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Evaluation of antihypertensive therapy among ischemic stroke survivors: impact of ischemic heart disease

Hassan Y, Aziz NA, Al-Jabi SW, Looi I, Zyoud SH

J Cardiovasc Pharmacol Ther, 2010 Sep;15(3):282-8.
PMID: 20472813 DOI: 10.1177/1074248410368049

BACKGROUND: Hypertension and ischemic heart disease (IHD) are among the most prevalent modifiable risk factors for stroke. Clinical trial evidence suggests that antihypertensive medications are recommended for prevention of recurrent ischemic stroke in hypertensive and normotensive patients.
OBJECTIVES: The objectives of this study were to analyze and evaluate the utilization of antihypertensive medication for acute ischemic stroke (AIS) or transient ischemic attack (TIA) survivors in relation to recent recommendations and guidelines and to compare their use among patients with or without IHD.
METHODS: This was a retrospective cohort study of all patients with AIS/TIA attending the hospital from July 1, 2008 to December 31, 2008. Demographic data, clinical characteristics, different classes of antihypertensive medications, and different antihypertensive combinations prescribed to AIS/TIA survivors were analyzed among patients with and without IHD. Statistical Package for Social Sciences (SPSS) program version 15 was used for data analysis.
RESULTS: In all, 383 AIS/TIA survivors were studied, of which 66 (19.5%) had a documented history of IHD. Three quarters (n = 260; 76.9%) of AIS or TIA survivors received antihypertensive medication, mostly as monotherapy, at discharge. The majority of patients (n = 201, 59.5%) were prescribed angiotensin-converting enzyme inhibitors (ACEIs). Patients with IHD were significantly prescribed more β-blockers than patients without IHD (P = .003). A history of hypertension, a history of diabetes mellitus, and age were significantly associated with prescription of antihypertensive medications at discharge (P < .001, P < .001, and P < .001, respectively).
CONCLUSION: Patterns of antihypertensive therapy were commonly but not adequately consistent with international guidelines. Screening stroke survivors for blood pressure control, initiating appropriate antihypertensive medications, and decreasing the number of untreated patients might help reduce the risk of recurrent strokes and increase survival.

Matched MeSH terms: Hypertension/complications
Paroxysmal Hypertension Associated With Urination

Lou Y, Fan L, Hou X, Dominiczak AF, Wang JG, Staessen JA, et al.

Hypertension, 2019 11;74(5):1068-1074.
PMID: 31564165 DOI: 10.1161/HYPERTENSIONAHA.119.13140
Matched MeSH terms: Hypertension/complications
A community-based comprehensive intervention to reduce cardiovascular risk in hypertension (HOPE 4): a cluster-randomised controlled trial

Schwalm JD, McCready T, Lopez-Jaramillo P, Yusoff K, Attaran A, Lamelas P, et al.

Lancet, 2019 10 05;394(10205):1231-1242.
PMID: 31488369 DOI: 10.1016/S0140-6736(19)31949-X

