The Association of Desert Dust with the Risk of Acute Coronary Syndrome in Subjects of a Younger Age.

Objectives: Recently, desert dust in Europe has been recognized as a cardiovascular health problem. In Spain, desert dust inflows in recent years have been associated with worsening air quality. The present study examines whether desert dust events are related to the incidence of acute coronary syndrome (ACS) in patients under 55 years of age. Methods: Data from 2416 consecutive patients admitted to a tertiary hospital due to ACS were prospectively analyzed. A case-crossover time-stratified design using Poisson conditional regression models was applied to estimate the impact of desert dust events involving particulate matter concentrations of an aerodynamic diameter <10 µm (PM10) on the incidence of ACS in patients under 55 years of age. Results: Desert dust intrusion on days 0 to 5 before ACS onset showed no significant association with the incidence of ACS in patients under 55 years of age. The incidence rate ratios of PM10 concentrations 1, 2, 3, 3, 4, and 5 days before ACS onset (for changes of 10 µg/m3) were 1.02 (95% CI 0.97-1.1; p = 0.41), 1.01 (95% CI 0.96-1.07; p = 0.66), 0.99 (95% CI 0.94-1.05; p = 0.78), 0.96 (95% CI 0.9-1.02; p = 0.18), and 0.97 (95% CI 0.91-1.04; p = 0.41). Conclusions: Our findings suggest that desert dust is unlikely to be related to the incidence of ACS in patients under 55 years of age.

Lipoprotein(a) and Low-Molecular-Weight Apo(a) Phenotype as Determinants of New Cardiovascular Events in Patients with Premature Coronary Heart Disease.

BACKGROUND: Lipoprotein(a) (Lp(a)) is a genetic risk factor of atherosclerotic cardiovascular diseases (ASCVDs). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is related to vascular inflammation and detected in atherosclerotic plaques. A temporary increase in the circulating concentration of PCSK9 and Lp(a) was shown in patients with myocardial infarction (MI). The aim of this study was to evaluate the role of the apo(a) phenotype and the Lp(a) concentration as well as its complex with PCSK9 in the development of cardiac events and MI in patients with a premature manifestation of coronary heart disease (CHD). METHODS: In a prospective study with retrospective data collection, we included 116 patients with premature CHD who were followed for a median of 14 years. The medical history and information on cardiovascular events after an initial exam as well as data on the levels of lipids, Lp(a), PCSK9, PCSK9-Lp(a) complex, and apo(a) phenotype were obtained. RESULTS: The patients were divided into two groups depending on the presence of a low- (LMW, n = 52) or high-molecular weight (HMW, n = 64) apo(a) phenotype. LMW apo(a) phenotype (odds ratio 2.3 (1.1 to 4.8), p = 0.03), but not elevated Lp(a) (1.9 (0.8-4.6), p = 0.13), was an independent predictor for the development of MI after adjustment for sex, age of CHD debut, initial lipids levels, and lipid-lowering treatment. The apo(a) phenotype also determined the relationship between Lp(a) and PCSK9 concentrations. The level of the PCSK9-Lp(a) complex was higher in LMW apo(a) patients. CONCLUSION: The LMW apo(a) phenotype is a risk factor for non-fatal MI in a long-term prospective follow-up of patients with premature CHD, and this link could be mediated via PCSK9.

Risk Factors for Premature Coronary Heart Disease in Women Compared to Men: Systematic Review and Meta-Analysis.

Background: We aimed to systematically examine literature on the prevalence of known modifiable and nonmodifiable risk factors for premature coronary heart disease (PCHD) in women compared with men. Materials and Methods: PubMed, CINAHL, Embase, and Web of Science databases were searched. Review protocol is registered in PROSPERO (CRD42020173216). Quality was assessed using the National Heart, Lung, and Blood Institute tool. Review Manager 5.3 was used for meta-analysis. Effect sizes were expressed as odds ratio (OR) and mean differences/standardized mean differences (SMD) with 95% confidence intervals (CIs) for categorical and continuous variables. Results: In this PCHD cohort (age <65 years), the mean age of presentation in women was 3 years older than men. Women had higher total cholesterol (SMD 0.11; 95% CI 0.00 to 0.23) and higher high-density lipoprotein cholesterol (SMD 0.49; 95% CI 0.29 to 0.69). Women were more likely to have hypertension (OR 1.51, 95% CI 1.42 to 1.60), diabetes mellitus (OR 1.78, 95% CI 1.55 to 2.04), obesity (OR 1.33, 95% CI 1.24 to 1.42), metabolic syndrome (OR 3.73, 95% CI 1.60 to 8.69), stroke (OR 1.63, 95% CI 1.51 to 1.77), peripheral vascular disorder (OR 1.67, 95% CI 1.43 to 1.96), and depression (OR 2.29, 95% CI 1.96 to 2.67). Women were less likely to be smokers (OR 0.60, 95% CI 0.55 to 0.66), have reported alcohol intake (OR 0.36, 95% CI 0.33 to 0.40), and reported use of illicit drug (OR 0.32, 95% CI 0.16 to 0.62). Conclusions: Risk factor profile in PCHD has a clear sex difference that supports early, aggressive, holistic, but sex-specific, approach to prevention.

