Hypertensive Vascular Changes Research Articles

Malignant hypertension as a rare cause of thrombotic microangiopathy associated with end-stage renal disease

Malignant hypertension (MH) can precipitate and worsen renal thrombotic microangiopathy. Also, renal thrombotic microangiopathies (TMA) can cause malignant hypertension. Case reports regarding this clinical presentation are limited. A 36-year-old man presented with low urine output and bilateral leg swelling for five days with two episodes of haemoptysis. He was identified as a patient with hypertensive emergency with hypertension mediated organ damage (HMOD) in cardiac and renal functions with thrombotic microangiopathy. Renal biopsy revealed focal acute tubular injury with moderate tubulointerstitial nephritis and hypertensive vascular changes. Multiple anti-hypertensive medications were used for adequate blood pressure control. Despite that, the patient had worsening renal function, and eventually became dependent on haemodialysis. Malignant hypertension has to be considered as one of the aetiologies of TMA as it can lead to end-stage renal disease (ESRD) and poor outcomes. Diagnosis is difficult when both entities are presenting together.

Abstract P451: Clinical, Demographic, and Geographic Trends in Cardiovascular Causes of Deaths Associated With Homelessness

Background: Cardiovascular disease (CVD) remains the leading cause of death in the United States, accounting for a staggering 928,741 fatalities in 2020. Persons experiencing homelessness (PEH) have a 3- to 5-fold excess risk of mortality from CVD, which ranks as a predominant cause of mortality in this setting, second only to overdose deaths. The elevated incidence of CVD mortality for PEH may be attributable to complex interactions between social determinants and risk factors that include delayed diagnosis, limited healthcare access, heightened smoking rates, and the increased incidence of diabetes and hypertension among other factors. Methods: This study utilized records from the county medical examiner in the third most populous county in the US from 2021-2022, focusing exclusively on CVD mortality in medicolegal cases to analyze the impact of specific risk factors for PEH. All medicolegal deaths involving CVD were analyzed to determine relative frequencies of associated or secondary causes between housed and PEH deaths along with insights into the influence of age, race, and gender. Results: The examination of the CVD mortality in PEH cases in 2021 (n=52) and 2022 (n=71) revealed important trends, yielding an estimated, unadjusted mortality rate of 23 deaths per 1,000 person-years-exposed-to-homelessness (compared to around 2 per 1,000 person-years in population). The mean age for CVD deaths in PEH was 58.6 and 60.6 years in 2021 and 2022 respectively (males increased 57.8 to 61.3 years; females increased 58.8 to 60.6 years), while the proportion of CVD deaths increased among males (30-32%) but decreased for females (29-22%). This widening gap in the percent of CVD deaths occurring among male PEH and female PEH is evident where the gap stood at 1% in 2021 but expanded to 10% in 2022 (p=n.s.). Racial disparities show a rapid increase in CVD deaths for Black/African American PEH (26.1-33.7%). Top conditions associated with CVD deaths were hypertension and atherosclerosis, regardless of housing status at death. Diabetes mellitus (25%), obesity (22%), and chronic ethanolism (16%) round out the top 5 conditions for housed decedents, while among the unhoused COPD (19.7%), CHF (12.7%), and diabetes mellitus (11.3%) were the most common. Conclusion: Exposure to homelessness and housing instability is a major driver of cardiovascular mortality. These findings suggest that PEH face ongoing challenges in the management and prevention of CVD. Additionally, CVD deaths associated with homelessness often point foremost to hypertensive and atherosclerotic vascular changes, contributing to natural deaths. These conditions point to persistent risk factors such as limited healthcare access, high smoking rates (contributing to COPD), and higher incidences of diabetes and hypertension. Additional research is needed on underlying causes of the identified gender disparities.

Fatal cerebrovascular accident in a captive red panda (Ailurus fulgens fulgens) with concurrent amdoparvovirus infection

