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The role of oxidative stress, antioxidants and vascular inflammation in cardiovascular disease (a review)

Siti HN, Kamisah Y, Kamsiah J

Vascul. Pharmacol., 2015 Aug;71:40-56.
PMID: 25869516 DOI: 10.1016/j.vph.2015.03.005

The concept of mild chronic vascular inflammation as part of the pathophysiology of cardiovascular disease, most importantly hypertension and atherosclerosis, has been well accepted. Indeed there are links between vascular inflammation, endothelial dysfunction and oxidative stress. However, there are still gaps in our understanding regarding this matter that might be the cause behind disappointing results of antioxidant therapy for cardiovascular risk factors in large-scale long-term randomised controlled trials. Apart from the limitations of our knowledge, limitations in methodology and assessment of the body's endogenous and exogenous oxidant-antioxidant status are a serious handicap. The pleiotropic effects of antioxidant and anti-inflammation that are shown by some well-established antihypertensive agents and statins partly support the idea of using antioxidants in vascular diseases as still relevant. This review aims to provide an overview of the links between oxidative stress, vascular inflammation, endothelial dysfunction and cardiovascular risk factors, importantly focusing on blood pressure regulation and atherosclerosis. In view of the potential benefits of antioxidants, this review will also examine the proposed role of vitamin C, vitamin E and polyphenols in cardiovascular diseases as well as the success or failure of antioxidant therapy for cardiovascular diseases in clinical trials.

Matched MeSH terms: Hypertension/drug therapy
Des-aspartate angiotensin I (DAA-I) reduces endothelial dysfunction in the aorta of the spontaneously hypertensive rat through inhibition of angiotensin II-induced oxidative stress

Loh WM, Ling WC, Murugan DD, Lau YS, Achike FI, Vanhoutte PM, et al.

Vascul. Pharmacol., 2015 Aug;71:151-8.
PMID: 25869508 DOI: 10.1016/j.vph.2015.03.011

Des-aspartate angiotensin I (DAA-I), an endogenous nonapeptide, counteracts several effects of angiotensin II on vascular tone. The aim of this study was to investigate the acute protective effect of DAA-I on endothelial function in the spontaneously hypertensive rat (SHR) as well as its effect on angiotensin II-induced contractions and oxidative stress. Aortic rings were incubated with DAA-I (0.1μM) for 30min prior to the assessment of angiotensin II-induced contractions (0.1nM-10μM) in WKY and SHR aortas. Total nitrate and nitrite levels were assessed using a colorimetric method and reactive oxygen species (ROS) were measured by dihydroethidium (DHE) fluorescence and lucigenin-enhanced chemiluminescence. The effect of DAA-I was also assessed against endothelium-dependent and -independent relaxations to acetylcholine and sodium nitroprusside, respectively. Angiotensin II-induced contractions were significantly reduced by DAA-I, losartan and tempol. Incubation with ODQ (soluble guanylyl cyclase inhibitor) and removal of the endothelium prevented the reduction of angiotensin II-induced contractions by DAA-I. Total nitrate and nitrite levels were increased in DAA-I, losartan and tempol treated-SHR tissues while ROS level was reduced by DAA-I and the latter inhibitors. In addition, DAA-I significantly improved the impaired acetylcholine-induced relaxation in SHR aortas whilst sodium nitroprusside-induced endothelium-independent relaxation remained unaffected. The present findings indicate that improvement of endothelial function by DAA-I in the SHR aorta is mediated through endothelium-dependent release of nitric oxide and inhibition of angiotensin II-induced oxidative stress.

Matched MeSH terms: Hypertension/drug therapy*
Effects of ascorbic acid on impaired vascular reactivity in aortas isolated from age-matched hypertensive and diabetic rats

Ajay M, Mustafa MR

Vascul. Pharmacol., 2006 Aug;45(2):127-33.
PMID: 16807125 DOI: 10.1016/j.vph.2006.05.001