The mediation effects of metabolic and immune-inflammation factors on the depression-premature coronary heart disease association.

BACKGROUND: Accumulated evidence confirmed depression was positively associated with coronary heart disease (CHD). But evidence of the association between depression and premature CHD is still unknown. OBJECTIVES: To explore the association between depression and premature CHD, and to investigate whether and to what extent the association is mediated by metabolic factors and systemic immune-inflammation index (SII). METHODS: In this large population-based cohort study based on the UK Biobank, 176,428 CHD-free (mean age: 52.70) adults were followed up for 15 years to detect incident premature CHD. Depression and premature CHD (mean age: female, 54.53; male, 48.13) were ascertained from self-report data and linked hospital-based clinical diagnosis. Metabolic factors included central obesity, hypertension, dyslipidemia, hypertriglyceridemia, hyperglycemia, and hyperuricemia. Systemic inflammation was evaluated by calculating SII, which equals platelet count (/L) × neutrophil count (/L) / lymphocyte count (/L). Data were analyzed using Cox proportional hazards models and generalized structural equation model (GSEM). RESULTS: During follow-up (median: 8.0 years, interquartile range: 4.0 to 14.0 years), 2990 participants developed premature CHD (1.7 %). The adjusted hazard ratio (HR) and 95 % confidence interval (CI) of premature CHD related to depression were 1.72 (1.44-2.05). The association between depression and premature CHD was 32.9 % mediated by comprehensive metabolic factors (ß = 0.24, 95 % CI: 0.17-0.32) and 2.7 % by SII (ß = 0.02, 95 % CI = 0.01-0.04), respectively. Concerning metabolic factors, the strongest indirect association was for central obesity, accounting for 11.0 % of the association between depression and premature CHD (ß = 0.08, 95 % CI: 0.05-0.11). CONCLUSIONS: Depression was associated with an increased risk of premature CHD. Our study provided evidence that metabolic and inflammatory factors might play a mediating role in the association between depression and premature CHD, especially central obesity.

Potential of immune-related genes as promising biomarkers for premature coronary heart disease through high throughput sequencing and integrated bioinformatics analysis.

Background: Coronary heart disease (CHD) is the most common progressive disease that is difficult to diagnose and predict in the young asymptomatic period. Our study explored a mechanistic understanding of the genetic effects of premature CHD (PCHD) and provided potential biomarkers and treatment targets for further research through high throughput sequencing and integrated bioinformatics analysis. Methods: High throughput sequencing was performed among recruited patients with PCHD and young healthy individuals, and CHD-related microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by using R software. Enrichment analysis and CIBERSORT were performed to explore the enriched pathways of DEGs and the characteristics of infiltrating immune cells. Hub genes identified by protein-protein interaction (PPI) networks were used to construct the competitive endogenous RNA (ceRNA) networks. Potential drugs were predicted by using the Drug Gene Interaction Database (DGIdb). Results: A total of 35 DEGs were identified from the sequencing dataset and GEO database by the Venn Diagram. Enrichment analysis indicated that DEGs are mostly enriched in excessive immune activation pathways and signal transduction. CIBERSORT exhibited that resting memory CD4 T cells and neutrophils were more abundant, and M2 macrophages, CD8 T cells, and naïve CD4 T cells were relatively scarce in patients with PCHD. After the identification of 10 hub gens, three ceRNA networks of CD83, CXCL8, and NR4A2 were constructed by data retrieval and validation. In addition, CXCL8 might interact most with multiple chemical compounds mainly consisting of anti-inflammatory drugs. Conclusions: The immune dysfunction mainly contributes to the pathogenesis of PCHD, and three ceRNA networks of CD83, CXCL8, and NR4A2 may be potential candidate biomarkers for early diagnosis and treatment targets of PCHD.

Analysis of the Correlation Between the Ratio of Monocytes to High-Density Lipoprotein Cholesterol and in-Stent Restenosis in Patients with Premature Coronary Heart Disease.