BACKGROUND: Hypertension is the leading cause of cardiovascular disease globally. Despite proven benefits, hypertension control is poor. We hypothesised that a comprehensive approach to lowering blood pressure and other risk factors, informed by detailed analysis of local barriers, would be superior to usual care in individuals with poorly controlled or newly diagnosed hypertension. We tested whether a model of care involving non-physician health workers (NPHWs), primary care physicians, family, and the provision of effective medications, could substantially reduce cardiovascular disease risk.
METHODS: HOPE 4 was an open, community-based, cluster-randomised controlled trial involving 1371 individuals with new or poorly controlled hypertension from 30 communities (defined as townships) in Colombia and Malaysia. 16 communities were randomly assigned to control (usual care, n=727), and 14 (n=644) to the intervention. After community screening, the intervention included treatment of cardiovascular disease risk factors by NPHWs using tablet computer-based simplified management algorithms and counselling programmes; free antihypertensive and statin medications recommended by NPHWs but supervised by physicians; and support from a family member or friend (treatment supporter) to improve adherence to medications and healthy behaviours. The primary outcome was the change in Framingham Risk Score 10-year cardiovascular disease risk estimate at 12 months between intervention and control participants. The HOPE 4 trial is registered at ClinicalTrials.gov, NCT01826019.
FINDINGS: All communities completed 12-month follow-up (data on 97% of living participants, n=1299). The reduction in Framingham Risk Score for 10-year cardiovascular disease risk was -6·40% (95% CI 8·00 to -4·80) in the control group and -11·17% (-12·88 to -9·47) in the intervention group, with a difference of change of -4·78% (95% CI -7·11 to -2·44, p<0·0001). There was an absolute 11·45 mm Hg (95% CI -14·94 to -7·97) greater reduction in systolic blood pressure, and a 0·41 mmol/L (95% CI -0·60 to -0·23) reduction in LDL with the intervention group (both p<0·0001). Change in blood pressure control status (<140 mm Hg) was 69% in the intervention group versus 30% in the control group (p<0·0001). There were no safety concerns with the intervention.
INTERPRETATION: A comprehensive model of care led by NPHWs, involving primary care physicians and family that was informed by local context, substantially improved blood pressure control and cardiovascular disease risk. This strategy is effective, pragmatic, and has the potential to substantially reduce cardiovascular disease compared with current strategies that are typically physician based.
FUNDING: Canadian Institutes of Health Research; Grand Challenges Canada; Ontario SPOR Support Unit and the Ontario Ministry of Health and Long-Term Care; Boehringer Ingelheim; Department of Management of Non-Communicable Diseases, WHO; and Population Health Research Institute. VIDEO ABSTRACT.

Matched MeSH terms: Hypertension/complications*
Fulltext ALLHAT in perspective: implications to clinical practice and clinical trials

Yusoff K

Med J Malaysia, 2005 Jun;60(2):239-45.
PMID: 16114170

ALLHAT study is the biggest randomized clinical trial in hypertension ever conducted. Its objective was to ompare the efficacy of newer (calcium channel blocker amlodipine and angiotensin-converting enzyme inhibitor inopril) to the older (diuretic chlorthalidone) antihypertensive agents in the treatment of patients with hypertension. After enrolling 42,000 patients who were followed for an average of 4.9 years, ALLHAT did not find significant differences in the primary end-points between these antihypertenive agents. ALLHAT however found significant differences in the secondary end-points such as heart failure and strokes between chlorthalidone and amlodipine or lisinopril. Based on these and on economic reasons, the investigators unequivocally recommended diuretics as the first line therapy for hypertension. Since its publication, ALLHAT has been much discussed, debated A and opined. The choice of drugs for study, the study design, the conduct of the study and the conclusions drawn by the investigators had all been criticised or controversial. Yet ALLHAT has been widely quoted, commented upon or referred to and it has been instrumental in initiating the JNC VII Guidelines. Thus a thorough understanding of ALLHAT is necessary for clinical practice and in designing and evaluating clinical trials in the future. Moving Points: in Medicine will capture the essence of ALLHAT, discusses its implications to clinical trials and explores its possible impact on the practice of medicine in this country.

Matched MeSH terms: Hypertension/complications
Fulltext Rare Copy Number Variants Identified Suggest the Regulating Pathways in Hypertension-Related Left Ventricular Hypertrophy

Boon-Peng H, Mat Jusoh JA, Marshall CR, Majid F, Danuri N, Basir F, et al.

PLoS One, 2016;11(3):e0148755.
PMID: 26930585 DOI: 10.1371/journal.pone.0148755

Left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular morbidity and mortality, and a powerful predictor of adverse cardiovascular outcomes in the hypertensive patients. It has complex multifactorial and polygenic basis for its pathogenesis. We hypothesized that rare copy number variants (CNVs) contribute to the LVH pathogenesis in hypertensive patients. Copy number variants (CNV) were identified in 258 hypertensive patients, 95 of whom had LVH, after genotyping with a high resolution SNP array. Following stringent filtering criteria, we identified 208 rare, or private CNVs that were only present in our patients with hypertension related LVH. Preliminary findings from Gene Ontology and pathway analysis of this study confirmed the involvement of the genes known to be functionally involved in cardiac development and phenotypes, in line with previously reported transcriptomic studies. Network enrichment analyses suggested that the gene-set was, directly or indirectly, involved in the transcription factors regulating the "foetal cardiac gene programme" which triggered the hypertrophic cascade, confirming previous reports. These findings suggest that multiple, individually rare copy number variants altering genes may contribute to the pathogenesis of hypertension-related LVH. In summary, we have provided further supporting evidence that rare CNV could potentially impact this common and complex disease susceptibility with lower heritability.