We report the pathological and molecular findings in an adult male Himalayan red panda (Ailurus fulgens fulgens) whose death was attributed to parenchymal brain haemorrhage (PBH) of the thalamus. Post-mortem examination revealed severe, acute PBH and intraventricular haemorrhage with major involvement of the thalamus, as well as scattered chronic microinfarctions. Vascular disease in the brain and other organs was suggestive of systemic hypertension. Histological lesions included arteriolar hyalinosis and varying degrees of arteriosclerosis, arterial tunica media hypertrophy and hyperplasia and infiltration of arterial walls by lipid-laden macrophages. Other relevant findings included marked myocardial fibrosis, lymphoplasmacytic tubulointerstitial nephritis, lymphoplasmacytic meningoencephalitis and chronic mitral valve degeneration. The changes in the cerebral vasculature were consistent with hypertensive encephalopathy and a cerebrovascular accident, specifically PBH, which has not been previously reported in this species. Additionally, polymerase chain reaction analysis for red panda amdoparvovirus (RPAV) was positive in the brain and kidneys. Preceded by hypertensive vascular changes and brain microinfarctions, sudden death in this animal likely resulted from fatal PBH with intraventricular haemorrhage. The clinicopathological role of RPAV infection is unknown in this case, although its contribution to the chronic renal disease is considered possible in the context of our current understanding of RPAV-associated pathology.

Vascular Changes in Hypertension: Is There Cell Death Involved? – A Narrative Review

"Background: Cardiovascular disease can be triggered and accelerated by hypertension and the underlying changes in the structure and function of arteries. The purpose of this review is to explore some vascular changes that occur in hypertension as a consequence of the imbalance between cell proliferation and cell death, processes that play an important role in stabilizing the thickness of the arterial wall during vascular remodeling. Methods: The authors conducted research through PubMed and Google Scholar databases using the following search formula: (hypertensive*) AND ((vascular modifications)) OR (vascular changes)) AND (cell death). Results: From 40 articles, only 17 publications were included in this study, taking into account four processes that can be preceded or followed by inflammation and depend on the interaction between local growth factors, vasoactive substances, and hemodynamic stimuli: Cell proliferation and growth; Cell migration; Cell death; Degradation or reorganization of extracellular matrix. Conclusions: To summarize, maladaptive vascular changes in hypertension can represent a major argument for prompt and maximal therapeutic intervention in patients with high cardiovascular risk. Moreover, they can represent an important step in discovering new markers of cardiovascular risk and in the development of new targeted therapies for different pathways of cellular signaling through which the reversibility of abnormal vascular changes could be obtained. "

Lung damage created by high tidal volume ventilation in rats with monocrotaline-induced pulmonary hypertension

BackgroundRats with chronic hypoxia-induced non-inflammatory pulmonary hypertension (PH) are resistant to ventilator-induced lung injury. We investigated the effect of high tidal volume ventilation in another model of PH, monocrotaline (MCT)-induced PH, which is a type of inflammatory PH.MethodsPH was induced in rats by subcutaneous injection with 60 mg/kg MCT. Normal control rats, rats at 2 weeks after MCT injection (MCT2), and rats at 3 weeks after MCT injection (MCT3) were ventilated with low tidal volume (LV, 6 mL/kg) or high tidal volume (HV, 35 mL/kg) for 2 h with room air without positive end-expiratory pressure. Arterial oxygen pressure (PaO2) and Evans blue dye (EBD) extravasation were measured. Hypertensive pulmonary vascular remodeling was assessed morphometrically by the percentage of muscularized peripheral pulmonary arteries (%Muscularization) and the media wall thickness to external diameter ratio, namely percentage medial wall thickness (%MWT). To assess inflammation, lung IκB protein and cytokine mRNA expression levels were assessed.ResultsBaseline mean pulmonary arterial pressure was significantly higher in MCT rats (normal, 15.4 ± 0.5 mmHg; MCT2, 23.7 ± 0.9; and MCT3, 34.5 ± 1.5). After 2-h ventilation, PaO2 was significantly lower in the HV groups compared with the LV groups in normal and MCT2 rats, but not in MCT3 rats. Impairment of oxygenation with HV was less in MCT3 rats compared with normal and MCT2 rats. Among the HV groups, MCT3 rats showed significantly lower levels of EBD extravasation than normal and MCT2 rats. HV significantly downregulated IκB protein expression in normal and MCT3 rats and increased IL-6, MCP-1, CXCL-1 (MIP-1), and IL-10 mRNA levels in MCT3 rats. %Muscularization, %MWT, and the expression of lung elastin were significantly higher in MCT3 rats than in normal and MCT2 rats.ConclusionWe found that HV-associated damage might be reduced in MCT-induced PH rats compared with normal rats. The results of this and earlier studies suggest that hypertensive pulmonary vascular structural changes might be protective against the occurrence of ventilator-induced lung injury, irrespective of the etiology of PH.

