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Biomedical subjects

Hoong Sern Lim

Publications and source records attributed to Hoong Sern Lim.

At least 19 recordsLinked to original sources
PubMed2006

Raised leptin concentrations among South Asian patients with chronic heart failure.

BACKGROUND: The disease presentation of chronic heart failure (CHF) is considered to progress with metabolic deterioration, underlined by changes in adipose associated hormones (adipocytokines). However, little is known about ethnic variations of adipocytokines amongst CHF patients, in particular South Asians, who are at an increased risk of CHF. METHODS: Using a cross-sectional study, South Asians (n=106) and Caucasians (n=105) living in the UK were compared by CHF status. We investigated ethnic differences in adipocytokines (leptin, adiponectin, tumor necrosis factor (TNF)alpha), and their association with CHF. Patients with mild to moderate CHF were recruited from heart failure clinics (47 Caucasian, 54 South Asian), and compared to healthy controls. Metabolic parameters (including insulin resistance using HOMA modelling), echocardiography and brain natriuretic peptide (BNP) were measured amongst patients and healthy controls, and compared across and within ethnic groups. RESULTS: Mean (log transformed) plasma leptin concentrations were highest amongst South Asian patients, being 5.25% (95%CI: 1.50-9.02) higher than Caucasian patients (P=0.007), and similarly raised with respect to controls (P< or =0.04). Indices of insulin resistance were higher amongst CHF patients compared with controls, with no ethnic variation. In addition to age, female gender and body-mass index, levels of leptin were also associated with South Asian ethnicity (P<0.001), insulin resistance (P=0.02), smoking habit (P=0.01) and HDL cholesterol (P=0.004). Levels of adiponectin showed no ethnic variation, but were associated with CHF and a previous history of myocardial infarction (P<0.001). On multivariate regression analysis of patients and healthy controls, CHF was independently associated with smoking habit, adiponectin and insulin resistance (all P<0.01). CONCLUSION: Metabolic abnormalities are present in CHF, which in turn, are influenced by ethnicity. The role of adipocytokines in CHF pathophysiology and prognosis merits further study.

Adiponectin↗
PubMed2006

Plasma von Willebrand factor and soluble E-selectin levels in stable outpatients with systolic heart failure: the Frederiksberg heart failure study.

BACKGROUND: Endothelial dysfunction is a well-established aspect of the pathophysiology of patients with systolic heart failure. We have previously reported that patients who have had multiple current or previous hospital admissions for decompensated heart failure have consistently shown abnormal levels of plasma von Willebrand factor (vWf, an index of endothelial damage/dysfunction) and soluble E-selectin (E-sel, an index of endothelial activation), as well as other indices of endothelial perturbation. METHODS: To investigate if endothelial abnormalities extend to CHF outpatients who have only been recently diagnosed or have relatively mild or few, stable symptoms (at baseline), given the better prognosis in these patients, we performed a cross-sectional analysis of CHF patients, where vWf and E-sel levels (as indices of endothelial perturbation) were measured (ELISA) and related to left ventricular ejection fraction (LVEF), exercise capacity (6-min walk test) and N-terminal pro-Brain Natiuretic Peptide (NT-proBNP). RESULTS: There were no statistically significant differences in vWf and E-sel levels amongst patients with systolic heart failure compared to controls. Plasma NT-proBNP levels in patients with CHF were significantly elevated compared to controls (p<0.0001). Among the patients with CHF, higher NT-proBNP levels correlated with poorer LVEF [Spearman r=-0.244, p<0.004] and shorter 6-min walk distance [Spearman r=-0.226, p=0.045] but not NYHA class. Plasma vWf or E-sel levels did not correlate with LVEF, 6-min walk test or NYHA class. NT-proBNP levels correlated weakly with E-sel [Spearman r=-0.211, p=0.015] but not vWf. CONCLUSION: The present observation suggests that stable CHF outpatients with few symptoms may in fact have less severe endothelial perturbation, as reflected by plasma indices such as vWf and E-selectin. There was limited association of endothelial indices to LVEF, exercise capacity, NYHA class and NT-proBNP levels.

Aged↗
PubMed2006

Endothelial activation, dysfunction, and damage in congestive heart failure and the relation to brain natriuretic peptide and outcomes.