Matched MeSH terms: Hypertension/complications
Fulltext Prevalence of primary aldosteronism among Asian hypertensive patients in Singapore

Loh KC, Koay ES, Khaw MC, Emmanuel SC, Young WF

J Clin Endocrinol Metab, 2000 Aug;85(8):2854-9.
PMID: 10946893

Recent studies using the ratio of plasma aldosterone concentration (PAC) to PRA as the screening test for primary aldosteronism in hypertensive populations suggested that the prevalence may be as high as 5-15%, with well over half of the subjects having normal serum potassium concentrations. Despite an increasing clinical awareness of this entity, many clinicians are reluctant to consider routine screening for primary aldosteronism in essential hypertensive patients because there are few community-based prevalence studies of primary aldosteronism in different populations. Furthermore, genetic and environmental differences may affect the prevalence and presentation of primary aldosteronism in distinct populations. This study was designed to determine the prevalence of primary aldosteronism in the predominantly Chinese population in Singapore. Three hundred and fifty unselected adult hypertensive patients attending two primary care clinics had random ambulatory measurements for PAC (nanograms per dL) and PRA (nanograms per mL/h). Serum urea, creatinine, and electrolyte measurements were obtained simultaneously. Subjects with renal insufficiency (serum creatinine, >140 micromol/L) and those treated with glucocorticoids or spironolactone were excluded. Screening was considered positive if the PAC: PRA ratio was more than 20 and the PAC was more than 15 ng/dL (>416 pmol/L). Primary aldosteronism was confirmed with the determination of PAC after 2 L saline administered iv over 4 h. Adrenal computed tomographic (CT) scans were performed in biochemically confirmed cases of primary aldosteronism. Further localization with adrenal vein sampling was carried out in selected patients with equivocal findings on adrenal CT scan. Sixty-three (18%) of the 350 hypertensive patients (215 women and 135 men; age range, 23-75 yr) were screened positive for primary aldosteronism. Only 13 of these 63 subjects (21%) were hypokalemic (serum potassium, <3.5 mmol/L). Confirmatory studies were carried out in 56 (89%) of the subjects with a positive PAC:PRA ratio. Using a PAC above 10 ng/dL (>277 pmol/L) after saline infusion as the diagnostic cut-off, 16 of the 56 patients had biochemically confirmed primary aldosteronism. Hypokalemia was found in 6 of the 16 patients (37.5%) with primary aldosteronism. Subtype evaluation with adrenal CT scan and adrenal vein sampling indicated that half of the patients with primary aldosteronism may have had potentially curable unilateral adrenal adenoma. Our data suggest that primary aldosteronism occurs in at least 5% of the adult Asian hypertensive population, and approximately half of these individuals may have potentially curable, unilateral, aldosterone-producing adrenal adenoma. Our findings also confirm the poor predictive value of hypokalemia in both the diagnosis and the exclusion of primary aldosteronism.

Matched MeSH terms: Hypertension/complications*
Fulltext Nutritional situation of a Chinese community

Suriah AR, Chong TJ, Yeoh BY

Singapore Med J, 1998 Aug;39(8):348-52.
PMID: 9844494

AIM: To evaluate the anthropometric measurements and dietary intake of the free-living elderly in a Chinese community.
METHOD: A survey was carried out on 48 male and female subjects aged 60 to 96 years using anthropometric, dietary intake and questionnaire techniques.
RESULTS: The study indicated female subjects to have more health problems, like pain at the joints (33%), hypertension (17%) and diabetes (27%) as compared to the male subjects. Dietary intake analysis showed the Chinese male subjects to have a higher energy intake (1,623 kcal) compared to the females (1,197 kcal) even though they did not fulfill the recommended dietary intake. The intake for energy, fats and carbohydrates, was found to be significantly different (p < 0.05) between both sexes. Anthropometric measurements indicated male elderly subjects to be significantly heavier (p < 0.05, 55.4 kg) and taller (161.8 cm) than female elderly subjects (49.5 kg; 146.2 cm respectively). About half of the elderly were normal in their BMI (male 55.6%; female 50%) and only 6.6% of the female subjects were obese. More male subjects were found to be underweight (33%) compared to female subjects (17%). Waist hip ratio was 0.92 for male and 0.87 for female.
CONCLUSION: Our study showed that female elderly subjects had more health problems compared to male elderly subjects. On the whole, the elderly did not fulfill the recommended amount for energy intake while the percentage for carbohydrates, fats and protein from the total calorie intake were not in accordance with the healthy diet guidelines. Anthropometrically, male subjects were heavier and taller than female subjects. Looking at body mass index, most of the male elderly subjects were in the normal to underweight range. With these results, more research is warranted to give a clearer picture of the Chinese elderly in the country.

