Novel Selective PPARα Modulator Pemafibrate for Dyslipidemia, Nonalcoholic Fatty Liver Disease (NAFLD), and Atherosclerosis

Statins, the intestinal cholesterol transporter inhibitor (ezetimibe), and PCSK9 inhibitors can reduce serum LDL-C levels, leading to a significant reduction in cardiovascular events. However, these events cannot be fully prevented even when maintaining very low LDL-C levels. Hypertriglyceridemia and reduced HDL-C are known as residual risk factors for ASCVD. Hypertriglyceridemia and/or low HDL-C can be treated with fibrates, nicotinic acids, and n-3 polyunsaturated fatty acids. Fibrates were demonstrated to be PPARα agonists and can markedly lower serum TG levels, yet were reported to cause some adverse effects, including an increase in the liver enzyme and creatinine levels. Recent megatrials of fibrates have shown negative findings on the prevention of ASCVD, which were supposed to be due to their low selectivity and potency for binding to PPAR α. To overcome the off-target effects of fibrates, the concept of a selective PPARα modulator (SPPARMα) was proposed. Kowa Company, Ltd. (Tokyo, Japan), has developed pemafibrate (K-877). Compared with fenofibrate, pemafibrate showed more favorable effects on the reduction of TG and an increase in HDL-C. Fibrates worsened liver and kidney function test values, although pemafibrate showed a favorable effect on liver function test values and little effect on serum creatinine levels and eGFR. Minimal drug-drug interactions of pemafibrate with statins were observed. While most of the fibrates are mainly excreted from the kidney, pemafibrate is metabolized in the liver and excreted into the bile. It can be used safely even in patients with CKD, without a significant increase in blood concentration. In the megatrial of pemafibrate, PROMINENT, for dyslipidemic patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia, and low HDL-C and LDL-C levels, the incidence of cardiovascular events did not decrease among those receiving pemafibrate compared to those receiving the placebo; however, the incidence of nonalcoholic fatty liver disease was lower. Pemafibrate may be superior to conventional fibrates and applicable to CKD patients. This current review summarizes the recent findings on pemafibrate

Effects of Occupational Noise Exposure on 24-Hour Ambulatory Vascular Properties in Male Workers

BACKGROUND: Epidemiologic studies have demonstrated that occupational noise exposure is associated with hypertension, but the related mechanism in vascular structural changes is unclear. OBJECTIVE: This panel study aimed to investigate effects of occupational noise exposure on ambulatory vascular structural properties in male workers. METHODS: We recruited 20 volunteers and divided them into a high-noise- exposure group of 15 and a low-noise-exposure group of 5 based on environmental noise measurement in an automobile manufacturing company. We determined individual noise exposure and measured personal ambulatory vascular property parameters simultaneously during 24 hr. Linear mixed-effects regression models were used to estimate transient and sustained effects of noise exposure on vascular parameters by adjusting some confounders collected from self- administrated questionnaires and health checkups. RESULTS: The high-noise- exposed (85 ± 8 dBA) workers had significantly higher systemic vascular resistance (SVR) than the low-noise-exposed workers (59 ± 4 dBA) during work and sleep periods. Contrarily, low-noise-exposed workers had significantly higher brachial artery compliance (BAC), brachial artery distensibility (BAD), and systemic vascular compliance (SVC; marginal, p = 0.07) than high-noise-exposed workers during off-duty periods. We also found that high- noise-exposed workers had significantly lower BAC (1.38 ± 0 .55 %mL/mmHg) and BAD (1.29 ± 0.51 %/mmHg), as well as lower SVC (0. 24 ± 0.10 mL/L/mmHg), but higher SVR (1.93 ±0.67 mL/L/min) compared with low-noise-exposed workers over a 24-hr period. CONCLUSIONS: Our findings suggest that in automobile workers, occupational noise exposure may have sustained, not transient, effects on vascular properties and also enhances the development of hypertension. [ABSTRACT FROM AUTHOR] Copyright of Environmental Health Perspectives is the property of Superintendent of Documents and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts

Effects of Particle Size Fractions on Reducing Heart Rate Variability in Cardiac and Hypertensive Patients

