Smoking, Alcohol Consumption, and Risk of Arterial Stiffness: A Two-Sample Mendelian Randomization Study.

Background: While observational studies have demonstrated connections between cigarette smoking, alcohol consumption, and arterial stiffness, establishing a causal relationship has proven challenging because of potential confounding factors. To address this problem, we employed a two-sample Mendelian randomization approach. Methods: We selected genetic instruments for these risk factors from genome-wide association studies encompassing 3,383,199 individuals at the genome-wide significance level (p < 5 × 10 - 9 ). Arterial stiffness data were acquired from the UK Biobank, which included 127,121 participants. Our primary analysis utilized the inverse variance-weighted method to explore causality. To confirm our results' robustness, we conducted sensitivity analyses using Egger regression, the weighted median method, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO). Results: Our analysis revealed a significant association between genetic inclination to smoking initiation and an increase in the arterial stiffness index ( ß = 0.11; 95% confidence interval [CI], 0.06 to 0.16; p = 1.95 × 10 - 5 ). Additionally, there was a suggestive connection between genetically predicted number of cigarettes per day and the arterial stiffness index ( ß = 0.05; 95% CI, 5.25 × 10 - 4 to 0.10; p = 4.75 × 10 - 2 ). No causal relationships were observed between the genetically predicted age of smoking initiation, smoking cessation, or alcohol consumption and the risk of arterial stiffness index. Conclusions: This Mendelian randomization study indicates that smoking initiation is likely a causative risk factor for arterial stiffness. However, further research is needed to determine if the quantity of daily cigarettes directly contributes to arterial stiffness development. Regarding alcohol consumption, age of smoking initiation, and smoking cessation, there was insufficient evidence to establish causality.

Obesity, birth weight, and lifestyle factors for frailty: a Mendelian randomization study.

Obesity, birth weight and lifestyle factors have been found associated with the risk of frailty in observational studies, but whether these associations are causal is uncertain. We conducted a two-sample Mendelian randomization study to investigate the associations. Genetic instruments associated with the exposures at the genome-wide significance level (p < 5 × 10-8) were selected from corresponding genome-wide association studies (n = 143,677 to 703,901 individuals). Summary-level data for the frailty index were obtained from the UK Biobank (n = 164,610) and Swedish TwinGene (n = 10,616). The ß of the frailty index was 0.15 (p = 3.88 × 10-9) for 1 standard deviation increase in the prevalence of smoking initiation, 0.19 (p = 3.54 × 10-15) for leisure screen time, 0.13 (p = 5.26 × 10-7) for body mass index and 0.13 (p = 1.80 × 10-4) for waist circumference. There was a suggestive association between genetically predicted higher birth weight and moderate-to-vigorous intensity physical activity with the decreased risk of the frailty index. We observed no causal association between genetically predicted age of smoking initiation and alcoholic drinks per week with the frailty index. This study supports the causal roles of smoking initiation, leisure screen time, overall obesity, and abdominal obesity in frailty. The possible association between higher birth weight, proper physical activity and a decreased risk of frailty needs further confirmation.

Serum CA 19-9 Level is Correlated to the Clinical Characteristics and Chronic Complications of Patients Newly Diagnosed with Type 2 Diabetes Mellitus.

AIM: This study investigated the relation of serum carbohydrate antigen 199 (CA 19-9) levels to the clinical characteristics and chronic complications of patients newly diagnosed with type 2 diabetes mellitus (T2DM). METHODS: A total of 371 patients newly diagnosed with T2DM and 133 healthy people with consecutively matched age were compared. The 371 patients with T2DM were divided into four groups by quartiles based on their serum CA 19-9 levels, in which clinical characteristics and chronic complications, such as diabetic retinopathy (DR), diabetic nephropathy, and macrovascular complications were compared. Logistic regression analysis was used to evaluate the risk factors of DR. RESULTS: Among the 371 patients newly diagnosed with T2DM, 60 had elevated CA 19-9 levels (16.17%). The frequencies of elevated serum CA 19-9 were 24.39% (30 of 123) for females and 12.10% (30 of 248) for males, in which the values for females were higher than those for males (P<0.01).Differences were observed among the serum CA 19-9 levels, hemoglobin A1c (HbA1c), and DR (P<0.05). Logistic regression analysis showed that serum CA 19-9 levels, fasting blood glucose (FBG) and fasting C-peptide (FC-P) were risk factors for DR (P<0.05). CONCLUSIONS: Serum CA 19-9 levels were correlated with HbA1c and DR in patients newly diagnosed with T2DM. The elevated serum CA 19-9 levels, high FC-P, and FBG levels were important risk factors for DR in patients newly diagnosed with T2DM.