Impaired vascular reactivity is a hallmark of several cardiovascular diseases that include hypertension and diabetes. This study compared the changes in vascular reactivity in age-matched experimental hypertension and diabetes, and, subsequently, tested whether these changes could be affected directly by ascorbic acid (10 microM). Endothelium-derived nitric oxide (NO) modulation of ascorbic acid effects was also investigated. All the experiments were performed in the presence of a cyclooxygenase inhibitor, indomethacin (10 microM). Results showed that the endothelium-dependent and -independent relaxations induced by acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, were blunted to a similar extent in isolated aortic rings from age-matched spontaneously hypertensive (SHR) (R(max): ACh = 72.83+/-1.86%, SNP = 96.6+/-1.90%) and diabetic (Rmax: ACh = 64.09+/-5.14%, SNP = 95.84+/-1.41%) rats compared with aortic rings of normal rats (Rmax: ACh = 89%, SNP = 104.0+/-1.0%). The alpha1-receptor-mediated contractions induced by phenylephrine (PE) were augmented in diabetic (Cmax = 148.8+/-9.0%) rat aortic rings compared to both normal (Cmax = 127+/-6.9%) and SHR (Cmax = 118+/-4.5%) aortic rings. Ascorbic acid pretreatment was without any significant effects on the vascular responses to ACh, SNP and PE in aortic rings from normal rats. Ascorbic acid significantly improved ACh-induced relaxations in SHR (Rmax = 89.09+/-2.82%) aortic rings to a level similar to that observed in normal aortic rings, but this enhancement in ACh-induced relaxations was only partial in diabetic aortic rings. Ascorbic acid lacked any effects on SNP-induced relaxations in both SHR and diabetic aortic rings. Ascorbic acid markedly attenuated contractions induced by PE in aortic rings from both SHR (Cmax = 92.9+/-6.68%) and diabetic (Cmax = 116.9+/-9.4%) rats. Additionally, following inhibition of nitric oxide synthesis with l-NAME, ascorbic acid attenuated PE-induced contractions in all aortic ring types studied. These results suggest that (1) vascular hyper-responsiveness to alpha(1)-receptor agonists in diabetic arteries is independent of endothelial nitric oxide dysfunction; (2) ascorbic acid directly modulates contractile responses of hypertensive and diabetic rat aortas, likely through mechanisms in part independent of preservation of endothelium-derived nitric oxide.

Matched MeSH terms: Hypertension/drug therapy*
Fulltext Cultural adaptation and linguistic validation of the Beliefs about Medicines Questionnaire in Malaysia

Tan CS, Hassali MA, Neoh CF, Saleem F, Horne R

Value Health Reg Issues, 2018 May;15:161-168.
PMID: 29730249 DOI: 10.1016/j.vhri.2017.12.010

BACKGROUND: Low rate of adherence was found strongly associated with patients' beliefs across the studies about chronic diseases with hypertension. A crucial move is needed to bridge the gap between appropriate assessment tools and local hypertensive patients' medication adherence.

OBJECTIVE: To produce a translated version in Malay language of Beliefs about Medicines Questionnaire (BMQ) that was "conceptually equivalent" to the original English version for use in local clinical practice and research.

METHODS: The forward translation process was conducted by two independent professional translators and back translation was done by two other independent translators. A reliability analysis was conducted on 238 conveniently selected hypertensive patients. Intraclass correlation coefficient (ICC) was used to assess test-retest reliability for the randomly selected 40 patients in a period of 2 weeks. Discriminant validity was tested through Necessity-Concerns differential, BMQ subscales, and other parameters.

RESULTS: The overall Cronbach alpha for the internal consistency was good (0.860). The subscales of the BMQ demonstrated adequate internal consistency, with Cronbach alpha value of 0.759 for Specific-Necessity, 0.762 for Specific Concern, 0.624 for General-Overuse, and 0.756 for General-Harm. The ICC was excellent (0.922). Discriminant validity revealed that BMQ Specific-Necessity score was significantly inversely correlated with the systolic blood pressure level. Systolic and diastolic blood pressure levels (P = 0.038; P = 0.05) were reported to be significantly correlated with the Necessity-Concerns differential, with Necessity score equal or exceeding Concerns score.

CONCLUSIONS: The Malay-translated version of BMQ is a reliable and valid tool to assess patient belief about medication, especially medication adherence among the hypertensive patients in Malaysia.

Matched MeSH terms: Hypertension/drug therapy
Fulltext An Asian regional analysis of cost-effectiveness of early irbesartan treatment versus conventional antihypertensive, late amlodipine, and late irbesartan treatments in patients with type 2 diabetes, hypertension, and nephropathy

Annemans L, Demarteau N, Hu S, Lee TJ, Morad Z, Supaporn T, et al.

