Long-term association of remnant cholesterol with all-cause and cardiovascular disease mortality: a nationally representative cohort study.

Background and objectives: Despite reducing low-density lipoprotein cholesterol (LDL-C) to the normal range, residual cardiovascular risk remain. Remnant cholesterol (RC) exerts a potential residual risk for cardiovascular disease (CVD) prevention, and the long-term longitudinal association between RC and mortality has yet to be well elucidated. Methods: This study examined a nationally representative sample of 13,383 adults aged 20 years or older (mean age 45.7 and 52% women) who participated in the NHANES III (from1988 to1994). Causes of death were ascertained by linkage to death records through December 31, 2019. The relations of RC with all-cause and CVD mortality were tested using weighted Cox proportional hazard models. Results: Through a median follow-up of 26.6 years, 5,044 deaths were reported, comprising 1,741 deaths of CVD [1,409 deaths of ischemic heart disease (IHD) and 332 deaths of stroke] and 1,126 of cancer. Compared to those with RC <14.26 mg/dl (lowest quartile), participants with RC ≥29.80 mg/dl (highest quartile) had multivariable-adjusted HRs of 1.23 (95% CI: 1.07-1.42) for all-cause mortality, 1.22 (95% CI: 0.97-1.53) for CVD mortality, and 1.32 (95% CI: 1.03-1.69) for IHD mortality, and 0.89 (95% CI: 0.55-1.43) for stroke mortality, and 1.17 (95% CI 0.90-1.52) for cancer mortality. We observed that elevated RC levels increased CVD risk and IHD mortality despite LDL-C being in the normal range. Conclusions: Elevated blood RC was associated with an increased long-term risk of all-cause, CVD, and IHD mortality. These associations were independent of socioeconomic factors, lifestyles, and history of diseases, and remained robust across the LDL-C stratum. Measuring RC levels might favor clinical assessment of early CVD risk. Further investigation is needed to elucidate the optimal range of RC levels for cardiovascular disease health in the general population.

Clinical Trials in Hypertrophic Cardiomyopathy Therapy: A Comprehensive Analysis of Trials Registered in Global Clinical Databases.

Background: With the disappointing results associated with the use of cardiac myosin inhibitors in the treatment of hypertrophic cardiomyopathy (HCM), the development of new therapies in clinical trials for HCM has rapidly increased. We assessed the characteristics of therapeutic intervention in HCM registered on ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP). Methods: We conducted a cross-sectional, descriptive study of clinical trials for therapeutic intervention in HCM registered on ClinicalTrials.gov and ICTRP. Results: This study analyzed 137 registered trials. Regarding study designs of these trials, 77.37% were purpose of treatment, 59.12% were randomized, 50.36% were parallel assignment, 45.26% were performed with masking, 48.18% recruited less than 50 participants, and 27.74% were Phase 2 trials. In total, 67 trials were new drug trials, of which 35 drugs were tested in these trials, and 13 trials involved treatment with mavacamten. Of these 67 clinical drug trials, 44.78% of trials involved the study of amines, and 16.42% involved 1-ring heterocyclic compounds. Regarding the NCI Thesaurus Tree, 23.81% of trials involved myosin inhibitors, 23.81% of trials involved drugs belonging to agents affecting the cardiovascular system, and 20.63% were involved in testing cation channel blockers. The drug-target network showed that myosin-7, potassium voltage-gated channel subfamily h member 2, beta-1 adrenergic receptor, carnitine o-palmitoyltransferase 1, and liver isoform were the most targeted pathways of the clinical trials analyzed in the drug-target network. Conclusion: The number of clinical trials investigating therapeutic interventions for HCM has increased in recent years. Ultimately, recent HCM therapeutic clinical trials generally did not incorporate either randomized controlled trials or masking and were small studies recruiting fewer than 50 participants. Although recent research has focused on targeting myosin-7, the molecular signaling mechanisms involved in the pathogenesis of HCM have the potential to elucidate novel target pathways.

Association of nocturia with cardiovascular and all-cause mortality: a prospective cohort study with up to 31 years of follow-up.

Background: Nocturia is a highly prevalent and under-considered condition and impacts the quality of life for many individuals. The long-term impact of nocturnal voiding on mortality, especially mortality from cardiovascular disease, remains unknown. The current study aimed to evaluate the relationship of nocturnal voiding episodes with cardiovascular and all-cause mortality among adults in the United States. Methods: This is a prospective cohort study of a nationally representative sample of 13,862 U.S. adults aged 20 years or older who participated in the National Health and Nutrition Examination Survey III (1988-1994). Nighttime urination frequency was reported during an in-house interview. All-cause and cause-specific mortality were ascertained by linking to National Death Index mortality data through December 31, 2019. The associations of nocturia with cardiovascular and all-cause mortality were estimated using weighted Cox proportional hazards regression models. Results: Throughout a median follow-up of 26.7 years, 5,029 deaths were reported, comprising 1,720 deaths from cardiovascular disease. In the fully adjusted model, participants who reported once, twice, and three or more times nocturnal voiding episodes have a higher risk of cardiovascular mortality (HR1, 1.22 [95% CI, 0.997-1.49], HR2, 1.47 [95% CI, 1.13-1.91], and HR ≥ 3, 1.96 [95% CI, 1.52-2.53]) as well as all-cause mortality (HR1, 1.12 [95% CI, 0.90-1.39], HR2, 1.54 [95% CI, 1.23-1.93], and HR ≥ 3, 2.48 [95% CI, 1.81-3.40]), compared to those without nocturia, and heart disease-specific mortality (HR1, 1.33 [95% CI, 1.08-1.64], HR2, 1.62 [95% CI, 1.25-2.10], and HR≥3, 2.07 [95% CI, 1.61-2.67]). Nevertheless, there was no significant relationship between the number of nocturia episode changes and stroke-specific mortality. Conclusion: Nocturia was associated with a significantly augmented risk of overall and heart disease-specific mortality in a dosage-dependent manner. Early recognition and taking precautions may benefit individuals with nocturia by promoting quality of life and cardiac health.

Detection of quantitative trait loci affecting haematological traits in swine via genome scanning.

BACKGROUND: Haematological traits, which consist of mainly three components: leukocyte traits, erythrocyte traits and platelet traits, play extremely important role in animal immune function and disease resistance. But knowledge of the genetic background controlling variability of these traits is very limited, especially in swine. RESULTS: In the present study, 18 haematological traits (7 leukocyte traits, 7 erythrocyte traits and 4 platelet traits) were measured in a pig resource population consisting of 368 purebred piglets of three breeds (Landrace, Large White and Songliao Black Pig), after inoculation with the swine fever vaccine when the pigs were 21 days old. A whole-genome scan of QTL for these traits was performed using 206 microsatellite markers covering all 18 autosomes and the X chromosome. Using variance component analysis based on a linear mixed model and the false discovery rate (FDR) test, 35 QTL with FDR < 0.10 were identified: 3 for the leukocyte traits, 28 for the erythrocyte traits, and 4 for the platelet traits. Of the 35 QTL, 25 were significant at FDR < 0.05 level, including 9 significant at FDR < 0.01 level. CONCLUSIONS: Very few QTL were previously identified for hematological traits of pigs and never in purebred populations. Most of the QTL detected here, in particular the QTL for the platelet traits, have not been reported before. Our results lay important foundation for identifying the causal genes underlying the hematological trait variations in pigs.