Different treatment options for Takayasu arteritis patients with moderate-to-severe aortic regurgitation: long-term outcomes.

OBJECTIVES: To determine the prognosis of Takayasu arteritis (TA) patients with moderate-to-severe aortic regurgitation treated with surgical vs conservative treatment and to identify independent prognostic factors of long-term outcomes. METHODS: Between January 2002 and January 2017, 101 consecutive TA patients with moderate-to-severe aortic regurgitation treated with either surgical (n = 38) or conservative (n = 63) treatments were investigated in this retrospective observational case-control study. The primary end point was all-cause mortality, and the secondary end point comprised the combined end points of death, non-fatal stroke and cardiac events (non-fatal myocardial infarction and congestive heart failure). Propensity score matching was used to reduce the bias of baseline risk factors. RESULTS: The unadjusted all-cause 10-year mortality in the conservative group was increased compared with the surgical group (28.2% vs 7.4%; log-rank P = 0.036), and the combined end points showed the same trend (52.1% vs 25.3%; log-rank P = 0.005). After an adjustment of baseline risk factors, the conservative treatment was associated with reduced survival rates of both all-cause mortality [hazard ratio (HR): 8.243; 95% CI: 1.069, 63.552; P = 0.007] and combined end points (HR: 6.341; 95% CI: 1.469, 27.375; P = 0.002). Conservative treatment (HR: 3.838, 95% CI: 1.333, 11.053; P = 0.013) and left ventricular end-diastolic diameter (HR: 1.036, 95% CI: 1.001, 1.071; P = 0.042) were risk factors for increased combined end points. CONCLUSION: Surgical treatment improves the outcomes of patients with moderate-to-severe aortic regurgitation due to TA. The dilated left ventricle indicated a worse prognosis.

Association between increased arterial stiffness measured by brachial-ankle pulse wave velocity and cardiovascular events in patients with Takayasu's arteritis.

OBJECTIVES: This study aims to investigate the association between arterial stiffness measured by brachial-ankle pulse wave velocity (baPWV) and cardiovascular events (CVEs) in patients with Takayasu's arteritis (TAK). METHODS: A total of 240 TAK patients, who underwent baPWV measurement, were included in the study. The primary outcome was CVEs, which was defined as presently or previously diagnosed with myocardial infarction, unstable angina, congestive heart failure, aortic aneurysm/dissection, cerebral infarction/transient ischaemic attack (TIA), or cerebral haemorrhage. RESULTS: A total of 74 (30.8%) patients with CVEs were included in the present cohort. Compared with the patients without CVEs, those with CVEs had a higher prevalence of hyperlipidaemia (HL), smoking history, active stage, angiographic type V, renal dysfunction (RDF), higher baPWV and high sensitive C-reactive protein (hs-CRP) level (all, p<0.05). The multivariate logistic regression analysis showed that HL (OR: 2.465, 95%CI: 1.308-4.648, p=0.005), smoking history (OR: 4.764, 95%CI: 1.623-13.985, p=0.004), baPWV (OR: 1.132, 95%CI: 1.063-1.204, p<0.001), and hs-CRP (OR: 1.111, 95%CI: 1.040-1.188, p=0.002) were independently associated with the presence of CVEs. The multiple linear regression analysis revealed that age (ß=0.100, p=0.002), mean blood pressure (ß=0.071, p<0.001), angiographic type V (ß=3.681, p<0.001) and RDF (ß=1.800, p=0.048) were independently correlated with baPWV. CONCLUSIONS: Increased baPWV was independently associated with CVEs in patients with TAK. Age, angiographic type V, mean blood pressure and RDF were the strongest determinants for baPWV in TAK. BaPWV may be a potential maker to predict CVEs in patients with TAK.

