Lipid Profile and Subsequent Cardiovascular Disease among Young Adults Aged < 50 Years.

Epidemiological evidence on the relationship between lipid profile and cardiovascular disease (CVD) events in young adults remains insufficient. Thus, we sought to explore the association of lipid profile with subsequent CVD among young adults. Medical records of 1,451,997 young adults (20 to 49 years old) without prior history of CVD and not taking lipid lowering medications were extracted from the Japan Medical Data Center, a nationwide epidemiological database. We conducted multivariable Cox regression analyses to identify the association between lipid profile and the subsequent risk of CVD and used multiple imputation for missing data on body mass index, waist circumference, hypertension, diabetes mellitus, and cigarette smoking in our database. The mean age was 39.0 ± 7.4 years, and 58.5% were men. After a mean follow-up of 1,148 ± 893 days, myocardial infarction, angina pectoris, stroke, and heart failure developed in 1,638 (0.1%), 15,887 (1.1%), 5,593 (0.4%), and 14,351 (1.0%) subjects, respectively. Multivariable Cox regression analyses including covariates after multiple imputation for missing values demonstrated that LDL-C ≥ 140 mg/dL, HDL-C < 40 mg/dL, and triglycerides ≥ 150 mg/dL were independently associated with the incidence of myocardial infarction, angina pectoris, and heart failure. However, they were not associated with the incidence of stroke. Multivariable Cox regression analyses including the number of abnormal lipid profiles and covariates showed that the incidence of myocardial infarction, angina, and heart failure increased stepwise with the number of abnormal lipid profiles. However, the number of abnormal lipid profiles was not associated with the subsequent risk of stroke. In conclusion, the comprehensive analysis of a nationwide epidemiological database demonstrated a close relationship between lipid profile and subsequent CVD, suggesting the importance of maintaining an optimal lipid profile for the primary prevention of CVD in young generations.

Effects of Altered Levels of Pro- and Anti-Inflammatory Mediators on Locations of In-Stent Reocclusions in Elderly Patients.

Imbalances of proatherogenic inflammatory and antiatherogenic inflammatory mediators were involved in the pathogenesis of atherosclerosis. This study sought to investigate the effects of proatherogenic inflammatory and antiatherogenic inflammatory mediators on the proximal, middle, and distal coronary artery reocclusions in elderly patients after coronary stent implantations. We measured the expression levels of proatherogenic inflammatory/antiatherogenic inflammatory cytokines. This included interleukin-1 ß (IL-1 ß), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hs-CRP), interleukin-10 (IL-10), interleukin-17 (IL-17), interleukin-13 (IL-13), and interleukin-37 (IL-37) in the elderly patients with the proximal, middle, and distal coronary artery reocclusions after coronary stent implantations. Levels of IL-1 ß, IL-6, IL-8, TNF-α, and hs-CRP were remarkably increased (P < 0.001), and levels of IL-10, IL-17, IL-13, and IL-37 were remarkably lowered (P < 0.001) in the elderly patients with the proximal, middle, and distal coronary artery reocclusions. Imbalances of proatherogenic inflammatory and antiatherogenic inflammatory mediators may be involved in the formation and progression of proximal, middle, and distal coronary artery reocclusions in elderly patients after coronary stent implantations.

Coronary Microvascular Endothelial Dysfunction in Patients With Angina and Nonobstructive Coronary Artery Disease Is Associated With Elevated Serum Homocysteine Levels.

Background Elevated levels of serum homocysteine, via impaired nitric oxide production, and coronary microvascular dysfunction are associated with increased risk of major adverse cardiovascular events. However, whether serum homocysteine levels and coronary microvascular endothelial dysfunction (CMED) are linked remains unknown. Methods and Results This study included 1418 patients with chest pain or an abnormal functional stress test and with nonobstructive coronary artery disease (<40% angiographic stenosis), who underwent CMED evaluation with functional angiography and had serum homocysteine levels measured. Patients were classified as having normal microvascular function versus CMED. Patients in the CMED group (n=743; 52%) had higher mean age (52.1±12.2 versus 50.0±12.4 years; P<0.0001), higher body mass index (29.1 [25.0-32.8] versus 27.5 [24.2-32.4]; P=0.001), diabetes mellitus (12.5% versus 9.4%; P=0.03), and fewer women (63.5% versus 68.7%; P=0.04) compared with patients in the normal microvascular function group. However, they had lower rates of smoking history, and mildly lower low-density lipoprotein cholesterol levels. Serum homocysteine levels were significantly higher in patients with CMED, and the highest quartile of serum homocysteine level (>9 µmol/L) was an independent predictor of CMED (odds ratio, 1.34 [95% CI, 1.03-1.75]; P=0.03) after adjustment for age; sex; body mass index; chronic kidney disease (CKD); diabetes mellitus; smoking exposure; low-density lipoprotein cholesterol; high-density lipoprotein cholesterol and triglycerides; and aspirin, statin, and B vitamin use. Conclusions Patients with CMED have significantly higher levels of serum homocysteine. Elevated serum homocysteine levels were associated with a significantly increased odds of an invasive diagnosis of CMED. The current study supports a potential role for homocysteine for diagnosis and target treatment in the patients with early coronary atherosclerosis.