BACKGROUND: High-density lipoprotein cholesterol (HDL-C) and monocytes are associated with coronary artery disease, and the ratio of monocytes to high-density lipoprotein (MHR) is associated with long-term adverse outcomes and the recurrence of atrial fibrillation. Currently, the trend of coronary heart disease proned to young people is becoming prominent. However, the relationship between MHR and in-stent restenosis (ISR) in patients with premature coronary heart disease (PCHD) has not been investigated. Therefore, we aimed to assess the relationship between MHR and ISR in patients with PCHD. METHODS: We retrospectively included 257 patients (men ≤ 55 years old, women ≤ 65 years old) with PCHD who underwent drug-eluting stent implantation and follow-up coronary angiography at the First Affiliated Hospital of Zhengzhou University from September 2016 to September 2019. Patients were divided into ISR and non-ISR groups depending on their follow-up coronary angiography results. Relative clinical information was recorded and analyzed. A receiver operating characteristic curve analysis was used to determine the optimum pre-procedural MHR cutoff value to predict ISR. RESULTS: Logistic regression analysis showed that MHR, smoking history, and fibrinogen were independent risk factors for ISR in patients with PCHD. The area under the receiver operating characteristic curve (AUC) of MHR was 0.750 (95% confidence interval, 0.695-0.820; P < .001), the cutoff value was 546.88, and the specificity and sensitivity were 65.2% and 78%, while the AUC of monocytes was 0.631 (95% confidence interval, 0.638-0.794; P < .001), the cutoff value was 590, and the specificity and sensitivity were 77.1% and 60.0%. CONCLUSION: MHR is an independent risk factor for ISR in patients with PCHD and showed a certain predictive value.

Risk factors of ankylosing spondylitis with premature coronary heart disease / 中华风湿病学杂志

Objective:To analyze the risk factors of patients with ankylosing spondylitis (AS) combined with premature coronary atherosclerotic heart disease (PCAD).Methods:A total of 74 patients with AS and coronary atherosclerotic heart disease (CAD) in Peking Union Medical College Hospital from January 1983 to July 2021 were enrolled. According to the age of onset of coronary heart disease, the 74 patients were divided into PCAD group and NPCAD (non-premature coronary heart disease) group. T test and Chi square test were used to analyze the data of the two groups, the risk factors for AS-PCAD were analyzed by multivariate Logistic regression. Results:① There were 37 cases in the PCAD group and 37 cases in the NPCAD group. In the PCAD group, there were 28 men and 9 women; wherease all were men in the NPCAD group. The difference was statistically significant ( χ2=10.25, P=0.001). ② Compared with the NPCAD group, the age of AS-PCAD group was younger [(23±10) years vs (29±12) years, t=-2.28, P=0.026], and the course from AS to CAD was shorter [(25±10) years vs (34±13) years, t=-3.00, P=0.004], hemoglobin (Hb) level was lower [(122±23) g/L vs(132±18) g/L, t=2.10, P=0.039], rate of anemia was higher [38.5%(14/37) vs 16.2%(6/37), χ2=4.39, P=0.037]. Proportion of increased C-reactive protein (CRP) was higher [65.5%(19/29) vs 35.5%(11/31), χ2=5.41, P=0.019]. ③ Juvenile onset AS (JoAS)[ OR(95% CI)=3.45(1.31, 9.10), P=0.012] and high levels of CRP [ OR (95% CI)=3.68 (1.44, 9.40), P=0.006] might berisk factors of AS-PCAD by multiple logisctic regression analysis. Conclusion:Patients with AS have a higher probability of PCAD, especially in those patients with JoAS, persistent inflammation and anemia. It is necessary to be alert to the risk of PCAD and early screening.

Mental health is correlated with lipoprotein(a) levels in male patients with premature coronary heart disease.

