Hoong Sern Lim

Atrial fibrillation and stroke prevention

Atrial fibrillation (AF) is a common arrhythmia that is associated with substantial morbidity and mortality, particularly due to stroke and thromboembolism. Anticoagulant therapy reduces the risk of stroke, and the greatest benefit is seen in patients at highest absolute risk. Aspirin is a less effective alternative, and any benefit of aspirin might be due to its favourable effects on arterial thrombosis caused by vascular disease. However, anticoagulant therapy remains underused, particularly in the elderly, who probably have the most to gain from stroke prevention owing to their high absolute risk. The underuse of anticoagulation might also be related to uncertain risk of thromboembolism in individual patients and a perceived overestimation of the benefit and underestimation of risk of bleeding with warfarin in clinical trials. In this Review, we summarise the data for and against warfarin and aspirin therapies and discuss the clinical assessments and risk stratifications that guide the use of antithrombotic therapy for stroke prevention in patients with AF. Possible barriers to the uptake of anticoagulation therapy are also discussed.

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.

Angiopoietin‐2 levels as a biomarker of cardiovascular risk in patients with hypertension

Background. Abnormal angiogenesis is a pathophysiological component of cardiovascular disease (CVD), where circulating biomarkers of angiogenesis are associated with increased CVD risk in hypertension. We hypothesized that raised levels of angiopoietin (Ang)‐1 and ‐2 would predict events in patients with hypertension treated for CVD. Methods. We measured angiopoietin levels by enzyme‐linked immunosorbent assay (ELISA) in 251 hypertensive participants (85% male; mean age 63.5 years; 192 free of previous CVD events). Plasma angiopoietin levels were related to the subsequent CVD events over a mean follow‐up period of 57.1 (SD 11) months. Results. There were 11 cases of myocardial infarction (MI) and 18 cases of stroke during follow‐up. Ang‐2 was a significant predictor of MI, stroke, and composite CVD events, with the greatest event‐free survival amongst those in the lower tertile (all P<0.05). Ang‐1 was not predictive of CVD outcomes. Of CVD risk factors at recruitment (blood pressure, body mass index, plasma glucose, serum and high‐density lipoprotein (HDL)‐cholesterol), Ang‐2 was the only discriminator of incident MI (area under curve (AUC) = 73%, P = 0.013), where a value >4.3 ng/mL optimized specificity and sensitivity. On Cox regression analysis (CVD treatments and risk factors), raised Ang‐2 was an independent predictor of MI, P<0.05, but not stroke or composite outcomes. Conclusions. Among patients with hypertension, raised levels of Ang‐2 were predictive of MI, and further study is warranted to evaluate the use of this biomarker in CVD management, risk stratification, and prevention.

Adiponectin and hypertension: a putative link between adipocyte function and atherosclerotic risk?

Adiponectin and hypertension: a putative link between adipocyte function and atherosclerotic risk?

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.

Asymptomatic Atrial Fibrillation on Device Interrogation

Atrial fibrillation (AF) is a chronic and often progressive arrhythmia. Initial episodes are frequently self-terminating and amenable to antiarrhythmic therapy, but over time, the occurrence and duration of AF episodes increases, becoming persistent in a large number of cases.1 That AF confers an increased risk of stroke and thromboembolism is well established,2 as is the role of anticoagulation therapy in the prevention of these devastating complications.3

The effect of multi-factorial intervention on plasma von Willebrand factor, soluble E-selectin and tissue factor in diabetes mellitus: implications for atherosclerotic vascular disease

Background  Endothelial abnormalities and a hypercoagulable state may contribute to increased cardiovascular risk in diabetes mellitus, particularly in patients with overt cardiovascular disease (CVD). We sought to determine the effect of intensified multi‐factorial cardiovascular risk intervention on indices of endothelial abnormality and hypercoagulability in diabetes, and if patients with overt CVD would derive similar benefit as those without.

Metabolic Syndrome: A Definition in Progress

We applaud the National Heart, Lung and Blood Institute and the American Heart Association in their efforts to define and outline the pathophysiology of the complex and still ill-defined metabolic syndrome.1 Although there is little doubt that obesity is closely linked to many components of the metabolic syndrome, we must also acknowledge that much of the data available on the metabolic syndrome are derived from (large) registries and post hoc analyses of clinical studies2,3 that are not specifically designed to address the relationship between obesity, measures of insulin resistance, other associated features of the metabolic syndrome, and eventual cardiovascular outcome. These studies provide useful associations but do not establish the temporal relationship …

Lipid lowering in hypertension and heart protection: observations from the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) and the Heart Protection Study

Lipid lowering in hypertension and heart protection: observations from the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) and the Heart Protection Study

Reactive oxygen species production by circulating monocytes: insights from pathophysiology to clinical hypertension

Reactive oxygen species production by circulating monocytes: insights from pathophysiology to clinical hypertension