Evaluation of arterial stiffness and central blood pressure by oscillometric method in normotensive offspring of hypertensive parents

Children with a family history of hypertension have higher blood pressure and hypertensive pathophysiological changes begin before clinical findings. Here, the presence of arterial stiffness was investigated using central blood pressure measurement and pulse wave analysis in normotensive children with at least one parent with essential hypertension. Twenty-four-hour ambulatory pulse wave analysis monitoring was performed by oscillometric method in a study group of 112 normotensive children of hypertensive parents aged between 7 and 18 comparing with a control group of 101 age- and gender-matched normotensive children of normotensive parents. Pulse wave velocity, central systolic and diastolic blood pressure, systolic, diastolic and mean arterial blood pressure values were higher in the study group than the control group (p < 0.001, p = 0.002, p = 0.008, p = 0.001, p = 0.005, p = 0.001, p = 0.001, respectively). In all age groups (7-10, 11-14, and 15-18 years), pulse wave velocity was higher in the study group than the control group (p < 0.001). Pulse wave velocity was higher in children whose both parents are hypertensive compared to the children whose only mothers are hypertensive (p = 0.011). Pulse wave velocity values were positively correlated with age, weight, height, and body mass index (p < 0.05). Higher pulse wave velocity, central systolic and diastolic blood pressure values detected in the study group can be considered as early signs of hypertensive vascular changes. Pulse wave analysis can be a reliable, non-invasive, and reproducible method that can allow taking necessary precautions regarding lifestyle to prevent disease and target organ damage by detecting early hypertensive changes in genetically risky children.

TISSUE NA+ EXCESS UPON EXPERIMENTAL SALT-LOADING IS SYSTEMIC AND REFLECTS ISOTONIC OEDEMA

Objective: Skin was identified as a large depot for Na+ accumulation. Its proposed water-independent (hypertonic) nature has the potential to induce local pathogenic changes, including activation of the osmotic stress sensor TonEBP-mediated lymphangiogenic signalling. Blockade of this response led to salt-sensitive hypertension. Our study tested the hypertonic nature and organ-specific distribution of tissue Na+ accumulation upon salt-loading. Design and method: Twelve weeks-old male and female stroke-prone spontaneously hypertensive (SHRSP) and control Wistar-Kyoto (WKY) rats were treated with 1% NaCl in drinking water (high salt, HS) or normal water (NS) for 3 weeks (n = 8–10/sex/group). Tissue water and Na+/K+ content, as well as TonEBP gene expression in abdominal skin, liver, lung, myocardium and skeletal muscle were measured by gravimetric approach (wet–dry weight), flame photometry and qRT-PCR, respectively. The functional effects of in-vivo and ex-vivo exposure of resistance arteries to salt excess (HS treatment and incubation in +15 mM NaCl, respectively) were assessed and compared by wire myography. Results: Tissue Na+ increased in skin (+20.7%), but also liver (+10.3%), lungs (+14.8%) and skeletal muscle (+23.6%) in HS-SHRSP compared to NS; apart from skeletal muscle, it was consistently paralleled by water (skin: +14.1%; liver: +4.8%; lungs: +9.0%; p &lt; 0.05 for all). Patterns were similar between males and females and absent in WKY. In both strains and all organs, K+ + Na+ concentration was not affected by HS and sat within physiological limits, thus pointing against hypertonicity. Nevertheless, TonEBP gene expression changes matched Na+ and water isotonic accumulation in SHRSP-HS skin, liver and lungs. Hypertonic incubation did not induce hypercontractile responses but exacerbated the sensitivity to NO-mediated relaxation in arteries from both strains (δIC50, p &lt; 0.001). The effect of in-vivo HS, in keeping with classic hypertensive vascular changes, was opposite (p &lt; 0.001, in SHRSP only). Conclusions: If water independent, interstitial Na accumulation is unlikely to underpin the development of experimental hypertension via a direct impact on vascular function. Tissue Na+ excess upon HS rather reflects isotonic oedema accumulation and systemic changes in tissue architecture, not solely confined to skin, and sensed by TonEBP.