Association of interleukin-6 and interleukin-10 expression, gene polymorphisms, and Takayasu arteritis in a Chinese Han population.

Takayasu arteritis (TA) is a chronic inflammatory disease. Interleukin (IL)-6 and IL-10 are important cytokines involved in the immune response of TA in some ethnicities. We investigated whether the single-nucleotide polymorphism (SNP) of IL-6 and IL-10 genes and their expressions were associated with TA in a Chinese Han population. One hundred eighty-four TA patients and 235 healthy controls (HC) were recruited. DNA and RNA were extracted from peripheral blood cells. Genotyping of IL-6 and -10 was performed using polymerase chain reaction-ligase detection reaction (PCR-LDR). The mRNA levels of IL-6 and IL-10 were semi-quantified using reverse transcription polymerase chain reaction (RT-PCR) and real-time polymerase chain reaction (real-time PCR). Plasma levels of them were examined by enzyme-linked immunosorbent assay (ELISA). The mRNA levels of IL-6 in active phase of TA were higher than those in stable phase (p = 0.015); the IL-10 in active phase was lower compared with stable phase (p = 0.046). Plasma levels of IL-6 in TA were higher than those in HC (p = 0.024). Plasma levels of IL-10 showed no difference between the two groups (p = 0.264). Plasma levels of IL-6 in active phase were increased than those in stable phase (p = 0.043) while those of IL-10 were decreased in active phase (p = 0.041). We found no significant differences between TA and HC in the frequency of any of the variations in the SNPs of IL-6 and IL-10 genes. The expression levels of both cytokines were associated with the disease status, indicating that they may serve as potential biomarkers for monitoring disease activity.

Long-term outcomes of coronary artery bypass grafting versus percutaneous coronary intervention for Takayasu arteritis patients with coronary artery involvement.

OBJECTIVE: Coronary artery involvement significantly increases mortality of patients with Takayasu arteritis (TA); however, the optimal revascularization strategy for this condition has not been established. We aimed to compare the long-term outcomes of TA patients with coronary artery involvement treated with coronary artery bypass grafting (CABG) and percutaneous coronary intervention with stenting (PCI). METHODS: Data from 46 TA patients with coronary artery involvement were analyzed according to their revascularization strategies. The resulting events included myocardial infarction, repeated revascularization, cardiac death, and the major adverse cardiac events (MACE), which is a combination of the former events. RESULTS: The risk of MACE was significantly higher in the PCI group than in the CABG group during a median of 41.0 months follow-up (P < 0.001), especially in those who underwent revascularization at the active stage of TA (P = 0.001), whereas no difference was found between PCI and CABG groups in patients who underwent revascularization at the stable stage of TA (P = 0.138). The incidence of MACE was higher in TA patients at the active stage than those at the stable stage in all patients (P < 0.001). For patients at the active stage, the risk of MACE was significantly lower in patients with than those without usage of prednisone (P = 0.028); while no difference was found between patients who were stable not requiring prednisone and patients who were stable on prednisone (P = 0.525). CONCLUSION: With regard to MACE, CABG is superior to PCI despite medical therapy in TA patients with coronary artery involvement. In TA patients at the stable stage, PCI is similar with CABG in prognosis. For patients at the active stage, if emergency revascularization is necessary, CABG is ideal; if not, receiving medical therapy until disease remission and then undergoing PCI may be an alternative choice of CABG.

Anaemia and low body mass index are associated with increased cardiovascular disease in patients with Takayasu arteritis.

