Controversies and discrepancies in the effect of dietary fat and cholesterol on cardiovascular risk

Cardiovascular disease (CVD) is the leading cause of death worldwide. The top ten causes of death in Singapore include many cardiovascular-related diseases such as ischaemic heart disease. The increasing prevalence of CVD poses a burden to both the economy and healthcare system of a country. Dietary habits, in particular dietary fats and cholesterol intake, have been shown to greatly influence CVD risks. Therefore, reference and adherence to relevant dietary guidelines could be crucial in CVD prevention. Recent research findings have provided novel insights into the relationship between certain dietary fats or cholesterol intake and CVD risks, challenging or reinforcing previous guidelines. These findings may, however, be conflicting, and there are still controversies over the effects of dietary fats and cholesterol as well as their association with cardiovascular risk. This review paper aims to evaluate common controversies, identify gaps in relevant research areas and summarise evidence-based dietary recommendations.

Convalescent COVID-19 patients are susceptible to endothelial dysfunction due to persistent immune activation

The rapid rise of coronavirus disease 2019 patients who suffer from vascular events after their initial recovery is expected to lead to a worldwide shift in disease burden. We aim to investigate the impact of COVID-19 on the pathophysiological state of blood vessels in convalescent patients. Here, convalescent COVID-19 patients with or without preexisting conditions (i.e. hypertension, diabetes, hyperlipidemia) were compared to non-COVID-19 patients with matched cardiovascular risk factors or healthy participants. Convalescent patients had elevated circulating endothelial cells (CECs), and those with underlying cardiovascular risk had more pronounced endothelial activation hallmarks (ICAM1, P-selectin or CX3CL1) expressed by CECs. Multiplex microbead-based immunoassays revealed some levels of cytokine production sustained from acute infection to recovery phase. Several proinflammatory and activated T lymphocyte-associated cytokines correlated positively with CEC measures, implicating cytokine-driven endothelial dysfunction. Finally, the activation markers detected on CECs mapped to the counter receptors (i.e. ITGAL, SELPLG, and CX3CR1) found primarily on CD8+ T cells and natural killer cells, suggesting that activated endothelial cells could be targeted by cytotoxic effector cells. Clinical trials in preventive therapy for post-COVID-19 vascular complications may be needed. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=69 SRC="FIGDIR/small/20232835v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@d34a61org.highwire.dtl.DTLVardef@1b82feeorg.highwire.dtl.DTLVardef@152ea88org.highwire.dtl.DTLVardef@a3b382_HPS_FORMAT_FIGEXP M_FIG C_FIG

Prevalence, Presentation, and Outcome of Heart Failure with Preserved Ejection Fraction among Patients Presenting with Undifferentiated Dyspnoea to the Emergency Room: A 10-year Analysis from a Tertiary Centre

<p><b>INTRODUCTION</b>We assessed the local prevalence, characteristics and 10-year outcomes in a heart failure (HF) cohort from the emergency room (ER).</p><p><b>MATERIALS AND METHODS</b>Patients presenting with acute dyspnoea to ER were prospectively enrolled from December 2003 to December 2004. HF was diagnosed by physicians' adjudication based on clinical assessment and echocardiogram within 12 hours, blinded to N-terminal-pro brain natriuretic peptide (NT-proBNP) results. They were stratified into heart failure with preserved (HFPEF) and reduced ejection fraction (HFREF) by left ventricular ejection fraction (LVEF).</p><p><b>RESULTS</b>At different cutoffs of LVEF of ≥50%, ≥45%, ≥40%, and >50% plus excluding LVEF 40% to 50%, HFPEF prevalence ranged from 38% to 51%. Using LVEF ≥50% as the final cutoff point, at baseline, HFPEF (n = 35), compared to HFREF (n = 55), had lower admission NT- proBNP (1502 vs 5953 pg/mL, P <0.001), heart rate (86 ± 22 vs 98 ± 22 bpm, P = 0.014), and diastolic blood pressure (DBP) (75 ± 14 vs 84 ± 20 mmHg, P = 0.024). On echocardiogram, compared to HFREF, HFPEF had more LV concentric remodelling (20% vs 2%, P = 0.003), less eccentric hypertrophy (11% vs 53%, P <0.001) and less mitral regurgitation from functional mitral regurgitation (60% vs 95%, P = 0.027). At 10 years, compared to HFREF, HFPEF had similar primary endpoints of a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and rehospitalisation for congestive heart failure (CHF) (HR 0.886; 95% CI, 0.561 to 1.399; P = 0.605), all-cause mortality (HR 0.663; 95% CI, 0.400 to 1.100; P = 0.112), but lower cardiovascular mortality (HR 0.307; 95% CI, 0.111 to 0.850; P = 0.023).</p><p><b>CONCLUSION</b>In the long term, HFPEF had higher non-cardiovascular mortality, but lower cardiovascular mortality compared to HFREF.</p>

Quantification of coronary artery Stenosis by Area Stenosis from cardiac CT angiography.

