Age and sex differences in the effects of short- and long-term exposure to air pollution on endothelial dysfunction.

BACKGROUND: The effects of air pollution on endothelial function remain unclear across populations. We aimed to use brachial artery flow-mediated dilatation (FMD) to identify demographic differences in the effects of air pollution exposure on endothelial dysfunction. METHODS: We measured FMD in 850 participants from October 2016 to January 2020. Location-specific concentrations of fine particulate matter < 2.5 µm aerodynamic diameter (PM2.5), inhalable particulate matter < 10 µm aerodynamic diameter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) measured by fixed ambient air monitoring stations were collected for short- and long-term exposure assessment. Multiple linear regression models and restricted cubic splines were used to assess the associations before and after stratification by age and sex. RESULTS: This study eventually included 828 participants [551 (66.5%) younger than 65 years and 553 (66.8%) men]. Each 10 µg/m3 increase in 7-day exposure to PM2.5 and PM10 was significantly linearly associated with a 0.07% (ß = -0.07, 95% CI: -0.13 to -0.004) and 0.05% (ß = -0.05, 95% CI: -0.10 to -0.004) decrease in FMD in the fully adjusted model. After full adjustment, long-term exposure to all air pollutants was significantly associated with impaired FMD. Each 10 µg/m3 increase in long-term exposure to PM2.5 and PM10 was significantly associated with a -0.18% (95% CI: -0.34 to -0.03) and - 0.23% (95% CI: -0.40 to -0.06) change in FMD, respectively. After stratification, the associations of lower FMD with long-term exposure to PM2.5, PM10, SO2, NO2, and CO significantly persisted in men and participants younger than 65 years instead of women or older participants. For short-term exposure, we observed differences consistent with long-term exposure and a stronger effect of 7-day exposure to SO2 in men due to a significant interaction effect. CONCLUSION: Short- and long-term exposure to different air pollutants are strongly associated with decreased endothelial function, and susceptibility to air pollution varies significantly with age and sex.

Association of prealbumin with short-term and long-term outcomes in patients with acute ST-segment elevation myocardial infarction.

BACKGROUND: Prealbumin is considered to be a useful indicator of nutritional status. Furthermore, it has been found to be associated with severities and prognosis of a range of diseases. However, limited data on the association of baseline prealbumin level with outcomes of patients with acute ST-segment elevation myocardial infarction (STEMI) are available. METHODS: We analyzed 2313 patients admitted for acute STEMI between October 2013 and December 2020. In-hospital outcomes and mortality during the 49 months (interquartile range: 26-73 months) follow-up period were compared between patients with the low prealbumin level (< 170 mg/L) and those with the high prealbumin level (≥ 170 mg/L). RESULTS: A total of 114 patients (4.9%) died during hospitalization. After propensity score matching, patients with the low prealbumin level than those with the high prealbumin level experienced higher incidences of heart failure with Killip class III (9.9% vs. 4.4%, P = 0.034), cardiovascular death (8.4% vs. 3.4%, P = 0.035) and the composite of major adverse cardiovascular events (19.2% vs. 10.3%, P = 0.012). Multivariate logistic regression analysis identified that the low prealbumin level (< 170 mg/L) was an independent predictor of in-hospital major adverse cardiovascular events (odds ratio = 1.918, 95% CI: 1.250-2.942, P = 0.003). The cut-off value of prealbumin level for predicting in-hospital death was 170 mg/L (area under the curve = 0.703, 95% CI: 0.651-0.754, P < 0.001; sensitivity = 0.544, specificity = 0.794). However, after multivariate adjustment of possible confounders, baseline prealbumin level (170 mg/L) was no longer independently associated with 49-month cardiovascular death. After propensity score matching, Kaplan-Meier survival curves revealed consistent results. CONCLUSIONS: Decreased prealbumin level closely related to unfavorable short-term outcomes. However, after multivariate adjustment and controlling for baseline differences, baseline prealbumin level was not independently associated with an increased risk of long-term cardiovascular mortality in STEMI patients.

Association between triglyceride-glucose index and endothelial dysfunction.

