Circulating palmitoyl sphingomyelin levels predict the 10-year increased risk of cardiovascular disease death in Chinese adults: findings from the Da Qing Diabetes Study.

BACKGROUND: Higher levels of palmitoyl sphingomyelin (PSM, synonymous with sphingomyelin 16:0) are associated with an increased risk of cardiovascular disease (CVD) in people with diabetes. Whether circulating PSM levels can practically predict the long-term risk of CVD and all-cause death remains unclear. This study aimed to investigate whether circulating PSM is a real predictor of CVD death in Chinese adults with or without diabetes. METHODS: A total of 286 and 219 individuals with and without diabetes, respectively, from the original Da Qing Diabetes Study were enrolled. Blood samples collected in 2009 were used as a baseline to assess circulating PSM levels. The outcomes of CVD and all-cause death were followed up from 2009 to 2020, and 178 participants died, including 87 deaths due to CVD. Cox proportional hazards regression was used to estimate HRs and their 95% CIs for the outcomes. RESULTS: Fractional polynomial regression analysis showed a linear association between baseline circulating PSM concentration (log-2 transformed) and the risk of all-cause and CVD death (p < 0.001), but not non-CVD death (p > 0.05), in all participants after adjustment for confounders. When the participants were stratified by PSM-tertile, the highest tertile, regardless of diabetes, had a higher incidence of CVD death (41.5 vs. 14.7 and 22.2 vs. 2.9 per 1000 person-years in patients with and without diabetes, respectively, all log-rank p < 0.01). Individuals with diabetes in the highest tertile group had a higher risk of CVD death than those in the lowest tertile (HR = 2.73; 95%CI, 1.20-6.22). CONCLUSIONS: Elevated PSM levels are significantly associated with a higher 10-year risk of CVD death, but not non-CVD death, in Chinese adults with diabetes. These findings suggest that PSM is a potentially useful long-term predictor of CVD death in individuals with diabetes.

An elevated triglyceride-glucose index predicts adverse outcomes and interacts with the treatment strategy in patients with three-vessel disease.

BACKGROUND: Insulin resistance is a pivotal risk factor for cardiovascular diseases, and the triglyceride-glucose (TyG) index is a well-established surrogate of insulin resistance. This study aimed to investigate the prognostic value of the TyG index and its ability in therapy guidance in patients with three-vessel disease (TVD). METHODS: A total of 8862 patients with TVD with available baseline TyG index data were included in the study. The endpoint was major adverse cardiac events (MACE). All patients received coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or medical therapy (MT) alone reasonably. RESULTS: An elevated TyG index was defined as the TyG index greater than 9.51. During a median follow-up of 7.5 years, an elevated TyG index was significantly associated with an increased risk of MACE (adjusted hazard ratio 1.161, 95% confidence interval 1.026-1.314, p = 0.018). The elevated TyG index was shown to have a more pronounced predictive value for MACE in patients with diabetes, but failed to predict MACE among those without diabetes, whether they presented with stable angina pectoris (SAP) or acute coronary syndrome (ACS). Meanwhile, the association between an elevated TyG index and MACE was also found in patients with left main involvement. Notably, CABG conferred a significant survival advantage over PCI in patients with a normal TyG index, but was not observed to be superior to PCI in patients with an elevated TyG index unless the patients had both ACS and diabetes. In addition, the benefit was shown to be similar between MT and revascularisation among patients with SAP and an elevated TyG index. CONCLUSIONS: The TyG index is a potential indicator for risk stratification and therapeutic decision-making in patients with TVD.

Association between stress hyperglycaemia and in-hospital cardiac events after coronary artery bypass grafting in patients without diabetes: A retrospective observational study of 5450 patients.