Value Health, 2008 May-Jun;11(3):354-64.
PMID: 17888064 DOI: 10.1111/j.1524-4733.2007.00250.x

OBJECTIVE: The prevalence of type 2 diabetes, often leading to diabetic nephropathy, has increased globally, especially in Asia. Irbesartan treatment delays the progression of kidney disease at the early (microalbuminuria) and late (proteinuria) stages of nephropathy in hypertensive type 2 diabetics. This treatment has proven to be cost-effective in Western countries. This study assessed the cost-effectiveness of early irbesartan treatment in Asian settings.
METHODS: An existing lifetime model was reprogrammed in Microsoft Excel to compare irbesartan started at an early stage to irbesartan or amlodipine started at a late stage, and standard treatments from a health-care perspective in China, Malaysia, Thailand, South Korea, and Taiwan. The main effectiveness parameters were incidences of end-stage renal disease, time in dialysis, and life expectancy. All costs were converted to 2004 US$ using official purchasing power parity. Local data were obtained for costs, transplantation,dialysis, and mortality rates. Probabilities regarding disease progression after treatment with the investigated drugs were extracted from two published clinical trials. A probabilistic sensitivity analysis was performed.
RESULTS: Early use of irbesartan yielded the largest clinical and economic benefits reducing need for dialysis by 61% to 63% versus the standard treatment, total costs by 9% (Thailand) to 42% (Taiwan), and increasing life expectancy by 0.31 to 0.48 years. Early irbesartan had a 66% (Thailand) to 95% (Taiwan) probability of being dominant over late irbesartan.
CONCLUSION: Although the absolute results varied in different settings, reflecting differences in epidemiology, management, and costs, early irbesartan treatment was a cost-effective alternative in the Asian settings.

Matched MeSH terms: Hypertension/drug therapy*
Systematic Review and Meta-Analysis for Sexual Dysfunction in Women With Hypertension

Choy CL, Sidi H, Koon CS, Ming OS, Mohamed IN, Guan NC, et al.

J Sex Med, 2019 Jul;16(7):1029-1048.
PMID: 31113742 DOI: 10.1016/j.jsxm.2019.04.007

INTRODUCTION: Sexual dysfunction in hypertensive women is an often-neglected subject despite a reported prevalence of 42.1%. Although few reviews exist, a definitive relationship between hypertension and sexual dysfunction in women has not been clearly established.
AIM: To review the existing literature to definitively examine sexual dysfunction in women with hypertension, in both treated and untreated subjects.
METHODS: We performed a systematic search for published literature of 3 electronic databases (Scopus, EBSCOhost Medline Complete, and Cochrane Library) in August 2018. The search terms with relevant truncation and Boolean were developed according to a population exposure-comparator-outcome model combining pilot searches. The quality of included studies was assessed with the McMaster Critical Review Form for Quantitative Studies. Initial search, limited to the English language, included a total of 2,198 studies. 31 studies (18,260 subjects) met our inclusion criteria and were included in the review. Sexual dysfunction in these studies was measured using different tools. We extracted information of study setting, country, number of subjects, participants' age and blood pressure, comparators, and outcome. We ran a meta-analysis on the presence of sexual dysfunction as an outcome from the following comparisons: (i) hypertensive vs normotensive (ii) treated vs untreated hypertension, and (iii) exposure vs absence of specific class of anti-hypertensive drug.
MAIN OUTCOME MEASURES: Women with sexual dysfunction and hypertension were included.
RESULTS: We found significant sexual dysfunction in women with hypertension compared with the normotensive group (pooled odds ratio [OR] = 2.789, 95% CI = 1.452-5.357, P = .002). However, there was no statistical difference of sexual dysfunction in women with treated or untreated hypertension (OR = 1.229, 95% CI = 0.675-2.236, P = .5). Treatment with alpha-/beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, and diuretics resulted in no statistical difference in sexual dysfunction in hypertensive women.
CLINICAL IMPLICATIONS: Because sexual dysfunction is prevalent in women with hypertension, it is imperative to address the underlying medical condition to manage this important clinical problem.
STRENGTH & LIMITATIONS: Many studies had to be excluded from the meta-analysis, due to unavailability and incompleteness of data. Nevertheless, results of the review are useful to derive recommendations for alerting physicians of the need to routinely assess the sexual functioning of women with hypertension.
CONCLUSION: We conclude that women with hypertension are at increased risk for sexual dysfunction, and our findings imply that evaluation for sexual dysfunction needs to be part of the clinical management guidelines for women with hypertension. Choy CL, Sidi H, Koon CS, et al. Systematic Review and Meta-Analysis for Sexual Dysfunction in Women With Hypertension. J Sex Med 2019;16:1029-1048.