BACKGROUND: Triglyceride-glucose (TyG) index, a simple surrogate marker for insulin resistance (IR), has been reported as an independent predictor of arterial structural damage and future cardiovascular events. The association between TyG index and endothelial dysfunction remains uncertain. OBJECTIVE: The purpose of this study was to investigate the association between TyG index and endothelial dysfunction. METHODS: Endothelial dysfunction was measured using flow-mediated dilation (FMD). A total of 840 subjects, who voluntarily accepted FMD measurement at the Health Management Department of Xuanwu Hospital from October 2016 to January 2020, were included in this study. TyG index was calculated as Ln [fasting triglyceride (TG)(mg/dL) × fasting plasma glucose (FPG) (mg/dL)/2]. RESULTS: The mean age was 59.92 ± 10.28 years and 559 (66.55%) participants were male. The TyG index was correlated with FMD values (P = 0.022). Each unit increment in TyG index was associated with lower FMD values (ß = -0.330, 95%CI -0.609 to -0.052, P = 0.020) after adjusting for covariates. Age (ß = -0.069, 95%CI -0.088 to -0.051, P < 0.001), female (ß = 0.592, 95%CI 0.172 to1.012, P = 0.006), smoking (ß = -0.430, 95%CI -0.859 to -0.002, P = 0.049) and hypertension (ß = -0.741, 95%CI -1.117 to -0.365, P < 0.001) were also independent predictors for endothelial dysfunction. A significant association between the TyG index and endothelial dysfunction was found only in populations younger than 60 years (ß = -0.843, 95%CI -1.371 to -0.316, P = 0.002), females (ß = -0.612, 95%CI -1.147 to -0.077, P = 0.025), and populations without diabetes mellitus (DM) (ß = -0.594, 95%CI -1.042 to -0.147, P = 0.009). CONCLUSIONS: Subjects with an elevated TyG index are more likely to have endothelial dysfunction, particularly in populations without DM.

Cerebral hypometabolism mediates the effect of stroke volume on cognitive impairment in heart failure patients.

AIMS: The present study aimed to phenotype the cerebral structural and glucose metabolic alterations in patients with heart failure (HF) using simultaneous positron emission tomography (PET)/magnetic resonance (MR) and to investigate their relationship to cardiac biomarkers and cognitive performance. METHODS AND RESULTS: Forty-two HF patients caused by ischaemic heart disease (mean age 67.2 ± 10.4, 32 males) and 32 age- and sex-matched healthy volunteers (mean age 61.3 ± 4.8, 18 males) were included in this study. Participants underwent simultaneous cerebral fluorine-18 (18 F) fluorodeoxyglucose PET/MR followed by cardiac MR scan, and neuropsychological scores were obtained to assess cognitive performance. The grey matter volume (GMV) and standardized uptake value ratio (SUVR) were calculated to examine cerebral structural and metabolic alterations. Cardiac biomarkers included cardiac MR parameters and cardiac serum laboratory tests. Mediation analysis was performed to explore the associations among cerebral alterations, cardiac biomarkers, and cognitive performance. HF patients demonstrated notable cognitive impairment compared with normal controls (P < 0.001). Furthermore, HF patients exhibited regional brain hypometabolism in the bilateral calcarine cortex, caudate nucleus, thalamus, hippocampus, precuneus, posterior cingulate cortex, lingual and olfactory cortex, and GMV reduction in bilateral thalamus and hippocampus (cluster level at P < 0.05, Gaussian random field correction). The SUVR of the hypometabolic brain regions was correlated with the Montreal Cognitive Assessment (MoCA) scores (r = 0.55, P = 0.038) and cardiac stroke volume (r = 0.49, P = 0.002). Cerebral hypometabolism played a key role in the relationship between the decreased stroke volume and MoCA scores, with a mediation effect of 33.2%. CONCLUSIONS: HF patients suffered cerebral metabolic and structural alterations in regions associated with cognition. The observed correlation between cardiac stroke volume and cognitive impairment underscored the potential influence of cerebral hypometabolism, suggesting that cerebral hypometabolism due to chronic systemic hypoperfusion may significantly contribute to cognitive impairment in HF patients.

The incidence of subclinical atherosclerosis in subjects with low and moderate cardiovascular risk.