AIMS: To investigate the impact of stress hyperglycaemia (SH) on in-hospital adverse cardiac events after coronary artery bypass grafting (CABG) in patients without diabetes. MATERIALS AND METHODS: In total, 5450 patients without diabetes who underwent CABG were analysed. SH was defined as any two instances in which the random blood glucose level was >7.8 mmol/L after CABG in the intensive care unit (ICU). The primary outcome was major adverse cardiac events (MACEs), including in-hospital mortality, acute myocardial infarction, stroke and acute renal failure. Secondary outcomes included surgical site infection (SSI) and length of ICU stay. RESULTS: Patients with SH had higher rates of MACEs (5.7% vs. 2.3%, p < .0001) and higher SSI (3.3% vs. 1.4%, p = .0003) and longer ICU stays (2.6 ± 2.0 vs. 1.3 ± 1.3 days, p < .0001) than those without SH. Furthermore, SH was associated with a higher risk of MACEs [odds ratio (OR): 2.32, 95% confidence interval (CI): 1.38-3.90], SSI (OR: 2.21, 95% CI: 1.20-3.95) and longer ICU stay (OR: 12.27, 95% CI: 9.41-16.92) after adjusting for confounders. Subgroup analysis showed that patients with SH >10 mmol/L or SH that occurred in the ICU and lasted more than 48 h had increased risks of postoperative complications (p < .05). CONCLUSIONS: SH was significantly associated with an increased risk of MACEs, SSI and longer ICU stay after CABG in patients without diabetes. In addition, SH >10 mmol/L or that occurred in the ICU and lasted more than 48 h increased the risk of adverse outcomes.

HMGCR gene polymorphism is associated with residual cholesterol risk in premature triple-vessel disease patients treated with moderate-intensity statins.

BACKGROUND: To investigate the association of HMGCR and NPC1L1 gene polymorphisms with residual cholesterol risk (RCR) in patients with premature triple-vessel disease (PTVD). METHODS: Three SNPs within HMGCR including rs12916, rs2303151, and rs4629571, and four SNPs within NPC1L1 including rs11763759, rs4720470, rs2072183, and rs2073547 were genotyped. RCR was defined as achieved low-density lipoprotein cholesterol (LDL-C) concentrations after statins higher than 1.8 mmol/L (70 mg/dL). RESULTS: Finally, a total of 609 PTVD patients treated with moderate-intensity statins were included who were divided into two groups: non-RCR group (n = 88) and RCR group (n = 521) according to LDL-C concentrations. Multivariate logistic regression showed the homozygotes for the minor allele of rs12916 within HMGCR gene (CC) were associated with a 2.08 times higher risk of RCR in recessive model [odds ratio (OR): 2.08, 95% confidence interval (CI): 1.16-3.75]. In codominant model, the individuals homozygous for the minor allele of rs12916 (CC) were associated with a 2.26 times higher risk of RCR (OR: 2.26, 95% CI: 1.16-4.43) while the heterozygous individuals (CT) were not, compared with the individuals homozygous for the major allele of rs12916 (TT). There was no significant association between the SNPs within NPC1L1 gene and RCR in various models. CONCLUSIONS: We first reported that the variant homozygous CC of rs12916 within HMGCR gene may incur a significantly higher risk of RCR in PTVD patients treated with statins, providing new insights into early individualized guidance of precise lipid-lowering treatment.

Sapphire optical fiber high-temperature vibration sensor.

A sapphire fiber high-temperature vibration sensor with an extrinsic Fabry-Perot interferometer (EFPI) structure is proposed and experimentally demonstrated. The vibrating diaphragm of the sensor is a supported beam structure fabricated by etching a single-side polished sapphire wafer using a femtosecond laser. The FP cavity of the sensor is composed of the sapphire fiber end face and the polished surface of the vibrating diaphragm. The interference signal of the sensor is picked up by the sapphire fiber and transmitted to a laser interferometry demodulator through a multimode fiber. Experimental results show that the acceleration response is linear in the range of 0-10 g along with an acceleration sensitivity of 20.91 nm/g. The resonance frequency of the sensor is 2700 Hz, which is consistent with the ANSYS simulation results. The sensor can also work in the temperature range from room temperature to 1500 ℃, providing a feasible method for vibration measurements in high-temperature environments.

Higher-order mode suppression technique for multimode sapphire fiber external Fabry-Perot interferometers.

