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Fulltext The Association between Inflammation and Pulse Wave Velocity in Dyslipidemia: An Evidence-Based Review

Aminuddin A, Lazim MRMLM, Hamid AA, Hui CK, Mohd Yunus MH, Kumar J, et al.

Mediators Inflamm, 2020;2020:4732987.
PMID: 32908450 DOI: 10.1155/2020/4732987

Dyslipidemia is associated with increased arterial stiffness (AS) which may lead to hypertension. Among the methods to assess AS are carotid-femoral and brachial-ankle pulse wave velocity. Dyslipidemia is also known to trigger inflammation. C-reactive protein (CRP) is one of the commonest inflammatory markers measured in the clinical setting. However, the association between inflammation and pulse wave velocity (PWV) in people with dyslipidemia is less studied. Therefore, this review investigated the association between inflammation (as measured by CRP) and PWV in dyslipidemia patients. The search of the literature was conducted via PubMed and Scopus database. The keywords used were "aortic stiffness" OR "arterial stiffness" OR "pulse wave velocity" OR "vascular stiffness" OR "carotid femoral pulse wave velocity" OR "pulse wave analysis" AND "inflammation" OR "c reactive protein" OR "c-reactive protein" OR "high sensitivity c reactive protein" AND "dyslipidemia" OR "hyperlipidemia" OR "hypercholesterolemia" OR "hyperlipoproteinemia" OR "hypertriglyceridemia". The following criteria were used: (1) only full-length original articles published in English language, (2) articles that reported the association between arterial stiffness measured as carotid-femoral PWV (cfPWV) or brachial-ankle PWV (baPWV) and CRP or high-sensitivity CRP, and (3) study involving human subjects. The search identified 957 articles published between 1980 and February 2020. Only eight articles fulfilled the inclusion criteria and were used for data extraction. Five of the studies were cross-sectional studies while another three studies were interventional studies. Seven out of eight papers found a significant positive association between AS and CRP, and the correlation ranged from mild to moderate association (Pearson r = 0.33 to r = 0.624). In conclusion, inflammation is associated with increased PWV in patients with dyslipidemia. This supports the involvement of inflammation in the development of AS in dyslipidemia.
Fulltext Effect of increasing heart rate on finger photoplethysmography fitness index (PPGF) in subjects with implanted cardiac pacemakers

Aminuddin A, Tan I, Butlin M, Avolio AP, Kiat H, Barin E, et al.

PLoS One, 2018;13(11):e0207301.
PMID: 30485318 DOI: 10.1371/journal.pone.0207301

Finger photoplethysmography (PPG) is a noninvasive method that measures blood volume changes in the finger. The PPG fitness index (PPGF) has been proposed as an index of vascular risk and vascular aging. The objectives of the study were to determine the effects of heart rate (HR) on the PPGF and to determine whether PPGF is influenced by blood pressure (BP) changes. Twenty subjects (78±8 years, 3 female) with permanent cardiac pacemakers or cardioverter defibrillators were prospectively recruited. HR was changed by pacing, in a random order from 60 to 100 bpm and in 10 bpm increments. At each paced HR, the PPGF was derived from a finger photoplethysmogram. Cardiac output (CO), stroke volume (SV) and total peripheral resistance (TPR) were derived from the finger arterial pressure waveform. Brachial blood pressure (BP) was measured by the oscillometric method. This study found that as HR was increased from 60 to 100 bpm, brachial diastolic BP, brachial mean BP and CO were significantly increased (p<0.01), whilst the PPGF and SV were significantly decreased (p<0.001). The effects of HR on the PPGF were influenced by BP, with a decreasing HR effect on the PPGF that resulted from a higher BP. In conclusion, HR was a significant confounder for PPGF and it must be taken into account in analyses of PPGF, when there are large changes or differences in the HR. The magnitude of this effect was BP dependent.
Fulltext Is Heart Rate a Confounding Factor for Photoplethysmography Markers? A Systematic Review

Md Lazin Md Lazim MR, Aminuddin A, Chellappan K, Ugusman A, Hamid AA, Wan Ahmad WAN, et al.