6\u03b2-Hydroxytestosterone, a metabolite of testosterone generated by CYP1B1, contributes to vascular changes in angiotensin II-induced hypertension in male mice

BackgroundPreviously, we showed that 6β-hydroxytestosterone (6β-OHT), a cytochrome P450 1B1 (CYP1B1)-derived metabolite of testosterone, contributes to angiotensin II (Ang II)-induced hypertension in male mice. This study was conducted to test the hypothesis that 6β-OHT contributes to increased vascular reactivity, endothelial dysfunction, vascular hypertrophy, and reactive oxygen species production associated with Ang II-induced hypertension.MethodsEight- to 10-week-old intact or castrated C57BL/6 J (Cyp1b1+/+ and Cyp1b1−/−) mice were anesthetized for implantation of a micro-osmotic pump which delivered Ang II (700 ng/kg/day) or saline for 14 days. Mice were injected with 6β-OHT (15 μg/g b.w every third day), flutamide (8 mg/kg every day), or its vehicle. Blood pressure was measured via tail-cuff. Vascular reactivity, endothelial-dependent and endothelial-independent vasodilation, media to lumen ratio, fibrosis by collagen deposition, and reactive oxygen species production by dihydroethidium staining were determined in the isolated thoracic aorta.ResultsThe response of thoracic aorta to phenylephrine and endothelin-1 was increased in Ang II-infused Cyp1b1+/+ mice compared to intact Cyp1b1−/− or castrated Cyp1b1+/+ and Cyp1b1−/− mice; these effects of Ang II were restored by treatment with 6β-OHT. Ang II infusion caused endothelial dysfunction, as indicated by decreased relaxation of the aorta to acetylcholine in Cyp1b1+/+ but not Cyp1b1−/− or castrated Cyp1b1+/+ and Cyp1b1−/− mice. 6β-OHT did not alter Ang II-induced endothelial dysfunction in Cyp1b1+/+ mice but restored it in Cyp1b1−/− or castrated Cyp1b1+/+ and Cyp1b1−/− mice. Ang II infusion increased media to lumen ratio and caused fibrosis and reactive oxygen species production in the aorta of Cyp1b1+/+ mice. These effects were minimized in the aorta of Cyp1b1−/− or castrated Cyp1b1+/+ and Cyp1b1−/− mice and restored by treatment with 6β-OHT. Treatment with the androgen receptor antagonist flutamide reduced blood pressure and vascular hypertrophy in castrated Ang II-infused mice injected with 6β-OHT.Conclusions6β-OHT is required for the action of Ang II to increase vascular reactivity and cause endothelial dysfunction, hypertrophy, and increase in oxygen radical production. The effect of 6β-OHT in mediating Ang II-induced hypertension and associated hypertrophy is dependent on the androgen receptor. Therefore, CYP1B1 could serve as a novel target for the development of therapeutics to treat vascular changes in hypertensive males.

Pulmonary Vascular Underperfusion Score in Premature Infants with Bronchopulmonary Dysplasia and Pulmonary Hypertension.

Pulmonary hypertension (PH) is a complication of bronchopulmonary dysplasia (BPD). The underlying pathophysiology of BPD-associated PH is complex and poorly understood. Echocardiogram may underestimate the severity of pulmonary hypertensive vascular disease in severe BPD. Digital subtraction pulmonary angiography (DSPA) is a potentially useful imaging modality for evaluating changes in the pulmonary vasculature of BPD-associated PH. In this study, we objectively quantified the pulmonary hypertensive vascular changes demonstrated by DSPA using a novel pulmonary vascular underperfusion score (PVUS) and correlated the scoring system with echocardiography parameters and cardiac hemodynamics by right heart catheterization.

Novel Classification of Early-stage Systemic Hypertensive Changes in Human Retina Based on OCTA Measurement of Choriocapillaris

The traditional classification of hypertensive retinopathy was based on the Keith–Wagener–Barker (KWB) grading, which is a subjective scaling system, and it is difficult to distinguish between the first and second grades. Retinal and choroidal vasculatures are affected by systemic hypertension, although retinal vasculature changes with age, axial length, intraocular pressure, and retinal diseases. It is necessary to establish a new objective method to assess hypertensive vascular changes. In the present study, we have examined the vasculature of the macular choriocapillaris in order to establish a new objective method to assess hypertensive vascular changes using optical coherence tomography angiography (OCTA). Choriocapillaris vessel density (VD), vessel length, and vessel diameter index in a 3 × 3 mm macular area were measured by OTCA in a total of 567 volunteers (361 healthy subjects and 206 subjects with systemic hypertension) who attended a basic health check-up. Ocular factors, systemic factors, and medications were evaluated. We detected significant differences in normative choriocapillaris vasculature between the left and right eyes in 53 healthy subjects and revealed correlations between age, intraocular pressure, axial length, and choriocapillaris vasculature in 308 healthy subjects. Normative foveal VD was correlated with age only and the efficiency was weak. The analysis of 206 right eyes (KWB grade 0, 159 eyes; grade 1, 35 eyes; and grade 2, 12 eyes) revealed that foveal VD was strongly correlated with KWB grade only (P < 0.001). This is the first report suggesting that OCTA for foveal choriocapillaris measurement by OCTA would might provide the advantage of evaluating be objective method for evaluating the progression of systemic hypertension.