OBJECTIVES: Despite the high prevalence of cardiovascular disease (CVD) among patients with Takayasu arteritis (TA), few studies have identified its clinical correlates. The aim of this study was to analyse the prevalence of CVD and its association with traditional CV risk factors and disease-related variables in patients with TA. METHODS: A total of 262 consecutive patients with a diagnosis of TA between January 2009 and July 2013 were included in this study. The primary outcome was CVD, defined as the presence of a previous history of myocardial infarction, angina, coronary disease, coronary bypass surgery, coronary angioplasty, and stroke. Multivariate logistic regression analysis was used to determine the relationship of conventional CV risk factors and TA-related variables to the presence of CVD. RESULTS: CVD was present in 64 (24.4%) of patients with TA. Of the total cohort, 16 (6.1%) had a history of myocardial infarction, 31 (11.8%) had angina and 24 (9.2%) had stroke. Multivariate logistic regression analysis revealed that anaemia (OR, 2.449; 95% CI: 1.167-5.141, p=0.018), low body mass index (OR, 0.821; 95% CI: 0.723-0.932, p=0.002), advancing age (OR, 1.050; 95% CI: 1.013-1.088, p=0.007), hyperlipidaemia (OR, 3.792; 95% CI: 1.647-8.727, p=0.002), and family history of CVD (OR, 2.915; 95% CI: 1.188-7.153, p=0.019) were significantly associated with the presence of CVD. CONCLUSIONS: Our study suggests that in addition to traditional CV risk factors, anaemia and low body mass index are independently associated with increased CVD in patients with TA.

The role of tumor necrosis factor-α promoter genetic variation in Takayasu arteritis susceptibility and medical treatment.

OBJECTIVE: Tumor necrosis factor-α (TNF-α) is a multifunctional proinflammatory cytokine that influences the pathogenesis of Takayasu arteritis (TA). There is still no evidence of the relationship between TNF-α gene promoter polymorphisms and TA. We examined whether variations in the TNF-α promoter region may lead to TA susceptibility and disease progression. METHODS: Five TNF-α gene promoter polymorphisms (-238G/A, -308G/A, -857C/T, -863C/A, and -1031C/T) were analyzed in 110 Chinese Han patients with TA, with a control group of 362 unrelated healthy individuals. Genotypes of TNF-α gene promoter polymorphisms were identified by direct sequencing. TNF-α plasma concentrations were determined by ELISA. RESULTS: Our results indicated that the frequency of the -863A allele was significantly lower in the patients with TA than in the controls (18.2% vs 25.7%; p = 0.011), but the significance was lost after Bonferroni correction (p(c) = 0.055). The frequency of -863CA/AA genotypes was significantly lower in the patients with refractory TA than in those with the 863CC genotype (22.4% vs 44.2%; p(c) < 0.01). The frequency of the GGCCT haplotype was significantly higher in patients than in the controls, while the frequencies of GGCAT and GGCCC haplotypes were significantly lower in patients than in controls. The plasma TNF-α concentrations were significantly lower in the subjects carrying the -863A allele than in those without. Patients with active TA had a significant increase in plasma levels of TNF-α compared with remission patients and the control group. CONCLUSION: Polymorphisms of the TNF-α promoter are not associated with TA in the Chinese Han population. The A allele of the -863C/A polymorphism is associated with decreased TNF-α expression, which might affect medical treatment.

Association between lipoprotein-associated phospholipase A2 gene polymorphism and coronary artery disease in the Chinese Han population.

The role of the lipoprotein-associated phospholipase A(2) gene (PLA2G7) in atherosclerosis remains controversial. We investigated the frequency of single-nucleotide polymorphisms (SNPs) of PLA2G7 (rs16874954 and rs1051931) and their association with coronary artery disease (CAD) in a cohort of CAD patients (n= 806) and age-matched healthy controls (n= 482) in the Chinese Han population. The VF and FF genotype of rs16874954 was significantly more frequent in the CAD patients (13.5%) than in the controls (9.3%, P= 0.024). The association remained after adjustment for age, gender, body mass index, smoking status, history of diabetes, positive family history of CAD, high-density lipoprotein cholesterol, and triglyceride (OR = 1.922; 95% CI [1.146-3.224]; P= 0.013). There was no significant difference in the frequency of any genotype of rs1051931 between the two groups. However, the frequency of the allele V379 was significantly greater in CAD patients with a history of myocardial infarction (MI) than in those without a history of MI (18.7% and 14.8%, P= 0.038). We conclude that there is significant association between the rs16874954 mutation and CAD in the Chinese Han population. The expression of rs1051931 variant in CAD patients may entail increased risk of MI.