle for 28 days. Results The SHR failed to develop reparative angiogenesis in response to ischemia, thus having inadequate perfusion recovery. Ramipril reduced both tail-cuff systolic blood pressure (180 ± 7 v 207 ± 2 mm Hg in the vehicle group at 28 days, P < .05) and intra-arterial mean blood pressure (115 ± 6 v 135 ± 5 mm Hg in the vehicle group, P < .05). These effects were associated with increased responsiveness to endothelium-dependent vasodilatation by acetylcholine. Treatment with ramipril did not influence muscular capillary and arteriole density but accelerated the rate of perfusion recovery, leading to complete healing within 28 days after surgery. Conclusions These results indicate that ACE inhibition by ramipril may be useful for the treatment of peripheral vascular complications in hypertension.

Endothelial dysfunction in hypertension.

The endothelium modulates the tone of the underlying vascular smooth muscle by releasing relaxing factors, including prostacyclin, nitric oxide (NO), and endothelium-derived hyperpolarizing factor (EDHF). In most types of hypertension, endothelium-dependent relaxations are impaired because of a reduced production and/or action of endothelium-derived NO and EDHF. In essential hypertension, endothelium-dependent relaxations are reduced because of a concomitant release of vasoconstrictor prostanoids (endoperoxides and thromboxane A2). These prostanoids may be produced in the vascular smooth muscle rather than in the endothelium. The endothelial dysfunction observed in hypertension is likely to be a consequence rather than a cause of the disease, representing premature aging of the blood vessels due to the chronic exposure to the high blood pressure. The endothelial dysfunction can be improved by antihypertensive therapy, favoring the prevention of the occurrence of vascular complications in hypertension.

Drug therapy for hypertension and hyperlipidemia.

Coronary heart disease and other vascular complications of hypertension and hyperlipidemia are leading causes of morbidity and mortality and adding to health care costs in the United States. Nonpharmacologic and pharmacologic treatment are available and have been successful in reducing the frequency and severity of these conditions. Appropriate detection, confirmation, evaluation, and treatment of at-risk individuals by the health care provider are the focus of the discussion that follows.

Determining Hypertensive End-Organ Damage in Trials

The determination of hypertensive end-organ damage is the most crucial aspect of any long-term hypertension trial. Definition of inclusion criteria and withdrawal rules, and the evaluation of the treatment regimen in light of the cardiovascular prognosis, are all largely dependent on the trialists' abilities to identify vascular lesions and/or functional deteriorations of the major target organs. Although the vascular complications of hypertension tend to be diffuse, some organs and tissues are particularly sensitive: brain, eye fundus, heart, conduit arteries, and kidneys. To achieve a modicum of diagnostic accuracy, trial investigators will have to combine clinical acumen with a selection of ancillary techniques. This article reviews the compromises resulting from weighing the available technological potential against such conflicting factors as convenience and compliance of trial subjects, and expenditure.

Sir Horace Smirk. Pioneer in drug treatment of hypertension.

Sir Horace Smirk deserves much of the credit for establishing the benefits of reducing blood pressure. He was one of the main early proponents of the idea that it was the raised intra-arterial pressure itself that caused many of the cardiac and vascular complications of hypertension. His training in both pharmacology and internal medicine enabled him to devise practical methods for successful treatment of hypertension with ganglion blocking drugs such as hexamethonium. The major clinical benefits that followed such drug treatment proved a great stimulus to the development of drugs with fewer disadvantages and to widespread acceptance of the beneficial effects of antihypertensive drug treatment.

Vascular Effects of Perindopril

Vascular remodeling is central to the pathophysiology of hypertension and atherosclerosis. The effects of antihypertensive drugs on this process are important to consider from a mechanistic and a pathogenetic point of view in relation to vascular complications of hypertension, e.g., decrease in vascular reserves, shift in cerebral blood flow autoregulation and atherosclerosis development. There is now evidence that, in addition to several other growth factors, vasoactive peptides such as angiotensin II may act as vascular smooth muscle growth promoting substances. Based on these data, the effects of perindopril, a potent and long-lasting angiotensin-converting enzyme (ACE) inhibitor, on structural and mechanical properties of the arterial wall, have been studied in animal models of hypertension as well as in humans. Perindopril completely reversed aortic medial hypertrophy and arterial stiffening observed in renovascular hypertensive rats. Similar benefits were reported in mesenteric resistance vessels of spontaneously hypertensive rats. The effect of perindopril was totally in keeping with potent inhibition of vascular ACE and emphasized the potential role of angiotensin II as a vascular growth modulator. Clinical studies confirmed animal experiments; both suggest that increases in arterial compliance and distensibility following perindopril is likely to be related to drug-induced modification of the arterial wall, at least partially independently of blood pressure reduction. The increase in arterial compliance was associated with a selective decrease in pulse pressure, a finding that is important, not only for the arterial wall, but also for the structure and function of the hypertensive heart.

The arterial smooth muscle cell in systemic hypertension

Both the pathogenesis and vascular complications of hypertension appear to involve change in vascular smooth muscle cell (SMC) structure and function. Recent data on vascular SMC biology are reviewed. Specific questions that should be addressed by future research on SMC polyploidy in hypertension; SMC differentiation, growth and function; SMC hypertrophy and hyperplasia in hypertension; and hypertension, vascular aging and atherogenesis are posed.

Effects of prazosin on platelet aggregation and plasma beta-thromboglobulin in essential hypertension

Platelet aggregation in response to adenosine 5'-diphosphate (ADP) and plasma levels of beta-thromboglobulin (beta-TG) were followed in 10 subjects with essential hypertension without any manifest vascular complications and in 14 age-matched normotensive controls. The effects of prazosin on blood pressure and platelet function were also examined in the subjects with hypertension. Platelet aggregation in response to 5 microM ADP was significantly greater in the subjects with hypertension than in the controls. Plasma beta-TG levels were 30% higher in the subjects with hypertension than in the controls. The increased platelet aggregation and plasma levels of beta-TG in the subjects with hypertension returned to normal after the blood pressure had been controlled by prazosin therapy. Our data suggest that the aggregation and release reactions of platelets increase in uncomplicated essential hypertension, and that prazosin may have some beneficial effects on the prevention of vascular complications in hypertension by normalizing platelet function as well as by lowering blood pressure.

How Should Hypertension During Pregnancy Be Managed?: An Internist's Approach

Hypertension may occur during pregnancy under different clinical circumstances. One cause is toxemia, a systemic disease unique to pregnant women, in which hypertension is associated with proteinuria, CNS irritability, hepatic and renal functional abnormalities, and, in fulminant disease, a consumptive coagulopathy. Since it is clear in the non-pregnant population that the vascular complications of hypertension can be prevented with antihypertensive therapy and since toxemia is the most common cause of maternal mortality, there is no reason not to treat pregnant women with hypertension.

Nephrology: An Annotated Bibliography of Recent Literature

Nephrology: An Annotated Bibliography of Recent Literature

Plasma Renin Levels and Vascular Complications in Hypertension

Plasma renin levels, measured in 39 untreated patients in 1967, under conditions of sodium loading and sodium depletion have been related to the incidence of stroke and myocardial infarction. Renin levels were not significantly different in patients with or without vascular complications. Out of 13 patients with persistently low renin levels 6 had suffered either a stroke or a myocardial infarction and 7 had not. Plasma renin levels were also measured in 116 treated hypertensive patients. There was no relation between plasma renin level and vascular complications. It is concluded that levels of plasma renin are not a reliable index of the probability of hypertensive patients suffering a stroke or myocardial infarction.