Abstract P520: Low Plasma Levels of Vitamin D are Not Associated With Carotid Artery Stiffness in Hypertension

Objectives: Recent studies suggest an association between vitamin D deficiency and prevalence of cardiovascular disease in the general population. However, the evidence of a relationship between vitamin D status and vascular functional changes in hypertension is currently controversial. We aimed to investigate if the presence of low serum vitamin D levels is associated with an increased arterial stiffness in essential hypertension. Design and Method: In 151 essential hypertensive patients (53±13 y, 71 males) we measured serum 25(OH)-vitamin D levels and performed a carotid ultrasound examination to determine variables of carotid stiffness, such as distensibility, compliance, Young elastic modulus and beta-stiffness. Furthermore, in a subgroup of 86 subjects we evaluated the augmentation index and the pulse wave velocity. The patients were subdivided into two groups according to the 25(OH)-vitamin D levels, lower or higher than 30 nmol/L. Results: A plasma vitamin D level lower than 30 nmol/L was found in 83 (55%) of 151 patients. Patients with low vitamin D levels were significantly older than those with a normal value of serum vitamin D. No significant differences in carotid artery distensibility, compliance, Young elastic modulus, and beta-stiffness were observed between patients with plasma vitamin D below or above 30 nmol/L. Also, the augmentation index and the pulse wave velocity were comparable in hypertensive patients with lower or higher plasma vitamin D levels. Conclusions: This study does not support the hypothesis of an association between vitamin D deficiency and functional vascular changes in hypertensive patients.

Abstract P159: MicroRNA Profiling in Small Resistance Arteries of Hypertensive Patients With or Without Chronic Kidney Disease

Background: Hypertension (HTN) and chronic kidney disease (CKD) are global health disorders that are epidemiologically associated. Vascular injury is an early manifestation in HTN and contributes to CKD. It is characterized by endothelial dysfunction and vascular remodeling that are accompanied by gene expression changes. MicroRNAs (miRs) are important non-coding RNA regulators of gene expression. Dysregulation of miRs has been shown in HTN and CKD, but their implication in vascular injury remains unclear. We aimed to identify differentially expressed (DE) miRs in small arteries of HTN and CKD human subjects to get further insight into pathophysiological molecular mechanisms in these conditions. Methods and Results: Normotensive, HTN (systolic blood pressure (BP) &gt; 135 mm Hg or diastolic BP of 85-115 mm Hg with BpTRU) and CKD subjects (estimated glomerular filtration rate &lt;60mL/min/m 2 ) (n=15-16) were studied. Small arteries were dissected from a subcutaneous gluteal biopsy under RNAse free condition and used for total RNA extraction with the mirVana miR isolation kit. cDNA libraries were prepared using the TruSeq small RNA prep kit and the TruSeq stranded total RNA prep kit, and sequenced by Illumina HiSeq 2500. DE miRs and DE mRNAs ( P &lt;0.05) were identified using EdgeR, which found 3 up- and 6 down-regulated miRs, as well as 134 up- and 149 down-regulated mRNAs uniquely associated with HTN, 42 up- and 39 down-regulated miRs, as well as 743 up- and 348 down-regulated mRNAs uniquely associated with CKD, while 2 up-regulated miRs and 101 up- and 75 down-regulated mRNAs were found in both groups. Target Scan was used to predict DE miR targets in the DE mRNAs. Enrichment analysis showed that the HTN-associated DE miR-targeting DE mRNAs were highly enriched in gene ontology (GO) terms involved in peptidase activity, mitochondrial activity and immune response ( q &lt;0.01), while the CKD-associated DE miR-targeting DE genes were highly enriched in GO terms involved in tube formation, fibroblast proliferation and EGF response ( q &lt;0.001). Conclusions: DE miRs were identified in small arteries of HTN and CKD patients. Enrichment analysis in DE miR-targeting DE mRNAs revealed GO terms that could be linked to different degrees of vascular changes in HTN and CKD.

