Low diastolic blood pressure is associated with a high atherosclerotic burden in patients with obstructive coronary artery disease

Background: The optimal blood pressure (BP) treatment target is still being debated, specifically di­astolic BP (DBP) in patients with obstructive coronary artery disease (CAD); a DBP which is too low could compromise myocardial perfusion and is associated with adverse outcomes. Methods: This study examined the relationship between DBP levels and the severity and atheroscle­rotic burden of CAD in 231 consecutive stable patients with evidence of obstructive CAD as detected by elective coronary angiography. The SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) Score and SYNTAX Score II were used to quantify the atherosclerotic burden. Results: The patients were male (71%), median age 62, interquartile range [IQR] of 57 to 67, and 84% had hypertension. The median DBP was 71.0 mmHg (IQR: 61 to 80) and the median SYNTAX Score was 16.0 (IQR 9.0–23.0). DBP levels were inversely correlated with SYNTAX Score (r = –0.61) and SYNTAX Score II (r = –0.73). Adjusting for traditional risk factors, unprotected left main CAD, systolic BP, renal function, and medications, DBP levels remained independently inversely associated with a higher tertile of SYNTAX Score (adjusted odds ratio [OR] 0.89; 95% confidence interval [CI] 0.85–0.92, p < 0.001) and SYNTAX Score II (adjusted OR 0.75; 95% CI 0.69–0.80, p < 0.001). The frequency of high athero­sclerotic burden identified by the presence of intermediate or high SYNTAX Score and SYNTAX Score II was significantly higher among patients with a DBP < 60 mmHg. Conclusions: Low DBP levels are independently associated with high SYNTAX Score and SYNTAX Score II in stable patients with obstructive CAD

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\u3c0.001). 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\u3c0.001). 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\u3c0.001) 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

Hysteresis response of daytime net ecosystem exchange during drought

Continuous measurements of net ecosystem CO<sub>2</sub> exchange (NEE) using the eddy-covariance method were made over an agricultural ecosystem in the southeastern US. During optimum environmental conditions, photosynthetically active radiation (PAR) was the primary driver controlling daytime NEE, accounting for as much as 67 to 89% of the variation in NEE. However, soil water content became the dominant factor limiting the NEE-PAR response during the peak growth stage. NEE was significantly depressed when high PAR values coincided with very low soil water content. The presence of a counter-clockwise hysteresis of daytime NEE with PAR was observed during periods of water stress. This is a result of the stomatal closure control of photosynthesis at high vapor pressure deficit and enhanced respiration at high temperature. This result is significant since this hysteresis effect limits the range of applicability of the Michaelis-Menten equation and other related expressions in the determination of daytime NEE as a function of PAR. The systematic presence of hysteresis in the response of NEE to PAR suggests that the gap-filling technique based on a non-linear regression approach should take into account the presence of water-limited field conditions. Including this step is therefore likely to improve current evaluation of ecosystem response to increased precipitation variability arising from climatic changes

Synthesis of oligodeoxyribonucleotides containing a tricyclic thio analogue of O6-methylguanine and their recognition by MGMT and Atl1

Promutagenic O6-alkylguanine adducts in DNA are repaired in humans by O6-methylguanine-DNA-methyltransferase (MGMT) in an irreversible reaction. Here we describe the synthesis of a phosphoramidite that allows the preparation of oligodeoxyribonucleotides (ODNs) containing a novel tricyclic thio analogue of O6-methylguanine in which the third ring bridges the 6-thio group and C7 of a 7-deazapurine. These ODNs are very poor substrates for MGMT and poorly recognised by the alkyltransferase-like protein, Atl1. Examination of the active sites of both MGMT and Atl1 suggest large steric clashes hindering binding of the analogue. Such analogues, if mutagenic, are likely to be highly toxic

Intestinal Microbiota-Generated Metabolite Trimethylamine-N-Oxide and 5-Year Mortality Risk in Stable Coronary Artery Disease: The Contributory Role of Intestinal Microbiota in A COURAGE-Like Patient Cohort