A signal picked-up technique to improve the demodulation stability and accuracy of sapphire fiber external Fabry-Perot interferometer is proposed and demonstrated. Through fusion splicing four pieces of multimode fiber in sequence with different core diameters, the in-step change of the core diameter is found to introduce a sufficient fliting effect on the transmitted higher-order guided modes in the sapphire fiber and further reduce their influence on the fundamental mode interference demodulation. Experimental results show that the proposed multi-stage coupling technique can suppress by five-fold the additional phase imposed on the fundamental mode demodulation when compared with the conventional single-stage coupling approach in which single-mode fiber is spliced with only one piece of multimode fiber. The standard deviation of the demodulated optical phase and cavity length can also be reduced by more than two times. The proposed technique provides a simple yet sufficient solution for the long-standing difficulty of multimode sapphire fiber Fabry-Perot interferometer demodulation.

Diaphragm-free gas pressure sensor based on all-sapphire fiber Fabry-Perot interferometers.

An all-sapphire fiber external Fabry-Perot interferometer (EFPI) sensor for measuring gas pressure is proposed and investigated. The sensor head is manufactured from a sapphire fiber ferrule and sapphire tube, and the same material can ensure the stability of the sensor structure at a high temperature. The refractive index of the gas is linearly related to the gas pressure. Therefore, the gas pressure can be measured by studying the optical cavity length of the EFPI. A multi-stage coupled multimode fiber is used to pick up the interference signal of the fiber EFPI. The pressure response of the sensor at different temperatures was measured in the experiment. The experimental results show that the sapphire fiber EFPI can measure 0-5 MPa gas pressure in the environment of 17-1400°C. The sensitivity of the sensor decreases with the increasing temperature, and the maximum sensitivity is 1.1673 µm/MPa (20°C). The sensor is compact and suitable for gas pressure measurement at a high temperature.

Low p-SYN1 (Ser-553) Expression Leads to Abnormal Neurotransmitter Release of GABA Induced by Up-Regulated Cdk5 after Microwave Exposure: Insights on Protection and Treatment of Microwave-Induced Cognitive Dysfunction.

With the wide application of microwave technology, concerns about its health impact have arisen. The signal transmission mode of the central nervous system and neurons make it particularly sensitive to electromagnetic exposure. It has been reported that abnormal release of amino acid neurotransmitters is mediated by alteration of p-SYN1 after microwave exposure, which results in cognitive dysfunction. As the phosphorylation of SYN1 is regulated by different kinases, in this study we explored the regulatory mechanisms of SYN1 fluctuations following microwave exposure and its subsequent effect on GABA release, aiming to provide clues on the mechanism of cognitive impairment caused by microwave exposure. In vivo studies with Timm and H&E staining were adopted and the results showed abnormality in synapse formation and neuronal structure, explaining the previously-described deficiency in cognitive ability caused by microwave exposure. The observed alterations in SYN1 level, combined with the results of earlier studies, indicate that SYN1 and its phosphorylation status (ser-553 and ser62/67) may play a role in the abnormal release of neurotransmitters. Thus, the role of Cdk5, the upstream kinase regulating the formation of p-SYN1 (ser-553), as well as that of MEK, the regulator of p-SYN1 (ser-62/67), were investigated both in vivo and in vitro. The results showed that Cdk5 was a negative regulator of p-SYN1 (ser-553) and that its up-regulation caused a decrease in GABA release by reducing p-SYN1 (ser-553). While further exploration still needed to elaborate the role of p-SYN1 (ser-62/67) for neurotransmitter release, MEK inhibition had was no impact on p-Erk or p-SYN1 (ser-62/67) after microwave exposure. In conclusion, the decrease of p-SYN1 (ser-553) may result in abnormalities in vesicular anchoring and GABA release, which is caused by increased Cdk5 regulated through Calpain-p25 pathway after 30 mW/cm2 microwave exposure. This study provided a potential new strategy for the prevention and treatment of microwave-induced cognitive dysfunction.

Body mass index and mortality in patients with severe coronary artery diseases: A cohort study from China.