ME 04-2 AORTIC PWV FOR RISK STRATIFICATION IN HYPERTENSION

High pressure of the blood in artery is a common condition and it is closely related to cardiovascular (CV) diseases in future. Blood pressure itself is the most important criteria for hypertension prognosis but attempts are being made to detect hypertensive vascular changes early. Healthy arteries are flexible, strong and elastic but if the condition of high blood pressure persists, arteries turn narrow, thick and stiff, become a condition of arteriosclerosis. And so now, pulse wave velocity (PWV) which measures arteriosclerosis became one of the clinically significant method that evaluates CV risks among patients in hypertension (yes, it is also very important for general population), detects biological changes in blood vessels caused by hypertension, and it is known as a guide for hypertension management. Other than hypertension, the importance of PWV on various pathological status such as diabetes and renal diseases has been known and it is widely used in clinical settings. There is a method which measures PWV between two blood vessels, regional PWV and arterial structure in one particular blood vessel site, local PWV. Controversies still exist over its accuracy but most of them were resolved and so now, it was introduced as a standard technique by American Heart Association (AHA), European Society of Hypertension and others. Once the problem of pricing is resolved, it can be broadly used as inexpensive technique in clinical settings. I will further discuss which PWV techniques to use and how to interpret aortic PWV data in CV risk stratification of hypertension in clinical settings.

PS 02-50 IMPACT OF HYPERTENSION ON SUBCLINICAL VASCULAR DAMAGE DETECTED BY DIFFERENT METHODS IN RUSSIAN POPULATION

Objective: Different diagnostic procedures of subclinical vascular damage detection are now suggested but unequal impact of cardiovascular risk factors on arterial wall is still discussed. The aim of our study was to assess the prevalence of subclinical vascular changes and possibility to reveal hypertensive vascular damage according to different diagnostic methods. Design and Method: 1382 apparently healthy participants aged 25–65 years were randomly selected from Saint-Petersburg inhabitants (a sample form ESSE-RF study). All participants signed informed consent and filled in the questionnaire regarding risk factors, concomitant diseases and therapy. Fasting lipids, glucose, anthropometry and BP measurement were performed. Cardio-ankle vascular index (CAVI), ankle brachial index (ABI) and measurement of intima-media thickness (IMT) were performed. The subclinical vascular damage was detected, if CAVI ≥ 9.0, ABI ≤ 0.9, IMT > 0.9 mm. Participants with BP > 140/90 mmHg and/or under antihypertensive therapy were referred to hypertensive patients group. Statistical analysis was performed using SPSS Statistics 20. Results: Most of patients 955 (76.7%) did not have subclinical vascular damage by any of methods. The subclinical vascular damage detected by IMT assessment was found out significantly more often (212 (24.7%)) in comparison with CAVI (75 (8.7%)) and ABI (18 (2.1%)) assessments, p < 0.005. According to results of multiple logistic regression adjusted by age, probability to reveal subclinical vascular damage by CAVI (OR = 3.7, 95%CI = 2.6–5.3, p < 0.0001) was higher in comparison with IMT (OR = 2.8, 95%CI = 1.7–4.8, p < 0.0001) in hypertensive patients. ABI increasing was not associated with hypertensive vascular changes by any method. Conclusions: IMT assessment allows detecting subclinical vascular damage more often than the other methods in relatively healthy population. CAVI seems to give the opportunity to reveal subclinical vascular damage at earlier stages of hypertension in comparison with ultrasound vascular assessment.

Retinal vascular changes in hypertensive patients in Ibadan, Sub-Saharan Africa.

BackgroundEarlier studies in Nigeria reported the rarity of retinal vascular changes in hypertensives. The aim of this study was to describe the various retinal vascular changes in the hypertensive patients of Nigeria.Patients and methodsNine hundred and three hypertensive patients were studied. This study was approved by the ethical and research committee of the University of Ibadan and University College Hospital, Ibadan, Nigeria. Blood pressure and anthropometric measurements were measured. Cardiac echocardiography was performed on 156 patients. All patients had dilated fundoscopy and fundus photography using the Kowa portable fundus camera and an Apple iPhone with 20 D lens. Statistical analysis was done with Statistical Packages for the Social Sciences (Version 21).ResultsThe mean age of patients was 57 years with a male:female ratio of 1. No retinopathy was found in 556 (61.5%) patients. In all, 175 (19.4%) patients had features of hypertensive retinopathy. Retinal vascular occlusion was a significant finding in 121 patients (13.4%), of which branch retinal vein occlusion, 43 (4.7%), and central retinal vein occlusion, 30 (3.3%), were the most prominent ones in cases. Hemicentral retinal vein occlusion, 26 (2.9%), and central retinal artery occlusion, 17 (1.9%), were significant presentations. Other findings included nonarteritic anterior ischemic optic neuropathy in five (0.6%) patients, hypertensive choroidopathy in seven (0.8%) patients, and hemorrhagic choroidal detachment in five (0.6%) patients. Left ventricular (LV) geometry was abnormal in 85 (55.5%) patients. Concentric remodeling, eccentric hypertrophy, and concentric hypertrophy were observed in 43 (27.6%), 26 (17.2%), and 15 (9.7%) patients, respectively. LV hypertrophy was found in 42 (27%) patients, while 60 (39%) patients had increased relative wall thickness. In this study, bivariate analysis showed a correlation between LV relative wall thickness and severity of retinopathy in both eyes (Spearman’s coefficient 0.6; P=0.0004).ConclusionHypertensive retinal vascular changes are not rare in Ibadan.