It is still unknown whether the associations between particulate matter (PM) and heart rate variability (HRV) differ by particle sizes with aerodynamic diameters between 0.3 μm and 1.0 μm (PM(0.3–1.0)), between 1.0 μm and 2.5 μm (PM(1.0–2.5)), and between 2.5 μm and 10 μm (PM(2.5–10)). We measured electrocardiographics and PM exposures in 10 patients with coronary heart disease and 16 patients with either prehypertension or hypertension. The outcome variables were standard deviation of all normal-to-normal (NN) intervals (SDNN), the square root of the mean of the sum of the squares of differences between adjacent NN intervals (r-MSSD), low frequency (LF; 0.04–0.15 Hz), high frequency (HF; 0.15–0.40 Hz), and LF:HF ratio for HRV. The pollution variables were mass concentrations of PM(0.3–1.0), PM(1.0–2.5), and PM(2.5–10). We used linear mixed-effects models to examine the association between PM exposures and log(10)-transformed HRV indices, adjusting for key personal and environmental attributes. We found that PM(0.3–1.0) exposures at 1- to 4-hr moving averages were associated with SDNN and r-MSSD in both cardiac and hypertensive patients. For an interquartile increase in PM(0.3–1.0), there were 1.49–4.88% decreases in SDNN and 2.73–8.25% decreases in r-MSSD. PM(0.3–1.0) exposures were also associated with decreases in LF and HF for hypertensive patients at 1- to 3-hr moving averages except for cardiac patients at moving averages of 2 or 3 hr. By contrast, we found that HRV was not associated with either PM(1.0–2.5) or PM(2.5–10). HRV reduction in susceptible population was associated with PM(0.3–1.0) but was not associated with either PM(1.0–2.5) or PM(2.5–10)

Segregation analysis of apolipoprotein A1 levels in families of adolescents: A community-based study in Taiwan

BACKGROUND: Apolipoprotein (Apo) A1 is a protective factor for cardiovascular events. This study aimed to perform complex segregation analyses of Apo A1 levels in families of adolescents systematically ascertained from the junior high school students in a rural community. Both siblings and parents of the adolescent probands were recruited for the study. Apo A1 concentrations were measured by turbidimetric immunoassay methods. After adjustment for gender, age, body mass index, smoking and drinking status, residual values of Apo A1 were subjected to subsequent analyses. RESULTS: Significant mother-father and parent-offspring correlations were found. Commingling analyses indicated that a four-component distribution model was needed to account for the Apo A1 variation. Segregation analysis using regressive models revealed that the best-fit model of Apo A1 was a model of environmental effect plus familial correlation (heritability = 23.9%), in which a significant mother-father correlation existed. Models containing major gene effect could be rejected. CONCLUSION: These results suggest that variations of Apo A1 levels in the normal range, especially during adolescence, are likely to be influenced by multiple factors without significant contribution from major genes

Consistency of genetic inheritance mode and heritability patterns of triglyceride vs. high density lipoprotein cholesterol ratio in two Taiwanese family samples

BACKGROUND: Triglyceride/HDL cholesterol ratio (TG/HDL-C) is considered as a risk factor for cardiovascular events. Genetic components were important in controlling the variation in western countries. But the mode of inheritance and family aggregation patterns were still unknown among Asian-Pacific countries. This study, based on families recruited from community and hospital, is aimed to investigate the mode of inheritance, heritability and shared environmental factors in controlling TG/HDL-C. RESULTS: Two populations, one from community-based families (n = 988, 894 parent-offspring and 453 sibling pairs) and the other from hospital-based families (n = 1313, 76 parent-offspring and 52 sibling pairs) were sampled. The population in hospital-based families had higher mean age values than community-based families (54.7 vs. 34.0). Logarithmic transformed TG/ HDL-C values, after adjusted by age, gender and body mass index, were for genetic analyses. Significant parent-offspring and sibling correlations were also found in both samples. The parent-offspring correlation coefficient was higher in the hospital-based families than in the community-based families. Genetic heritability was higher in community-based families (0.338 ± 0.114, p = 0.002), but the common shared environmental factor was higher in hospital-based families (0.203 ± 0.042, p < 0.001). Commingling analyses showed that more than one-component distribution models were the best-fit models to explain the variance in both populations. Complex segregation analysis by regressive models revealed that in both samples the best-fit model of TG/HDL-C was the model of environmental effects plus familial correlation, in which significant parent-offspring and sibling correlations were demonstrated. Models of major gene effects were rejected in both samples. CONCLUSION: Variations of TG/HDL-C in the normal ranges were likely to be influenced by multiple factors, including environmental and genetic components. Higher genetic factors were proved in younger community-based families than in older hospital-based families