Study site: Kampung Baru Tabuh Naning, Alor Gajah, Malacca

Matched MeSH terms: Hypertension/complications
Prevalence and risk factors for peripheral artery disease in an Asian population with diabetes mellitus

Tavintharan S, Ning Cheung, Su Chi Lim, Tay W, Shankar A, Shyong Tai E, et al.

Diab Vasc Dis Res, 2009 Apr;6(2):80-6.
PMID: 20368197 DOI: 10.1177/1479164109336043

We describe the prevalence and risk factors for PAD in Asian Malays with diabetes. A population-based study of 3,280 (78.7% response) Malay persons aged 40-80 years in Singapore was conducted. ABI was measured in all participants with a history of diabetes (N=634). PAD was defined to be present if ABI

Matched MeSH terms: Hypertension/complications
Primary and secondary risk factors for coronary heart disease: their role in prevention

Wilhelmsen L

Med J Malaysia, 1977 Jun;31(4):296-301.
PMID: 927236
Matched MeSH terms: Hypertension/complications
Women are at a higher risk of metabolic syndrome in rural Malaysia

Jan Mohamed HJ, Mitra AK, Zainuddin LR, Leng SK, Wan Muda WM

Women Health, 2013;53(4):335-48.
PMID: 23751089 DOI: 10.1080/03630242.2013.788120

Metabolic syndrome has been associated with an increased risk of cardiovascular disease and diabetes mellitus. The objective of this study was to determine gender differences in the prevalence and factors associated with metabolic syndrome in a rural Malay population. This cross-sectional study, conducted in Bachok, Kelantan, involved 306 respondents aged 18 to 70 years. The survey used a structured questionnaire to collect information on demographics, lifestyle, and medical history. Anthropometric measurements, such as weight, height, body mass index, waist and hip circumference, and blood pressure were measured. Venous blood samples were taken by a doctor or nurses and analyzed for lipid profile and fasting glucose. The overall prevalence of metabolic syndrome was 37.5% and was higher among females (42.9%). Being unemployed or a housewife and being of older age were independently associated with metabolic syndrome in a multivariate analysis. Weight management and preventive community-based programs involving housewives, the unemployed, and adults of poor education must be reinforced to prevent and manage metabolic syndrome effectively in adults.

Matched MeSH terms: Hypertension/complications
Fulltext Hypertension and associated cardiovascular risk factors in Kelantan

Mafauzy M, Mokhtar N, Wan Mohamad WB

Med J Malaysia, 2003 Oct;58(4):556-64.
PMID: 15190632

Two thousand five hundred and eight subjects from the state of Kelantan in North-East Peninsular Malaysia were included in this study to determine the prevalence of hypertension and their association with cardiovascular risk factors. The overall prevalence of hypertension was 13.9%. There was no difference in the prevalence of hypertension between the males and females. The prevalence increased with age--the highest being in those above 70-years old. Subjects with hypertension also had a higher prevalence of diabetes mellitus (19.0%), obesity (39.4%) and hypercholesterolaemia (70.7%) than non-hypertensive subjects. Of the hypertensive subjects, 83.3% had 1 other risk factor for cardiovascular disease, 66.7% had 2 other risk factors and 16.7% had more than 2 risk factors. Other than age, body mass index, plasma glucose, total cholesterol and LDL-cholesterol, hypertensive subjects also had a higher mean serum urea, creatinine, uric acid and triglyceride than non-hypertensive subjects. In conclusion, hypertension is a common disease in this area and is associated with multiple risk factors for cardiovascular disease. The prevalence is likely to increase in the near future with increasing affluence and becoming a major health problem.

