Journal of Cardiovascular Pharmacology最新文献

Abstract: Imipramine was one of the first antidepressant drugs that entered the clinic and is still used to this day. The antidepressant action of imipramine is, at least in part, because of an inhibition of noradrenaline and serotonin transport in the brain. Binding studies indicated that imipramine binds to H 1 -histamine receptors with high affinity. We have recently generated mice that overexpress the human H 1 -histamine receptor in the heart (H 1 -TG). On stimulation of these hearts with H 1 -histamine receptor agonists, a positive inotropic effect was observed which was reversed by mepyramine, a selective H 1 -histamine receptor antagonist. Moreover, we have recently described that stimulation of H 1 -histamine receptors in the human atrium also increases force of contraction which was similarly reversed by mepyramine. Consequently, we investigated whether these H 1 -histamine receptor-mediated increases of force in atria from H 1 -TG and human atrium could be reversed by imipramine. We stimulated H 1 -histamine receptors in atria from H 1 -TG and noted that imipramine, starting at 100 nM, reduced force of contraction. To study imipramine in the human heart, we obtained human right atrial muscle preparations from adult patients succumbing to cardiac bypass surgery. Such as in H 1 -TG, imipramine, starting at 300 nM, antagonized the positive inotropic effects of H 1 -histamine receptor stimulation in human atrial preparations. We conclude that imipramine can antagonize H 1 -histamine receptor mediated positive inotropic effects in the mammalian atrium in general and, of note, in the human atrium. This may explain cardiac side effects of imipramine.

Abstract: Elevated lipoprotein(a) [Lp(a)] is a known risk factor for cardiovascular disease and may accelerate chronic kidney disease (CKD) progression. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated renal protective effects, but their role in patients with concomitantly elevated Lp(a) remains unclear. We conducted a retrospective cohort study using the TriNetX network. Adults (≥18 years) with CKD and Lp(a) ≥50 mg/dL were included. Patients on SGLT2 inhibitors were propensity score-matched 1:1 to those not on therapy (n = 2813 each). Outcomes included CKD progression and cardiovascular events at 1-year, 3-year, and 5-year follow-up. Risk ratios, hazard ratios, and 95% confidence intervals were calculated. SGLT2 inhibitor use was associated with reduced CKD progression at 3 and 5 years and a higher likelihood of achieving Lp(a) normalization. At 5 years, the risks of ischemic stroke and peripheral artery disease were also lower in the SGLT2 cohort. No significant differences were observed for myocardial infarction at earlier follow-up, whereas composite outcomes were reduced at longer follow-up. In patients with CKD and elevated Lp(a), SGLT2 inhibitors were associated with slower CKD progression and a greater likelihood of achieving Lp(a) normalization over 5 years, suggesting a potential benefit in this high-risk population.

Abstract: Highly protein-bound anticoagulants such as warfarin and rivaroxaban have increased therapeutic effects in the setting of hypoalbuminemia due to increased free concentrations in the drug which result in increased bleed risk. Apixaban is also heavily protein bound at 87% but bleeding in hypoalbuminemic patients receiving apixaban has largely been unevaluated. Therefore, this retrospective, cohort study of hospitalized adults who received apixaban and had a serum albumin level measured was conducted. Included patients were evaluated for bleeding events in accordance with International Society on Thrombosis and Hemostasis criteria. Patients were grouped by bleeding status (bleed vs. nonbleed) and multivariable logistic regression modeling was used to evaluate the relationship between albumin, covariables, and bleeding events. A total of 391 patients were included, 49 who bled and 342 who did not. Multivariable modeling determined a significant association between bleeding events and serum albumin level (adjusted odds ratio [OR] 2.10 for every 1 g/dL reduction in serum albumin, 95% confidence interval [CI]: 1.26-3.60), high-risk IMPROVE Bleeding scores (adjusted OR 2.17, CI: 1.127-4.181), and active gastroduodenal ulcer (adjusted OR 5.20, CI: 1.11-24.39). Consideration of serum albumin levels may be relevant when treating patients with highly protein-bound anticoagulants such as apixaban.