Congestive heart failure (CHF) is associated with marked endothelial dysfunction. We hypothesized that acute and chronic CHF may manifest different degrees of endothelial damage/dysfunction and activation, as reflected by different plasma endothelial markers, such as von Willebrand factor (vWF) and soluble thrombomodulin (both are indexes of endothelial damage/dysfunction) and soluble E-selectin (an index of endothelial activation). Second, we hypothesized a relation between endothelial markers and B-type natriuretic peptide (BNP, an index of cardiac function) in acute and chronic CHF that could be linked to prognosis. To test this hypothesis, we studied 35 patients with acute CHF, 40 patients with chronic CHF, and 32 healthy controls. The patients with CHF were followed up for the combined outcomes of cardiovascular death, nonfatal myocardial infarction, stroke, thromboembolism, and recurrent admissions to the hospital. vWF (p = 0.001), soluble thrombomodulin, E-selectin, and BNP (all p <0.0001) were higher in patients with acute and chronic CHF compared with controls. When the 2 CHF groups were compared, no significant differences were found in vWF or E-selectin (p = NS), but soluble thrombomodulin was significantly elevated in acute CHF (Tukey's post hoc test, p <0.05). Only high vWF was associated with a poorer outcome (log-rank test, p = 0.0188). None of the endothelial indexes correlated with plasma BNP. After a median follow-up of 18 months, only high (median or higher) vWF levels were predictive of adverse outcomes in the patients with CHF (log-rank statistic = 5.52, degree of freedom 1, p = 0.0188). In conclusion, despite similar ejection fractions, patients with acute and chronic CHF have different degrees of endothelial damage/dysfunction and activation, which may be related to differences in pathophysiology. High levels of vWF were associated with a worse short-term outcome. These endothelial markers were unrelated to plasma BNP levels and may imply a different release mechanism.

Acute Disease↗
PubMed2006

Abnormal soluble CD40 ligand and C-reactive protein concentrations in hypertension: relationship to indices of angiogenesis.

BACKGROUND: Abnormal inflammation, platelets and angiogenesis are involved in the pathophysiology of cardiovascular disease (CVD). OBJECTIVE: To test the hypothesis that concentrations of high sensitive C-reactive protein (CRP, an index of inflammation) and soluble CD40 ligand (sCD40L, an index of platelet activation) would be abnormal in hypertension, and in turn, be related to plasma indices of angiogenesis, the angiopoietins-1 and -2, and vascular endothelial growth factor (VEGF), in addition to the presence or absence of CVD. METHODS: Using a cross-sectional approach, we measured plasma concentrations of CRP, sCD40L, VEGF, and angiopoietins-1 and -2 in 147 patients with hypertension (85 with a history of CVD event/s, 62 CVD event-free) and 68 age- and sex-matched healthy controls. RESULTS: Concentrations of sCD40L (P = 0.039), CRP (P < 0.001), angiopoietin-1 (P < 0.001), angiopoietin-2 (P = 0.003) and VEGF (P < 0.001) were all greater amongst hypertensive patients than in controls. There were no significant differences in sCD40L and VEGF concentrations between hypertensive individuals with and without CVD events, but CRP and angiopoietin-1 concentrations were significantly greater amongst those with CVD events. On multiple regression analysis, sCD40L was associated with angiopoietin-2 (P = 0.01) and VEGF (P = 0.007) in hypertensive individuals, but no such associations were found within the healthy control group. CONCLUSION: In patients with hypertension, sCD40L was associated with increased circulating markers of abnormal angiogenesis (angiopoietin-2, VEGF). The interaction between sCD40L and angiogenesis may contribute to the pathophysiology of CVD in hypertension.

Adult↗
PubMed2006

The role of hyperglycaemia and the hypercoagulable state in the pathogenesis of cardiovascular events in diabetes mellitus: implications for hypertension management.

Population studies have identified diabetes mellitus as a risk factor for cardiac and vascular events, with a common association with hypertension. Observational studies have consistently demonstrated blood glucose as a continuous cardiovascular risk factor. Experimental studies suggest that elevated blood glucose, through a range of biochemical pathways can promote atherogenesis and increase the tendency for thrombosis. The resultant state promotes occlusion of arterial flow and increase cardiovascular event rates. However, an unconvincing temporal relationship (raised blood glucose preceding cardiovascular events) and the limited impact of glucose reduction in patients with diabetes on cardiovascular events do not support blood glucose as a major cause of cardiovascular disease. In this review, we discuss the relationship between hyperglycaemia and a hypercoagulable state in diabetes and the implications of this relationship for the treatment of patients with diabetes, who also commonly have hypertension.