The Biochemical Markers Associated with the Occurrence of Coronary Spasm.

Coronary artery spasm (CAS) is one of the mechanisms of angina pectoris. Unlike the diagnosis of acute myocardial infarction which is based on the elevation of cardiac markers, the diagnosis of CAS is difficult and sometimes requires sophisticated and risky provocative test which is not widely accepted in China. There is no well-established biomarker for the diagnosis or prediction of CAS. However, there are some biomarkers proven to be associated with the occurrence of CAS. For example, inflammatory factors including C-reactive protein and cytokines, lipoprotein (a), and cystatin-C might be precipitating factor for CAS. Rho-kinase as a mediator involved in multiple mechanisms of CAS, serotonin, and endothelin-1 as powerful vasoconstrictors leading to vasospasm were all observed being elevated in patients with CAS. Thioredoxin and nitrotyrosine reflected the oxidative status and could be observed to be elevated after the occurrence of CAS. In some cases doubted to be CAS without the evidence of provocative test, the blood test for the biomarkers mentioned above could be useful for the diagnosis of CAS.

[Correlation of lipoprotein(a) with clinical stability and severity of coronary artery lesions in patients with coronary artery disease].

OBJECTIVE: To analyze the correlation of lipoprotein(a) [Lp(a)] with the clinical stability and severity of coronary artery stenosis in patients with coronary artery disease (CAD). METHODS: A total of 531 patients undergoing coronary angiography in Nanfang Hospital between January, 2013 and December, 2016 were enrolled in this study. At the cutoff Lp(a) concentration of 300 mg/L, the patients were divided into high Lp(a) group (n=191) and low Lp(a) group (n=340). In each group, the patients with an established diagnosis of CAD based on coronary angiography findings were further divided into stable angina pectoris (SAP) group and acute coronary syndrome (ACS) group. The correlation between the severity of coronary artery stenosis and Lp(a) was evaluated. RESULTS: The patients in high and low Lp(a) groups showed no significant differences in age, gender, body mass index, smoking status, hypertension, or diabetes (P>0.05). Multivariate logistic regression analysis revealed that age, gender, and serum levels of low-density lipoprotein cholesterol (LDL-C) and Lp(a) were independent risk factors for CAD in these patients. A high Lp(a) level was associated with an increased risk of CAD (OR=2.443, 95%CI: 1.205-4.951, P=0.013). The patients with a high Lp(a) level were at a significantly higher risk of CAD than those with a low Lp(a) level irrespective of a low or high level of LDL-C (P=0.006 and 0.020). In the patients with CAD, the ACS group had a significantly higher Lp(a) level than the SAP group (P < 0.001); the proportion of the patients with high Gensini scores was significantly greater in high Lp(a) group than in low Lp(a) group (17.3% vs 5.6%, P=0.026), and a linear relationship was found between Lp(a) level and Gensini score (R=0.130, P=0.006). CONCLUSIONS: Serum level of Lp(a) is an independent risk factor for CAD, and an increased Lp(a) is the residual risk for CAD. In patients with CAD, a high Lp(a) level is associated with the clinical instability and severity of coronary artery stenosis.

Osteoprotegerin and Cardiovascular Events in High-Risk Populations: Meta-Analysis of 19 Prospective Studies Involving 27 450 Participants.