BACKGROUND: The cardiovascular risk models and subclinical atherosclerotic indicators are both recommended for cardiovascular risk stratification. The accordance between the incidence of subclinical atherosclerosis and subjects with low and moderate cardiovascular risk is unclear. HYPOTHESIS: Subjects with low and moderate cardiovascular risk have a lower incidence of subclinical atherosclerosis compared with subjects with high risk. METHODS: Brachial-ankle pulse wave velocity (BaPWV) and brachial flow-mediated dilation (BFMD) were measured in 421 subjects without a history of atherosclerotic cardiovascular disease (ASCVD) from October 2016 to January 2020. All subjects were classified into low, moderate, and high risk based on Framingham and China-par risk models respectively. RESULTS: Mean age was 57.05 ± 9.35 years and 248 (58.9%) were male. In subjects with low, moderate, and high risk assessed by Framingham and China-par risk models, the percentage of abnormal BaPWV ( > 1400 cm/s) was 42.9%, 70.1%, 85.7%, and 40.4%, 71.4%, 89.7%, respectively. Meanwhile, the percentage of abnormal BFMD ( ≤ 7%) was 43.8%, 68.5%, 77.3%, and 44.9%,72.1%, and 76.6%. According to Framingham-based high-risk categories, positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity for BaPWV abnormality were 85.7%, 39.4%, 36.1%, and 87.5%, respectively. For BFMD abnormality, the values were 77.3%, 40.1%, 34.1%, and 81.8%, respectively. According to China-par high-risk categories, the values for BaPWV abnormality were 89.7%, 43.8%, 45.6%, and 89.0%, respectively. For BFMD abnormality, the values were 76.6%, 41.3%, 40.7%, and 77%, respectively. In multivariate analysis, age and blood pressure were the independent predictors for subclinical atherosclerosis in subjects with low-moderate risk. CONCLUSIONS: More than one-half of subjects with low and moderate risk already have detectable subclinical atherosclerosis, indicating higher cardiovascular risk beyond the traditional stratification.

Incidence, predictors and prognosis of acute kidney injury in acute ST-segment elevation myocardial infarction patients undergoing emergent coronary angiography/primary percutaneous coronary intervention.

BACKGROUND: Acute kidney injury (AKI) after coronary angiography (CAG) and primary percutaneous coronary intervention (PPCI) is frequently observed, and often interpreted as contrast induced-AKI. This study aimed to investigate the incidence, predictors and outcomes of AKI in acute ST-segment elevation myocardial infarction (STEMI) patients undergoing emergent CAG/PPCI using the control group of STEMI patients who were not exposed to contrast agents within the first 72 h. METHODS: We performed a retrospective analysis of 1670 STEMI patients. Of them, 673 patients underwent emergent CAG/PPCI, and 997 patients treated with thrombolysis or no reperfusion therapy who were not exposed to contrast material during the first 72 h. AKI was defined as an increase of serum creatinine ≥ 44.2 mmol/L or ≥ 25% from baseline within 72 h. Patents were then followed up for the occurrence of all-cause mortality for 40 months (interquartile range: 24-55 months). RESULTS: After propensity score matching, 505 pairs of patients were matched. Overall, the incidence of AKI was 27.4%, and AKI rates were not significantly different in patients with and without emergent CAG/PPCI procedure (27.5% vs. 27.3%, P = 0.944). Multivariate logistic regression analysis identified that the independent predictors of AKI were female, elevated interleukin-6 level, decreased lymphocyte count, left ventricular ejection fraction < 50% and use of diuretics in patients with emergent CAG/PPCI. Patients with AKI than those without AKI experienced higher incidence of acute heart failure with Killip class III (9.4% vs. 3.3%, P = 0.005; 15.2% vs. 6.8%, P = 0.003, respectively) and mortality (5.8% vs. 1.4%, P = 0.014; 12.3% vs. 4.6%, P = 0.002, respectively) in patients with and without emergent CAG/PPCI. Multivariate Cox regression analysis confirmed that AKI was independently associated with long-term mortality rate at 40 months follow-up in patients with and without emergent CAG/PPCI (HR = 1.867, 95% CI: 1.086-3.210, P = 0.024; HR = 1.700, 95% CI: 1.219-2.370, P = 0.002, respectively). CONCLUSIONS: Approximately 27.0% of STEMI patients experience AKI, which is strongly associated with an increased short- and long-term mortality regardless of emergent CAG/PPCI procedure. The development of AKI is mainly related to female gender, inflammation reaction, heart failure and use of diuretics in STEMI patients undergoing emergent CAG/PPCI.

Association of vascular endothelial function and quality of life in patients with ischemia and non-obstructive coronary artery disease.

Improvements are required in the quality of life (QoL) of patients with ischemia and non-obstructive coronary artery disease (INOCA). Several patients with INOCA experience vascular endothelial dysfunction. However, the relationship between endothelial function and QoL remains unelucidated. This study aimed to initially investigate the relationship between endothelial function and QoL in patients with INOCA. This prospective observational study included 121 patients with INOCA (aged 31-85 years). Vascular endothelial function was assessed by flow-mediated dilatation (FMD) of the peripheral brachial artery. QoL was evaluated using the 36-Item Short-Form Health Survey (SF-36). Patients with INOCA were divided into two groups according to the median FMD change during the 1-year follow-up (group A, ≥ median FMD change cut-off; group B, < median FMD change cut-off). The median change in FMD was 0.92%. The mean baseline SF-36 scores were comparable between the two groups (53.95 ± 6.46 vs. 53.92 ± 4.29, p = 0.98). The QoL at follow-up was better in group A than in group B (56.61 ± 5.50 vs. 53.32 ± 5.58, p = 0.002). The change in FMD (r = 0.34, p < 0.01), rather than FMD at baseline (r = - 0.01, p = 0.89) or follow-up (r = 0.13, p = 0.15), was related to the follow-up SF-36 scores. FMD improvement was an independent predictor of increased QoL (odds ratio, 3.90; 95% confidence interval: 1.59-9.53, p = 0.003). Endothelial function change is associated with QoL, and patients with improved endothelial function have a better QoL than those without.

