Vichai Senthong

Trimethylamine N‐Oxide and Mortality Risk in Patients With Peripheral Artery Disease

Background Production of the proatherogenic metabolite, trimethylamine N‐oxide (TMAO), from dietary nutrients by intestinal microbiota enhances atherosclerosis development in animal models and is associated with atherosclerotic coronary artery disease in humans. The utility of studying plasma levels of TMAO to risk stratify in patients with peripheral artery disease (PAD) has not been reported. Methods and Results We examined the relationship between fasting plasma TMAO and all‐cause mortality (5‐year), stratified by subtypes of PAD and presence of coronary artery disease in 935 patients with PAD who underwent elective angiography for cardiac evaluation at a tertiary care hospital. Median plasma TMAO was 4.8 μmol/L (interquartile range, 2.9–8.0 μmol/L). Elevated TMAO levels were associated with 2.7‐fold increased mortality risk (fourth versus first quartiles, hazard ratio 2.86, 95% CI 1.82–3.97, P<0.001). Following adjustments for traditional risk factors, inflammatory biomarkers, and history of coronary artery disease, the highest TMAO quartile remained predictive of 5‐year mortality (adjusted hazard ratio 2.06, 95% CI 1.36–3.11, P<0.001). Similar prognostic value for elevated TMAO was seen for subjects with carotid artery, non–carotid artery, or lower extremity PAD. TMAO provided incremental prognostic value for all‐cause mortality (net reclassification index, 40.22%; P<0.001) and improvement in area under receiver operator characteristic curve (65.7% versus 69.4%; P=0.013). Conclusions TMAO, a pro‐atherogenic metabolite formed by gut microbes, predicts long‐term adverse event risk and incremental prognostic value in patients with PAD. These findings point to the potential for TMAO to help improve selection of high‐risk PAD patients with or without significant coronary artery disease, who likely need more aggressive and specific dietary and pharmacologic therapy.

Clinical factors predictive of encephalitis caused by Angiostrongylus cantonensis.

Angiostrongylus cantonensis is mainly caused eosinophilic meningitis in humans, whereas a minority of patients develop encephalitic angiostrongyliasis (EA). EA is an extremely fatal condition, and the clinical factors predictive of EA have never been reported. A comparison study was conducted in a hospital situated in an endemic area of Thailand. We enrolled 14 and 80 angiostrongyliasis patients who developed encephalitis and meningitis, respectively. Logistic regression analysis was used to assess the clinical variables predictive of encephalitis. Age (adjusted odds ratio [OR], 1.22; 95% confidence interval [CI], 1.05-1.42), duration of headache (adjusted OR, 1.26; 95% CI, 1.03-1.55), and fever > 38.0 degrees C (adjusted OR, 37.05; 95% CI, 1.59-862.35) were identified as statistically significant factors for EA prediction. Elderly patients with angiostrongyliasis experiencing fever and prolonged headaches were at the highest risk of developing EA.

Clinical Manifestations of Eosinophilic Meningitis Due to Infection with Angiostrongylus cantonensis in Children

Eosinophilic meningitis, caused by the nematode Angiostrongylus cantonensis, is prevalent in northeastern Thailand, most commonly in adults. Data regarding clinical manifestations of this condition in children is limited and may be different those in adults. A chart review was done on 19 eosinophilic meningitis patients aged less than 15 years in Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Thailand. Clinical manifestations and outcomes were reported using descriptive statistics. All patients had presented with severe headache. Most patients were males, had fever, nausea or vomiting, stiffness of the neck, and a history of snail ingestion. Six patients had papilledema or cranial nerve palsies. It was shown that the clinical manifestations of eosinophilic meningitis due to A. cantonensis in children are different from those in adult patients. Fever, nausea, vomiting, hepatomegaly, neck stiffness, and cranial nerve palsies were all more common in children than in adults.

Association of arterial stiffness with single nucleotide polymorphism rs1333049 and metabolic risk factors

BackgroundIncreased arterial stiffness is a cardiovascular outcome of metabolic syndrome (MetS). The chromosome 9p21 locus has been identified as a major locus for risk of coronary artery disease (CAD). The single nucleotide polymorphism (SNP), rs1333049 on chromosome 9p21.3 has been strongly associated with CAD and myocardial infarction. Increased arterial stiffness could be the link between the 9p21 polymorphism and increased cardiovascular risk. Since the impact of a genetic polymorphism on arterial stiffness especially in Asian populations has not been well defined, we aimed to investigate the association of arterial stiffness with rs 1333049 variant on chromosome 9p21.3 in Thai subjects with and without MetS risk factors.MethodsA total of 208 Thai subjects, aged 35–75 years, 135 with and 73 without MetS, according to IDF and NCEP-ATPIII criteria, were included in this study. Aortic-femoral pulse wave velocity (afPWV), brachial-ankle pulse wave velocity (baPWV) and aortic ankle pulse wave velocity (aaPWV) were measured and used as markers of arterial stiffness. The chromosome 9p21.3 locus, represented by the rs 1333049 variant and blood biochemistry were evaluated.ResultsArterial stiffness was elevated in subjects with MetS when compared with nonMetS subjects. PWV, especially afPWV increased progressively with increasing number of MetS risk factors (r = 0.322, P <0.001). We also found that the frequency distribution of the rs1333049 genotypes is significantly associated with the afPWV (P <0.05). In multivariate analyses, there was an association between homozygous C allele and afPWV (Odds ratio (OR), 8.16; 95% confidence interval (CI), 1.91 to 34.90; P = 0.005), while the GC genotype was not related to afPWV (OR, 1.79; 95% CI, 0.84 to 3.77; P = 0.129) when compared with the GG genotype.ConclusionsOur findings demonstrate for the first time that arterial stiffness is associated with genetic polymorphism in 9p21 and metabolic risk factors in a Thai population.