Background Osteoprotegerin is a cytokine involved in bone metabolism as well as vascular calcification and atherogenesis. Although circulating osteoprotegerin levels are robustly associated with incident cardiovascular disease ( CVD ) in the general population, its relevance as a biomarker among populations at high CVD risk is less clear. Methods and Results Three independent reviewers systematically searched PubMed, EMBASE , and Web of Science to identify prospective studies that had recruited participants on the basis of having conditions related to high CVD risk. A total of 19 studies were eligible for inclusion, reporting on 27 450 patients with diabetes mellitus (2 studies), kidney disease (7 studies), preexisting heart disease (5 studies), or recent acute coronary syndromes (5 studies) at baseline. Over a mean follow-up of 4.2 years, 4066 CVD events were recorded. In a random-effects meta-analysis, the pooled risk ratio for CVD events comparing people in the top versus the bottom tertile of osteoprotegerin concentration was 1.30 (95% confidence interval, 1.12-1.50; P<0.001; I2=68.3%). There was evidence for presence of publication bias ( P value from Egger's test=0.013). Correction for publication bias using the trim-and-fill method reduced the risk ratio to 1.21 (95% confidence interval, 1.03-1.42; P<0.001). The risk ratios did not vary significantly by population type, geographical region, statistical adjustment, sample or assay type, age, sex, or length of follow-up. Conclusions In populations at high CVD risk, elevated circulating osteoprotegerin levels are associated with a higher risk for future CVD events. The magnitude of association appears weaker than in the general population.

Progenitor Cells and Clinical Outcomes in Patients With Acute Coronary Syndromes.

RATIONALE: Circulating progenitor cells (CPCs) mobilize in response to ischemic injury, but their predictive value remains unknown in acute coronary syndrome (ACS). OBJECTIVE: We aimed to investigate the number of CPCs in ACS compared with those with stable coronary artery disease (CAD), relationship between bone marrow PCs and CPCs, and whether CPC counts predict mortality in patients with ACS. METHODS AND RESULTS: In 2028 patients, 346 had unstable angina, 183 had an acute myocardial infarction (AMI), and the remaining 1499 patients had stable CAD. Patients with ACS were followed for the primary end point of all-cause death. CPCs were enumerated by flow cytometry as mononuclear cells expressing a combination of CD34+, CD133+, vascular endothelial growth factor receptor 2+, or chemokine (C-X-C motif) receptor 4+. CPC counts were higher in subjects with AMI compared those with stable CAD even after adjustment for age, sex, race, body mass index, renal function, hypertension, diabetes mellitus, hyperlipidemia, and smoking; CD34+, CD34+/CD133+, CD34+/CXCR4+, and CD34+/VEGFR2+ CPC counts were 19%, 25%, 28%, and 142% higher in those with AMI, respectively, compared with stable CAD. There were strong correlations between the concentrations of CPCs and the PC counts in bone marrow aspirates in 20 patients with AMI. During a 2 (interquartile range, 1.31-2.86)-year follow-up period of 529 patients with ACS, 12.4% died. In Cox regression models adjusted for age, sex, body mass index, heart failure history, estimated glomerular filtration rate, and AMI, subjects with low CD34+ cell counts had a 2.46-fold (95% confidence interval, 1.18-5.13) increase in all-cause mortality, P=0.01. CD34+/CD133+ and CD34+/CXCR4+, but not CD34+/VEGFR2+ PC counts, had similar associations with mortality. Results were validated in a separate cohort of 238 patients with ACS. CONCLUSIONS: CPC levels are significantly higher in patients after an AMI compared with those with stable CAD and reflect bone marrow PC content. Among patients with ACS, a lower number of hematopoietic-enriched CPCs are associated with a higher mortality.

Association between brain-derived neurotrophic factor and von Willebrand factor levels in patients with stable coronary artery disease.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in angiogenesis and maintenance of endothelial integrity. Whether circulating BDNF levels are associated with von Willebrand factor (vWF) levels, which are indicators of endothelial dysfunction is not known. This study investigated the association between plasma BNDF and vWF levels and whether these biomarkers could predict cardiovascular events at a 12-month follow-up in patients with stable coronary artery disease (CAD). METHODS: We recruited 234 patients with suspected angina pectoris. Subjects were divided into CAD (n = 143) and control (n = 91) groups based on coronary angiography. Plasma BDNF and vWF levels were measured using ELISA. Patients were followed-up for one year, and information on adverse cardiac events was collected. RESULTS: CAD patients exhibited significantly lower plasma BDNF and higher vWF levels than those of control patients. High vWF levels were associated with low BDNF levels even after adjustment for age, gender, low-density lipoprotein (LDL) levels, and the presence of diabetes mellitus. A receiver operating characteristic curve was used to determine whether low BDNF and high vWF levels could predict adverse cardiovascular events. The area under the curve for vWF and the inverse of BDNF were 0.774 and 0.804, respectively. CONCLUSIONS: These findings suggest that endothelial dysfunction is an important determinant of the impaired circulating BDNF levels, and they further reflected cardiovascular prognosis in stable CAD patients.