Matched MeSH terms: Hypertension/complications*
Fulltext Blood pressure and risk of cancer in the European Prospective Investigation into Cancer and Nutrition

Christakoudi S, Kakourou A, Markozannes G, Tzoulaki I, Weiderpass E, Brennan P, et al.

Int J Cancer, 2020 May 15;146(10):2680-2693.
PMID: 31319002 DOI: 10.1002/ijc.32576

Several studies have reported associations of hypertension with cancer, but not all results were conclusive. We examined the association of systolic (SBP) and diastolic (DBP) blood pressure with the development of incident cancer at all anatomical sites in the European Prospective Investigation into Cancer and Nutrition (EPIC). Hazard ratios (HRs) (95% confidence intervals) were estimated using multivariable Cox proportional hazards models, stratified by EPIC-participating center and age at recruitment, and adjusted for sex, education, smoking, body mass index, physical activity, diabetes and dietary (in women also reproductive) factors. The study included 307,318 men and women, with an average follow-up of 13.7 (standard deviation 4.4) years and 39,298 incident cancers. We confirmed the expected positive association with renal cell carcinoma: HR = 1.12 (1.08-1.17) per 10 mm Hg higher SBP and HR = 1.23 (1.14-1.32) for DBP. We additionally found positive associations for esophageal squamous cell carcinoma (SCC): HR = 1.16 (1.07-1.26) (SBP), HR = 1.31 (1.13-1.51) (DBP), weaker for head and neck cancers: HR = 1.08 (1.04-1.12) (SBP), HR = 1.09 (1.01-1.17) (DBP) and, similarly, for skin SCC, colon cancer, postmenopausal breast cancer and uterine adenocarcinoma (AC), but not for esophageal AC, lung SCC, lung AC or uterine endometroid cancer. We observed weak inverse associations of SBP with cervical SCC: HR = 0.91 (0.82-1.00) and lymphomas: HR = 0.97 (0.93-1.00). There were no consistent associations with cancers in other locations. Our results are largely compatible with published studies and support weak associations of blood pressure with cancers in specific locations and morphologies.

Matched MeSH terms: Hypertension/complications*
The impact of diabetes mellitus and other chronic medical conditions on health-related Quality of Life: is the whole greater than the sum of its parts?

Wee HL, Cheung YB, Li SC, Fong KY, Thumboo J

Health Qual Life Outcomes, 2005;3:2.
PMID: 15644146

Diabetes mellitus (DM) is an important public health concern, the impact of which is increased by the high prevalence of co-existing chronic medical conditions among subjects with DM. The aims of this study were therefore to (1) evaluate the impact of DM and co-existing chronic medical conditions on health-related quality of life (HRQoL) (which could be additive, synergistic or subtractive); (2) to determine the extent to which the SF-6D (a single-index preference measure) captures the multidimensional information provided by the SF-36 (a profile measure).

Matched MeSH terms: Hypertension/complications
Fulltext Efficacy and safety of sildenafil in Asian males with erectile dysfunction and cardiovascular risk

Buranakitjaroen P, Mangklabruks A, Leungwattanakij S, Ngaothamatasn W, Malhotra C, Chee C, et al.

J Med Assoc Thai, 2007 Jun;90(6):1100-8.
PMID: 17624203

OBJECTIVE:
Assess the effectiveness of sildenafil in Asian males with erectile dysfunction (ED) and one or more of the co-morbidities, mild-to-moderate hypertension, dyslipidemia, and diabetes.

MATERIAL AND METHOD:
A six-week, double-blind, randomized, placebo-controlled, multicenter study was carried out in Thailand, Malaysia and Singapore. One hundred and fifty five male subjects were randomized (2:1) to sildenafil (n = 104) or placebo (n = 51). Sildenafil was started at 50 mg and increased (100 mg) or decreased (25 mg) at week 2 if necessary.

