Background: In obstructive hypertrophic cardiomyopathy (HCM), New York Heart Association (NYHA) class has been associated with increased risks of adverse cardiovascular (CV) outcomes that may require more intensive healthcare. Research Question: Is NYHA class associated with healthcare resource utilization (HCRU) and costs in obstructive HCM? Aims: To describe all-cause and CV-related HCRU and costs by NYHA class in obstructive HCM. Methods: This was a retrospective cohort study of adults with obstructive HCM and ≥1 documented NYHA class in Optum’s de-identified Market Clarity database (administrative claims linked with electronic health records [EHR]) from 1/1/2017 to 3/31/2022. Index date was the date of the first NYHA class (i.e., index NYHA class) on or after the earliest date for diagnosis of obstructive HCM or, if any, septal reduction therapy. Annualized all-cause and CV-related HCRU and costs, overall and stratified by the index NYHA class, were assessed using claims during the 182 days after index (i.e., follow-up). Costs were adjusted to 2022 USD. Results: A total of 754 patients were included, with 20.0%, 44.0%, 30.2%, and 5.7% having NYHA class I, II, III, and IV at index, respectively ( Table ). The annual number of all-cause hospitalizations increased with higher index NYHA classes (mean ± SD 0.3 ± 1.0, 1.0 ± 1.8, 1.6 ± 2.6, and 2.1 ± 2.8 for class I, II, III, and IV, respectively). A similar trend was observed for emergency room visits, outpatient visits, and other visits. The total all-cause costs were higher for patients with worse index NYHA classes (mean ± SD $35,339 ± 64,594, $62,899 ± 86,765, $77,727 ± 109,519, and $123,058 ± 139,867 for class I, II, III, and IV, respectively). CV-related HCRU and costs were also generally higher for patients with a worse index NYHA class. Conclusion(s): Obstructive HCM was associated with a substantial economic burden. A worse NYHA class was associated with higher all-cause and CV-related HCRU and costs in obstructive HCM.
Abstract Uromodulin, also named Tamm Horsfall protein, have been associated with renal function and sodium homeostasis regulation. The authors sought to examine the effects of salt intake on plasma and urinary uromodulin levels and the association of its genetic variants with salt sensitivity in Chinese adults. Eighty patients from our natural population cohort were maintained sequentially either on a usual diet for 3 days, a low‐salt diet (3.0 g) for 7 days, and a high‐salt diet (18.0 g) for an additional 7 days. In addition, the authors studied 514 patients of the Baoji Salt‐Sensitive Study, recruited from 124 families who received the same salt intake intervention, and investigated the association of genetic variations in uromodulin gene with salt sensitivity. Plasma uromodulin levels were significantly lower on a high‐salt diet than on a baseline diet (28.3 ± 4.5 vs . 54.9 ± 8.8 ng/ml). Daily urinary excretions of uromodulin were significantly decreased on a high‐salt diet than on a low‐salt diet (28.7 ± 6.7 vs . 157.2 ± 21.7 ng/ml). SNPs rs7193058 and rs4997081 were associated with the diastolic blood pressure (DBP), mean arterial pressure (MAP) responses to the high‐salt diet. In addition, several SNPs in the uromodulin gene were significantly associated with pulse pressure (PP) response to the low‐salt intervention. This study shows that dietary salt intake affects plasma and urinary uromodulin levels and that uromodulin may play a role in the pathophysiological process of salt sensitivity in the Chinese populations.