Co-administration of cyclosporine and ticagrelor may lead to a higher exposure to cyclosporine: a case report of a 49-year-old man.

ADVERSE EVENT: A drug interaction leading to higher exposure to cyclosporine. DRUGS IMPLICATED: Cyclosporine and ticagrelor. THE PATIENT: A 49-year-old man with a stable renal graft, managed with cyclosporine with stable trough blood concentrations for several years, was treated with ticagrelor for unstable angina pectoris. EVIDENCE THAT LINKS THE DRUG TO THE EVENT: The timeline was consistent with the appearance of an interaction, the interaction was confirmed by an increase in trough concentration of cyclosporine, and there were no alternative causes that by themselves could have caused the increase in cyclosporine exposure. MANAGEMENT: Cessation of ticagrelor. MECHANISM: Inhibition of CYP3A4 and P-glycoprotein by ticagrelor. IMPLICATIONS FOR THERAPY: Clinicians should be aware of this potential interaction as ticagrelor is frequently prescribed in individuals using cyclosporine. Close monitoring of cyclosporine serum concentrations is warranted to avoid overdosing of cyclosporine. A pharmacokinetic study is needed to further examine the probable interaction between cyclosporine and ticagrelor.

Interrelationships of Cadmium, Smoking, and Angina in the National Health and Nutrition Examination Survey, a Cross-Sectional Study.

The interrelationships between cadmium biomarker levels, smoking, and myocardial infarction and stroke have been established. In this cross-sectional analysis, we explored the interrelationships of blood cadmium levels, smoking, and angina. We analyzed the National Health and Nutrition Examination Survey (NHANES, 2003-2014) accounting for the multi-staged complex sampling design. Participants 40-79 years of age with blood cadmium levels but without a history of myocardial infarction and/or stroke were included (n = 14,832). We examined blood cadmium levels (3 tertile groups) in relation to 3 (diagnosed, undiagnosed, and composite diagnosed and/or undiagnosed) angina outcomes. Multivariable logistic regression models adjusted for age, diabetes, smoking status, and household income were used to estimate odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). Of 14,832 participants, 741 (4.2%) had positive composite angina. The crude and adjusted ORs comparing those in the lowest tertile (referent group) of blood cadmium to those in the highest tertile for the composite outcome were 1.82 (95% CI 1.42-2.34) and 1.45 (95% CI 1.12-1.88), respectively. These cross-sectional data from a nationally representative sample contribute to the hypothesis that there are interrelationships between smoking, cadmium, and angina.

Uric Acid Level Has a U-shaped Association with Clinical Outcomes in Patients with Vasospastic Angina.

No data are available on the association of serum uric acid and vasospastic angina (VSA) which has endothelial dysfunction as a possible pathophysiologic mechanism. Low uric acid level might cause adverse outcomes in VSA in connection with endothelial dysfunction. We enrolled 818 VSA patients whose uric acid level was measured at admission. Patients were categorized according to tertiles of uric acid level: group I, ≤ 4.8 mg/dL; group II, 4.9-5.9 mg/dL; and group III, ≥ 6.0 mg/dL. Primary outcome was major adverse cardiac events (MACEs), defined as a composite of cardiac death, acute myocardial infarction (MI), ischemic stroke, coronary revascularization, and rehospitalization for angina. Median follow-up duration was 49.2 months. Median uric acid values were 4.1 mg/dL for group I, 5.4 mg/dL for group II, and 6.7 mg/dL for group III. In the overall population, group II had a significantly lower incidence of MACE compared to group I (47 [17.1%] vs. 66 [24.6%]; hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.02-2.26; P = 0.040) and a tendency of lower incidence of MACEs compared to Group III (47 [17.1%] vs. 62 [22.5%]; HR, 1.44; 95% CI, 0.98-2.13; P = 0.067). Among group I patients, those who received nitrates had a higher incidence of MACEs than those without nitrate therapy (P < 0.001). Low uric acid level was associated with adverse clinical outcomes, while high uric acid level had a trend toward an increase in it. Use of nitrate in patients with low uric acid level might have adverse effects on clinical outcomes of VSA.

