OBJECTIVES: To determine the effectiveness of ACE inhibitor administration in people with sickle cell disease for decreasing intraglomerular pressure, microalbuminuria and proteinuria and to to assess the safety of ACE inhibitors as pertains to their adverse effects.
SEARCH METHODS: The authors searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Hameoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 03 June 2015.
SELECTION CRITERIA: Randomized or quasi-randomized controlled trials of ACE inhibitors designed to reduce microalbuminuria and proteinuria in people with sickle cell disease compared to either placebo or standard treatment regimen.
DATA COLLECTION AND ANALYSIS: Three authors independently applied the inclusion criteria in order to select studies for inclusion in the review. Two authors assessed the risk of bias of studies and extracted data and the third author verified these assessments.
MAIN RESULTS: Five studies were identified through the searches, only one met our inclusion criteria. The included study randomized 22 participants (seven males and 15 females) having proteinuria or microalbuminuria with sickle cell disease and treated the participants for six months (median length of follow up of three months) with captopril or placebo. The overall quality of the outcomes reported was high, since most aspects that may contribute to bias were regarded to be of low risk, although allocation concealment was not reported. At six months, the study reported no significant difference in urinary albumin excretion between the captopril group and the placebo group, although the mean urinary albumin excretion in the captopril group was lower by a mean difference of -49.00 (95% confidence interval -124.10 to 26.10) compared to that of placebo. However, our analysis on the absolute change score showed significant changes between the two groups by a mean difference of -63.00 (95% confidence interval -93.78 to -32.22). At six months albumin excretion in the captopril group was noted to decrease from baseline by a mean of 45 ± 23 mg/day and the placebo group was noted to increase by 18 ± 45 mg/day. Serum creatinine and potassium levels were reported constant throughout the study. The potential for inducing hypotension should be highlighted; the study reported a decrease of 8 mmHg in systolic pressure and 5 mmHg in diastolic and mean blood pressure.
AUTHORS' CONCLUSIONS: There is not enough evidence to show that the administration of ACE inhibitors is associated with a reduction of microalbuminuria and proteinuria in people with sickle cell disease, although a potential for this was seen. More long-term studies involving multiple centers and larger cohorts using a randomized-controlled design are warranted, especially among the pediatric age group. Detailed reporting of each outcome measure is necessary to allow a clear cut interpretation in a systematic review. One of the difficulties encountered in this review was the lack of detailed data reported in the included study.
MATERIALS AND METHODS: This was a retrospective study conducted at nephrology unit of a tertiary hospital in Kedah. All diabetic ESRD patients who fulfilled the inclusion criteria were identified and recruited for analysis.
RESULTS: The mean duration of DM to ESRD was found to be 14.37 ± 4.42 years. Mean duration for the onset of diabetic nephropathy was 8.73 ± 3.37 years. There was a relative short duration from diabetic nephropathy to ESRD noted, which was 5.63 ± 2.06 years. The mean duration of DM to ESRD for patients receiving RAAS blocker was found to be 18.23 ± 2.38 years as compared to 11.41 ± 2.94 years for those who did not (95% CI: -0.64 to -2.46). For different type of RAAS blockers, namely ACE inhibitor and angiotensin receptor blocker (ARB), there was no significant difference observed pertaining to mean duration of DM to ESRD; 17.89 ± 1.97 years for ACEi and 19.00 ± 4.16 years for ARB (95% CI: -4.74 to 2.52).
DISCUSSION: Time frame from diabetic nephropathy to ESRF among Malaysian population was shorter as compared to findings from other countries with an average period of 15 to 25 years. RAAS blockers should be initiated early in diabetic patients.
OBJECTIVES: To document the prevalence of CHF in the multiracial population of Malaysia, and to describe the clinical features and management of these patients.
SETTING: Busy city centre general hospital in Kuala Lumpur, Malaysia.
RESULTS: Of 1435 acute medical admissions to Kuala Lumpur General Hospital over the 4-week study period, 97 patients (6.7%) were admitted with the primary diagnosis of CHF. Coronary artery disease was the main aetiology of CHF, accounting for almost half (49.5%) the patients, followed by hypertension (18.6%). However, there were variations in associated aetiological factors between ethnic groups, with diabetes mellitus affecting the majority of Indians-as well as underutilisation of standard drugs for CHF, such as the angiotensin converting enzyme (ACE) inhibitors, which were only used in 43.3%.
CONCLUSION: Amongst acute medical admissions to a single centre in Malaysia the prevalence of CHF was 6.7%. Coronary artery disease was the major aetiological factor in heart failure accounting for almost half the admissions. The under-prescription of ACE inhibitors was similar to other clinical surveys carried out amongst Caucasian populations in the West.