Hypertensive Crisis-A Serious Problem in Medical Practice

There has recently been a considerable increase in interest in hypertensive crisis-a life-threatening condition. Recent publications indicate that hypertensive crisis is a problem not only in general medicine but also in ophthalmology. Visual disturbances may be the initial symptoms of severe hypertension and can reflect severe systemic changes. It seems appropriate to conduct further studies on the pathogenesis of vascular hypertensive changes, and particularly any associated inflammatory reactions. It also seems justified to introduce screening for hypertensive changes on the eye fundus photographs in emergency departments.

Sarpogrelate hydrochloride, a serotonin 5HT2A receptor antagonist, ameliorates the development of chronic hypoxic pulmonary hypertension in rats.

The purpose of the present study was to determine if sarpogrelate hydrochloride (SPG), a serotonin 5HT2A receptor antagonist, prevented the development of chronic hypoxia-induced pulmonary hypertension (PH) and hypertensive pulmonary vascular remodeling. Forty-one male Sprague-Dawley rats were exposed to hypobaric hypoxia (380 mmHg, 10 % oxygen) or room air and administered 50 mg/kg SPG or vehicle by gavage once daily from day -2 to day 14. The mean pulmonary artery pressure (PAP) and right ventricular hypertrophy (RVH) were measured. Hypertensive pulmonary vascular remodelings were assessed morphometrically by light microscopy. Serotonin-induced contraction was determined in isolated pulmonary artery rings from 24 rats. In another set of rats, Western blotting, real-time polymerase chain reaction and immunofluorescent staining (n = 9) for lung tissue were performed. Chronic hypoxia induced a rise in mean PAP and RVH, increased the percentage of muscularized arteries in peripheral pulmonary arteries and medial wall thickness in small muscular arteries, and potentiated serotonin-induced contraction, each of which was significantly (p < 0.05) ameliorated by SPG. Chronic hypoxia significantly increased the expression of endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (peNOS) protein levels, cyclic guanosine monophosphate, and matrix metalloproteinase-13 (MMP-13) mRNA levels in whole lung tissues. SPG increased peNOS expression in the immunofluorescent staining of peripheral pulmonary arteries from chronic hypoxic rats and decreased the MMP-13 mRNA in lung tissue in chronic hypoxic rats. The administration of SPG ameliorated the development of chronic hypoxic PH and hypertensive pulmonary vascular changes.

Histological antiphospholipid-associated nephropathy versus lupus nephritis in patients with systemic lupus erythematosus: an observational cross-sectional study with longitudinal follow-up.

