Association of D-dimer with long-term prognosis in type 2 diabetes mellitus patients with acute coronary syndrome.

BACKGROUND AND AIMS: Type 2 diabetes mellitus (DM) accounts for more and more individuals worldwide. D-dimer has been demonstrated to be associated with cardiovascular diseases. The aim is to study the potential impact of D-dimer on the long-term prognosis of acute coronary syndrome (ACS) in the special population with type 2 DM. METHODS AND RESULTS: A total of 2265 consecutive patients with DM and ACS were eligible in the study. Patients were divided into four groups according to quartiles of D-dimer concentration. Univariate and multivariate Cox regression analysis were conducted to explore the prognostic value of D-dimer for future outcomes. Patients with higher level of D-dimer presented with higher percentage of major adverse cardiovascular events (MACEs) (23.7%), all-cause death (18.3%) and cardiovascular (CV) death (9.4%) in Quartile 4. In multivariate Cox regression analysis, D-dimer was demonstrated to be independently associated with MACEs, all-cause death and CV death. The prognostic value of D-dimer is still significant in subgroups of HbA1C <7% and ≥7%. In Kaplan-Meier analysis, higher D-dimer showed poorer prognosis in MACEs, all-cause death and CV death (all log rank p < 0.001). The area under the curve (AUC) by receiver operating characteristic (ROC) curve analysis is 0.609 for MACEs, 0.708 for all-cause death, 0.747 for CV death (p < 0.001). CONCLUSION: The present study demonstrated the independent predictive value of D-dimer for outcomes in DM patients with ACS. In addition, for the first time, we explored the prognostic value in different glucose control status.

Plasma Lipoprotein(a) Concentration Is Associated With the Coronary Severity but Not With Events in Stable Coronary Artery Disease Patients: A Chinese Cohort Study.

BACKGROUND: Although lipoprotein(a) (Lp(a)) has been regarded as an independent risk factor for atherosclerotic cardiovascular disease (ASCVD), its predictive role in outcomes in stable coronary artery disease (CAD) has been undetermined. The aim of the present study was to investigate the relations of Lp(a) to the coronary severity and events in Chinese patients with angiography-proven stable CAD. METHODS: A total of 3,278 patients with stable CAD were consecutively enrolled and the coronary severity was evaluated by the Gensini Score (GS) system. Patients were divided into two groups according to the median of GS: high GS group (n=1,585) and low GS group (n=1,693). The associations of continuous Lp(a), Lp(a) ≥300mg/L, and tertiles of Lp(a) with GS and events were respectively evaluated. RESULTS: Patients in the high GS group had significantly higher concentrations of Lp(a). In addition, the multivariate Cox regression analysis indicated that elevated Lp(a) (odds ratio: 1.164, 95% confidence interval: 1.005-1.349), Lp(a) ≥300mg/L (odds ratio: 1.200, 95% confidence interval: 1.028-1.401), and the highest tertile of Lp(a) (odds ratio: 1.205, 95% confidence interval: 1.010-1.438) were statistically associated with GS after adjusted for potential confounders. However, although 215 (6.56%) events were established during a median of follow-up over 10,170 patient-years, no relationship between Lp(a) and events was found. CONCLUSIONS: In this Chinese cohort study on stable CAD with moderate sample size and follow-up duration, data showed that Lp(a) was significantly associated with the coronary severity while not with cardiovascular events, similar to several studies, suggesting that further study is needed regarding the role of Lp(a) in ASCVD.

Genetic basis of index patients with familial hypercholesterolemia in Chinese population: mutation spectrum and genotype-phenotype correlation.

BACKGROUND: Although there have been many reports in the genetics of familial hypercholesterolemia (FH) worldwide, studies in regard of Chinese population are lacking. In this multi-center study, we aim to characterize the genetic spectrum of FH in Chinese population, and examine the genotype-phenotype correlations in detail. METHODS: A total of 285 unrelated index cases from China with clinical FH were consecutively recruited. Next-generation sequencing and bioinformatics tools were used for mutation detection of LDLR, APOB and PCSK9 genes and genetic analysis. RESULTS: Overall, the detection rate is 51.9% (148/285) in the unrelated index cases with a total of 119 risk variants identified including 84 in the LDLR gene, 31 in APOB and 4 in PCSK9 gene. Twenty-eight variants were found in more than one individual and LDLR c.1448G > A (p. W483X) was most frequent one detected in 9 patients. Besides, we found 8 (7 LDLR and 1 APOB) novel variants referred as "pathogenic (or likely pathogenic) variants" according to in silico analysis. In the phenotype analysis, patients with LDLR null mutation had significantly higher LDL cholesterol level than LDLR defective and APOB/PCSK9 mutation carriers and those with no mutations (p < 0.001). Furthermore, 13 double heterozygotes, 16 compound heterozygotes and 5 true LDLR homozygotes were identified and the true LDLR homozygotes had the most severe phenotypes. CONCLUSIONS: The present study confirmed the heterogeneity of FH genetics in the largest Chinese cohort, which could replenish the knowledge of mutation spectrum and contribute to early screening and disease management.