RESULTS:
On the primary efficacy endpoint, sildenafil-treated subjects had significantly better scores on the International Index of Erectile Function (IIEF) questions 3 and 4 than placebo (p < 0.001, both questions). When accumulated into IIEF domains, all five domains were significant in favor of sildenafil. In addition, sildenafil-treated subjects were more satisfied with treatment and had a higher intercourse success rate. The majority of adverse events were mild in severity; the most commonly reported treatment-related events were dizziness (7.7%) and tinnitus (2.9%).

CONCLUSION:
Sildenafil (25, 50, and 100 mg) was found to be an effective, safe, and well-tolerated treatment for ED in the present study population of Thai, Malaysian, and Singaporean males who also had increased cardiovascular risk.

Matched MeSH terms: Hypertension/complications*
Fulltext Prevalence of diabetes, hypertension and renal disease amongst railway workers in Malaysia

Khalid BA, Usha R, Ng ML, Norella Kong CT, Tariq AR

Med J Malaysia, 1990 Mar;45(1):8-13.
PMID: 2152075

A survey was done to determine the prevalence of diabetes mellitus, hypertension and renal disease, as well as extent of diabetic control, amongst the workers of Malaysian Railways. The prevalence of diabetes was high at 6.6%, with 3.8% of these being insulin dependent diabetes. The highest prevalence was in Indians (16.0%) followed by Chinese (4.9%) and Malays (3.0%). Using HbA1 measurements, diabetic control was poor in 70.6% of the diabetics. Hypertension was found in 37% and proteinuria in 35%. Renal impairment was present in 30% of the diabetics. This survey shows that diabetes, hypertension and renal disease are high amongst the railway workers in Malaysia.

Matched MeSH terms: Hypertension/complications
Diabetes mellitus exacerbates advanced glycation end product accumulation in the veins of end-stage renal failure patients

Nazratun N, Mahmood AA, Kuppusamy UR, Ahmad TS, Tan SY

Vasc Med, 2006 Nov;11(4):245-50.
PMID: 17390548

The excess accumulation of advanced glycation end products (AGEs) contributes to the chronic complications of type 2 diabetes mellitus (DM) and renal failure. Biopsy specimens (n = 184) of arterial (n = 92) and venous (n = 92) tissues were obtained (radial artery and cephalic vein) from end-stage renal disease (ESRD) patients with or without DM and normal healthy subjects (n = 12) requiring surgery (trauma patients). Immunohistochemical assessment of the blood vessels revealed the presence of pentosidine (AGE marker) in both veins and arteries in 72% of the ESRD patients. The percentage of arteries and veins that showed positive pentosidine staining in ESRD patients with type 2 DM alone was 100% and 92% respectively, in the non-diabetic ESRD patients it was < 70% (for arteries and veins), and in the ESRD patients with hypertension as an additional co-morbidity to type 2 DM it was 70% and 82%, respectively. The veins of ESRD patients with DM showed a strong (+++) positive staining and very strong (++++) positive staining was observed in the patients with DM and hypertension. Only mild (+) or moderate (++) pentosidine staining intensity was observed in the arteries of ESRD patients without or with comorbidities, respectively. The accumulation of AGE in the vein rather than the artery may be a better reflection of the extent of complications of ESRD.

Matched MeSH terms: Hypertension/complications
Fulltext Pulmonary atelectasis from compression of the left main bronchus by an aortic aneurysm

Yap KH, Sulaiman S

Singapore Med J, 2009 Jul;50(7):e247-9.
PMID: 19644610

Pulmonary atelectasis may be caused by endobronchial lesions or by extrinsic compression of the bronchus. However, lung collapse due to compression from a thoracic aneurysm is uncommon. We report a 76-year-old hypertensive female patient who has pulmonary atelectasis due to an extrinsic compression from a descending thoracic aortic aneurysm, and discuss possible treatment options.

Matched MeSH terms: Hypertension/complications
Fulltext Thrombolytic failure with streptokinase in acute myocardial infarction using electrocardiogram criteria

Lee YY, Tee MH, Zurkurnai Y, Than W, Sapawi M, Suhairi I

Singapore Med J, 2008 Apr;49(4):304-10.
PMID: 18418522

This study was primarily aimed to determine the failure rate of thrombolysis with streptokinase in acute myocardial infarction using electrocardiogram criteria and its association between various independent variables and outcome parameters.