Ratios of One-Carbon Metabolites Are Functional Markers of B-Vitamin Status in a Norwegian Coronary Angiography Screening Cohort.

Background: Functional (metabolic) markers of B-vitamin status, including plasma total homocysteine (tHcy) for folate and plasma methylmalonic acid (MMA) for vitamin B-12, suffer from moderate sensitivity and poor specificity. Ratios of metabolites belonging to the same pathway may have better performance characteristics.Objective: We evaluated the ratios of tHcy to total cysteine (tCys; Hcy:Cys), tHcy to creatinine (Hcy:Cre), and tHcy to tCys to creatinine (Hcy:Cys:Cre) as functional markers of B-vitamin status represented by a summary score composed of folate, cobalamin, betaine, pyridoxal 5'-phosphate (PLP), and riboflavin concentrations measured in plasma.Methods: Cross-sectional data were obtained from a cohort of patients with stable angina pectoris (2994 men and 1167 women) aged 21-88 y. The relative contribution of the B-vitamin score, age, sex, smoking, body mass index, and markers of renal function and inflammation to the variance of the functional B-vitamin markers was calculated by using multiple linear regression.Results: Compared with tHcy alone, Hcy:Cys, Hcy:Cre, and Hcy:Cys:Cre all showed improved sensitivity and specificity for detecting plasma B-vitamin status. Improvements in overall performance ranged from 4-fold for Hcy:Cys to ∼8-fold for Hcy:Cys:Cre and were particularly strong in subjects with the common 5,10-methylenetetrahydrofolate reductase (MTHFR) 677CC genotype.Conclusions: Ratios of tHcy to tCys and/or creatinine showed a severalfold improvement over tHcy alone as functional markers of B-vitamin status in Norwegian coronary angiography screenees. The biological rationale for these ratios is discussed in terms of known properties of enzymes involved in the catabolism of homocysteine and synthesis of creatine and creatinine.

Serum Cytokine Profile in Relation to the Severity of Coronary Artery Disease.

Objectives. To investigate the potential association of a set of serum cytokines with the severity of coronary artery disease (CAD). Methods. A total of 201 patients who underwent coronary angiography for chest discomfort were enrolled. The concentrations of serum IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10, IL-9, and IL-17 were determined by xMAP multiplex technology. The CAD severity was assessed by Gensini score (GS). Results. The serum levels of TNF-α, IL-6, IL-9, IL-10, and IL-17 were significantly higher in high GS group (GS ≥ 38.5) than those in low GS group (GS < 38.5). Positive correlations were also found between these cytokines and the severity of CAD. After adjustment for other associated factors, three serum cytokines (IL-6, IL-9, and IL-17) and two clinical risk factors (creatinine and LDL-C) were identified as the independent predictors of increased severity of CAD. ROC curve analysis revealed that the logistic regression risk prediction model had a good performance on predicting CAD severity. Conclusions. Combinatorial analysis of serum cytokines (IL-6, IL-9, and IL-17) with clinical risk factors (creatinine and LDL-C) may contribute to the evaluation of the severity of CAD and may help guide the risk stratification of angina patients, especially in primary health facilities and in the catheter lab resource-limited settings.

Serum Acylcarnitines and Risk of Cardiovascular Death and Acute Myocardial Infarction in Patients With Stable Angina Pectoris.