Matched MeSH terms: Hypertension/drug therapy
Sublingual nifedipine compared with intravenous hydrallazine in the acute treatment of severe hypertension in pregnancy: potential for use in rural practice

Jegasothy R, Paranthaman S

J Obstet Gynaecol Res, 1996 Feb;22(1):21-4.
PMID: 8624887

OBJECTIVES: The purposes of this study were to compare the efficacy of sublingual nifedipine with intravenous hydrallazine in the control of acute hypertension of pregnancy and to make a preliminary assessment whether sublingual nifedipine could be recommended for use by midwives faced with severe hypertension in pregnancy in a rural setting.
METHODS: Subjects were 200 consecutive patients admitted to Kuala Tereng-ganu General Hospital, Malaysia with severe hypertension in pregnancy between August 1989 and June 1990. Admission criteria were an ongoing viable pregnancy more than 28 weeks and diastolic blood pressure (DBP) more than 120 mmHg. The patients were randomly divided into 2 groups. In group I, sublingual nifedipine 5 mg was administered and repeated after 15 minutes if DBP > 120 mmHg; and in group II hydrallazine 5 mg was intravenously injected and repeated after 15 minutes if DBP > 120 mmHg. Both groups were put on hydrallazine infusion if DBP > 120 mmHg after 30 minutes. The Chi-square test was used for analysis with significance at p < 0.05.
RESULTS: There was no statistical difference in the efficacy of therapy for decreasing blood pressure between the 2 groups. The groups were comparable by age, parity, gestational age at presentation, birth weight of infants, incidence of postpartum haemorrhage and fetal distress. Caesarian section rates were similar. In the observational studies on nurses administering the drugs, no significant difficulties were observed.
CONCLUSION: Sublingual nifedipine was comparable to IV hydrallazine in the treatment of acute hypertension of pregnancy. Nurses were able to administer lingual nifedipine without difficulty.

Matched MeSH terms: Hypertension/drug therapy*
Fulltext Blood pressure control among diabetic hypertensives under cardiology follow-up at a regional hospital in rural Malaysia

Azarisman SM, Aszrin A, Marzuki AO, Fatnoon NN, Hilmi A, Hadzri MH, et al.

Southeast Asian J. Trop. Med. Public Health, 2010 Jul;41(4):973-81.
PMID: 21073073

Three hundred thirty-one consecutive patients presenting with hypertension to the outpatient medical clinic of Tengku Ampuan Afzan Hospital, Kuantan, Malaysia were screened and 150 patients with concurrent diabetes were enrolled into a cross-sectional study. The majority of patients were male (60.6%) with a mean age of 60.0 +/- 11.0 years. The mean systolic blood pressure (SBP) was 140.9 +/- 20.1 mmHg and the mean diastolic blood pressure (DBP) was 81.7 +/- 9.8 mmHg. Only 38.0% (57/150) of patients had blood pressures within recommended guidelines (130/80 mmHg). The mean blood pressure in this group was 123.7 +/- 8.5/76.4 +/- 5.6 mmHg. The majority of patients were on either 2 (41.3%) or 3 (31.3%) anti-hypertensives. Females had a significantly higher SBP 145.4 +/- 22.7 vs. 138.0 +/- 17.8 mmHg in males (p = 0.026). The level of blood pressure control in diabetics was unsatisfactory, especially in females and the elderly. A reassessment of priorities in the management of patients with concurrent hypertension and diabetes is therefore, urgently needed.