Matched MeSH terms: Hypertension/complications
Fulltext COVID-19 as a viral functional ACE2 deficiency disorder with ACE2 related multi-organ disease

Gan R, Rosoman NP, Henshaw DJE, Noble EP, Georgius P, Sommerfeld N

Med Hypotheses, 2020 Nov;144:110024.
PMID: 32758871 DOI: 10.1016/j.mehy.2020.110024

SARS-CoV-2, the agent of COVID-19, shares a lineage with SARS-CoV-1, and a common fatal pulmonary profile but with striking differences in presentation, clinical course, and response to treatment. In contrast to SARS-CoV-1 (SARS), COVID-19 has presented as an often bi-phasic, multi-organ pathology, with a proclivity for severe disease in the elderly and those with hypertension, diabetes and cardiovascular disease. Whilst death is usually related to respiratory collapse, autopsy reveals multi-organ pathology. Chronic pulmonary disease is underrepresented in the group with severe COVID-19. A commonality of aberrant renin angiotensin system (RAS) is suggested in the at-risk group. The identification of angiotensin-converting-enzyme 2 (ACE2) as the receptor allowing viral entry to cells precipitated our interest in the role of ACE2 in COVID-19 pathogenesis. We propose that COVID-19 is a viral multisystem disease, with dominant vascular pathology, mediated by global reduction in ACE2 function, pronounced in disease conditions with RAS bias toward angiotensin-converting-enzyme (ACE) over ACE2. It is further complicated by organ specific pathology related to loss of ACE2 expressing cells particularly affecting the endothelium, alveolus, glomerulus and cardiac microvasculature. The possible upregulation in ACE2 receptor expression may predispose individuals with aberrant RAS status to higher viral load on infection and relatively more cell loss. Relative ACE2 deficiency leads to enhanced and protracted tissue, and vessel exposure to angiotensin II, characterised by vasoconstriction, enhanced thrombosis, cell proliferation and recruitment, increased tissue permeability, and cytokine production (including IL-6) resulting in inflammation. Additionally, there is a profound loss of the "protective" angiotensin (1-7), a vasodilator with anti-inflammatory, anti-thrombotic, antiproliferative, antifibrotic, anti-arrhythmic, and antioxidant activity. Our model predicts global vascular insult related to direct endothelial cell damage, vasoconstriction and thrombosis with a disease specific cytokine profile related to angiotensin II rather than "cytokine storm". Our proposed mechanism of lung injury provides an explanation for early hypoxia without reduction in lung compliance and suggests a need for revision of treatment protocols to address vasoconstriction, thromboprophylaxis, and to minimize additional small airways and alveolar trauma via ventilation choice. Our model predicts long term sequelae of scarring/fibrosis in vessels, lungs, renal and cardiac tissue with protracted illness in at-risk individuals. It is hoped that our model stimulates review of current diagnostic and therapeutic intervention protocols, particularly with respect to early anticoagulation, vasodilatation and revision of ventilatory support choices.

Matched MeSH terms: Hypertension/complications
Fulltext Blood pressure in acute intracerebral haemorrhage

Rasool AH, Rahman AR, Choudhury SR, Singh RB

J Hum Hypertens, 2004 Mar;18(3):187-92.
PMID: 14973513 DOI: 10.1038/sj.jhh.1001647

Stroke is one of the leading causes of death worldwide, and spontaneous bleeding into the brain parenchyma, intracerebral haemorrhage (ICH), is a stroke subtype associated with high morbidity and mortality. Overall, it comprises about 15% of all stroke in Caucasians, this figure being much higher in Asians and black people. Blood pressure (BP) appears to play an important role in this disease. We have reviewed available literature on the relationship of BP to the occurrence of primary and secondary ICH, the association of BP levels measured early after stroke with prognosis and complications, and evidence about the effects of early BP lowering treatments on post-stroke outcomes. BP appears to be an important risk factor for primary and secondary ICH. In addition, high BP early after ICH may be detrimental to outcome, possibly contributing to complications such as rebleeding and haematoma enlargement. Few data are available about the effects of early lowering of BP on outcome after ICH with no reliable trial yet conducted. Proper randomised trials are required to establish the effect of early lowering of BP on outcome after ICH.

Matched MeSH terms: Hypertension/complications*

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