BACKGROUND: Excess levels of serum acylcarnitines, which are intermediate products in metabolism, have been observed in metabolic diseases such as type 2 diabetes mellitus. However, it is not known whether acylcarnitines may prospectively predict risk of cardiovascular death or acute myocardial infarction in patients with stable angina pectoris. METHODS AND RESULTS: This study included 4164 patients (median age, 62 years; 72% men). Baseline serum acetyl-, octanoyl-, palmitoyl-, propionyl-, and (iso)valerylcarnitine were measured using liquid chromatography/tandem mass spectrometry. Hazard ratios (HRs) and 95% CIs for quartile 4 versus quartile 1 are reported. The multivariable model included age, sex, body mass index, fasting status, current smoking, diabetes mellitus, apolipoprotein A1, apolipoprotein B, creatinine, left ventricular ejection fraction, extent of coronary artery disease, study center, and intervention with folic acid or vitamin B6. During median 10.2 years of follow-up, 10.0% of the patients died of cardiovascular disease and 12.8% suffered a fatal or nonfatal acute myocardial infarction. Higher levels of the even-chained acetyl-, octanoyl-, and palmitoyl-carnitines were significantly associated with elevated risk of cardiovascular death, also after multivariable adjustments (HR [95% CI]: 1.52 [1.12, 2.06]; P=0.007; 1.73 [1.23, 2.44]; P=0.002; and 1.61 [1.18, 2.21]; P=0.003, respectively), whereas their associations with acute myocardial infarction were less consistent. CONCLUSIONS: Among patients with suspected stable angina pectoris, elevated serum even-chained acylcarnitines were associated with increased risk of cardiovascular death and, to a lesser degree with acute myocardial infarction, independent of traditional risk factors. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00354081.

The effects of percutaneous transluminal coronary intervention on biomarkers of oxidative stress in the erythrocytes of elderly male patients.

OBJECTIVES: Oxidative stress plays a key role in the pathogenesis of coronary artery disease. The aim of this study was to compare the effects of percutaneous transluminal coronary angioplasty (PTCA) and elective coronary angiography (EC) on erythrocytic antioxidant defense in elderly male patients. METHODS: Twenty-three stable angina pectoris (SAP) patients undergoing PTCA and 18 patients with ischemic symptoms scheduled to undergo diagnostic EC were included in the study. The concentrations of malondialdehyde (MDA) and reduced glutathione (GSH) and the activities of Zn,Cu-superoxide dismutase (SOD-1), catalase (CAT), and cytosolic glutathione peroxidase (GSH-Px) were examined in the erythrocytes before, immediately after and 2 weeks following PTCA or EC. RESULTS: The MDA concentrations were significantly higher and SOD-1, CAT, and GSH-Px activities were significantly lower in the PTCA group than in the EC group at baseline. Two weeks after treatment, the activities of the enzymes significantly increased in both groups, whereas the MDA concentrations decreased only in the PTCA patients. CONCLUSIONS: The results confirm that an advanced state of atherosclerosis is related to greater levels of oxidative stress. The study indicates that both procedures may induce antioxidant defenses; however, PTCA exclusively induces a long-term reduction in lipid peroxidation.

Variant Aldehyde Dehydrogenase 2 (ALDH2*2) in East Asians Interactively Exacerbates Tobacco Smoking Risk for Coronary Spasm　- Possible Role of Reactive Aldehydes.

BACKGROUND: Coronary spastic angina (CSA) is common among East Asians and tobacco smoking (TS) is an established risk factor for CSA. Aldehyde dehydrogenase 2 (ALDH2) plays a key role in removing reactive toxic aldehydes and a deficient variant ALDH2 genotype (ALDH2*2) is prevalent among East Asians. We examined the interaction between TS andALDH2*2as a risk factor for CSA to better understand the disease pathogenesis.Methods and Results:The study subjects comprised 410 patients (258 men, 152 women; mean age, 66.3±11.5) in whom intracoronary injection of acetylcholine was performed on suspicion of CSA.ALDH2genotyping was performed by direct application of the Taqman polymerase chain reaction system. Of the study subjects, 244 had CSA proven and 166 were non-CSA. The frequencies of male sex,ALDH2*2, alcohol flushing syndrome, TS, coronary organic stenosis, and plasma levels of uric acid were higher (P<0.001, P<0.001, P<0.001, P<0.001, P<0.001, and P=0.015, respectively) and that of high-density lipoprotein cholesterol lower (P=0.002) in the CSA than non-CSA group. Multivariable logistic regression analysis revealed thatALDH2*2and TS were significant risk factors for CSA (P<0.001 and P=0.002, respectively).ALDH2*2exacerbated TS risk for CSA more than the multiplicative effects of each. CONCLUSIONS: ALDH2*2synergistically exacerbates TS risk for CSA, probably through aldehydes.

Explaining the Decline in Coronary Heart Disease Mortality in the Netherlands between 1997 and 2007.