Lipoprotein(a) level associates with coronary artery disease rather than carotid lesions in patients with familial hypercholesterolemia.

BACKGROUND: Lipoprotein(a) [Lp(a)] level is a novel risk factor for atherosclerotic cardiovascular disease in patients with familial hypercholesterolemia (FH), while its impact on the different sites of arteries remains undetermined. We aim to examine the associations of Lp(a) levels with coronary and carotid atherosclerosis in patients with heterozygous FH (HeFH). METHODS: A total of 148 patients with HeFH who have received carotid ultrasonography and coronary angiography due to chest pain were enrolled. Plasma Lp(a) was measured using immunoturbidimetric method. Finally, the associations between Lp(a) and coronary as well as carotid lesions were evaluated. RESULTS: Patients with Lp(a) ≥ 300 mg/L had similar carotid intima-media thickness (IMT, 0.782 ± 0.16 mm vs 0.798 ± 0.18 mm, P = .579) and plaque prevalence (66.7% vs 65%, P = .833) compared to those with Lp(a) < 300 mg/L, but had a higher prevalence of coronary artery disease (CAD, 69.7% vs 50.0%, P = .016) and higher Gensini score (GS, median 27 vs 3, P = .006). Moreover, no correlations were found between carotid mean IMT with either Lp(a) level or Lp(a) year score, while positive relation of Lp(a) with GS did. Multivariate regression analysis revealed that Lp(a), Lp(a) year score, and Lp(a) ≥ 300 g/L were all independent predictors for the presence of CAD (OR = 4.99, P = .007; OR = 4.73, P = .009; OR = 4.46, P = .006, respectively) but not for carotid plaques. CONCLUSIONS: This study suggested that Lp(a) level was associated with the presence and severity of CAD but not with carotid atherosclerosis in patients with HeFH.

Correlation of ABO blood groups with spontaneous recanalization in acute myocardial infarction.

OBJECTIVES: Although previous studies have demonstrated the relationship between ABO blood groups and cardiovascular disease, the association of ABO blood type with spontaneous recanalization (SR) in patients with acute myocardial infarction (AMI) has not been previously investigated. METHODS: We performed an initial exploratory study on the association of ABO blood groups with the presence of SR in 1209 patients with AMI. They were divided into two groups according to the thrombolysis in myocardial infarction (TIMI) grades: no-SR group (TIMI 0-1, n = 442) and SR group (TIMI 2-3, n = 767). To confirm our primary findings, data from a second AMI population (n = 200) was analyzed. RESULTS: In the initial data, SR group had a significantly higher percentage of blood type O and a lower percentage of blood type A compared to the no-SR group. Multivariate logistic regression analysis showed that blood type O was positively associated with SR (odds ratio: 1.40, 95% confidence interval: 1.05-1.87, p = .02), and this finding was confirmed in our second population. CONCLUSION: The present study demonstrates that blood type O was independently and positively associated with an open culprit artery in patients with AMI, suggesting that the ABO blood type is not only associated with the susceptibility to coronary artery disease but also to spontaneous reperfusion in AMI patients.

Distribution of ABO Blood Groups and Coronary Artery Calcium.

BACKGROUND: ABO blood groups have been confirmed to be associated with cardiovascular diseases such as coronary artery disease. However, whether ABO blood group is correlated with coronary artery calcium (CAC) is still unknown. METHOD: 301 patients with coronary artery calcium score (CACS) assessed by computed tomography were consecutively enrolled and divided into two groups: with calcium group (CACS>0, n=104) and without calcium group (CACS=0, n=197). Distribution of ABO blood groups was evaluated between the two groups. RESULTS: The percentage of A blood type was significantly higher (p=0.008) and O blood type was significantly lower (p=0.037) in the calcium group. Univariate regression analysis showed that age, total cholesterol, low density lipoprotein cholesterol, high-sensitivity C-reactive protein, A blood type were positively correlated with CAC, and O blood type was inversely associated with CAC. Multivariate regression analysis showed that A blood type was independently associated with CAC (odds ratio: 2.217, 95% confidence interval: 1.260-3.900, p=0.006) even after further adjustment for variables that were clearly different between the two groups. CONCLUSIONS: Our data has suggested for the first time that A blood type was an independent risk marker for CAC.

Prognostic performance of multiple biomarkers in patients with acute coronary syndrome without standard cardiovascular risk factors.