Abstract: Diabetes mellitus is an emerging global health concern, with its prevalence rising at an alarming rate. Cardiovascular complications are significantly more pronounced in diabetic individuals, underscoring the urgent need for effective therapeutic interventions. Significant efforts and investments have been dedicated to developing pharmacological treatments for diabetes. While each therapy offers its own advantages and disadvantages, their effectiveness in slowing disease progression remains limited. By contrast, exercise has gained recognition as a potent therapeutic strategy for diabetes and its complications, exerting metabolic and cardioprotective effects through various physiological and molecular mechanisms. Engaging in regular physical activity reduces cellular stress and inflammation, inhibits cardiomyocyte apoptosis and myocardial fibrosis, and improves endothelial and mitochondrial function, thereby maintaining cardiomyocyte homeostasis. In addition, recent studies have investigated the potential synergistic effects of combining exercise with novel pharmacological agents, emphasizing its complementary role in managing diabetic heart failure. This review aimed to discuss the mechanistic pathways through which structured physical exercise alleviates diabetic cardiomyopathy with additional consideration of its synergistic effects when combined with antidiabetic pharmacotherapies.

To identify diuretic resistance (DR) in patients with congestive heart failure (CHF) during intensive care treatment by analyzing the diuretic effect (DE) and to investigate their clinical characteristics and prognosis. Data of 1,744 patients with CHF in the MIMIC-IV database were analyzed. The trajectory of DE was examined by group-based trajectory modeling and its relationship with the diuretic dose-response then evaluated. The area under the curve (AUC) was used to assess the characteristics of DE at different time points of DR. The association between DE, DR, and clinical outcomes was investigated using logistic and Cox regression with different covariate adjustment strategies. The final model identified four trajectories of DE, among which Class 1 patients were identified as having DR, defined as having a minimal diuretic response of 3.819 mL/mg (95% CI 3.223-4.414, p < 0.001) before peak dosing, and minimal changes in diuretic adjustments. The DE at different time points effectively distinguished DR, with AUC values of 0.966 (95% CI 0.959-0.973) and 0.979 (95% CI 0.973-0.985) and optimal cut-off values of 6.515 and 12.557 at 6 h and 24 h, respectively. The DR group had significantly higher rates of in-hospital mortality (20.08% vs. 8.92%, p < 0.001), all-cause re-admission (23.11% vs. 17.08%, p = 0.012), and one-year mortality (40.45% vs. 26.26%, p < 0.001) compared to those observed in the non-DR group. The method of constructing DE trajectory models offers an effective approach to identify DR and provides novel insights for analyzing its characteristics and prognostic implications.

Abstract: Mechanical heart valve replacement necessitates long-term warfarin anticoagulation to prevent thromboembolic complications, yet achieving adequate anticoagulation control remains challenging. This study evaluated whether mean platelet volume (MPV) could serve as a biomarker for anticoagulation quality in mechanical heart valve recipients. We conducted a retrospective longitudinal cohort analysis of 370 patients with mechanical heart valves receiving warfarin therapy. MPV and international normalized ratio (INR) were measured at 5 time points. Time in therapeutic range (TTR) was calculated using the Rosendaal method, with effective anticoagulation defined as TTR ≥60%. Correlations between MPV, INR, and TTR were analyzed overall and stratified by valve type. Only 34.1% of patients achieved effective TTR. Mean MPV was 10.31 ± 1.04 fL and mean INR was 2.79 ± 0.54. No significant correlation was identified between MPV and TTR. However, patients with mean INR ≤3.0 exhibited significantly higher MPV values than those with INR >3.0 (10.40 vs. 10.13 fL). Subgroup analysis revealed a significant inverse correlation between MPV and INR in patients with mitral valve replacement but not in patients with aortic valve replacement, with temporal variation across measurement periods. MPV showed poor discriminatory ability for predicting effective TTR. Multivariable regression identified atrial fibrillation, older age, higher platelet counts, and higher hemoglobin as independent predictors of effective TTR, while MPV showed no independent association. In conclusion, MPV does not serve as a reliable biomarker for anticoagulation quality in patients with mechanical heart valve. Enhanced anticoagulation management strategies are needed to improve TTR in this high-risk population.