Study site: outpatient medical clinic of Tengku Ampuan Afzan Hospital,

Matched MeSH terms: Hypertension/drug therapy*
Fulltext A profile of hypertension among rural elderly Malaysians

Srinivas P, Wong KS, Chia YC, Poi PJ, Ebrahim S

Southeast Asian J. Trop. Med. Public Health, 1998 Dec;29(4):821-6.
PMID: 10772571

The main objective of this study was to survey the prevalence of hypertension in Malaysians aged 55 years and above who responded to a public health screening campaign in Kuala Langat district, Selangor, Malaysia. The relationship between the detection, treatment and control in the study population was also examined. An epidemiological survey of the elderly was conducted in Kuala Langat, a rural district in Malaysia for a consecutive period of six weeks. The survey was conducted using a standardized questionnaire and interview by trained research assistants. The medical students and nurses were trained on the correct protocol of measuring blood pressure based on the recommendations of the British Hypertension Society. Newly detected persons with blood pressure readings 160/95 mmHg and above, were given a green card to return to the nearest health center for a further 2 visits to check his/her blood pressure. A total of 1,392 people with a mean age of 65 years and comprising of 53.1% males and 46.9% females responded to the health survey. Based on the history 335 (24.1%) of the respondents were known hypertensives and 82.1% of this hypertensive group were on regular treatment. However good control of hypertension was achieved only in 161 (48.1%) of them. Newly detected hypertension was found in 204 (14.6%) of the respondents. The overall prevalence of hypertension in our sample of respondents was 25.6%. There was no significant difference between the sexes and the races in terms of their detection, treatment and control. However there was a significant difference between the persons aged less than 65 years of age and those older than 65 years. There was a large proportion of previously known hypertensives among the survey population. Of those detected, not all were on regular medications and the majority on medications were not well controlled. Education of the public through intensive public health campaigns is vital to improve their knowledge on hypertension and the need for effective control. More community studies are needed to formulate better methods in the detection, treatment and control of hypertension.

Matched MeSH terms: Hypertension/drug therapy
Necrotizing gingivitis: a possible oral manifestation of ticlopidine-induced agranulocytosis

Rajandram RK, Ramli R, Karim F, Rahman RA, Fun LC

N Z Med J, 2007;120(1256):U2590.
PMID: 17589558

Agranulocytosis is a rare complication of ticlopidine and can be life-threatening. We report a case of ticlopidine-induced agranulocytosis and neutropenia (neutrophil count of 0.1 x 10(9)/L) with necrotizing gingivitis in a 54-year-old Malaysian-Chinese female. She was started on ticlopidine 250 mg twice daily 3 weeks prior to this hospital admission. We started her on intravenous metronidazole and amoxicillin and clavulanic acid (Augmentin) and concurrently stopped ticlopidine. A series of clinical and laboratory investigations were carried out and a final diagnosis of necrotizing gingivitis possibly secondary to agranulocytosis was made. The patient was discharged home after 2 weeks of hospitalisation.

Matched MeSH terms: Hypertension/drug therapy
Seeking the ideal anti-hypertensive agent: a practical review of the hypertension drug trials

Ong HT, Cheah JS

N Z Med J, 2004 Feb 20;117(1189):U773.
PMID: 15014562

Numerous trials and meta-analyses have been conducted over the last five years to identify an ideal anti-hypertensive drug. These reports, and the JNC 7 and European hypertension guidelines, have generated some controversy and confusion. A review of the comparative anti-hypertensive drug trials shows that the differences between drugs are minor and not consistently demonstrated by different studies. However, much data have now accumulated on the safety and value of diuretics, beta blockers, calcium-channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs) in reducing blood pressure and preventing clinical disease. The importance of tight blood pressure control in reducing adverse events has been clearly shown, and clinicians should concentrate on achieving target blood pressure levels, which often requires a combination of anti-hypertensive drugs. The choice of anti-hypertensive drug should be guided by the presence of concomitant clinical disease, as evidence has accumulated on the special efficacy of certain drugs in reducing damage to particular organ systems. In the absence of any associated clinical disease, it is good to initiate anti-hypertensive therapy with diuretics, provided the metabolic parameters are regularly reviewed.

Matched MeSH terms: Hypertension/drug therapy*
Fulltext Blood-pressure and cholesterol lowering in persons without cardiovascular disease

Yusuf S, Lonn E, Pais P, Bosch J, López-Jaramillo P, Zhu J, et al.