Int J Environ Res Public Health, 2020 04 10;17(7).
PMID: 32290168 DOI: 10.3390/ijerph17072591

Finger photoplethysmography (PPG) waveform is blood volume change of finger microcirculation that reflects vascular function. Reflection index (RI), stiffness index (SI) and second derivative of photoplethysmogram (SDPPG) are derived from PPG waveforms proposed as cardiovascular disease (CVD) markers. Heart rate (HR) is a known factor that affects vascular function. Individual resting HR variation may affect RI, SI and SDPPG. This review aims to identify studies about the relationship between HR with RI, SI and SDPPG among humans. A literature search was conducted in Medline via the Ebscohost and Scopus databases to find relevant articles published within 11 years. The main inclusion criteria were articles in the English language that discuss the relationship between HR with RI, SI and SDPPG using PPG among humans. The search found 1960 relevant articles but only six articles that met the inclusion criteria. SI and RI showed an association with HR. SDPPG (SDPPG-b/SDPPG-a ratio, SDPPG-d/SDPPG-a ratio, aging index (AGI) and revised aging index (RAGI)) also had an association with HR. Only RI had a considerable association with HR, the association between SI and HR was non-considerable and the association between HR and SDPPG was inconclusive. Further interventional studies should be conducted to investigate this issue, as a variation in resting HR may challenge the validity of PPG-based CVD markers.
Pharmacological interventions for intraplaque neovascularization in atherosclerosis

Ugusman A, Hisam NSN, Othman NS, Anuar NNM, Hamid AA, Kumar J, et al.

Pharmacol Ther, 2024 Jul 06;261:108685.
PMID: 38977083 DOI: 10.1016/j.pharmthera.2024.108685

Advanced atherosclerosis is linked to plaque instability, which can result in rupture and the onset of a heart attack. Evidence gathered from human atheroma plaques indicates that intraplaque neovascularization poses a risk to plaque stability and may lead to plaque hemorrhage. Hence, targeting the neovascularization within the atheroma plaque has the potential to mitigate the plaque's vulnerability. While neovascularization has been extensively explored in the context of cancer, research on pharmacological inhibition of this phenomenon in atherosclerosis remains limited. This systematic review aimed to comprehensively assess current and emerging pharmacological interventions for inhibiting intraplaque neovascularization in preclinical settings. Electronic databases (Web of Science, PubMed, Scopus, and Ovid) were searched from January 2013 until February 1, 2024. Preclinical studies reporting the effect of any pharmacological interventions targeting intraplaque neovascularization were included. A total of 10 articles involving in vivo animal studies were eligible for inclusion, with five of them incorporating in vitro experiments to complement their in vivo findings. The pharmacological interventions studied were axitinib, ghrelin, K5, rosuvastatin, atorvastatin, 3PO, everolimus, melatonin, Si-Miao-Yong-A, and protocatechuic aldehyde. All the interventions showed a positive impact in inhibiting intraplaque neovascularization in various atherosclerotic animal models through various signaling pathways. This review provides valuable insights into pharmacological approaches to attenuate intraplaque neovascularization that could serve as a promising therapeutic avenue to enhance plaque stability.
Fulltext Role of Honey in Obesity Management: A Systematic Review

Ugusman A, Shahrin SAS, Azizan NH, Pillai SB, Krishnan K, Salamt N, et al.

Front Nutr, 2022;9:924097.
PMID: 35811958 DOI: 10.3389/fnut.2022.924097

Obesity is a metabolic disorder that has become critically prevalent throughout the world. Obesity has been linked to other chronic diseases such as diabetes mellitus, cardiovascular diseases and cancer. Natural products such as honey have been investigated for their potential effect on obesity. Hence, this study systematically reviewed the recent literature concerning the effects of honey on obesity in obese animal models and in people with obesity. The Ovid MEDLINE, PubMed, Scopus, Web of Science and Google Scholar electronic databases were searched for relevant articles. A total of 130 relevant articles were obtained from the initial search. Following a thorough screening, nine articles were selected for data extraction, including six animal studies and three clinical trials. In most of the animal studies, honey demonstrated an anti-obesity effect by reducing body weight, body fat composition and adipocyte size, among others. However, supplementation of honey in clinical trials showed conflicting results. Even though honey supplementation did not demonstrate any weight-reducing effect in some of the clinical trials, none of the trials showed that honey increases body weight. However, the results should be interpreted with caution as most of the studies involved animal models and there is a limited number of high quality, randomized, controlled clinical trials.
SYSTEMATIC REVIEW REGISTRATION: https://inplasy.com/inplasy-2022-6-0038/ PROSPERO, identifier 10.37766/inplasy2022.6.0038.
Fulltext Roselle attenuates cardiac hypertrophy after myocardial infarction in vivo and in vitro

Si LY, Ramalingam A, Ali SS, Aminuddin A, Ng PY, Latip J, et al.