METHOD: Literature search was performed within the PubMed, ScienceDirect.com and Google Scholar.
RESULTS: The presence of proline at the C-terminal tripeptide of ACE inhibitor can competitively inhibit the ACE activity. The effects of other amino acids are less studied leading to difficulties in predicting potent peptide sequences. The broad specificity of the enzyme may be due to the dual active sites observed on the somatic ACE. The inhibitors may not necessarily competitively inhibit the enzyme which explains why some reported inhibitors do not have the common ACE inhibitor characteristics. Finally, the in vivo assay has to be carried out before the peptides as the antihypertensive agents can be claimed. The peptides must be absorbed into circulation without being degraded, which will affect their bioavailability and potency. Thus, peptides with strong in vitro IC50 values do not necessarily have the same effect in vivo and vice versa.
CONCLUSION: The relationship between peptide amino acid sequence and inhibitory activity, in vivo studies of the active peptides and bioavailability must be studied before the peptides as antihypertensive agents can be claimed.
METHODS: A case-control, cross-sectional population-based nested study (n = 142) included hypertensive subjects treated with ACEI drugs, either lisinopril or enalapril (20 mg, once daily) as monotherapy for 24 weeks. In total seven possible polymorphisms of RAS genes were genotyped. The association between those polymorphisms and the changes in blood pressure were observed in the 24 week treatment.
RESULTS: Statistically significant associations of I, G, T, M and G alleles of ACE (I/D, G2350A), AGT (M235T, T175M and G-6A) respectively were observed in essential hypertensive subjects. The decrease in systolic blood pressure and diastolic blood pressure after 24 weeks of treatment of the patients carrying II, GG, and TT genotypes were greater than the groups carrying DD, AA, MM, MM and GG of I/D, G2350A, M235T, T174M and G-6A genotypes respectively. In contrast, No significant difference was observed between renin gene polymorphisms (Bg/I and MboI) and hypertensives.
CONCLUSIONS: Although this study shows a possible association of polymorphisms of RAS genes with the risk of non-control of HT in ACEI-treated patients and indicates the importance of all this system's components in regulating HT, it needs to be replicated in other data sources.
OBJECTIVES: To study the trends in sex and gender differences in ACS using the Malaysian NCVD-ACS Registry.
METHODS: Data from 24 hospitals involving 35,232 ACS patients (79.44% men and 20.56% women) from 1st. Jan 2012 to 31st. Dec 2016 were analysed. Data were collected on demographic characteristics, coronary risk factors, anthropometrics, treatments and outcomes. Analyses were done for ACS as a whole and separately for ST-segment elevation myocardial infarction (STEMI), Non-STEMI and unstable angina. These were then compared to published data from March 2006 to February 2010 which included 13,591 ACS patients (75.8% men and 24.2% women).
RESULTS: Women were older and more likely to have diabetes mellitus, hypertension, dyslipidemia, previous heart failure and renal failure than men. Women remained less likely to receive aspirin, beta-blocker, angiotensin-converting enzyme inhibitor (ACE-I) and statin. Women were less likely to undergo angiography and percutaneous coronary intervention (PCI) despite an overall increase. In the STEMI cohort, despite a marked increase in presentation with Killip class IV, women were less likely to received primary PCI or fibrinolysis and had longer median door-to-needle and door-to-balloon time compared to men, although these had improved. Women had higher unadjusted in-hospital, 30-Day and 1-year mortality rates compared to men for the STEMI and NSTEMI cohorts. After multivariate adjustments, 1-year mortality remained significantly higher for women with STEMI (adjusted OR: 1.31 (1.09-1.57), p<0.003) but were no longer significant for NSTEMI cohort.
CONCLUSION: Women continued to have longer system delays, receive less aggressive pharmacotherapies and invasive treatments with poorer outcome. There is an urgent need for increased effort from all stakeholders if we are to narrow this gap.
SETTING: Five medical and cardiology wards of a tertiary care center in Malaysia.
SUBJECTS: Five hundred cardiac inpatients, who received ACEIs concomitantly with other interacting drugs.
METHOD: This was a prospective cohort study of 500 patients with cardiovascular diseases admitted to Penang Hospital between January to August 2006, who received ACEIs concomitantly with other interacting drugs. ACEI-drug interactions of clinical significance were identified using available drug information resources. Drug Interaction Probability Scale (DIPS) was used to assess the causality of association between ACEI-drug interactions and the adverse outcome (hyperkalemia).
MAIN OUTCOME MEASURE: Hyperkalemia as an adverse clinical outcome of the interaction was identified from laboratory investigations.
