Impact of shock index before IABP implantation on recent prognosis of patients with cardiogenic shock complicating acute myocardial infarction.

OBJECTIVE: To investigate the impact of shock index before Intra-Aortic Balloon Pump (IABP) implantation on recent prognosis of patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI) underwent primary percutaneous coronary intervention (PCI). METHODS: A total of 103 patients with CS complicating AMI admitted in our hospital from June 2014 to May 2019 who underwent primary PCI with IABP support were enrolled in the study. We collected the data according to the medical records and collected their clinical manifestation and laboratory examination, as well as 28-day mortality, and also calculated the shock index (ratio of heart rate to systolic blood pressure) before IABP implantation. RESULTS: Patients with higher SI at IABP insertion were associated with higher proportion of anterior infarction (81.5% vs. 61.2%, p = 0.022), previous history of PCI (24.1% vs. 8.16%, p = 0.030), culprit leision at left main (31.5% vs. 12.2%, p = 0.019), and final TIMI flow ≤ 2(55.5% vs. 26.5%, p = 0.003), invasive ventilation(40.7% vs. 20.4%, p = 0.026) as well as 28-day-mortality (81.5% vs. 61.2%, p = 0.022). SI at insertion may help predict recent outcome, with a cutoff value of 1.625, a sensitivity of 0.655 and a specificity of 0.708, and areas under the receiver-operating characteristic curve (AUCROC) was 0.713. On multiple analysis, SI, together with final TIMI flow, arterial pH and creatinine were independent predictive factors of recent prognosis among this population. CONCLUSION: Among CS patients complicating AMI undergoing PCI with the support of IABP, higher SI before IABP implantation was associated with poorer prognosis, SI was an independent risk factor of 28-day mortality and may predict the 28-day outcome.

Prevalence and patient characteristics of familial hypercholesterolemia in a Chinese population aged 35-75 years: Results from China PEACE Million Persons Project.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a genetic disorder with a high burden of arteriosclerotic cardiovascular disease. The prevalence of heterozygous FH is currently 0.2%-0.5% in Europe, while no such data has yet been published about the general population in China. We aimed to investigate the prevalence and characteristics of FH in a Chinese population aged 35-75 years. METHODS: We used a nationwide general population from 31 provinces in mainland China (n = 1,059,936, age 35-75) based on the China PEACE (Patient-centered Evaluative Assessment of Cardiac Events) MPP (Million Persons Project). The diagnosis of FH was based on 2 (untreated LDL-C ≥4.7 mmol/L and first-degree relatives with premature ASCVD history) of the 3 diagnostic criteria from the Chinese expert consensus on diagnosis of FH (CEFH criteria). FH prevalence was estimated and clinical phenotypic characteristics were further analyzed. RESULTS: The overall FH prevalence was 0.13% (95% confidence interval [CI], 0.12-0.14) by the CEFH criteria, and age and sex standardized FH prevalence was slightly lower (0.11%; 95%CI, 0.10-0.12). FH prevalence in female was twice as high as in male (0.16% vs. 0.08%, p < 0.001). Across different age groups, the prevalence also varied and peaked among 55-to 64-year-olds. Regarding geographical areas, the prevalence ranged from 0.19% in Eastern, to 0.11% in Central, and 0.08% in Western China (p < 0.001). Participants living in rural areas had a lower prevalence than urban participants (0.10% vs. 0.18%, p < 0.001). The rate of coronary artery disease in FH patients was 5 folds higher than in the general population (10.5% vs. 2.1%, p < 0.001). The rate of FH patients receiving lipid-lowering medications was 18.1%. None of the treated patients achieved guideline recommended LDL-C targets. CONCLUSIONS: The prevalence of FH in the Chinese population aged 35-75 years was 0.13% (about 1 in 769) defined by 2 of the CEFH criteria, and the patients were seriously undertreated and under-controlled. The screened FH prevalence varied by age, sex, geographical distributions, and urban/rural areas.

Effects of Doxorubicin on Heme Biosynthesis and Metabolism in Cardiomyocyte. / Os Efeitos da Doxorrubicina na Biossíntese e no Metabolismo do Heme em Cardiomiócitos.

BACKGROUND: Doxorubicin is associated with cardiotoxicity and late cardiac morbidity. Heme is related to cellular oxidative stress. However, its specific regulation in cardiomyocytes under doxorubicin effects has not yet been documented. OBJECTIVE: This study seeks to evaluate the changing profiles of rate-limiting enzymes in the heme metabolism pathway under the effect of doxorubicin. METHODS: H9c2 cardiomyocytes were incubated with doxorubicin at different concentrations (1,2,5,10µM respectively). The real-time PCR and Western Blot were used to determine the mRNA and protein expression for four pivotal enzymes (ALAS1, ALAS2, HOX-1, and HOX-2) regulating cellular heme metabolism, as well as the levels of heme were detected by ELISA. p<0.01 was considered significant. RESULTS: This study observed a dose-dependent changing pattern in heme levels in H9c2 cells with the highest level at the 5µM concentration for doxorubicin, which occurred synchronously with the highest upregulation level of ALAS1, as well as the degradative enzymes, HOX-1, and HOX-2 in mRNA and protein expression. By contrast, ALAS2, contrary to the increasing concentrations of doxorubicin, was found to be progressively down-regulated. CONCLUSION: The increase in ALAS1 expression may play a potential role in the heme level elevation when H9c2 cardiomyocyte was exposed to doxorubicin and may be a potential therapeutic target for doxorubicin-induced myocardial toxicity. (Arq Bras Cardiol. 2021; 116(2):315-322).