BACKGROUND: High levels of lipoprotein(a) (Lp(a)) is an independent risk factor for premature coronary heart disease (PCHD). It is also considered a residual risk for controlled low density lipoprotein cholesterol (LDL-C). Dietary control, exercise, and drugs have limited effects on the levels of Lp(a). Recently, mental health was found to be associated with lipid levels and increased risk of PCHD. However, the relationship between mental health and Lp(a) is still unknown. This study explored the association between mental health and Lp(a) levels in men with PCHD. METHODS: A retrospective, observational study was conducted. A total of 226 male patients with PCHD, aged 49.65±3.68 years, was included in this study. The control group consisted of 230 age-matched healthy male volunteers. Serum Lp(a) levels ≥30 mg/dL, as measured by the immunoturbidimetry method, were considered high. All participants received health related quality of life (HRQoL) scores using the self-assessed 36-Item Short Form Health Survey (SF-36). The HRQoL includes both a physical component summary (PCS) and a mental component summary (MCS). RESULTS: Patients with PCHD were found to have higher levels of Lp(a) (51.61±33.39 vs. 26.42±21.93, P<0.001), and lower MCS (35.83±4.21 vs. 39.85±4.12) and PCS scores (38.02±3.73 vs. 39.63±3.21) compared to healthy volunteers. The MCS score was negatively correlated with Lp(a) levels in the PCHD group (R=-0.295, P<0.001), but no correlation was detected in the control group. There was no relationship between the PCS score and Lp(a) levels in neither the PCHD group nor the healthy control group. Multivariate logistic regression analysis indicated that the MCS and PCS scores were negatively correlated with the risk of PCHD. CONCLUSIONS: These findings suggested that poor mental health may be associated with high levels of Lp(a) and increased risk of PCHD in men. Therefore, improving the mental state in men with PCHD may be crucial.

TRPM2, PDLIM5, BCL3, CD14, GBA Genes as Feasible Markers for Premature Coronary Heart Disease Risk.

Background: Beyond non-genetic risk factors, familial hypercholesterolemia (FH) plays a major role in the development of CHD. FH is a genetic disorder characterized by heritable and severely elevated levels of low-density lipoprotein (LDL) cholesterol, which can lead to premature cardiovascular disease, particularly familial coronary heart disease (FH-CHD). Method: To explore genes indicating a risk of familial (premature) coronary heart disease (FH-CHD) development in FH, 30 Thai male volunteers were enrolled: 7 healthy controls (N), 6 patients with hypercholesterolemia (H), 4 with FH, 10 with CHD, and 3 with FH-CHD. Transcriptome data were investigated using next-generation sequencing analysis in whole blood (n = 3). Genes that were significantly expressed in both FH and FH-CHD, but not in N, H, and CHD groups, were selected and functionally analyzed. Results: The findings revealed that 55 intersecting genes were differentially expressed between FH and FH-CHD groups. Ten of the 55 genes (MAPK14, TRPM2, STARD8, PDLIM5, BCL3, BLOC1S5, GBA, RBMS1, CD14, and CD36 were selected for validation. These 10 genes play potential roles in chronic inflammation and are involved in pathways related to pathogenesis of CHD. Using quantitative real-time PCR, we evaluated the mRNA expression of the selected genes in all 30 volunteers. TRPM2, PDLIM5, BCL3 were significantly upregulated and GBA was significantly downregulated in both FH and FH-CHD compared with the N, H, and CHD groups. Conclusion: our preliminary investigation reveals that the TRPM2, PDLIM5, BCL3, and GBA genes may have potential for further development as predictive markers for FH-CHD.

[Related factors and the long-term outcome after percutaneous coronary intervention of premature acute myocardial infarction].

Objective: To explore the related factors of premature acute myocardial infarction(AMI), and to compare the the long-term outcomes in patients with and without premature AMI after percutaneous coronary intervention (PCI). Methods: This study was a prospective cohort study.From January 2013 to December 2013, 10 724 consecutive patients with coronary heart disease undergoing PCI in Fuwai Hospital were enrolled. Among them 1 920 patients with the diagnosis of AMI were divided into two groups: premature AMI (man≤50 years old, woman≤60 years old) and non-premature AMI. The baseline characteristics were collected, and multivariate logistic regression was uesed to analysis the related factors of premature AMI. The clinical outcomes, including the major adverse cardiovascular and cerebrovascular events(MACCE) which was the composite of cardiac death, myocardial infarction, revascularization, stroke and stent thrombosis, as well as bleeding events, during hospitalization, at 2 years and 5 years follow-up were analyzed. Results: A total of 1 920 AMI patiens were included(age was (56.5±11.3) years old)，with 1 612(84.0%) males. There were statistically significant differences between the two groups in gender, body mass index, blood lipid, complications, inflammatory markers, etc (all P<0.05). Multivariate logistic regression analysis showed body mass index(OR=1.06, 95%CI 1.01-1.10, P<0.01), triglyceride(OR=1.47, 95%CI 1.14-1.90, P<0.01), serum uric acid level(OR=1.02, 95%CI 1.01-1.04, P<0.01), high density lipoprotein cholesterol level(OR=0.33, 95%CI 0.14-0.78, P=0.01) and history of hypertension(OR=0.72, 95%CI 0.56-0.93, P=0.01) were independent related factors of premature AMI. The incidence of all-cause death and cardiac death were lower during hospitalization, at 2 years and 5 years follow-up in the premature AMI group than in non-premature AMI group(all P<0.05). In the premature AMI group, the incidence of MACCE and stroke was lower, with more bleeding events in 5 years follow-up(all P<0.05). Conclusions: Metabolic abnormalities, including high BMI, high triglyceride level and high serum uric acid, low high-density lipoprotein cholesterol level are the related factor of premature AMI. The incidence of ischemic events in patients with premature AMI is lower, while the incidence of bleeding events is higher than non-premature AMI patients.