OBJECTIVE: We set out to determine what proportion of the mortality decline from 1997 to 2007 in coronary heart disease (CHD) in the Netherlands could be attributed to advances in medical treatment and to improvements in population-wide cardiovascular risk factors. METHODS: We used the IMPACT-SEC model. Nationwide information was obtained on changes between 1997 and 2007 in the use of 42 treatments and in cardiovascular risk factor levels in adults, aged 25 or over. The primary outcome was the number of CHD deaths prevented or postponed. RESULTS: The age-standardized CHD mortality fell by 48% from 269 to 141 per 100.000, with remarkably similar relative declines across socioeconomic groups. This resulted in 11,200 fewer CHD deaths in 2007 than expected. The model was able to explain 72% of the mortality decline. Approximately 37% (95% CI: 10%-80%) of the decline was attributable to changes in acute phase and secondary prevention treatments: the largest contributions came from treating patients in the community with heart failure (11%) or chronic angina (9%). Approximately 36% (24%-67%) was attributable to decreases in risk factors: blood pressure (30%), total cholesterol levels (10%), smoking (5%) and physical inactivity (1%). Ten% more deaths could have been prevented if body mass index and diabetes would not have increased. Overall, these findings did not vary across socioeconomic groups, although within socioeconomic groups the contribution of risk factors differed. CONCLUSION: CHD mortality has recently halved in The Netherlands. Equally large contributions have come from the increased use of acute and secondary prevention treatments and from improvements in population risk factors (including primary prevention treatments). Increases in obesity and diabetes represent a major challenge for future prevention policies.

Low Volume Aerobic Training Heightens Muscle Deoxygenation in Early Post-Angina Pectoris Patients.

The aim of this study was to investigate the effect of low volume aerobic exercise training on muscle O2 dynamics during exercise in early post-angina pectoris (AP) patients, as a pilot study. Seven AP patients (age: 72 ± 6 years) participated in aerobic exercise training for 12 weeks. Training consisted of continuous cycling exercise for 30 min at the individual's estimated lactate threshold, and the subjects trained for 15 ± 5 exercise sessions over 12 weeks. Before and after training, the subjects performed ramp cycling exercise until exhaustion. Muscle O2 saturation (SmO2) and relative changes from rest in deoxygenated hemoglobin concentration (∆Deoxy-Hb) and total hemoglobin concentration (∆Total-Hb) were monitored at the vastus lateralis by near infrared spatial resolved spectroscopy during exercise. The SmO2 was significantly lower and ∆Deoxy-Hb was significantly higher after training than before training, while there were no significant changes in ∆Total-Hb. These results indicated that muscle deoxygenation and muscle O2 extraction were potentially heightened by aerobic exercise training in AP patients, even though the exercise training volume was low.

MiR-23a Regulates the Vasculogenesis of Coronary Artery Disease by Targeting Epidermal Growth Factor Receptor.

OBJECTIVE: Circulating microRNAs (miRNAs) in patient body fluids have recently been considered to hold the potential of being novel disease biomarkers and drug targets. We aimed to investigate the correlation between the levels of circulating miR-23a and the expression of epidermal growth factor receptor (EGFR) in the pathogenesis of patients with coronary heart disease to further explore the mechanism involved in its vasculogenesis. METHOD: Three different cohorts, including 13 acute myocardial infarction (AMI) patients, 176 angina pectoris patients, and 127 control subjects, were enrolled to investigate the expression levels of circulating miR-23a in patients with myocardial ischemia and also the relationship between plasma miR-23a and severity of coronary stenosis. Plasma miR-23a levels of participants were examined by real-time quantitative PCR. Simultaneously, plasma cardiac troponin I (cTnI) concentrations were measured by ELISAs. We further detected the correlation of miR-23a and EGFR by molecular and animal assays. RESULT: MiR-23a was enriched in not only diseased endothelial progenitor cells (EPCs) but also in the plasma of patients with coronary artery disease (CAD). Besides, we found out miR-23a was able to suppress EGFR expression and EPC activities. Reporter assays confirmed the direct binding and repression of miR-23a to the 3'-UTR of EGFR mRNA. Knockdown of miR-23a not only restored EGFR levels and angiogenic activities of diseased EPCs in vitro, but further promoted blood flow recovery in ischemic limbs of mice. CONCLUSION: Circulating miR-23a may be a new biomarker for CAD and as a potential diagnostic tool. And increased miR-23a level may be used to predict the presence and severity of coronary lesions in patients with CAD.