EXCLI J, 2019;18:876-892.
PMID: 31645847 DOI: 10.17179/excli2019-1792

Roselle (Hibiscus sabdariffa Linn) has been traditionally used as folk medicine for hypertension and maintaining cardiovascular health, with therapeutic potential in protecting against numerous cardiovascular diseases. However, it remains unclear whether roselle can be used for management of cardiac hypertrophy seen after myocardial infarction (MI). This study therefore investigated the effects of aqueous roselle extract on cardiac hypertrophy arising from myocardial infarction both in vivo and in vitro. For in vivo study, male Sprague-Dawley rats were divided into control or MI groups (receiving 85 mg/kg isoproterenol s.c. for 2 days) and were given roselle extract (100 mg/kg, p.o daily) for 28 days. Cardiac structure and functional changes were evaluated at study end-point using histology, Langendorff analysis and gene expression analysis. In vitro effects of roselle were also assessed on ANG II-induced cardiomyocytes hypertrophy using H9c2 cells, simulating cardiac hypertrophy evident after MI. Roselle significantly ameliorated MI-induced cardiac systolic and diastolic dysfunction, as seen across improvement in left ventricular developed pressure (LVDP) and its derivative (LVdP/dtmax) and isovolumic relaxation (Tau). Oxidative stress evident across elevated pro-oxidant markers (NOX2 subunit of NADPH oxidase and 8-isoprostane) as well as reduced antioxidant markers (superoxide dismutase and glutathione) were also significantly attenuated by roselle. Furthermore, roselle treatment markedly reduced markers of cardiac remodeling (cardiac hypertrophy and fibrosis) compared to the untreated MI rats. On in vitro analysis, roselle significantly attenuated ANG II-induced cardiomyoycte hypertrophy in dose-dependent manner. This study demonstrated that roselle attenuates cardiac hypertrophy and dysfunction seen after MI both in vivo and in vitro, and these effects are likely mediated by phenolic compounds found in roselle extract.
Fulltext Profiling of Differentially Expressed MicroRNAs in Human Umbilical Vein Endothelial Cells Exposed to Hyperglycemia via RNA Sequencing

Othman NS, Aminuddin A, Zainal Abidin S, Syafruddin SE, Ahmad MF, Mohd Mokhtar N, et al.

Life (Basel), 2023 May 31;13(6).
PMID: 37374078 DOI: 10.3390/life13061296

Hyperglycemia is the hallmark of diabetes mellitus that results in oxidative stress, apoptosis, and diabetic vascular endothelial dysfunction. An increasing number of microRNAs (miRNAs) have been found to be involved in the pathogenesis of diabetic vascular complications. However, there is a limited number of studies that characterize the miRNA profile of endothelial cells exposed to hyperglycemia. Therefore, this study aims to analyze the miRNA profile of human umbilical-vein endothelial cells (HUVECs) exposed to hyperglycemia. HUVECs were divided into two groups: the control (treated with 5.5 mM glucose) and hyperglycemia (treated with 33.3 mM glucose) groups. RNA sequencing identified 17 differentially expressed miRNAs between the groups (p < 0.05). Of these, 4 miRNAs were upregulated, and 13 miRNAs were downregulated. Two of the most differentially expressed miRNAs (novel miR-1133 and miR-1225) were successfully validated with stem-loop qPCR. Collectively, the findings show that there is a differential expression pattern of miRNAs in HUVEC following exposure to hyperglycemia. These 17 differentially expressed miRNAs are involved in regulating cellular functions and pathways related to oxidative stress and apoptosis that may contribute to diabetic vascular endothelial dysfunction. The findings provide new clues on the role of miRNAs in the development of diabetic vascular endothelial dysfunction, which could be useful in future targeted therapy.
Fulltext Impact of offspring endothelial function from de novo hypertensive disorders during pregnancy: An evidence-based review

Abdull Sukor AN, Ankasha SJ, Ugusman A, Aminuddin A, Mokhtar NM, Zainal Abidin S, et al.

Front Surg, 2022;9:967785.
PMID: 36420416 DOI: 10.3389/fsurg.2022.967785

De novo hypertensive disorders of pregnancy (HDP) which consist of gestational hypertension and preeclampsia affect maternal and offspring morbidity and mortality, and potentially increase the risk of cardiovascular disease in the offspring. It is well known that de novo HDP causes various maternal complications, including cardiovascular diseases, placental abruption and liver and kidney failure. However, there are studies suggesting that offspring of pregnancies complicated by de novo HDP have an increased risk of long-term cardiovascular disease. The endothelium is an important regulator of vascular function, and its dysfunction is highly associated with the development of cardiovascular diseases. Hence, this review aimed to systematically identify articles related to the effect of de novo HDP on the endothelial function of the offspring. A computerized database search was conducted on PubMed, Scopus, and Medline from 1976 until 2022. A total of 685 articles were obtained. We identified another three additional articles through review articles and Google Scholar. Altogether, we used 13 articles for data extraction. All studies reported that endothelial function was impaired in the offspring of de novo HDP. This is most likely attributed to impaired vasodilation, subclinical atherosclerosis formation, inflammation, and dysregulated epigenetic regulation of endothelial functions.
Prognostic value of pulse wave velocity for cardiovascular disease risk stratification in diabetic patients: A systematic review and meta-analysis

Cheong SS, Samah N, Che Roos NA, Ugusman A, Mohamad MSF, Beh BC, et al.