RESULTS: Of the 489 patients included in the analysis, 48 (9.8%) had hyperkalemia thought to be associated with ACEI-drug interactions. Univariate analysis using binary logistic regression revealed that advanced age (60 years or more), and taking more than 15 medications were independent risk factors significantly associated with hyperkalemia. However, current and previous smoking history appeared to be a protective factor. Risk factors identified as predictors of hyperkalemia secondary to ACEI-drug interactions by multi-logistic regression were: advanced age (adjusted OR 2.3, CI 1.07-5.01); renal disease (adjusted OR 4.7, CI 2.37-9.39); hepatic disease (adjusted OR 5.2, CI 1.08-25.03); taking 15-20 medications (adjusted OR 4.4, CI 2.08-9.19); and taking 21-26 medications (adjusted OR 9.0, CI 1.64-49.74).
CONCLUSION: Cardiac patients receiving ACEIs concomitantly with potentially interacting drugs are at high risk of experiencing hyperkalemia. Old age, renal disease, hepatic disease, and receiving large number of medications are factors that may significantly increase their vulnerability towards this adverse outcome; thus, frequent monitoring is advocated.
OBJECTIVE: The current study aimed to investigate the potential of MKP as a pharmaceutical against AD by examining MKP's effect on cognitive function and molecular changes in the brain using double transgenic (APP/PS1) mice.
METHODS: Experimental procedures were conducted in APP/PS1 mice (n = 38) with a C57BL/6 background. A novel object recognition test was used to evaluate recognition memory. ELISA was used to measure insoluble Aβ40, Aβ42, and TNF-α levels in brain tissue. Immunohistochemical analysis allowed the assessment of glial cell activation in MKP-treated APP/PS1 mice.
RESULTS: The novel object recognition test revealed that MKP-treated APP/PS1 mice showed significant improvement in recognition memory. ELISA of brain tissue showed that MKP significantly reduced insoluble Aβ40, Aβ42, and TNF-α levels. Immunohistochemical analysis indicated the suppression of the marker for microglia and reactive astrocytes in MKP-treated APP/PS1 mice.
CONCLUSION: Based on these results, we consider that MKP could ameliorate pathological Aβ accumulation-induced cognitive impairment in APP/PS1 mice. Furthermore, our findings suggest that MKP potentially contributes to preventing cognitive decline in AD.
METHODS: From the Malaysian National Neurology Registry, we included hypertensive patients with first ischemic stroke who presented within 48 hours from ictus. Antihypertensive drugs were divided into Ang II increasers (angiotensin-I receptor blockers (ARBs), calcium channel blockers (CCBs) and diuretics) and Ang II suppressors (angiotensin-converting-enzyme inhibitors (ACEIs) and beta blockers). We evaluated stroke severity during admission with the National Institute of Health Stroke Scale (NIHSS). We performed a multivariable logistic regression with the score being dichotomized at 15. Scores of less than 15 were categorized as less severe stroke.
RESULTS: A total of 710 patients were included. ACEIs was the most commonly prescribed antihypertensive drug in patients using Ang II suppressors (74%) and CCBs, in patients prescribed with Ang II increasers at 77%. There was no significant difference in the severity of ischemic stroke between patients who were using Ang II increasers in comparison to patients with Ang II suppressors (OR: 1.32, 95%CI: 0.83-2.10, p = 0.24).
CONCLUSION: In our study, we found that use of antihypertensive drugs that increase Ang II formation was not associated with less severe ischemic stroke as compared to use of antihypertensive drugs that suppress Ang II formation.
DESIGN: A retrospective analysis of STEMI patients from 18 hospitals across Malaysia contributing to the Malaysian National Cardiovascular Database-acute coronary syndrome) registry (NCVD-ACS) year 2006-2013.
PARTICIPANTS: 16 517 patients diagnosed of STEMI from 18 hospitals in Malaysia from the year 2006 to 2013.
PRIMARY OUTCOME MEASURES: In-hospital and 30 day post-discharge mortality.
RESULTS: CS complicates 10.6% of all STEMIs in this study. They had unfavourable premorbid conditions and poor outcomes. The in-hospital mortality rate was 34.1% which translates into a 7.14 times mortality risk increment compared with STEMI without CS. Intravenous thrombolysis remained as the main urgent reperfusion modality. Percutaneous coronary interventions (PCI) in CS conferred a 40% risk reduction over non-invasive therapy but were only done in 33.6% of cases. Age over 65, diabetes mellitus, hypertension, chronic lung and kidney disease conferred higher risk of mortality.
CONCLUSION: Mortality rates of CS complicating STEMI in Malaysia are high. In-hospital PCI confers a 40% mortality risk reduction but the rate of PCI among our patients with CS complicating STEMI is still low. Efforts are being made to increase access to invasive therapy for these patients.