IntroductionRenal involvement is a severe complication in systemic lupus erythematosus (SLE). Moreover, a subset of SLE patients develop the anti-phospholipid syndrome (APS), characterised by the occurrence of anti-phospholipid antibodies in combination with macro- and microvascular thrombotic manifestations, including acute and chronic antiphospholipid-associated nephropathy (APLN). Clinical presentations of lupus nephritis and APLN are similar and a renal biopsy is necessary to differentiate between the conditions. Our aim with this study was to investigate the occurrence of histopathological findings consistent with APLN (hAPLN) in renal biopsies from SLE patients and to investigate associations with anti-phospholipid antibody specificities, clinical manifestations, HLA-DRB1 alleles, and long-term renal outcome.MethodConsecutive renal biopsies from 112 SLE patients with renal involvement were investigated and evaluated for findings of hAPLN; in all there were 236 renal biopsies. Data from biopsy reports and clinical information were collected. Autoantibodies against cardiolipin and β2-glycoprotein-1 were measured by enzyme-linked immunosorbent assay. A lupus anticoagulant test was determined with a modified Dilute Russel Viper Venom method. HLA genotyping was performed by sequence-specific primer PCR. Renal outcome was determined at study end.ResultsThe prevalence of hAPLN was 14.3% among SLE patients with renal involvement. Compared to patients with pure lupus nephritis, occurrence of hAPLN was associated with intima changes (odds ratio (OR) = 24; 95% confidence interval (CI), 3.0 to 189.8; P < 0.0001), hypertensive vascular changes (OR = 7.8; 95% CI, 1.6 to 39.4; P = 0.01), inflammatory infiltrates (OR = 6.5; 95% CI, 1.7 to 25.1; P = 0.007) and tubular atrophy (OR = 13.1; 95% CI, 1.7 to 103.6; P = 0.002). hAPLN was associated with the presence of cardiolipin antibodies (OR = 3.3; 95% CI, 1.0 to 10.8; P = 0.05) and triple anti-phospholipid antibody positivity (OR = 4.2; 95% CI, 1.3 to 13.7; P = 0.02). Patients with hAPLN were more hypertensive (OR = 3.8; 95% CI, 1.2 to 12.3; P = 0.03) and had higher levels of creatinine as compared to lupus nephritis patients (median 116 versus 75 μmol/L; P < 0.0001). We found significantly higher frequency of HLA-DRB1*13 (OR = 5.1; 95% CI, 1.7 to 15.4; P = 0.03) and development of end-stage renal disease (OR = 5.8; 95% CI, 1.7 to 19.7; P = 0.008) in hAPLN compared with lupus nephritis.ConclusionhAPLN is a severe and often unrecognized condition in SLE patients with renal involvement. We have demonstrated an increased risk for development of renal impairment and a genetic predisposition in hAPLN patients compared to lupus nephritis patients.

Pulmonary hypertensive vascular changes in lungs of patients with sudden unexpected death. Emphasis on congenital heart disease, Eisenmenger syndrome, postoperative deaths and death during pregnancy and postpartum

AimsPulmonary hypertension (PH) in asymptomatic patients is a rare cause of sudden death. This study aims to determine the incidence of this entity and raise awareness among pathologists.MethodsWe retrospectively investigated...

Prevalence and Clinicoradiological Analyses of Patients with Alzheimer Disease Coexisting Multiple Microbleeds

Pathologic findings of cerebral amyloid angiopathy (CAA) and Alzheimer disease (AD) coexist frequently. Both diseases are associated with β-amyloid deposition and dementia. We aimed to evaluate frequency and clinicoradiological profile of AD patients with multiple microbleeds (MBs). We reviewed clinical records and magnetic resonance imaging (MRI) findings in patients with probable AD diagnosed by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), and National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria from 2009 to 2012. Brain MRI was performed at 1.5-T superconducting system, including T2*-weighted gradient-echo imaging. MBs were defined as rounded, hypointense foci less than or equal to 10 mm in size in the brain parenchyma. MBs topography was divided into the lobar (L) and the deep/infratentorial (D/I) region. Multiple MBs were defined as the number greater than or equal to 8 in the L and the D/I territory, respectively. White matter hyperintensities (WMHs) were assessed using the age-related white matter changes scale. Clinicoradiological findings were examined for 1 year. Prevalence and clinicoradiological profiles were studied in patients with multiple L or D/I MBs. Five hundred fifty patients (238 men and 312 women) participated in the present study. Mean age (standard deviation) was 78.4 (7.7) years, 78.3 (8.1) years in men and 78.6 (7.5) years in women. A total of 132 patients (55 men and 78 women) had at least 1 MB. Prevalence of MB ≥ 1 was 24%, 23 in men and 25 in women. The ratio of L and D/I MBs were 1.1, .6 in men and 1.8 in women. Multiple MBs were detected in 93 patients (17%), 38 (16%) men and 55 (17%) in women. L distribution was found in 49 patients (9%), 15 men (6%) and 34 women (11%), and D/I distribution in 44 patients (8%), 23 men (10%) and 21 women (7%). Multiple L MBs was associated with faster progression of dementia, cerebral hemorrhage, and increased number of MBs. Multiple D/I MBs were linked to hypertension and WMH scores. The present study indicated that the prevalence of multiple MBs was 17% in Japanese AD patients. The clinicoradiological profile suggested severe degree of CAA in patients with multiple L MBs (9%) and hypertension and aged changes in patients with multiple D/I MBs (8%). T2*-weighted imaging is a useful tool for evaluating degree of CAA and hypertensive vascular changes. We should pay more attention to management and care in AD patients with multiple MBs.