N Engl J Med, 2016 May 26;374(21):2032-43.
PMID: 27039945 DOI: 10.1056/NEJMoa1600177

BACKGROUND: Elevated blood pressure and elevated low-density lipoprotein (LDL) cholesterol increase the risk of cardiovascular disease. Lowering both should reduce the risk of cardiovascular events substantially.
METHODS: In a trial with 2-by-2 factorial design, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to rosuvastatin (10 mg per day) or placebo and to candesartan (16 mg per day) plus hydrochlorothiazide (12.5 mg per day) or placebo. In the analyses reported here, we compared the 3180 participants assigned to combined therapy (with rosuvastatin and the two antihypertensive agents) with the 3168 participants assigned to dual placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included heart failure, cardiac arrest, or revascularization. The median follow-up was 5.6 years.
RESULTS: The decrease in the LDL cholesterol level was 33.7 mg per deciliter (0.87 mmol per liter) greater in the combined-therapy group than in the dual-placebo group, and the decrease in systolic blood pressure was 6.2 mm Hg greater with combined therapy than with dual placebo. The first coprimary outcome occurred in 113 participants (3.6%) in the combined-therapy group and in 157 (5.0%) in the dual-placebo group (hazard ratio, 0.71; 95% confidence interval [CI], 0.56 to 0.90; P=0.005). The second coprimary outcome occurred in 136 participants (4.3%) and 187 participants (5.9%), respectively (hazard ratio, 0.72; 95% CI, 0.57 to 0.89; P=0.003). Muscle weakness and dizziness were more common in the combined-therapy group than in the dual-placebo group, but the overall rate of discontinuation of the trial regimen was similar in the two groups.
CONCLUSIONS: The combination of rosuvastatin (10 mg per day), candesartan (16 mg per day), and hydrochlorothiazide (12.5 mg per day) was associated with a significantly lower rate of cardiovascular events than dual placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.).
Note: Malaysia is a study site (Author: Yusoff K)

Matched MeSH terms: Hypertension/drug therapy*
Fulltext Blood-pressure lowering in intermediate-risk persons without cardiovascular disease

Lonn EM, Bosch J, López-Jaramillo P, Zhu J, Liu L, Pais P, et al.

N Engl J Med, 2016 May 26;374(21):2009-20.
PMID: 27041480 DOI: 10.1056/NEJMoa1600175

BACKGROUND: Antihypertensive therapy reduces the risk of cardiovascular events among high-risk persons and among those with a systolic blood pressure of 160 mm Hg or higher, but its role in persons at intermediate risk and with lower blood pressure is unclear.
METHODS: In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to receive either candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; the second coprimary outcome additionally included resuscitated cardiac arrest, heart failure, and revascularization. The median follow-up was 5.6 years.
RESULTS: The mean blood pressure of the participants at baseline was 138.1/81.9 mm Hg; the decrease in blood pressure was 6.0/3.0 mm Hg greater in the active-treatment group than in the placebo group. The first coprimary outcome occurred in 260 participants (4.1%) in the active-treatment group and in 279 (4.4%) in the placebo group (hazard ratio, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P=0.40); the second coprimary outcome occurred in 312 participants (4.9%) and 328 participants (5.2%), respectively (hazard ratio, 0.95; 95% CI, 0.81 to 1.11; P=0.51). In one of the three prespecified hypothesis-based subgroups, participants in the subgroup for the upper third of systolic blood pressure (>143.5 mm Hg) who were in the active-treatment group had significantly lower rates of the first and second coprimary outcomes than those in the placebo group; effects were neutral in the middle and lower thirds (P=0.02 and P=0.009, respectively, for trend in the two outcomes).
CONCLUSIONS: Therapy with candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day was not associated with a lower rate of major cardiovascular events than placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.).
Note: Malaysia is a study site (Author: Yusoff K)

Matched MeSH terms: Hypertension/drug therapy*
Fulltext Prevention and management of new-onset diabetes mellitus in kidney transplantation