Blood Coagulation↗
PubMed2005

Comparison of brain natriuretic peptide and left ventricular diastolic function determined by tissue Doppler in patients with diabetes mellitus, patients with hypertension without diabetes, and in healthy subjects.

In this study, it was found that increased plasma B-type natriuretic peptide (BNP) levels in patients with diabetes may be related to left ventricular (LV) diastolic relaxation, independent of LV mass and atherosclerosis (using common carotid intima-media thickness as a surrogate index). A "package of care" of glycemic control and cardiovascular risk management was not associated with reduction in BNP levels.

Aged↗
PubMed2005

Angiogenic factors in atrial fibrillation: a possible role in thrombogenesis?

BACKGROUND: The precise pathophysiological processes underlying the prothrombotic or hypercoagulable state in atrial fibrillation (AF) remain uncertain. We hypothesized a relationship between abnormal endothelial damage/dysfunction, coagulation, and angiogenic factors, thereby contributing to increased thrombogenicity. METHODS: Plasma levels of von Willebrand factor (vWF, an index of endothelial damage/dysfunction) and tissue factor (TF, an index of coagulation), as well as the angiogenic factors, vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2), were measured by enzyme-linked immunosorbant assay (ELISA) in 59 chronic AF patients. Data were compared to 40 age- and sex-matched healthy controls in sinus rhythm. RESULTS: Plasma vWF, VEGF and Ang-2 were significantly higher in AF patients compared to healthy controls (P=0.005, P=0.0055 and P<0.0001 respectively) but there were no significant differences in plasma Ang-1 or TF levels between the two groups (P=0.925 and P=0.121 respectively). Significant correlations were found between VEGF and vWF levels (Spearman, r=0.262, P=0.011) and between VEGF and Ang-2 (r=0.333, P=0.001). CONCLUSIONS: Raised VEGF in association with Ang-2 and vWF may reflect a link between abnormal endothelial damage/dysfunction and angiogenic factors. These may act together to alter TF expression and endothelial integrity, thereby contributing to the prothrombotic state in AF.

Aged↗
PubMed2004

Angiopoietin-1 and angiopoietin-2 in diabetes mellitus: relationship to VEGF, glycaemic control, endothelial damage/dysfunction and atherosclerosis.

BACKGROUND: microvascular complications in diabetes identify those at risk of cardiovascular disease (CVD), suggesting a link between abnormal neovascularisation and CVD. This may be related to high plasma vascular endothelial growth factor (VEGF). We hypothesised increased angiopoietins (Ang)-1 and -2 in patients with diabetes that are related to VEGF, medium-term glycaemic control, endothelial damage/dysfunction and atherosclerosis. METHODS AND PATIENTS: we measured plasma Ang-1 and Ang-2 alongside VEGF (all by ELISA) in 96 patients with type-2 diabetes mellitus (41 with and 56 without overt CVD) who were compared to 35 age- and sex-comparable healthy controls. Common carotid intima-media thickness (CC-IMT) was used to assess carotid atherosclerosis, plasma von Willebrand factor (vWf) and urine albumin:creatinine ratio (UACr) to quantify and endothelial damage/dysfunction, and HbA1c to mark medium-term hypergylcaemia. RESULTS: Ang-2 (but not Ang-1) was higher in patients with diabetes compared to controls (p<0.01), with no significant difference between patients with and without CVD. As expected, CC-IMT, UACr, HbA1c, vWf, and VEGF were also abnormal in the patients. Within the patient group alone, and in the entire cohort, VEGF and Ang-2 correlated strongly (both p<0.001) and with several other markers. However, in multivariate analysis, the only significant relationship that remained after adjustments was between VEGF and HbA1c (p<0.001). CONCLUSIONS: Angiogenic growth factor Ang-2, like VEGF, is raised in diabetes regardless of vascular disease. Both growth factors correlated with HbA1c and with each other, not with endothelial injury or atherosclerosis, but after multiple adjustment, only that between HbA1c and VEGF significant remained. VEGF is likely to have a more prominent role in diabetes than Ang-2.

Aged↗
PubMed2004

Diabetes mellitus, the renin-angiotensin-aldosterone system, and the heart.