BACKGROUND AND AIMS: It is still controversial whether obesity and overweight increase the risk of mortality for patients with coronary artery disease. The current study aimed to investigate the relationship between body mass index (BMI) and mortality in patients with triple-vessel disease (TVD). METHODS AND RESULTS: From April 2004 to February 2011, 8943 patients with angiographically confirmed TVD were consecutively enrolled. Patients were divided into five groups according to BMI: underweight (<18.5 kg/m2), normal weight (18.5-23.9 kg/m2), overweight: (24-27.9 kg/m2), mild obesity (28-31.9 kg/m2), and severe obesity (≥32 kg/m2). The primary end point was all-cause death. Subgroup analysis was performed for treatment strategies: revascularization and medical treatment alone. During a median follow-up of 7.5 years, lower risks of mortality were observed in patients with overweight (adjusted HR 0.85, 95% CI 0.75-0.97) and mild obesity (adjusted HR 0.83, 95% CI 0.69-1.00) compared to those with normal weight. Polynomial Cox regression suggested a U-shape association between BMI and adjusted mortality risk. In the revascularization subgroup, there was a significantly higher mortality risk in patients with severe obesity (adjusted HR 1.57, 95% CI 1.03-2.40) than in those with normal weight. While in the medical treatment subgroup, mortality risk decreased as BMI increased, with the lowest risk being observed in patients with severe obesity. CONCLUSION: There is a U-shape relationship between BMI and all-cause death in patients with TVD, with increased risks among both underweight and severely obese patients. This relationship may be influenced by treatment strategies.

Fiber-optic Michelson magnetic field sensor based on a mechanical amplifier structure.

A magnetic field sensor based on a mechanical amplifier structure is proposed and experimentally demonstrated. The sensor is composed of a 3×3 coupler-based Michelson interferometer. The magnetic field transducer is a mechanical amplifier structure, in which a TbDyFe rod is wrapped by the polarization-maintaining (PM) fiber. The deformation produced by the TbDyFe rod is amplified and transferred to the PM fiber, causing the fiber length to change. The time-varying phase shift caused by the applied magnetic field is recovered by a passive demodulation method. Experimental results show that the average magnetic field sensitivity of the sensor is 0.4471 V/µT (rms), corresponding to a phase shift sensitivity of 0.2581 rad/µT (rms) and minimum detectable magnetic field of 0.0755 nT/√Hz (rms). The maximum response time is 22.77 ms. The proposed magnetic sensor has a simple design with fast response time and is preferable for detecting weak magnetic fields.

Comparison of Percutaneous Coronary Intervention, Coronary Artery Bypass Grafting and Medical Therapy in Non-ST Elevation Acute Coronary Syndrome Patients With 3-Vessel Disease.

BACKGROUND: The aim of this study is to compare the long-term prognosis of non-ST elevation acute coronary syndrome (NSTE-ACS) patients with 3-vessel disease (3VD) who underwent percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) or medical therapy (MT).Methods and Results:Overall, 3,928 NSTE-ACS patients with 3VD were consecutively enrolled from April 2004 to February 2011 at Fu Wai Hospital. Patients were followed up for a median of 7.5 years, and were divided into PCI, CABG or MT groups according to their treatment. Compared with patients undergoing PCI, CABG patients had lower rates of myocardial infarction (MI), unplanned revascularization, major adverse cardiovascular and cerebrovascular events (MACCE) and a higher rate of stroke (all P<0.05). Compared with MT, PCI and CABG had lower incidences of all adverse outcomes (all P<0.05), except for a similar rate of stroke between PCI and MT. Kaplan-Meier analysis showed similar results. After adjusting for confounders, CABG was independently associated with a lower risk of cardiac death, revascularization and MACCE compared with PCI (all P<0.05). Compared with MT, PCI reduced long-term risk of death, whereas CABG reduced long-term risk of death, revascularization and MACCE events (all P<0.05). CONCLUSIONS: In NSTE-ACS patients with 3VD, CABG is independently associated with a lower risk of long-term cardiac death, revascularization and MACCE compared with PCI. Patients who received MT alone had the highest risk of long-term MACCE.