FUNDAMENTO: A doxorrubicina está associada à cardiotoxicidade e à morbidade cardíaca tardia. O heme está relacionado ao stress oxidativo celular. Entretanto, sua regulação específica em cardiomiócitos sob os efeitos de doxorrubicina ainda não foi documentada. OBJETIVO: Nosso objetivo é avaliar as alterações de enzimas limitantes de velocidade no caminho metabólico do heme sob o efeito de doxorrubicina. MÉTODOS: Cardiomiócitos H9c2 com doxorrubicina em concentrações diferentes (1, 2, 5, 10µM respectivamente). Os testes de PCR em tempo real e Western Blot foram usados para determinar a expressão de proteína e mRNA para quatro enzimas cruciais (ALAS1, ALAS2, HOX-1, e HOX-2) que regulam o metabolismo do heme celular, e os níveis de heme foram detectados por ELISA. Um p<0,01 foi considerado significativo. RESULTADOS: Observamos um padrão com alteração dependendo da dose nos níveis de heme nas células H9c2 com o nível mais alto na concentração de 5µM de doxorrubicina, o que ocorreu sincronicamente com o nível mais alto de regulação para cima de ALAS1, bem como as enzimas degenerativas HOX-1 e HOX-2 na expressão de proteína e mRNA. Em contraste, observamos que a ALAS2 foi regulada para baixo gradualmente, inversamente proporcional às concentrações de doxorrubicina. CONCLUSÃO: O aumento da expressão de ALAS1 pode ter um papel na elevação do nível do heme quando o cardiomiócito H9c2 for exposto à doxorrubicina, e pode ser um alvo terapêutico para a toxicidade miocárdica induzida por doxorrubicina. (Arq Bras Cardiol. 2021; 116(2):315-322).

Os Efeitos da Doxorrubicina na Biossíntese e no Metabolismo do Heme em Cardiomiócitos / Effects of Doxorubicin on Heme Biosynthesis and Metabolism in Cardiomyocyte

Resumo Fundamento A doxorrubicina está associada à cardiotoxicidade e à morbidade cardíaca tardia. O heme está relacionado ao stress oxidativo celular. Entretanto, sua regulação específica em cardiomiócitos sob os efeitos de doxorrubicina ainda não foi documentada. Objetivo Nosso objetivo é avaliar as alterações de enzimas limitantes de velocidade no caminho metabólico do heme sob o efeito de doxorrubicina. Métodos Cardiomiócitos H9c2 com doxorrubicina em concentrações diferentes (1, 2, 5, 10μM respectivamente). Os testes de PCR em tempo real e Western Blot foram usados para determinar a expressão de proteína e mRNA para quatro enzimas cruciais (ALAS1, ALAS2, HOX-1, e HOX-2) que regulam o metabolismo do heme celular, e os níveis de heme foram detectados por ELISA. Um p<0,01 foi considerado significativo. Resultados Observamos um padrão com alteração dependendo da dose nos níveis de heme nas células H9c2 com o nível mais alto na concentração de 5μM de doxorrubicina, o que ocorreu sincronicamente com o nível mais alto de regulação para cima de ALAS1, bem como as enzimas degenerativas HOX-1 e HOX-2 na expressão de proteína e mRNA. Em contraste, observamos que a ALAS2 foi regulada para baixo gradualmente, inversamente proporcional às concentrações de doxorrubicina. Conclusão O aumento da expressão de ALAS1 pode ter um papel na elevação do nível do heme quando o cardiomiócito H9c2 for exposto à doxorrubicina, e pode ser um alvo terapêutico para a toxicidade miocárdica induzida por doxorrubicina. (Arq Bras Cardiol. 2021; 116(2):315-322)

Abstract Background Doxorubicin is associated with cardiotoxicity and late cardiac morbidity. Heme is related to cellular oxidative stress. However, its specific regulation in cardiomyocytes under doxorubicin effects has not yet been documented. Objective This study seeks to evaluate the changing profiles of rate-limiting enzymes in the heme metabolism pathway under the effect of doxorubicin. Methods H9c2 cardiomyocytes were incubated with doxorubicin at different concentrations (1,2,5,10μM respectively). The real-time PCR and Western Blot were used to determine the mRNA and protein expression for four pivotal enzymes (ALAS1, ALAS2, HOX-1, and HOX-2) regulating cellular heme metabolism, as well as the levels of heme were detected by ELISA. p<0.01 was considered significant. Results This study observed a dose-dependent changing pattern in heme levels in H9c2 cells with the highest level at the 5μM concentration for doxorubicin, which occurred synchronously with the highest upregulation level of ALAS1, as well as the degradative enzymes, HOX-1, and HOX-2 in mRNA and protein expression. By contrast, ALAS2, contrary to the increasing concentrations of doxorubicin, was found to be progressively down-regulated. Conclusion The increase in ALAS1 expression may play a potential role in the heme level elevation when H9c2 cardiomyocyte was exposed to doxorubicin and may be a potential therapeutic target for doxorubicin-induced myocardial toxicity. (Arq Bras Cardiol. 2021; 116(2):315-322)