2022年 · 第02卷第01期

The 2021 Nobel Prize in Physiology or Medicine was awarded to David Julius for his discovery of capsaicin receptors in 1997.^[1]The capsaicin receptor is also called transient receptor potential vanilloid subfamily member 1 (TRPV1) and belongs to the transient receptor potential channels family. TRPV1 possesses a tetrameric structure consisting of 6 transmembrane regions, a pore-shaped region between the fifth (S5) and sixth transmembrane regions (S6), a cytoplasmic amino group, and a carboxyl terminus, which is selectively permeable for cations such as H⁺, Na⁺, and Ca²⁺.^[1]TRPV1 can be activated by nociceptive thermal stimulation (temperature > 43°C), pH values less than 5.96, and capsaicin, a pungent component of chili peppers, and other factors including free oxygen radicals, 12-lipoxygenase, 20-hydroxyeicosatetraenoic acid, etc. Activation of TRPV1-induced neuronal depolarization transmitted to the central nervous system creates thermal and pain sensations.^[2]In addition, activation of TRPV1 can also promote the release of calcitonin gene-related peptide (CGRP), substance P (SP), and other neurotransmitters.^[3,4]The discovery of TRPV1 has increased our understanding of how temperature triggers nerve impulses, because our ability to perceive ambient temperature is essential for survival and the basis of our interaction with the world around us. This perspective focuses on the actions of TRPV1 in the regulation of cardiometabolic function and beneficial effects of spicy food on the prevention of cardiometabolic diseases.

This study aimed to examine the associations of waist circumference with hypertension and cardiometabolic dysregulation among normal-weight adults.

This cross-sectional study included 8795 normal-weight participants aged 20 to 79 years from the 2009-2018 US National Health and Nutrition Examination Survey. The demographic characteristics and cardiometabolic risk factors across waist circumference quartiles were summarized. We used adjusted multivariate logistic regression models, subgroup analysis, and restricted cubic spline to analyze the association between waist circumference and the prevalence of hypertension. Thereafter, we used the random forest supervised machine learning method, together with least absolute shrinkage and selection operator regression, to select hypertension-related features and created a predictive model based on regression analysis to identify hypertension in normal-weight individuals.

Waist circumference was positively correlated with hypertension in the non-adjusted, minimally adjusted, and fully adjusted models, with odds ratios (95% confidence interval) of 2.28 (2.14-2.44), 1.27 (1.12-1.44), and 1.27 (1.12-1.44), respectively. In the fully adjusted model, participants in the highest waist circumference quartile had a higher risk of hypertension relative to those in the lowest quartile, with an odds ratio (95% confidence interval) of 3.87 (1.59-10.34). Sensitivity analysis demonstrated the robustness of the association. In the testing set, the predictive model exhibited good performance, with an area under the curve of 0.803, sensitivity of 0.72, specificity of 0.76, and negative predictive value of 0.84.

Measuring waist circumference may improve the evaluation of the risk of hypertension and help to manage cardiometabolic risk in normal-weight individuals.

Long-term diabetes can result in ventricular hypertrophic remodeling, tissue fibrosis, myocardial metabolic defection, and eventually, heart failure. Silent information regulator 6 (SIRT6) exerts beneficial effects against cardiovascular diseases. This study is aimed to investigate whether the direct regulation of myocardial SIRT6 signaling affects cardiac performance in the case of diabetes. Meanwhile, we sought to explore the underlying mechanisms.

Sprague Dawley (SD) rats were used in this experiment. Briefly, type 2 diabetic animal model was generated by streptozotocin administration along with feeding a high-fat diet. The SD rats were randomly assigned to non-diabetic group, diabetic group, diabetic injected with empty adenoviral vectors group and diabetic injected with adenoviral vectors expressing SIRT6 group (n = 10, respectively). The animals were kept for another 4 weeks before sacrifice. Cardiac performance was evaluated by echocardiography. Myocardial fibrosis was determined by Masson’s trichrome staining. Myocardial SIRT6 signaling and fibrosis related molecules were measured by western blotting.

The diabetic myocardium exhibited markedly enhanced TGFβ1-Smad2/3-induced myocardial fibrosis and reduced SIRT6 and AMP-activated protein kinase (AMPK) signaling. After 4 weeks of SIRT6 adenoviral vector infection, myocardial tissues exhibited markedly enhanced SIRT6 and AMPK signaling. Additionally, myocardial fibrosis and TGFβ1 -Smad2/3 signaling were both attenuated in the diabetic injected with adenoviral vectors expressing SIRT6 group.

SIRT6-AMPK signaling suppressed the progression of tissue fibrosis in diabetes mellitus rats by inhibiting TGFβ1 and its downstream effector Smad2/3. SIRT6 might serve as an alternative therapeutic target for diabetes-related cardiovascular diseases.

Fish oil (FO) contains omega-3 that inhibits inflammation and blood lipid metabolism, giving it a protective cardiovascular effect. Due to dietary habits, a majority of large-scale clinical trials examining FO and cardiovascular health have been conducted in the Caucasian populations. However, the effects of FO on cardiovascular inflammation indicators and blood lipid metabolism in the Chinese population remain unclear. This study aimed to perform a meta-analysis to elucidate the impact of FO on cardiovascular health in the Chinese population.