Neural precursor cell expressed developmentally downregulated 4-like (NEDD4L), a member of the E3 ubiquitin-protein ligases, encoded by NEDD4L gene, was found to be involved in in salt sensitivity by regulating sodium reabsorption in salt-sensitive rats. The authors aimed to explore the associations of NEDD4L genetic variants with salt sensitivity, blood pressure (BP) changes and hypertension incidence in Chinese adults. Participants from 124 families in Northern China in the Baoji Salt-Sensitive Study Cohort in 2004, who received the chronic salt intake intervention, including a 7-day low-salt diet (3.0 g/day) and a 7-day high-salt diet (18 g/day), were analyzed. Besides, the development of hypertension over 14 years was evaluated. NEDD4L single nucleotide polymorphism (SNP) rs74408486 was shown to be significantly associated with systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure (MAP) responses to low-salt diet, while SNPs rs292449 and rs2288775 were significantly associated with pulse pressure (PP) response to high-salt diet. In addition, SNP rs4149605, rs73450471, and rs482805 were significantly associated with the longitudinal changes in SBP, DBP, MAP, or PP at 14 years of follow-up. SNP rs292449 was significantly associated with hypertension incidence over the 14-year follow-up. Finally, this gene-based analysis found that NEDD4L was significantly associated with longitudinal BP changes and the incidence of hypertension over the 14-year follow-up. This study indicated that gene polymorphism in NEDD4L serve an important function in salt sensitivity, longitudinal BP change and development of hypertension in the Chinese population.
An 8-week feeding trial was conducted to evaluate the effects of dietary fermented rapeseed meal (FRM), potassium iodide, and their interactions on growth performance, approximate composition, and antioxidant capacity in tilapia, Oreochromis niloticus (initial body weight: 3.50 ± 0.15 g). Six isonitrogenous and isolipidic diets from a 2 × 3 factorial design were formulated with two levels of FRM (25.8 and 51.6%) and three levels of potassium iodide (0, 6, and 12 mg/kg), respectively. The results indicated that dietary levels of FRM and iodine had no significant influence on the SR of tilapia but exerted significant effects on weight gain (WG), specific growth rate (SGR), feed intake (FI), hepatosomatic index, and viscerosomatic index. The WG, SGR, and FI of tilapia in the 51.6% FRM groups were significantly lower than those in other groups (p < 0.05), and iodine inclusion in the 51.6% FRM diet significantly enhanced WG, SGR, and FI of tilapia (p < 0.05). Dietary iodine significantly increased the whole-body and muscle lipid content in the tilapia (p < 0.05). The content of total bilirubin (T-Bil) and the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the tilapia serum were significantly reduced by the inclusion of 6–12 mg/kg iodine in 51.6% FRM level (p < 0.05), and the serum total triiodothyronine content was significantly elevated by the supplementation of 12 mg/kg iodine (p < 0.05). Significant interactions between dietary FRM and iodine were found in serum T-Bil content and triglyceride and AST activity (p < 0.05). Dietary supplementation of iodine in high FRM diets (51.6%) significantly increased the activities of total superoxide dismutase (T-SOD), catalase (CAT), and total antioxidant capacity (T-AOC) and decreased the content of malondialdehyde (MDA) in the liver of tilapia (p < 0.05). The activity of T-SOD, CAT, and T-AOC and the content of MDA in the liver of tilapia significantly interacted with the levels of dietary FRM and iodine (p < 0.05). Furthermore, the liver cell structure was further ameliorated, and the liver health status was significantly enhanced in each iodine treatment group.
This experiment was conducted to determine the effect of dietary paeonol levels on growth performance, serum biochemical parameters, antioxidant enzyme activities and transcriptional expression of antioxidant- and immune-related genes in Genetic Improvement of Farmed Tilapia (GIFT) juveniles. Six diets supplemented with 0, 60, 120, 240, 480 and 960 mg kg−1 paeonol were formulated, and each diet was randomly assigned to three replicate groups of 25 fish with an average initial weight of 23.10 ± 0.90 g for 53 days. Our results showed that weight gain (WG) increased first and then decreased with the increase of dietary paeonol levels. Serum alkaline phosphatase (ALP), albumin (ALB) and total protein (TP) were significantly increased as the increasing dietary paeonol levels. Lactate dehydrogenase (LDH) contents, alanine aminotransferase (ALT) and aspartate transaminase (AST) activities displayed a trend of decreasing or significantly decreasing in the paeonol-added groups. Supplemental paeonol in diets significantly elevated the activities of catalase (CAT), glutathione peroxidase (GPx) and Lysozymes (LYZ) in both serum and liver, while decreased the malondialdehyde (MDA) values. Furthermore, the levels of dietary paeonol had significant effects on the mRNA expression of antioxidant genes (including CAT, GPx, Maf, HMOX1) and immune genes (including irak1, IL-8, CC1, LYZ). These data suggested that dietary paeonol could improve the growth performance and some serum biochemical indices of GIFT, enhanced the antioxidant enzyme activities, and induced the expression of antioxidant- and immune-related genes. Analysis based on broken-line regression, 90.55 mg kg−1 paeonol would be suitable for tilapia juveniles.