Family history of cardiovascular disease and risk of premature coronary heart disease: A matched case-control study.

Background: Self-reported family history of cardiovascular disease (CVD) is an independent risk factor for future coronary heart disease (CHD) events. However, inclusion of family history of CVD in the traditional risk scores failed to improve risk prediction of CHD. It is proposed that family history of CVD may substantially increase the risk of CHD among younger individuals. Methods: We conducted a matched case-control study with 170 hospital-based premature CHD patients (<55 years in men and <65 years in women) from a tertiary care centre in Thiruvananthapuram, Kerala and age and sex matched community-based controls in 1:1 ratio. Conditional logistic regression analysis was conducted to assess the independent association of family history of cardiovascular disease (CVD) and premature CHD. We estimated McNemar's odds ratios and their 95 percent confidence intervals. Results: The prevalence of any family history of CVD and CHD in the control population was 24% and 21%, respectively. The family history of CVD was independently associated with premature CHD (odds ratio (OR) = 9.0; 95% confidence interval (CI) 4.7-17.3). There was a dose-response relationship between family history and premature CHD as the risk increased linearly with increase in number of affected family members. Conclusions: Family history of CVD is an independent risk factor for premature CHD. The risk of premature CHD increases linearly with increase in number of affected family members. Collecting family history beyond parental history of CVD is important for risk stratification. Targeting young individuals with family history of CVD for intensive risk reduction interventions may help to prevent future events.

Characteristics of culprit lesions in young patients with metabolic syndrome and classic cardiovascular risk factors.

The association between cardiovascular risk factors (CVRFs) and characteristics of coronary plaque in young patients has remained to be fully elucidated. Therefore, the present study sought to determine the association between CVRFs and phenotypes of culprit coronary plaques revealed by optical coherence tomography (OCT) in young patients with stable coronary heart disease (CHD) and acute coronary syndrome (ACS). OCT imaging pullback was performed at corresponding sites on 123 lesions in 123 young patients (age, 36±7 years), including those with stable CHD and ACS. Patients with analyzable OCT images were classified as having thin-cap fibroatheromas (TCFAs), plaque rupture, macrophage accumulation, calcified nodule, vasa vasorum, cholesterol crystal and erosion. TCFAs were more prevalent in patients with metabolic syndrome (MetS) than in those without MetS (P=0.020). Plaque rupture was more common in smokers than in non-smokers (P=0.002). Multivariate analysis indicated that MetS was independently associated with TCFAs (P=0.041) and smoking was independently associated with plaque rupture (P=0.006). Young patients with MetS were demonstrated to have more extensive TCFAs and young smokers had a higher prevalence of culprit plaque rupture.

Coronary plaque tissue characterization in patients with premature coronary artery disease.

Premature coronary artery disease (CAD) studies rarely involve coronary plaque characterization. We characterize coronary plaque tissue by radiofrequency intravascular ultrasound (IVUS) in patients with premature CAD. From July 2015 to December 2017, 220 patients from the Department of Cardiology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine with first occurrence of angina or myocardial infarction within 3 months were enrolled. Patients with premature CAD (n = 47, males aged < 55 years, and females aged < 65 years) or later CAD (n = 155) were retrospectively compared for cardiovascular risk factors, laboratory examination findings, coronary angiography data, gray-scale IVUS, and iMap-IVUS. The mean age was 53.53 ± 7.24 vs. 70.48 ± 8.74 years (p < 0.001). The groups were similar for traditional coronary risk factors except homocysteine (18.60 ± 5.15 vs. 17.08 ± 4.27 µmol/L, p = 0.043). After matching for baseline characteristics, LDL cholesterol (LDL-C) was higher for premature CAD than later CAD (2.50 ± 0.96 vs. 2.17 ± 0.80 mmol/L, p = 0.019). Before the matching procedure, the premature CAD group had shorter target lesion length [18.50 (12.60-32.00) vs. 27.90 (18.70-37.40) mm, p = 0.002], less plaque volume [175.59 (96.60-240.50) vs. 214.73 (139.74-330.00) mm3, p = 0.013] than the later CAD group. After the matching procedure, the premature CAD group appeared to be less plaque burden (72.69 ± 9.99 vs. 74.85 ± 9.80%, p = 0.005), and positive remodeling (1.03 ± 0.12 vs. 0.94 ± 0.18, p = 0.034), and lower high risk feature incidence (p = 0.006) than the later CAD group. At the plaque's minimum lumen, premature CAD had more fibrotic (p < 0.001), less necrotic (p = 0.001) and less calcified areas (p = 0.012). Coronary plaque tissue was more fibrotic with less necrotic and calcified components in premature than in later CAD, and the range and degree of atherosclerosis were significantly lower.