Non-invasive cardiac computed tomography angiography (CTA) is widely used to assess coronary artery stenosis and give clinical decision-making support to clinicians. The severity of stenosis lesion is commonly graded by a range of percent Diameter Stenosis (DS), which can introduce false positive diagnoses or over-estimation, triggering unnecessary further procedures. In this paper, a system and the associate methods to quantify stenosis by the percent Area Stenosis (AS) from cardiac CTA is presented. In the process, coronary artery tree is segmented and the centerline is extracted by Hessian filtering and the minimal path method. After a serial of 2D cross-sectional artery images along the artery centerline are obtained, lumen areas are segmented by ellipse-fitting with deformable models, and consequently to compute the lesion's AS. Experimental results on 5 CTA data sets show that compared to DS, AS better correlates to the reference standard for stenosis quantification, suggesting the efficacy of the proposed system.

Stroke prevention in atrial fibrillation: understanding the new oral anticoagulants dabigatran, rivaroxaban, and apixaban.

Unlike vitamin K antagonists (VKAs), the new oral anticoagulants (NOACs)-direct thrombin inhibitor, dabigatran, and direct activated factor X inhibitors, rivaroxaban, and apixaban-do not require routine INR monitoring. Compared to VKAs, they possess relatively rapid onset of action and short halflives, but vary in relative degrees of renal excretion as well as interaction with p-glycoprotein membrane transporters and liver cytochrome P450 metabolic enzymes. Recent completed phase III trials comparing NOACs with VKAs for stroke prevention in atrial fibrillation (AF)-the RE-LY, ROCKET AF, and ARISTOTLE trials-demonstrated at least noninferior efficacy, largely driven by significant reductions in haemorrhagic stroke. Major and nonmajor clinically relevant bleeding rates were acceptable compared to VKAs. Of note, the NOACs caused significantly less intracranial haemorrhagic events compared to VKAs, the mechanisms of which are not completely clear. With convenient fixed-dose administration, the NOACs facilitate anticoagulant management in AF in the community, which has hitherto been grossly underutilised. Guidelines should evolve towards simplicity in anticipation of greater use of NOACs among primary care physicians. At the same time, the need for caution with their use in patients with severely impaired renal function should be emphasised.

Attenuation of stress-based ventricular contractility in patients with heart failure and normal ejection fraction

<p><b>INTRODUCTION</b>The maximal rate of change of pressure-normalised wall stress dσ*/dtmax has been proposed as cardiac index of left ventricular (LV) contractility. In this study, we assessed the capacity of dσ*/dtmax to diagnose heart failure with normal ejection fraction (HFNEF).</p><p><b>MATERIALS AND METHODS</b>One hundred healthy normal controls and 140 patients admitted with heart failure (100, HFREF and 40, HFNEF) underwent echocardiography for stress-based contractility dσ*/dtmax. Patients with signifi cant valvular heart disease were excluded. Tissue Doppler indices were also measured.</p><p><b>RESULTS</b>dσ*/dtmax was 4.43 ± 1.27 s-1 in control subjects; reduced in HFNEF, 3.02 ± 0.98 s-1; and HFREF, 2.00 ± 0.67 s-1 (P <0.001). In comparison with age- and sex-matched groups (n = 26 each), we found similar trend on reduction of dσ*/dtmax (normal control; 3.91 ± 0.87 s-1; HFNEF, 2.90 ± 0.84 s-1; HFREF, 1.84 ± 0.59 s-1, P <0.001). On multivariate analysis, dσ*/dtmax was found to be the independent predictor of HFNEF and HFREF. The area under the curve of the receiver operating characteristics (ROC) in detecting HFNEF compared with normal controls (dσ*/dtmax>3.2 s-1) was 0.84 (P <0.0001), and in detecting HFREF compared with HFNEF (dσ*/dtmax>2.32 s-1) was 0.88 (P <0.0001).</p><p><b>CONCLUSION</b>This data confi rms that dσ*/dtmax on echocardiography is a powerful independent predictor in patients with HFNEF. In a population with a high suspicion of HFNEF, dσ*/dtmax may significantly contribute to early diagnosis and hence be useful in the triage and management of HFNEF patients.</p>

Risk factor profile and treatment patterns of patients with atherothrombosis in Singapore: insight from the REACH Registry