Implications of N-terminal pro-B-type natriuretic peptide in patients with three-vessel disease.

AIMS: Risk assessment and treatment stratification for three-vessel disease (3VD) remain challenging. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is an established biomarker for prognostication and treatment in heart failure. The present study aimed to evaluate the prognostic value of NT-proBNP beyond the SYNTAX score II (SSII), and its association with long-term outcome after three strategies [percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), and medical therapy (MT)] in a cohort of patients with 3VD. METHODS AND RESULTS: A total of 6597 patients with available baseline NT-proBNP data were included in the study. Baseline, procedural, and follow-up data were collected. The primary endpoint was all-cause death. Secondary endpoints included cardiac death and major adverse cardiac and cerebrovascular events (MACCE), a composite of death, myocardial infarction, and stroke. During a median follow-up of 7.0 years, higher NT-proBNP levels were strongly associated with increased risks of all-cause death, cardiac death, and MACCE (all adjusted P < 0.01). Moreover, NT-proBNP significantly improved discrimination and reclassification of the SSII. Notably, there was a significant interaction between NT-proBNP quartiles and treatment strategies for MACCE (P = 0.004). Revascularization was associated with lower risks of MACCE than MT, except for patients in the lowest quartile wherein no such association was observed. Among patients in the highest quartile, PCI was associated with an increased risk of MACCE compared with CABG (hazard ratio 1.43, 95% confidence interval 1.09-1.87). CONCLUSION: N-terminal pro-BNP is a potential biomarker for risk stratification and therapeutic decision-making in patients with 3VD. Further randomized studies are needed to confirm these findings.

Ultrahigh sensitivity refractive index sensor of a D-shaped PCF based on surface plasmon resonance.

We propose a D-shaped photonic crystal fiber (PCF) refractive index sensor with ultrahigh sensitivity and a wide detection range. The gold layer is deposited on the polished surface, avoiding filling or coating inside the air holes of the PCF. The influences of the gold layer thickness and the diameter of the larger air holes are investigated. The sensing characteristics of the proposed sensor are analyzed by the finite element method. The maximum sensitivity can reach 31,000 nm/RIU, and the refractive index detection range is from 1.32 to 1.40. Our proposed PCF has excellent sensing characteristics and is competitive in sensing devices.

Familial hypertrophic cardiomyopathy caused by a de novo Gly716Arg mutation of the ß-myosin heavy chain.

The present study was performed to identify the genotype of a hypertrophic cardiomyopathy family and investigate the clinicopathogenic characteristics and prognostic features of relevant genetic abnormalities. Target sequence capture sequencing was performed to screen for pathogenic alleles in a 32-year-old female patient (proband). Sanger sequencing was carried out to verify the results. Sanger sequencing was also performed on other family members to identify allele carriers. A survival analysis was carried out using published literature and our findings. We found that the proband and her son harboured a Gly716Arg sequence variant of the ß-myosin heavy chain. Neither the proband's father nor the mother were carriers of this sequence variant; thus, the mutation was classified as "de novo". Further survival analysis revealed that female patients appear to have a longer life expectancy compared with males. Our study may provide an effective approach for the genetic diagnosis of hypertrophic cardiomyopathy.

Rare variants in genes encoding MuRF1 and MuRF2 are modifiers of hypertrophic cardiomyopathy.

Modifier genes contribute to the diverse clinical manifestations of hypertrophic cardiomyopathy (HCM), but are still largely unknown. Muscle ring finger (MuRF) proteins are a class of muscle-specific ubiquitin E3-ligases that appear to modulate cardiac mass and function by regulating the ubiquitin-proteasome system. In this study we screened all the three members of the MuRF family, MuRF1, MuRF2 and MuRF3, in 594 unrelated HCM patients and 307 healthy controls by targeted resequencing. Identified rare variants were confirmed by capillary Sanger sequencing. The prevalence of rare variants in both MuRF1 and MuRF2 in HCM patients was higher than that in control subjects (MuRF1 13/594 (2.2%) vs. 1/307 (0.3%), p = 0.04; MuRF2 22/594 (3.7%) vs. 2/307 (0.7%); p = 0.007). Patients with rare variants in MuRF1 or MuRF2 were younger (p = 0.04) and had greater maximum left ventricular wall thickness (p = 0.006) than those without such variants. Mutations in genes encoding sarcomere proteins were present in 19 (55.9%) of the 34 HCM patients with rare variants in MuRF1 and MuRF2. These data strongly supported that rare variants in MuRF1 and MuRF2 are associated with higher penetrance and more severe clinical manifestations of HCM. The findings suggest that dysregulation of the ubiquitin-proteasome system contributes to the pathogenesis of HCM.