Background: Trimethylamine-N-oxide (TMAO), a metabolite derived from gut microbes and dietary phosphatidylcholine, is linked to both coronary artery disease pathogenesis and increased cardiovascular risks. The ability of plasma TMAO to predict 5-year mortality risk in patients with stable coronary artery disease has not been reported. This study examined the clinical prognostic value of TMAO in patients with stable coronary artery disease who met eligibility criteria for a patient cohort similar to that of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial. Methods and Results: We examined the relationship between fasting plasma TMAO and all-cause mortality over 5-year follow-up in sequential patients with stable coronary artery disease (n=2235) who underwent elective coronary angiography. We identified the COURAGE-like patient cohort as patients who had evidence of significant coronary artery stenosis and who were managed with optimal medical treatment. Higher plasma TMAO levels were associated with a 4-fold increased mortality risk. Following adjustments for traditional risk factors, high-sensitivity C-reactive protein, and estimated glomerular filtration rate, elevated TMAO levels remained predictive of 5-year all-cause mortality risk (quartile 4 versus 1, adjusted hazard ratio 1.95, 95% CI 1.33–2.86; P=0.003). TMAO remained predictive of incident mortality risk following cardiorenal and inflammatory biomarker adjustments to the model (adjusted hazard ratio 1.71, 95% CI 1.11–2.61; P=0.0138) and provided significant incremental prognostic value for all-cause mortality (net reclassification index 42.37%, P\u3c0.001; improvement in area under receiver operator characteristic curve 70.6–73.76%, P\u3c0.001). Conclusions: Elevated plasma TMAO levels portended higher long-term mortality risk among patients with stable coronary artery disease managed with optimal medical treatment

A web-based surveillance model of eosinophilic meningitis: future prediction and distribution patterns

Background: web-based surveillance is a useful tool for predicting future cases of various emerging infectious diseases. There are limited data available on web-based surveillance and patterns of distribution of eosinophilic meningitis (EOM), which is an emerging infectious disease in various countries around the world.  Methods: this study applied web-based surveillance to the prediction of EOM incidence and the analysis of its distribution pattern by using a national database, which may be used for future prevention and control. The number cases of EOM in each month over a period of 12 years (between 2006 to 2017) from Loei province were retrieved from the National Disease Surveillance (Report 506) website, operated by Thailand's Public Health Center.  Results: we developed autoregressive integrated moving average (ARIMA) models and seasonal ARIMA (SARIMA) models. The best model was used for predicting numbers of future cases. The forecast values from the SARIMA (1, 1, 2)(0,1,1)6 model were close to actual values and were the most valid, as they had the lowest RMSE and AIC. The predictive model for future cases of EOM was related to previous numbers of EOM cases over the past eight months. The disease exhibited a seasonal pattern during the study period.  Conclusions: web-based surveillance can be used for future prediction of EOM, that the predictive model applied here was valid, and that EOM exhibits a seasonal pattern

Plasma Trimethylamine N-Oxide, a Gut Microbe–Generated Phosphatidylcholine Metabolite, Is Associated With Atherosclerotic Burden

Background: Trimethylamine N-oxide (TMAO), a gut microbiota metabolite from dietary phosphatidylcholine, has mechanistic links to atherosclerotic coronary artery disease (CAD) pathogenesis and is associated with adverse outcomes. Objectives: This study sought to examine the relationship between plasma TMAO levels and the complexity and burden of CAD and degree of subclinical myonecrosis. Methods: We studied 353 consecutive stable patients with evidence of atherosclerotic CAD detected by elective coronary angiography between 2012 and 2014. Their high-sensitivity cardiac troponin T (hs-cTnT) levels were measured. SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) scores and lesion characteristics were used to quantify atherosclerotic burden. Fasting plasma TMAO was measured by mass spectrometry. Results: In this prospective cohort study, the median TMAO level was 5.5 μM (interquartile range [IQR]: 3.4 to 9.8 μM), the median SYNTAX score was 11.0 (IQR: 4.0 to 18.5), and 289 (81.9%), 40 (11.3%), and 24 (6.8%) patients had low (0 to 22), intermediate (23 to 32), and high (≥33) SYNTAX scores, respectively. Plasma TMAO levels correlated (all p \u3c 0.0001) with the SYNTAX score (r = 0.61), SYNTAX score II (r = 0.62), and hs-cTnT (r = 0.29). Adjusting for traditional risk factors, body mass index, medications, lesion characteristic, renal function, and high-sensitivity C-reactive protein, elevated TMAO levels remained independently associated with a higher SYNTAX score (odds ratio [OR]: 4.82; p \u3c 0.0001), SYNTAX score II (OR: 1.88; p = 0.0001), but were not associated with subclinical myonecrosis (OR: 1.14; p = 0.3147). Elevated TMAO level was an independent predictor of the presence of diffuse lesions, even after adjustments for traditional risk factors and for hs-cTnT (OR: 2.05; 95% confidence interval: 1.45 to 2.90; p = 0.0001). Conclusions: Fasting plasma TMAO levels are an independent predictor of a high atherosclerotic burden in patients with CAD

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

The electronic version of this article is the complete one and can be found online at: http://www.cardiab.com/content/12/1/93. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.BACKGROUND: Increased 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. METHODS: A 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. RESULTS: Arterial 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. CONCLUSIONS: Our findings demonstrate for the first time that arterial stiffness is associated with genetic polymorphism in 9p21 and metabolic risk factors in a Thai population