Web searches were utilized to locate records of clinical trials related to cardiovascular health and consumption of FO capsules or fish containing omega-3 in several databases, including PubMed, Medline, Embase, Cochrane Library, CNKI, and ClinicalTrial.gov, etc. We obtained lipid metabolism and related proinflammatory markers as the study outcome. We used Review Manager 5.4 and Stata 16 for the statistical analysis. If the I² ≥ 30%, a random effects model was used, and if the I² < 30%, a fixed effects model was used.

Twenty eligible trials were shortlisted from >1000 records. The meta-analysis revealed that supplementation with eicosapentaenoic acid and docosahexaenoic acid reduced systolic blood pressure by 1.88 mmHg (95% CI: -4.97 to -1.20, P = 0.23), diastolic blood pressure by 0.86 mmHg (95% CI: -1.79 to 0.06, P = 0.07), fasting blood glucose by 0.05 mmol/L (95% CI: -0.16 to 0.06, P = 0.40), and low-density lipoprotein-cholesterol by 0.12 mmol/L (95% CI: -0.23 to -0.01, P = 0.04), when compared to placebo. However, these supplements increased high-density lipoprotein-cholesterol by 0.03 mmol/L (95% CI: 0.01 to 0.05, P < 0.001), when compared to placebo. Dose subgroup analyses examining total cholesterol found that the low-dose group (mean difference = -0.44, 95% CI: -0.55 to -0.34, P < 0.001) demonstrated the best results. Further, results from dose subgroup analyses showed that the all-dose group demonstrated a decrease in tumor necrosis factor (TNF-α) levels among the study subjects, when compared to other groups.

Consumption of FO containing omega-3 fatty acids in the Chinese population can improve lipid metabolism and reduce levels of proinflammatory markers. Therefore, it is necessary to vigorously promote the benefits of consuming FO to prevent cardiovascular diseases throughout China.

Diverse antithrombotic strategies were applied to patients undergoing aortic valve replacement. However, the optimal therapeutic regimen for patients undergoing transcatheter aortic valve implantation/replacement (TAVI/TAVR) remains unclear. The purpose of this study was to compare the efficacy and safety of various antithrombotic therapies following TAVI/TAVR.

Relevant clinical trials evaluating the effect of anticoagulation or antiplatelet regimens on patients after TAVI/TAVR from inception to September 2020 were identified using the PubMed, EMBASE, and the Cochrane Library databases. The inclusion criteria including (1) all patients underwent TAVI/TAVR; (2) the interventions were antithrombotic strategies that prevent the occurrence of thrombotic events in patients; (3) randomized controlled trials or prospective observational studies; and (4) investigation of at least 1 outcome with a follow-up period of ≥3 months. The exclusion criteria including (1) research content was identical or irrelevant to the purpose of the present study; (2) lack of the required outcome index or availability of fragmentary original information; and (3) the full text is not available. The major outcomes were all-cause mortality, thromboembolic complications, and bleeding events. The Cochrane Collaboration’s tool and the Newcastle-Ottawa Scale were used for assessing the risk of bias in included studies.

Thirteen studies (3 randomized controlled trials and 10 non-randomized studies) were identified, with a total of 23,497 patients. Four studies compared direct oral anticoagulants (DOACs) with warfarin, 1 study compared aspirin with warfarin, 6 studies compared aspirin plus clopidogrel (dual antiplatelet therapy (DAPT)) with aspirin monotherapy, and 2 studies compared DAPT and aspirin monotherapy with warfarin concurrently. There were no significant differences found between the DOAC and warfarin groups regarding all-cause mortality (risk ratio (RR): 1.03; 95% confidence interval (CI): 0.65-1.64; P = 0.909; P_het = 0.105), clinical adverse events (RR: 1.59; 95% CI: 0.99-2.58; P = 0.057; P_het = 0.738), or bleeding events (RR: 0.93; 95% CI: 0.78-1.11; P = 0.437; P_het = 0.338). The rates of all-cause mortality (RR: 0.71; 95% CI: 0.54-0.93; P = 0.012; P_het = 0.845) and bleeding events (RR: 0.43; 95% CI: 0.22-0.83; P = 0.012; P_het = 0.569) were lower in the aspirin group versus the warfarin group; however, there was no difference in the rate of clinical adverse events (RR: 0.38; 95% CI: 0.14-1.07; P = 0.068; P_het = 0.593). The DAPT group had an advantage versus the aspirin group in all-cause mortality (RR: 0.89; 95% CI: 0.82-0.98; P = 0.013; P_het = 0.299); however, the incidence of bleeding events (RR: 2.06; 95% CI: 1.39-3.07; P < 0.001; P_het = 0.001) exhibited an increasing trend. Notably, there was a slight decrease in the incidence of clinical adverse events (RR: 1.09; 95% CI: 0.94-1.26; P = 0.268; P_het = 0.554).

The present meta-analysis integrates the latest published results on antithrombotic strategies in patients after TAVI/TAVR. Aspirin showed a favorable risk-benefit profile versus warfarin, with lower rates of all-cause mortality and bleeding events. Although DAPT was also associated with a significantly lower rate of all-cause mortality, it was linked to a higher incidence of bleeding events. The DOACs did not show significant benefits compared with warfarin. Some certain limitations should be noted, such as different types of trails produce heterogeneity and finite inclusion of TAVI/TAVR patients increased selection bias.