Khong MJ, Chong CP

Neth J Med, 2014 Apr;72(3):127-34.
PMID: 24846925

New-onset diabetes mellitus after transplantation (NODAT) is one of the complications that is increasingly occurring among kidney transplanted patients. It is associated with the risk of cardiovascular disease, graft failure and mortality. The risk of NODAT development increases with time from transplantation. Therefore, early detection and prompt action are essential in reducing the risk of NODAT and its complications. This paper aims to review the screening parameters, prevention and management strategies for NODAT in both pre- and post-transplantation conditions. The pre-transplant patient should be screened for diabetes and cardiometabolic risk factors. Blood glucose evaluation for the pre-transplantation period is important for early detection of impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), which are highly associated with the incidence of NODAT. Post-kidney transplant patients should have periodical blood glucose monitoring with more frequent assessment in the initial phase. As early hyperglycaemia development is a strong predictor for NODAT, prompt intervention is needed. When NODAT develops, monitoring and control of blood glucose profile, lipid profile, microalbuminuria, diabetic complications and comorbid conditions is recommended. Immunosuppressive regimen modification may be considered as suggested by the Kidney Disease: Improving Global Outcomes (KDIGO) guideline to reverse or to improve the diabetes after weighing the risk of rejection and other potential adverse effects. Strategies for modifying immunosuppressive agents include dose reduction, discontinuation, and selection of calcineurin inhibitor (CNI), anti-metabolite agents, mammalian target of rapamycin inhibitors (mTORi), belatacept and corticosteroids. Lifestyle modification and a conventional anti-diabetic approach, as in the type 2 diabetes mellitus guidelines, are also recommended in NODAT management.

Matched MeSH terms: Hypertension/drug therapy
Fulltext Effectiveness of antihypertensive drugs in hypertensive patients with end stage renal failure

Kumolosasi E, Ng WB, Abdul Aziz SA

Med J Malaysia, 2012 Aug;67(4):379-85.
PMID: 23082445 MyJurnal

Hypertension has been identified as one of the causes for end stage renal failure (ESRF) and is likely to worsen kidney function. This retrospective study was carried out at a tertiary hospital in Malaysia with the objective of determining the effectiveness of combination antihypertensive drugs in hypertensive patients with ESRF admitted between 2006 and 2008. Patients with incomplete data and who were on monotherapy were excluded from this study. Although six different combinations gave significant reductions in systolic blood pressure (SBP) (13.38 +/- 9.11 mmHg, p < 0.05) and diastolic blood pressure (DBP) (6.03 +/- 11.39 mmHg, p < 0.05), 69.16% patients did not achieve target blood pressure (BP) (< or = 130/80 mmHg). Combination of beta blocker (BB) with calcium channel blocker (CCB) was the most commonly used. The CCB-diuretic regimen achieved highest percentage of BP control compared to others (40%). Comparison of blood pressure reduction between different combinations of antihypertensive drugs were not significant (p > 0.05) except for CCB-diuretics and BB-CCB-alpha blocker. The findings suggested better BP control with CCB-diuretic relative to other combinations used.

Matched MeSH terms: Hypertension/drug therapy*
Fulltext Hypertension control in chronic kidney disease: don't miss the forest for the trees

Ong HT, Ong LM, Ho JJ

Med J Malaysia, 2012 Aug;67(4):359-62.
PMID: 23082441 MyJurnal
Matched MeSH terms: Hypertension/drug therapy*
Fulltext Hypertension in a residential home for the elderly in Penang, Malaysia

Ong HT, Oung LS, Ong LM, Tan KP

Med J Malaysia, 2010 Mar;65(1):18-20.
PMID: 21265241 MyJurnal

A study of residents at the Silver Jubilee Home for the Aged was conducted to determine the prevalence, awareness and control of hypertension in this elderly community in Penang, Malaysia. Prevalence of hypertension was 36%, with 81% of patients being initially aware of this diagnosis. This relatively low hypertension prevalence rate may be because residents have a fairly sheltered lifestyle with less social stress and a daily routine that incorporates adequate exercise. Similarly, the high hypertension awareness rate compared to reported figures in the community may be because residents are more regularly monitored by the attending medical care-givers. At the beginning of the study, only 34% of hypertensive patients were well controlled with a blood pressure less than 140/90 mm Hg. This proportion rose to 53% at the end of study period. Compliance is better at a residential home because medication is served by their care-givers and cost is absorbed in this charitable organization. Our study suggests that hypertension awareness and control can be reasonable for the elderly in a residential home.