J Diabetes Complications, 2024 Dec;38(12):108894.
PMID: 39531755 DOI: 10.1016/j.jdiacomp.2024.108894

AIM: Arterial stiffness, a significant cardiovascular risk marker, is particularly important in patients with diabetes mellitus (DM). Pulse wave velocity (PWV), a non-invasive measure of arterial stiffness, has emerged as an independent predictor of cardiovascular morbidity and mortality. However, its precise prognostic value in DM patients for cardiovascular risk stratification remains unclear. To address this, a systematic review was conducted.
METHOD: A thorough search of Ovid and Scopus databases was performed for cohort studies on PWV measurements for cardiovascular risk stratification in DM patients. Nine studies were included, examining the relationship between PWV and cardiovascular events or composite endpoints in DM patients asymptomatic of cardiovascular diseases (CVD).
RESULTS: The review revealed that optimal PWV cutoffs to predict composite cardiovascular events ranged from 10 to 12.16 m/s (aortic PWV) and 14 to 16.72 m/s (brachial-ankle PWV). In addition, meta-analysis yielded a HR of 1.15 (95 % CI 1.07-1.24, p
Fulltext Solid-pseudopapillary carcinoma: a case study and literature review

Mat Zin AA, Shakir KA, Aminuddin AR, Mahedzan MR, Irnawati WA, Andee DZ, et al.

BMJ Case Rep, 2012;2012.
PMID: 22927280 DOI: 10.1136/bcr-2012-006495

Solid-pseudopapillary tumour (SPT) is a rare exocrine tumour of the pancreas and is considered to have low malignant potential. Few morphological criteria are used to predict malignant behaviour such as equivocal perineural invasion, angioinvasion and invasion to surrounding tissue, and should be designated as solid-pseudopapillary carcinoma (SPC). We report a case of SPC. Clinical and radiological findings are typical for SPT with no metastatic disease. There is no tumour recurrence after 4&emsp14;months postresection. Clinical history and radiological findings were retrieved from the patient's record sheet and Viarad system. H&E staining and few immunoproxidase staining were reviewed by several pathologists. The histological findings are typical for SPT, with additional perineural invasion. There is no angioinvasion or capsular invasion identified. This is our first experience in diagnosing and managing SPC. We look forward to seeing the patient's disease status during her next routine follow-up. We expect good disease-free survival and very low risk of tumour recurrence, in view of only one risk factor (perineural invasion) and uninvolved surgical margins by the tumour.
Testosterone is associated with age-related changes in bone health status, muscle strength and body composition in men

Chin KY, Soelaiman IN, Naina Mohamed I, Shahar S, Teng NI, Suhana Mohd Ramli E, et al.

Aging Male, 2012 Dec;15(4):240-5.
PMID: 23098182 DOI: 10.3109/13685538.2012.724740

OBJECTIVE: Variations in testosterone levels are associated with several outcomes of aging. The present study aimed to examine the relationship between age-related decline of testosterone levels and changes in bone health status, handgrip strength, body fat percentage and fat-free mass.
MATERIALS AND METHODS: A total of 335 Malaysian Chinese and Malay men aged 40 years and above were recruited for this study. Their body compositions, calcaneal speed of sound and handgrip strength were measured and their blood was collected. Linear regression analysis was done to examine the relationship among age, testosterone levels and outcomes of aging.
RESULTS: The results indicated significant changes in all testosterone measurements, sex hormone binding globulin level, calcaneal speed of sound, handgrip strength, body fat percentage and fat-free mass with age (p < 0.05). Age-dependent decline in bioavailable and free testosterone levels were significantly associated with reduction in calcaneal speed of sound, fat-free mass and handgrip strength (p < 0.05). Age-dependent decline in the total testosterone level was significantly associated with an increase in body fat percentage among the elderly men (p < 0.05).
CONCLUSION: Testosterone levels are associated with changes in outcome of aging such as bone health status, muscle strength and body composition, and the relationships are age-dependent.
High C reactive protein associated with increased pulse wave velocity among urban men with metabolic syndrome in Malaysia

Aminuddin A, Zakaria Z, Fuad AF, Kamsiah J, Othman F, Das S, et al.

Saudi Med J, 2013 Mar;34(3):266-75.
PMID: 23475091

To determine the association between carotid femoral pulse wave velocity (PWVCF); augmentation index (AI); and high-sensitivity C reactive protein (hs-CRP) with metabolic syndrome (MetS), and to determine the influence of ethnicity on PWVCF and AI, and the association between high hs-CRP and increased PWV, and AI in MetS.

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