[Pro731Ser mutation in the ß-myosin heavy chain and hypertrophic cardiomyopathy in a Chinese pedigree].

OBJECTIVE: To identify the casual mutation of a Chinese pedigree with hypertrophic cardiomyopathy (HCM), and to analyze the genotype-phenotype relationship. METHODS: The coding exons of 26 reported disease genes were sequenced by targeted resequencing in the proband and the identified mutation were detected with bi-directional Sanger sequencing in all family members and 307 healthy controls. The genotype-phenotype correlation was analyzed in the family. RESULTS: A missense mutation (c.2191C > T, p. Pro731Ser) in the 20th exon of MYH7 gene was identified. This mutation was absent in 307 healthy controls and predicted to be pathogenic by PolyPhen-HCM. Totally 13 family members carried this mutation, including 10 patients with HCM and 3 asymptomatic mutation carriers. The proband manifested severe congestive heart failure and 8 patients expressed various clinical manifestations of heart failure, including dyspnea, palpitations, chest pain, amaurosis or syncope. Five patients were diagnosed as HCM at the age of 16 or younger. One family member suffered sudden cardiac death. CONCLUSIONS: The Pro731Ser of MYH7 gene mutation is a causal and malignant mutation linked with familiar HCM.

In Situ Polymerization of Antibacterial Modification Polyamide 66 with Au@Cu2O-ZnO Ternary Heterojunction.

In situ polymerization has proven to be an effective route through which to introduce function materials into polyamide materials. In this work, a nano-heterojunction material was evenly dispersed in PA66 via in situ polymerization methods to yield the antimicrobial PA66. The composites showed excellent antibacterial activity against Staphylococcus aureus and Escherichia coli, with strong mechanical properties. Fourier transform infrared spectroscopy (FTIR) showed that metal ions reacted with oxygen-containing functional groups. In addition, the shift of oxygen peaks in XPS spectra confirmed the occurrence of a complexation reaction. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) confirmed the effect of nano-heterojunction, which induced crystallization. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed uniform dispersion of heterojunctions in PA66. Tensile testing revealed decreased toughness with higher loadings. The nanocomposite polyamide material has good processing properties which can be processed into thin films, molds, and wires without changing the morphology, and can be widely used in a variety of fields.

Long-Term Outcomes of Sex Differences in Three-Vessel Coronary Disease with Different Treatment Strategies: A Large Cohort Study.

Aim: The information assessing sex differences in outcomes of patients with three-vessel coronary disease (TVD) after different treatment strategies is sparse. This study aimed to investigate long-term outcomes of TVD among women compared with men after medical therapy (MT) alone, percutaneous coronary intervention (PCI), or coronary artery bypass grafting surgery (CABG). Methods: Consecutive 8943 patients with TVD were enrolled. Associations between sex and all-cause death and major adverse cardiac and cerebrovascular events (MACCE) (all-cause death, myocardial infarction, or stroke) were assessed. Results: Of the 8943 patients, 1821 (20.4%) were women. During a median follow-up of 6.6 years, women had comparable incidences of all-cause death (16.6% vs. 14.9%, P = 0.079) and MACCE (27.2% vs. 26.1%, P = 0.320) to men. After multivariable analysis, women showed lower adjusted risks of all-cause death (HR: 0.777; P = 0.001) and MACCE (HR: 0.870; P = 0.016) than men in the entire cohort. Subgroup analysis revealed that the less all-cause death risk of women relative to men was significant in PCI (HR: 0.702; P = 0.009), and CABG groups (HR: 0.708; P = 0.047), but not in MT alone group. Lower MACCE risk for women vs. men was significant only in PCI group (HR: 0.821; P = 0.037). However, no significant interaction between sex and three strategies was observed for all-cause death (P for interaction = 0.312) or MACCE (P for interaction = 0.228). Conclusions: The cardiovascular prognosis of TVD female patients is better than that of men, which has no interaction with the treatment strategies received (MT alone, PCI, or CABG).