Soluble RAGEs and cardiovascular risk factors in adult offspring of patients with premature coronary heart disease.

Purpose: Advanced glycation end products (AGEs) are a heterogeneous group of highly oxidant compounds which can potentiate microvascular and macrovascular complications through the formation of irreversible cross-links between molecules in the basal membrane and also by engaging the receptor for AGEs (RAGE). Soluble receptor for AGEs (sRAGE) is suggested to have a protective role neutralizing the toxic action of AGEs. We aimed to investigate differences in plasma levels of sRAGE alongside with classic cardiovascular risk factors between offspring of patients with early onset of coronary heart disease (CHD) and healthy controls.Materials and methods: In a cross-sectional design, we examined 114 adult offspring of patients with premature CHD and 194 controls. Concentrations of soluble RAGE were quantified by ELISA methods. Aortic PWV was measured using Sphygmocor device. Multivariate logistic regressions were used to compare differences between the offspring and controls.Results: In the offspring group there were more men (p = 0.023), both groups had similar age (28.5 vs. 28.9 years; p = 0.51). After adjustment for covariates, we observed significantly higher aPWV (6.17 vs. 5.82 m s-1; p = 0.001) and lower sRAGE (1308.11 vs. 1475.59; p = 0.009) in the offspring group compared to controls. The significant determinants of the intergroup difference were sRAGE (p = 0.0017), aPWV (p = 0.011) and current smoking (p = 0.0053).Conclusion: Offspring of patients with early onset of CHD compared to age-matched healthy controls had significantly lower sRAGE levels suggesting a shift in the oxidative balance between stressors and defence mechanisms that may influence a higher cardiovascular risk in the future. The measurement of sRAGE might be a valuable predictor for more precise stratification of cardiovascular risk.

Related factors and the long-term outcome after percutaneous coronary intervention of premature acute myocardial infarction / 中华心血管病杂志

Objective: To explore the related factors of premature acute myocardial infarction(AMI), and to compare the the long-term outcomes in patients with and without premature AMI after percutaneous coronary intervention (PCI). Methods: This study was a prospective cohort study.From January 2013 to December 2013, 10 724 consecutive patients with coronary heart disease undergoing PCI in Fuwai Hospital were enrolled. Among them 1 920 patients with the diagnosis of AMI were divided into two groups: premature AMI (man≤50 years old, woman≤60 years old) and non-premature AMI. The baseline characteristics were collected, and multivariate logistic regression was uesed to analysis the related factors of premature AMI. The clinical outcomes, including the major adverse cardiovascular and cerebrovascular events(MACCE) which was the composite of cardiac death, myocardial infarction, revascularization, stroke and stent thrombosis, as well as bleeding events, during hospitalization, at 2 years and 5 years follow-up were analyzed. Results: A total of 1 920 AMI patiens were included(age was (56.5±11.3) years old)，with 1 612(84.0%) males. There were statistically significant differences between the two groups in gender, body mass index, blood lipid, complications, inflammatory markers, etc (all P<0.05). Multivariate logistic regression analysis showed body mass index(OR=1.06, 95%CI 1.01-1.10, P<0.01), triglyceride(OR=1.47, 95%CI 1.14-1.90, P<0.01), serum uric acid level(OR=1.02, 95%CI 1.01-1.04, P<0.01), high density lipoprotein cholesterol level(OR=0.33, 95%CI 0.14-0.78, P=0.01) and history of hypertension(OR=0.72, 95%CI 0.56-0.93, P=0.01) were independent related factors of premature AMI. The incidence of all-cause death and cardiac death were lower during hospitalization, at 2 years and 5 years follow-up in the premature AMI group than in non-premature AMI group(all P<0.05). In the premature AMI group, the incidence of MACCE and stroke was lower, with more bleeding events in 5 years follow-up(all P<0.05). Conclusions: Metabolic abnormalities, including high BMI, high triglyceride level and high serum uric acid, low high-density lipoprotein cholesterol level are the related factor of premature AMI. The incidence of ischemic events in patients with premature AMI is lower, while the incidence of bleeding events is higher than non-premature AMI patients.