<p><b>INTRODUCTION</b>Atherothrombosis is the leading cause of cardiovascular mortality. The Reduction of Atherothrombosis for Continued Health (REACH) Registry provided information on atherosclerosis risk factors and treatment. Singapore was one of the 44 participating countries in the REACH Registry. The objective of this study was to determine the atherosclerosis risk factor profile and treatment patterns in Singapore patients enrolled in the REACH Registry.</p><p><b>MATERIALS AND METHODS</b>The REACH Registry is an international prospective observational registry of subjects with or at risk for atherothrombosis. Patients aged 45 years or older with established vascular disease [coronary artery disease (CAD), cerebrovascular disease (CVD), peripheral arterial disease (PAD)] or 3 or more atherosclerosis risk factors were recruited between 2003 and 2004.</p><p><b>RESULTS</b>A total of 881 patients (64.4% male) were recruited in Singapore by 63 physicians. The mean age was 64 +/- 9.8 years (range, 45 to 95). Seven hundred and one (79.6%) patients were symptomatic (CAD 430, CVD 321, PAD 72) while 180 (20.4%) patients had > or =3 risk factors. Approximately 13% of symptomatic patients had symptomatic polyvascular disease. There was a high proportion of diabetes mellitus (57%), hypertension (80.6%) and hypercholesterolemia (80.1%). A substantial proportion of symptomatic patients were current smokers (14.1%). Approximately half of the patients were either overweight or obese [abdominal obesity, 54.3%; body mass index (BMI) 23-27.5, 45.9%; BMI > or =27.5, 23.3%]. Patients were undertreated with antiplatelet agents (71.9% overall; range, 23.9% for > or =3 risk factors to 84.7% for PAD) and statins (76.2% overall; range, 73.6% for PAD to 82.1% for CAD). Risk factors remained suboptimally controlled with a significant proportion of patients with elevated blood pressure (59.4% for > or =3 risk factors and 48.6% for symptomatic patients), elevated cholesterol (40% for > or =3 risk factors and 24.4% for symptomatic patients) and elevated blood glucose (45% for > or =3 risk factors and 19.8% for symptomatic patients).</p><p><b>CONCLUSION</b>Established atherosclerosis risk factors are common in Singapore patients in the REACH Registry; and obesity is a major problem. Most of these risk factors remained suboptimally controlled.</p>

Paradoxical orthodeoxia in a patient with a large thoracic aortic aneurysm

<p><b>INTRODUCTION</b>Orthodeoxia is a rare clinical syndrome characterised by dyspnoea and arterial deoxygenation that accompanies a change from a supine to erect position.</p><p><b>CLINICAL PICTURE</b>We describe an unusual case of "paradoxical orthodeoxia" in a 70-year-old man with a thoracic aortic aneurysm: arterial desaturation when supine that improved when erect.</p><p><b>TREATMENT AND OUTCOME</b>Non-invasive imaging revealed compression of the left pulmonary artery by the aneurysm (thoracic computed tomography) and patent foramen ovale (transesophageal echocardiography). Nuclear studies show decreased relative left lung perfusion attributable to the former, and right-to-left atrial shunt attributable to the latter. The degree of right-to-left shunt increases in the supine position: nuclear pulmonary shunt study shows shunt extent of 21% when supine versus 10% erect.</p><p><b>CONCLUSION</b>A physioanatomical explanation is proposed.</p>

Late complications following tetralogy of Fallot repair: the need for long-term follow-up

<p><b>INTRODUCTION</b>We report a series of operated tetralogy of Fallot (TOF) patients focusing on complications and outcomes.</p><p><b>MATERIALS AND METHODS</b>Data from TOF patients seen at our centre's adult congenital heart disease clinic was analysed.</p><p><b>RESULTS</b>There were 21 patients: the mean age was 32.2 +/- 12.4 years; the age at first operation was 9.0 +/- 7.9 years; the mean postoperative follow-up duration was 23.5 +/- 12.1 years; and the current New York Heart Association (NYHA) status: I, 82%; II, 4%; III, 14%. Fourteen patients had complete operative notes. All these patients underwent total TOF correction; 2 had staged aortopulmonary shunt with total correction at a mean of 3.2 years later, pulmonary artery patch augmentation in 8 patients and pulmonary valvotomy in 8 patients. Three patients required pulmonary valve homograft replacement for severe pulmonary regurgitation (PR) at 13, 28 and 36 years after the initial corrective operation.</p><p><b>CURRENT INVESTIGATIONS</b>RBBB on ECG (91%), QRS duration 137 +/- 29 ms. Echocardiography showed dilated right ventricular end-diastolic (RVED) diameters (3.2 +/- 0.8 cm); severe PR (67%), residual right ventricular outflow tract obstruction (RVOTO) (42%) and VSD patch leakage (9%). Cardiac magnetic resonance (CMR) (8 patients) showed dilated RVED volumes 252.6 +/- 93.8 mL, indexed RV volume 165.7 +/- 34.8 mL; RV systolic function was preserved in most patients with a RV ejection fraction of 49.5 +/- 5.7%. One patient had atrial tachycardia and another had frequent non-sustained ventricular tachycardia that required radiofrequency ablation.</p><p><b>CONCLUSION</b>Patients with TOF who had full corrective surgery during childhood are now surviving into adulthood. Many challenges arising from complications in the postoperative period remain. It is imperative that adult TOF patients should have regular followup to monitor development and subsequent management of these complications.</p>