Peripheral eosinophilia as an indicator of meningitic angiostrongyliasis in exposed individuals.

The diagnosis of meningitic angiostrongyliasis (MA) is based on clinical criteria. A lumbar puncture is used as a diagnostic tool, but it is an invasive procedure. The blood eosinophil levels are also assessed and used in the diagnosis of this disease. We enrolled 47 patients with serologically proven MA and 131 controls with intestinal parasite infections. An absolute eosinophil count model was found to be the best marker for MA. An eosinophil count of more than 798 cells led to sensitivity, specificity, positive predictive and negative predictive values of 76.6%, 80.2%, 58.1% and 90.5%, respectively. These data support the use of testing for high blood eosinophil levels as a diagnostic tool for MA in individuals that are at risk for this disease.

Clinical Phenotyping of Heart Failure with Biomarkers: Current and Future Perspectives

IntroductionHeart failure (HF) is a complex clinical syndrome with diverse risk factors and etiologies, differing underlying pathophysiology, and large phenotypic heterogeneity.Recent FindingsAdvances in imaging techniques coupled with clinical trials that targeted only in those with impaired left ventricular ejection fraction (LVEF) have largely shaped the current management strategy for HF that focuses predominantly in patients with systolic HF. In contrast, there are no effective treatments for HF with preserved ejection fraction (HFpEF). Instead of this “one-size-fits-all” approach to treatment, better precision to define HF phenotypic classifications may lead to more efficient and effective HF disease management.ConclusionIntegrating variables—including clinical variables, HF biomarkers, imaging, genotypes, metabolomics, and proteomics—can identify different pathophysiologies, lead to more precise phenotypic classification, and warrant investigation in future clinical trials.

How Can Clinicians Ensure the Diagnosis of Meningitic Angiostrongyliasis

Meningitic angiostrongyliasis (MA), caused by Angiostrongylus cantonensis, is often diagnosed by clinical criteria alone, because the confirmative serologic tests are not always available in the rural endemic areas. In this study, we evaluated the relationship between various clinical parameters of MA and the sero-positivity to sort out the predictive parameters to ensure the diagnosis. We enrolled consecutive adults in whom MA had been clinically diagnosed, who had serologic results for A. cantonensis, and negative serologic results for Gnathostoma spinigerum. There were 75 eligible patients; 26 (34.7%) and 49 (65.3%) patients who had negative and positive serologic tests for A. cantonensis, respectively. Baseline characteristics and laboratory results were comparable between sero-positive and -negative groups. Only the cerebrospinal fluid (CSF) eosinophil counts of 40% or higher was significantly predictive for positive serologic test with the adjusted odds ratio of 4.970 (95% confidence interval of 1.337-18.477). In diagnostic facilities in the endemic areas with the limited availability of serologic tests, clinicians can ensure the diagnosis of MA by using CSF eosinophil level.

Continuous positive airway pressure therapy converted atrial fibrillation in a patient with obstructive sleep apnea

Obstructive sleep apnea (OSA) is one of the possible causes of atrial fibrillation (AF). Continuous positive airway pressure (CPAP) therapy may lower the recurrence rate of AF after cardioversion to normal sinus rhythm. We report a case of AF caused by OSA and successfully converted by CPAP therapy.

Cpap Pressure by Cpap Titration or Prediction Formula

Obstructive sleep apnea (OSA) is a common disease in clinical practice and can lead to several cardiovascular complications such as death, heart failure, stroke, or atrial fibrillation [1]. The estimated prevalence is about 5-10% of general population [2]. Successful treatment with continuous positive airway pressure machine (CPAP) significantly reduces cardiovascular events [2,3]. Appropriate CPAP pressure can be determined by two methods: in hospital and home CPAP titration [4].

Association of TAFI gene polymorphisms with severity of coronary stenosis in stable coronary artery disease

INTRODUCTION Coronary stenosis is a consequence of atherosclerotic plaque progression that is associated with impaired fibrinolysis. Thrombin-activatable fibrinolysis inhibitor (TAFI) and plasminogen activator inhibitor 1 (PAI-1) are fibrinolysis inhibitors whose levels are influenced by acquired conditions and by polymorphisms. This study therefore aimed to investigate the association of TAFI and PAI-1 gene polymorphisms with severity of coronary stenosis in subjects with stable coronary artery disease (CAD). MATERIALS AND METHODS A total of 327 subjects suspected with CAD who underwent a coronary angiogram were recruited. Gensini score was applied to stratify the severity of coronary stenosis. Based on the Gensini score, the subjects were categorized into low-medium (<20) or high (≥20) groups. The study polymorphisms included TAFI Ala147Thr (505G/A), Thr325Ile (1040C/T), +1542C/G, +1583T/A and PAI-1 -675 4G/5G. Most polymorphisms were genotyped by allele-specific polymerase chain reaction, except for TAFI Thr325Ile that was genotyped by polymerase chain reaction-restriction fragment length polymorphism. RESULTS A significant increase in the Gensini score was found in TAFI 505A and +1583A allele carriers. Binary regression analysis revealed the independent association of the TAFI 505G/A and +1583T/A polymorphisms with a high Gensini score [adjusted OR = 1.67 (95% CI: 1.03, 2.73) and 1.69 (95% CI: 1.04, 2.76), respectively]. Neither the homozygous PAI-1 -675 4G/4G nor the heterozygous 4G/5G was associated with a high Gensini score. CONCLUSIONS The results indicated the contribution of TAFI polymorphisms to atherosclerosis progression and severity of coronary stenosis in stable CAD.