Genetic diagnosis of familial hypercholesterolemia is associated with a premature and high coronary heart disease risk.

BACKGROUND: Familial hypercholesterolemia (FH) is a common autosomal dominant disease associated with premature coronary heart disease (CHD). Studies tend to show that patients with FH associated with an identified mutation (mutation+ FH) are at higher risk than patients without an identified mutation (mutation- FH). We compared the clinical and biological profile and the risk of CHD in patients with mutation+ FH and mutation- FH. HYPOTHESIS: In addition to LDL-C, a pathogenic mutation predicts premature CHD in FH. METHODS: We successively included all patients with suspected FH (LDL-C > 190 mg/dL if age > 18 years; LDL-C > 160 mg/dL if age < 18 years) and compared patients with a pathogenic mutation with those without an identified pathogenic mutation. RESULTS: We studied 179 patients with mutation+ FH and 147 with mutation- FH. The mean age was 44 (± 18) years. The lipid profile was more atherogenic in those with mutation+ FH, who had higher LDL-C (254 ± 69 mg/dL vs 218 ± 35 mg/dL; P < 0.01) and lower HDL-C (53 ± 14 mg/dL vs 58 ± 17 mg/dL; P < 0.01). Despite the more atherogenic nonlipid cardiovascular profile of patients with mutation- FH, the age of CHD onset was earlier in patients with mutation+ FH (48 vs 56 years; P = 0.026). After multiple adjustment, the presence of a positive mutation was significantly associated with premature CHD (OR: 3.0, 95% CI: 1.38-6.55, P < 0.01). CONCLUSIONS: Patients with mutation+ FH have a more atherogenic lipid profile and a 3-fold higher risk of premature CHD, as well as earlier onset of CHD, than patients with mutation- FH.

A case of sitosterolemia misdiagnosed as familial hypercholesterolemia: A 4-year follow-up.

Familial hypercholesterolemia (FH) is a common inherited disease that exhibits significantly increased levels of low-density lipoprotein cholesterol (LDL-C), skin or tendon xanthomas, corneal arcus and premature coronary heart disease (CHD). The prevalence of heterozygous FH is nearly 1/300 worldwide, and the prevalence of homozygous FH (HoFH) is 1/160,000 - 1/300,000. The Dutch Lipid Clinic Network diagnostic (DLCN) criteria is the most commonly recommended criteria for diagnosing FH patients. However, another disease with a similar clinical phenotype to FH must be differentiated from FH. This disease is a rare autosomal recessive disorder, sitosterolemia, and its incidence rate is approximately 1/5 million. We report a 16-month-old child with suspected HoFH and LDL-C levels that were reduced from 14.69 mmol/L to 3.24 mmol/L after dietary control without statin therapy. Gas chromatography detection of plant sterol levels and targeted exon sequencing chips for genetic testing were used to reach confirmed the diagnosis of sitosterolemia.

Analysis of the Relationship between Red Blood Cell Distribution Width and Serum Leptin Level in Patients with Premature Coronary Artery Disease / 现代检验医学杂志

Objective To investigate the red blood cell distribution width (RDWC)and serum leptin (Leotin)levels in pa-tients with early onset coronary heart disease (CHD)and their correlation.Methods From January 2013 to April 2016,320 cases of hospitalized patients with chest pain,chest tightness in the cardiovascular department of the Gaoming District People's Hospital of Foshan City,Guangdong Province,were examined by coronary artery.Of which 240 cases were male under 55 years old,female under 65 years old patients with coronary heart disease (coronary heart disease group),another 80 cases of normal coronary angiography and treadmill negative males under 5 5 years old,female under 6 5 years old patients,as the con-trol group.Gensini score in patients with premature coronary heart disease was calculated according to the coronary artery imaging results,Comparison between the two groups of red blood cell distribution width and serum leptin levels were differ-ent,analysis of red blood cell distribution width and serum leptin levels and the correlation between the degree of coronary artery lesions.Results The red blood cell distribution width and the serum leptin level in patients with early onset coronary heart disease were (13.87 ± 0.31)% and (12.24 ± 2.21)μg/L,significantly higher than the control group (14.31 ± 0.22)% and (9.21±1.78)μg/L (t=11.742,11.116,P<0.001).And Gensini score was positively correlated with coro-nary artery (r=0.413,0.124,P=0.000,0.041).Correlation of red cell distribution width and serum leptin levels were posi-tively (r=0.107,P=0.008).The research object curve the predictive value of red cell distribution width in patients with premature coronary heart disease (ROC)analysis showed that the area of ROC curve of red cell distribution width (AUC) under 0.725(95%CI:0.679~0.764),red cell distribution width value 12.85%,the sensitivity was 68.1%,specificity was 65.4%.Conclusion In patients with premature coronary heart disease,the red blood cell distribution width and serum leptin levels were significantly increased,and was positively correlated with the degree of coronary artery disease,can be used as an independent predictor of premature coronary heart disease.