Renalase, a novel secretory flavoprotein with amine oxidase activity, is secreted into the blood by the kidneys and is hypothesized to participate in blood pressure (BP) regulation. We investigated the associations of renalase with BP and the risk of hypertension by examining renalase single nucleopeptide polymorphism (SNPs), serum renalase levels, and renal expression of renalase in humans.① Subjects (n = 514) from the original Baoji Salt-Sensitive Study cohort were genotyped to investigate the association of renalase SNPs with longitudinal BP changes and the risk of hypertension during 14 years of follow-up. ② Two thousand three hundred and ninety two participants from the Hanzhong Adolescent Hypertension Study cohort were used to examine the association of serum renalase levels with hypertension. Renalase expression in renal biopsy specimens from 193 patients were measured by immunohistochemistry. ③ Renalase expression was compared in hypertensive vs. normotensive patients.① SNP rs7922058 was associated with 14-year change in systolic BP, and rs10887800, rs796945, rs1935582, rs2296545, and rs2576178 were significantly associated with 14-year change in diastolic BP while rs1935582 and rs2576178 were associated with mean arterial pressure change over 14 years. In addition, SNPs rs796945, rs1935582, and rs2576178 were significantly associated with hypertension incidence. Gene-based analysis found that renalase gene was significantly associated with hypertension incidence over 14-year follow-up after adjustment for multiple measurements. ② Hypertensive subjects had higher serum renalase levels than normotensive subjects (27.2 ± 0.4 vs. 25.1 ± 0.2 μg/mL). Serum renalase levels and BPs showed a linear correlation. In addition, serum renalase was significantly associated with the risk of hypertension [OR = 1.018 (1.006-1.030)]. ③ The expression of renalase in human renal biopsy specimens significantly decreased in hypertensive patients compared to non-hypertensive patients (0.030 ± 0.001 vs. 0.038 ± 0.004).These findings indicate that renalase may play an important role in BP progression and development of hypertension.
Objective: Atherosclerotic diseases are the leading cause of death worldwide. This study aimed to investigate the predictors of brachial–ankle pulse wave velocity (baPWV) and carotid intima–media thickness (CIMT) progression in a Chinese cohort over a 12-year follow-up period and to determine whether these predictors differ by follow-up time. Methods: A total of 202 participants were recruited from a previously established cohort in Shaanxi Province, China. Both baPWV and CIMT were measured in 2013 and 2017. Multivariable regression was used to determine the predictors of CIMT and baPWV progression. Results: Men had higher CIMT and baPWV and a higher rate of CIMT progression during two follow-ups than women. A 4-year change in SBP was associated with baPWV progression, whereas a 12-year change in DBP was associated with baPWV progression. The increased progression of baPWV presented a linear trend when subgrouping all the participants according to SBP and DBP changes over 4 and 12 years, respectively. In addition, heart rate (HR) change over 4 and 12 years was consistently associated with CIMT progression, and a linear trend was also seen when subgrouping the population. Conclusion: Our study demonstrated that SBP and DBP contributed differently in different stages to the progression of arterial stiffness in this Chinese cohort. Moreover, HR was consistently involved in the increased progression of CIMT in all periods. These findings underline the importance of early detection and control of blood pressure and resting HR for the prevention of arterial stiffness progression.
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