Prognostic Value of Normal Thyroid Stimulating Hormone in Long-Term Mortality in Patients With STEMI.

Background: Although within the normal range, thyroid stimulating hormone (TSH) levels are associated with cardio-metabolic disorders and have an effect on the cardiovascular system. The aim of our study was to assess the prognostic value of normal TSH on long-term mortality in patients with ST-segment elevation myocardial infarction (STEMI). Methods: Consecutive STEMI patients who had a TSH level within the normal range (0.55-4.78 µIU/ml) were enrolled from November 2013 to December 2018. Patients were stratified into three groups depending on the tertile of TSH level, and all-cause mortality and cardiac death were compared. TSH concentrations associated with risk of all-cause mortality were evaluated in a continuous scale (restricted cubic splines) and the Cox proportional hazards regression model. Results: A total of 1,203 patients with STEMI were eligible for analysis. During a median follow-up of 39 months, patients in the 3rd tertile group had higher all-cause mortality (20.1% vs. 12.2% and 14.3%, p = 0.006) and cardiac death (15.4% vs. 7.7% and 12.3%, p = 0.001) as compared to the 1st and 2nd tertile groups. The Cox proportional hazards model showed that TSH was an independent predictor on long-term all-cause mortality (HR: 1.248, 95% CI: 1.046-1.490, p = 0.014). However, subgroup analysis indicated that TSH (HR: 1.313, 95% CI: 1.063-1.623, p = 0.012) was only significantly associated with long-term all-cause mortality in the patients without emergency reperfusion therapy. Restricted cubic spline analyses showed a linear relationship between TSH concentrations and all-cause mortality (P for non-linearity = 0.659). Conclusions: A Higher TSH level - even in a normal range is associated with long-term mortality in patients with STEMI, proposing an additional indication to identify STEMI patients with poor prognosis.

Air pollution and recurrence of cardiovascular events after ST-segment elevation myocardial infarction.

BACKGROUND AND AIMS: The effects of air pollution on discharged patients after ST-segment elevation myocardial infarction (STEMI) still remain uncertain. We examined the association between air pollutants and recurrent cardiovascular events in STEMI survivors. METHODS: A retrospective cohort of 1641 discharged patients after STEMI was established in 2013 and followed until the end of 2019. Concentrations of air pollutants including fine particles <2.5 µm aerodynamic diameter (PM2.5), inhalable particles <10 µm aerodynamic diameter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO) and ozone (O3) measured by fixed ambient air monitoring stations were collected for exposure assessment. Multivariate-adjusted Cox proportional hazards models were used to estimate the increased risks of recurrent cardiovascular events. RESULTS: Compared with the first exposure quartile, for short-term exposure, hazard ratios (HRs) of recurrent cardiovascular events associated with the fourth exposure quartiles of PM2.5, PM10, NO2, SO2, CO, and O3 were 4.06 (95% CI: 2.62-6.30), 3.79 (95% CI: 2.57-5.58), 2.22 (95% CI: 1.67-2.94), 4.47 (95% CI: 3.08-6.48), 3.73 (95% CI: 2.54-5.48), and 5.35 (95% CI: 3.12-9.20), respectively. For long-term exposure, HRs associated with the fourth exposure quartiles of PM2.5, PM10, NO2, SO2, CO, and O3 were 6.43 (95% CI: 3.60-11.47), 4.77 (95% CI: 2.85-7.99), 3.22 (95% CI: 2.00-5.19), 3.20 (95% CI: 2.05-5.01), 4.44 (95% CI: 2.65-7.45), and 1.07 (95% CI: 0.80-1.42), respectively. The risks of recurrent cardiovascular events brought by air pollutants mostly increased nonlinearly. CONCLUSIONS: Short- and long-term exposure to air pollutants except ozone increases the risks of recurrent cardiovascular events in STEMI survivors. Better environmental policies and secondary prevention strategies should be developed to protect STEMI survivors as a susceptible population.