Relativity of gene polymorphism of aldehyde dehydrogenase 2 to premature coronary heart disease / 解放军医学杂志

Objective To investigate the relationship between aldehyde dehydrogenase 2 (ALDH2) gene polymorphism and premature coronary heart disease (CHD) in Chinese Han population.Methods A total of 505 patients were enrolled in the present study.Of them,375 were definitely diagnosed as CHD and another 130 were excluded from CHD by coronary angiography.Coronary heart disease patients were divided into premature coronary heart disease (male ＜55 years,female ＜65 years) group (n=150) and late onset coronary heart disease (male ≥ 55 years,female ≥ 65 years) group (n=225);According to whether after drinking flushing,the enrolled 505 patients were divided into alcohol flushing syndrome(AFS) group (n=135) and no AFS group (n=370);According to whether used to drinking,they were divided into accustomed to drinking group (n=189) and no drinking custom group (n=316).The ALDH2 gene polymorphism was analyzed by sanger sequencing.Results There was no significant difference in the distribution ofALDH2 genotype between the patients with premature CHD and late-onset CHD,also between CHD and non-CHD (P＞0.05).The logistic regression analysis showed that ALDH2 gene was not a predisposing factor of PCHD and CHD after adjusting for gender,age,smoking,drinking,body mass index (BMI),hypertension,diabetes,hyperlipidemia and family history of CHD (P=0.729,OR=1.098,95％CI 0.648-1.859;P=0.581,OR=1.156,95％CI 0.692-1.930).The incidence of ALDH2 mutant (GA+AA) was significantly higher in AFS group than in no AFS group (67.4％ vs.10.5％,P＜0.01).The gene mutation frequency was markedly higher in no drinking custom group than in accustomed to drinking group (29.7％ vs.19.1％,P＜0.01).Conclusions No obvious correlation exists between ALDH2 gene polymorphism and the incidence of premature CHD or the onset of CHD in Chinese Han population.There is a certain relationship between ALDH2 mutant gene and AFS.

Premature coronary heart disease and autosomal dominant hypercholesterolemia: Increased risk in women with LDLR mutations.

BACKGROUND: For patients with autosomal dominant hypercholesterolemia (ADH), it remains unclear whether differences exist in the risk of premature coronary heart disease (CHD) between patients with confirmed mutations in low-density lipoprotein receptor (LDLR) vs those without detectable mutations. OBJECTIVE: This study sought to assess the risk of premature CHD in ADH patients with mutations in LDLR (referred to as familial hypercholesterolemia [FH]) vs those without detectable mutations (unexplained ADH), stratified by sex. METHODS: Comparative study of premature CHD in a multiethnic cohort of 111 men and 165 women meeting adult Simon-Broome criteria for ADH. RESULTS: Women with FH (n = 51) had an increased risk of premature CHD compared with unexplained ADH women (n = 111; hazard ratio [HR], 2.74; 95% confidence interval, 1.40-5.34; P = .003) even after adjustment for lipid levels and traditional CHD risk factors (HR, 2.53 [1.10-5.83]; P = .005). Men with FH (n = 42), in contrast, had a similar risk of premature CHD when compared with unexplained ADH men (n = 66; unadjusted: HR, 1.48 [0.84-2.63]; P = .18; adjusted: HR, 1.04 [0.46-2.37]; P = .72). To address whether mutation status provides additional information beyond LDL-cholesterol level, we analyzed premature CHD risk for FH vs unexplained ADH at various percentiles of LDL-cholesterol: the risk ratios were significant for women at 25th percentile (HR, 4.90 [1.69-14.19]) and 50th percentile (HR, 3.44 [1.42-8.32]) but not at 75th percentile (HR, 1.99 [0.95-4.17]), and were not significant for men at any percentile. CONCLUSIONS: Our findings suggest that genetic confirmation of ADH may be important to identify patient's risk of CHD, especially for female LDLR mutation carriers.