Background and aims: Acute coronary syndrome (ACS) without standard modifiable cardiovascular risk factors (SMuRFs) represents a special case of ACS. Multiple biomarkers have been shown to improve risk stratification in patients with ACS. However, the utility of biomarkers for prognostic stratification in patients with ACS without SMuRFs remains uncertain. The aim of the present study was to evaluate the prognostic value of various biomarkers in patents with ACS without SMuRFs. Methods: Data of consecutive patients with ACS without SMuRFs who underwent coronary angiography in Tianjin Chest Hospital between January 2014 and December 2017 were retrospectively collected. The primary outcome was the occurrence of major adverse cardiovascular event (MACE), defined as a composite of cardiovascular death, myocardial infarction and stroke. Seven candidate biomarkers analyses were analyzed using models adjusted for established risk factors. Results: During a median 5-year follow-up, 81 of the 621 patients experienced a MACE. After adjustment for important covariates, elevated fibrinogen, D-dimer, N-terminal proB-type natriuretic peptide (NT-proBNP), and lipoprotein (a) [Lp(a)] were found to be individually associated with MACE. However, only D-dimer, NT-proBNP and Lp(a) significantly improved risk reclassification for MACE (all P < 0.05). The multimarker analysis showed that there was a clear increase in the risk of MACE with an increasing number of elevated biomarkers and a higher multimarker score. The adjusted hazard ratio- for MACE (95% confidential intervals) for patients with 4 elevated biomarkers was 6.008 (1.9650-18.367) relative to those without any elevated biomarker-. Adding- the 4 biomarkers or the multimarker score to the basic model significantly improved the C-statistic value, the net reclassification index and the integrated discrimination index (all P < 0.05). Conclusion: Fibrinogen, D-dimer, NT-proBNP and Lp(a) provided valuable prognostic information for MACE when applied to patients with ACS without SMuRFs. The multimarker strategy, which combined multiple biomarkers reflecting different pathophysiological process with traditional risk factors improved the cardiovascular risk stratification.

Differences in phenotype, genotype and cardiovascular events between patients with probable and definite heterozygous familial hypercholesterolemia.

Aim: To investigated the potential differences between probable and definite heterozygous familial hypercholesterolemia (HeFH) patients diagnosed by Dutch Lipid Clinic Network criteria. Methods: Clinical characteristics, lipid profile, severity of coronary artery stenosis and gene mutations were compared. Kaplan-Meier curve was performed to evaluate the cardiovascular events. Results: Overall, 325 participants were included and divided into two groups: probable (n = 233) and definite HeFH (n = 92). Definite HeFH patients had higher low-density lipoprotein cholesterol (LDL-C), oxidized-LDL and proprotein convertase subtilisin/kexin 9 levels, and higher prevalence of tendon xanthomas. The incidence of genetic mutations was statistically higher in definite HeFH than probable HeFH patients. The coronary stenosis calculated by Gensini score was statistically severer in definite HeFH patients. The best LDL-C threshold for predicting mutations was 5.14 mmol/l. Definite HeFH had lower event-free survival rates. Conclusion: Definite HeFH patients had higher severity of phenotype and genotype, and higher risk of cardiovascular events.

Association of invasive treatment and lower mortality of patients ≥ 80 years with acute myocardial infarction: a propensity-matched analysis.

OBJECTIVE: To investigate whether invasive strategy was associated with lower mortality in Chinese patients ≥ 80 years with acute myocardial infarction (AMI). METHODS: We used retrospective data from our center between 2013 and 2017. During a median of 17.4 (interquartile range: 7.3-32.3) months follow-up, 120 deaths were recorded among 514 consecutive patients ≥ 80 years with AMI. The patients were divided into two groups: invasive treatment group (IT group, n = 269) and conservative treatment group (CT group, n = 245), which were also then compared with propensity score matching. RESULTS: High mortality was found in CT group compared with that in the IT one. Cox proportional hazard regression analysis showed that invasive treatment was associated with lower mortality of patients ≥ 80 years. Moreover, the results revealed that the patients in IT group had lower in-hospital mortality (3.35% vs. 9.39%, P = 0.005). Besides, the Kaplan-Meier analysis revealed that the mortality was significantly lower in IT group compared with that in CT group using entire and propensity-matched cohort analysis (P < 0.001, respectively). CONCLUSIONS: Our data suggested that IT appeared to be associated with lower mortality in Chinese patients ≥ 80 years with AMI, which consists with previous studies in spite of either ST elevated myocardial infarction (STEMI) or non-STEMI (NSTEMI) patients.

Predictive value of big endothelin-1 on outcomes in patients with myocardial infarction younger than 35 years old.

AIM: The predictive value of big endothelin-1 (ET-1) for cardiovascular outcomes in myocardial infarction (MI) patients younger than 35 years old has not been characterized. METHODS: A total of 565 consecutive MI patients younger than 35 years old were studied and followed up for 37.78 ± 24.9 months. RESULTS: Multivariable Cox regression analysis showed that big ET-1 was positively correlated with major adverse cardiovascular events [MACEs] (odds ratio: 3; 95% CI: 1.92-4.68; p < 0.001). The area under receiver operating characteristics curve showing the predictive value of big ET-1 on MACEs was 0.67. CONCLUSION: The study first demonstrated that big ET-1 was an independent predictor for MACEs in MI patients younger than 35 years old.