With diabetes mellitus reaching epidemic proportions, mainly secondary to obesity, the impact of cardiovascular disease due to this combination makes it a dominant public health problem during the first quarter of the 21st century. The complex interaction that results in diabetic heart disease is created by overlapping mechanisms. There is a propensity to develop premature, diffuse atherosclerotic coronary disease, which is associated with adverse short- and long-term morbidity and mortality. There are structural and functional abnormalities of the microvasculature, autonomic dysfunction, and intrinsic failure of myocardial contraction (so-called diabetic cardiomyopathy). These changes are amplified by arterial hypertension and kidney disease. In this review, we consider the role of the renin-angiotensin-aldosterone system and how it is a crucial driver of most of the pathophysiologic mechanisms behind diabetic heart disease and why in the past 5 years blocking this system in diabetic patients has emerged as a critical therapeutic intervention.

Clinical Trials as Topic↗
PubMed2004

Soluble CD40 ligand, soluble P-selectin, interleukin-6, and tissue factor in diabetes mellitus: relationships to cardiovascular disease and risk factor intervention.

BACKGROUND: High levels of the soluble fragment of CD40 ligand (sCD40L) have previously been associated with adverse cardiovascular outcomes. CD40L-CD40 interaction has been linked to the pathogenesis of atherothrombotic complications in cardiovascular disease (CVD). We sought to determine whether a "package of care" of intensified multifactorial cardiovascular risk intervention could reduce indices of platelet activation, inflammation, and coagulation in diabetes and whether patients with overt CVD would derive similar benefit compared with those without. METHODS AND RESULTS: We measured plasma sCD40L, soluble P-selectin (sP-sel, an index of platelet activation), interleukin-6 (IL-6, a proinflammatory cytokine), and tissue factor (TF, an initiator of coagulation) in 97 patients with diabetes mellitus (41 with and 56 without overt CVD) and 39 comparable healthy control subjects. Thirty-six patients with and 32 without overt CVD then participated in a package of care of cardiovascular risk intervention over a period of 1 year. Plasma levels of sCD40L (P<0.001), sP-sel (P<0.001), IL-6 (P=0.001), and TF (P<0.001) were higher in patients with diabetes than in control subjects, with TF levels highest in patients with overt CVD. Multifactorial intervention was associated with significant reductions in sCD40L in both patient groups (both P<0.001), but reductions in sP-sel and TF were seen only in patients without overt CVD. There was no significant change in IL-6 levels in both patient groups. CONCLUSIONS: Intensive multifactorial risk management can reduce high levels of sCD40L but can only partially correct abnormal platelet activation, inflammation, and coagulation in diabetes, particularly in patients with overt CVD.

Aged↗
PubMed2004

Clinical review: clinical management of atrial fibrillation - rate control versus rhythm control.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in the critically ill and is associated with adverse outcomes. Although there are plausible benefits from conversion and maintenance of sinus rhythm (the so-called 'rhythm-control' strategy), recent randomized trials have failed to demonstrate the superiority of this approach over the rate-control strategy. Regardless of approach, continuous therapeutic anticoagulation is crucial for stroke prevention. This review addresses the findings of these studies and their implications for clinical management of patients with atrial fibrillation.

Anti-Arrhythmia Agents↗
PubMed2004

Plasma von Willebrand factor and the development of the metabolic syndrome in patients with hypertension.

Although the metabolic syndrome is associated with endothelial damage/dysfunction, the effect of risk factors and their relationship with the development of this condition are unclear. We hypothesized that plasma von Willebrand factor (vWf, marking endothelial damage/dysfunction) increases with the number of components of metabolic syndrome and that increased levels precede its development. To test this, fasting vWf, glucose and lipids were measured in 161 patients (mean age 63 +/- 7 yr, 85% males) with hypertension. Using World Health Organization (WHO) criteria, 32 (19.9%), and using National Cholesterol Education Program (NCEP) criteria, 70 (43.5%) had metabolic syndrome. Plasma vWf was higher in these patients regardless of defining criteria and increased with the number of the components of metabolic syndrome (both P < 0.001). After 4 yr, patients who did not have metabolic syndrome at baseline were reassessed for the development of this condition. Of the 129 patients who did not meet the WHO criteria at baseline, 38 (29.5%) subsequently developed the condition, whereas 36 of the 91 (39.6%) who did not meet the NCEP criteria at baseline subsequently developed metabolic syndrome. Baseline vWf levels did not predict development of metabolic syndrome, regardless of criteria (P = 0.071 for WHO and P = 0.639 for NCEP). Our data suggest more severe endothelial damage/dysfunction with cumulative metabolic syndrome-related risk factors. The failure of plasma vWf to predict the development of metabolic syndrome suggests that endothelial damage/dysfunction is a consequence, not a cause, of these risk factors.