Matched MeSH terms: Hypertension/drug therapy
Fulltext Selecting antihypertensive medication in patients with essential hypertension in Malaysia

Ong HT, Rozina G

Med J Malaysia, 2009 Mar;64(1):3-11.
PMID: 19852313 MyJurnal

Since hypertension is generally asymptomatic, in treating hypertension we are actually seeking to prevent target organ damage and reduce adverse clinical outcome. There have been numerous large clinical trials addressing the question of whether any antihypertensive drug has special protective effects on the cardiovascular and renal systems in addition to the benefit from blood pressure (BP) reduction1-15. In seeking to correctly interpret the message from these trials, it is important to avoid the confusion that can occur when pharmaceutical companies seek to make the results suit their marketing needs 16-18. The aim of this article is thus to provide an unbiased review of the value of the different antihypertensive drugs for the clinician treating essential hypertension in Malaysia.

Matched MeSH terms: Hypertension/drug therapy*
Fulltext Use of complementary medicine amongst hypertensive patients in a public primary care clinic in Ipoh

Mahfudz AS, Chan SC

Med J Malaysia, 2005 Oct;60(4):454-9.
PMID: 16570707

The use and reasons for use of Complementary Medicine (CM) amongst hypertensive patients attending the Hypertension/ Diabetes/ Asthma Clinic in Greentown Health Clinic, Ipoh was assessed. One hundred and twenty patients were selected by systematic random sampling (1:5) over a 2-week period commencing 26/04/04. Data was obtained from interviews, questionnaires and medical records. Twenty seven percent were on CM. Most commonly used CM was herbal medicine. Majority of those using CM for BP control were Malays. The Chinese and Indians were using CM mainly for other health problems. Ninety six percent were using both CM and conventional therapy concurrently. Therefore doctors should enquire about CM usage during patient assessment to prevent possible drug interactions.

Matched MeSH terms: Hypertension/drug therapy*
Fulltext A comparison of valsartan and perindopril in the treatment of essential hypertension in the Malaysian population

Bavanandan S, Morad Z, Ismail O, Chandran A, Thayaparan T, Singaraveloo M

Med J Malaysia, 2005 Jun;60(2):158-62.
PMID: 16114156 MyJurnal

This study was conducted to determine the tolerability and efficacy of valsartan (DIOVAN) compared to perindopril (COVERSYL) in Malaysian patients with mild to moderate hypertension. Two hundred and fifty adult Malaysian patients with a mean sitting diastolic blood pressure of more than 95 mmHg and less than 115 mmHg after a 14 day washout period were randomized to receive either valsartan 80 mg once daily (n=125) or perindopril 4 mg daily (n=125) for eight weeks. The primary end point for efficacy was the change in mean sitting systolic and diastolic blood pressure (SiSBP and SiDBP). The primary criteria for evaluation of tolerability was the incidence of adverse events. There were no significant differences between the two groups with respect to sex, age, weight, baseline sitting and standing systolic and diastolic blood pressure. At 0, 4 and 8 weeks the mean SiDBP in the valsartan group were 101.4, 92.8 and 91.0 mmHg respectively. The corresponding BP for the perindopril treated group was 102.6, 93.8 and 93.2 mmHg. (95% CI -1.39 to +3.27). There were no significant differences in the mean BP measurements between the valsartan and perindopril group at 0, 4 and 8 weeks. In each group there were significant differences between the BP at 4 and 8 weeks compared to baseline. A similar pattern was seen with SiSBP. At 4 weeks 28.7% of the valsartan and 25% of the perindopril group had their BP normalized (SiDBP <90 mmHg) The percentages of patients who responded (SiDBP reduction >10 mmHg but SiDBP >90 mmHg) were 21.3 in the valsartan group and 20.8 in the perindopril group. At 8 weeks, 31.1% of the valsartan group and 30.8% of the perindopril group had their BP normalized. The response rate was 27% and 22.5% for valsartan and perindopril respectively. The major adverse event was cough which occurred in 18 patients (14.4%) in the perindopril and 1 (0.8%) in the valsartan group at 4 weeks. At 8 weeks the figures were 24 (19.2%) and 2 (1.6%) respectively. The results indicate that Valsartan is safe and efficacious in the treatment of mild to moderate hypertension. It is equally efficacious to Perindopril and not associated with any major adverse event. It has a better tolerability profile with respect to dry cough.

Matched MeSH terms: Hypertension/drug therapy*

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