Implications of left atrial volume index in patients with three-vessel coronary disease: A 6.6-year follow-up cohort study.

BACKGROUND: Risk assessment and treatment stratification for three-vessel coronary disease (TVD) remain challenging. This study aimed to investigate the prognostic value of left atrial volume index (LAVI) with the Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score II, and its association with the long-term prognosis after three strategies (percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], and medical therapy [MT]) in patients with TVD. METHODS: This study was a post hoc analysis of a large, prospective cohort of patients with TVD in China, that aimed to determine the long-term outcomes after PCI, CABG, or optimal MT alone. A total of 8943 patients with TVD were consecutively enrolled between 2004 and 2011 at Fuwai Hospital. A total of 7818 patients with available baseline LAVI data were included in the study. Baseline, procedural, and follow-up data were collected. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which was a composite of all-cause death, myocardial infarction (MI), and stroke. Secondary endpoints included all-cause death, cardiac death, MI, revascularization, and stroke. Long-term outcomes were evaluated among LAVI quartile groups. RESULTS: During a median follow-up of 6.6 years, a higher LAVI was strongly associated with increased risk of MACCE (Q3: hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.06-1.37, P = 0.005; Q4: HR 1.85, 95%CI 1.64-2.09, P <0.001), all-cause death (Q3: HR 1.41, 95% CI 1.17-1.69, P <0.001; Q4: HR 2.54, 95%CI 2.16-3.00, P <0.001), and cardiac death (Q3: HR 1.81, 95% CI 1.39-2.37, P <0.001; Q4: HR 3.47, 95%CI 2.71-4.43, P <0.001). Moreover, LAVI significantly improved discrimination and reclassification of the SYNTAX score II. Notably, there was a significant interaction between LAVI quartiles and treatment strategies for MACCE. CABG was associated with lower risk of MACCE than MT alone, regardless of LAVI quartiles. Among patients in the fourth quartile, PCI was associated with significantly increased risk of cardiac death compared with CABG (HR: 5.25, 95% CI: 1.97-14.03, P = 0.001). CONCLUSIONS: LAVI is a potential index for risk stratification and therapeutic decision-making in patients with three-vessel coronary disease. CABG is associated with improved long-term outcomes compared with MT alone, regardless of LAVI quartiles. When LAVI is severely elevated, PCI is associated with higher risk of cardiac death than CABG.

Multiple gene mutations, not the type of mutation, are the modifier of left ventricle hypertrophy in patients with hypertrophic cardiomyopathy.

Genotype-phenotype correlation of hypertrophic cardiomyopathy (HCM) has been challenging because of the genetic and clinical heterogeneity. To determine the mutation profile of Chinese patients with HCM and to correlate genotypes with phenotypes, we performed a systematic mutation screening of the eight most commonly mutated genes encoding sarcomere proteins in 200 unrelated Chinese adult patients using direct DNA sequencing. A total of 98 mutations were identified in 102 mutation carriers. The frequency of mutations in MYH7, MYBPC3, TNNT2 and TNNI3 was 26.0, 18.0, 4.0 and 3.5 % respectively. Among the 200 genotyped HCM patients, 83 harbored a single mutation, and 19 (9.5 %) harbored multiple mutations. The number of mutations was positively correlated with the maximum wall thickness. We found that neither particular gene nor specific mutation was correlated to clinical phenotype. In summary, the frequency of multiple mutations was greater in Chinese HCM patients than in the Caucasian population. Multiple mutations in sarcomere protein may be a risk factor for left ventricular wall thickness.