Aged↗
PubMed2004

Plasma vascular endothelial growth factor, angiopoietin-1, and angiopoietin-2 in diabetes: implications for cardiovascular risk and effects of multifactorial intervention.

OBJECTIVE: Vascular endothelial growth factor (VEGF) and angiopoietin (Ang)-1 and Ang-2 are mediators of angiogenesis. More recent data suggest that the balance between these growth factors may affect vascular endothelial integrity. Because diabetes is closely associated with endothelial perturbation, we studied plasma levels of these angiogenic growth factors in patients with diabetes; their relationship with glycemia, inflammation, and endothelial damage/dysfunction; and the effect of intensified cardiovascular risk management. RESEARCH DESIGN AND METHODS: We measured plasma VEGF, Ang-1, and Ang-2 alongside plasma von Willebrand factor (vWf) and urine albumin-to-creatinine ratio (marking endothelial damage/dysfunction) and interleukin (IL)-6 in 94 patients (38 with overt cardiovascular disease [CVD]) with diabetes and 34 normal control subjects. RESULTS: Plasma vWf (P=0.009), IL-6 (P <0.001), VEGF (P=0.001), and Ang-2 (P=0.001), but not Ang-1 (P=0.635), were higher in diabetic patients with and without CVD than in control subjects. On multivariate analysis, HbA1c was an independent predictor of plasma VEGF (P=0.032) and Ang-2 (P=0.015). Of the 94 patients, a subgroup of 33 patients with and 31 patients without CVD participated in a year of intensified cardiovascular risk management. HbA1c and LDL cholesterol reduced significantly with treatment, along with associated reductions in plasma vWf and VEGF in both groups (P <0.001). Ang-2 decreased (P <0.001) only in patients without CVD. There were no significant changes in plasma IL-6 levels in both groups. CONCLUSIONS: Plasma Ang-2 (but not Ang-1), like VEGF levels, are selectively elevated in patients with diabetes and are associated with indexes of endothelial damage/dysfunction, regardless of vascular disease. Intensive multifactorial intervention is associated with reductions in plasma VEGF, vWf, and (in patients without CVD) Ang-2 levels, possibly reflecting an improved vascular profile with treatment.

Aged↗
PubMed2003

Implications of the LIFE trial.

The recent Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study was conducted in patients with essential hypertension with electrocardiogram evidence of left ventricular hypertrophy. This showed that losartan compared to atenolol resulted in a significant reduction in the primary endpoint of cardiovascular morbidity and mortality, as well as a greater reduction in electrocardiographically-defined left ventricular hypertrophy. Importantly, this was despite a mean blood pressure reduction which was similar in both groups. Furthermore, the atenolol arm was associated with higher incidence of newly diagnosed diabetics. The LIFE study has firmly confirmed a place for losartan (and other angiotensin receptor blockers) in the management of hypertension. Losartan has also been shown to be effective in diabetics and in patients with atrial fibrillation, as well as in left ventricular hypertrophy regression. This trial also raises the possibility that beta-blockers should perhaps not be used as first-line monotherapy.

Adrenergic beta-Antagonists↗
PubMed2003

Diabetes, the renin-angiotensin system and heart disease.

Despite recent advances, cardiovascular disease continues to be the leading cause of death among patients with diabetes. Diabetes-related heart disease makes up the majority of the cardiovascular morbidity and mortality and this clinical entity results from synergistic interaction amongst various overlapping mechanisms. Diabetes-related heart disease is characterised by a propensity to develop premature, diffuse atherosclerotic disease, structural and functional abnormalities of the microvasculature, autonomic dysfunction and intrinsic myocardial dysfunction (the so-called diabetic 'cardiomyopathy'), all of which are exacerbated by hypertension and diabetic nephropathy. The renin-angiotensin-aldosterone system possesses various autocrine and paracrine effects which drive most of the pathophysiological mechanisms in diabetes-related heart disease. This review aims to describe the expanding role of the renin-angiotensin-aldosterone system, the complex entity of diabetes-related heart disease and the (emerging) evidence for specific inhibition of the renin-angiotensin-aldosterone system in diabetes.

Clinical Trials as Topic↗