Elevated platelet microparticle levels in nonvalvular atrial fibrillation: relationship to p-selectin and antithrombotic therapy

BACKGROUND: Platelet microparticles (PMPs), are procoagulant membrane vesicles that are derived from activated platelets, the levels of which are elevated in patients with hypertension, coronary artery disease (CAD), diabetes, and stroke, all of which are conditions that lead to (and are associated with) atrial fibrillation (AF). We hypothesized the following: (1) PMP levels are elevated in patients with AF compared to levels in both healthy control subjects (ie, patients without cardiovascular diseases who are in sinus rhythm) and disease control subjects (ie, patients with hypertension, CAD, diabetes or stroke, but who are in sinus rhythm); (2) PMP levels correlate with levels of soluble P-selectin (sP-selectin) [a marker of platelet activation]; and (3) PMP levels are related to the underlying factors in patients with AF that contribute to the overall risk of stroke secondary to AF. METHODS: We performed a case-control study of 70 AF patients, 46 disease control subjects and 33 healthy control subjects. Peripheral venous levels of PMP and sP-selectin were analyzed by flow cytometry and enzyme-linked immunosorbent assay, respectively. RESULTS: Both AF patients and disease control subjects had significantly higher levels of PMPs (p < 0.001) and sP-selectin (p = 0.001) compared to healthy control subjects, but there was no difference between AF patients and disease control subjects. There was no difference in PMP levels between patients with paroxysmal and permanent AF (p = 0.581), and between those receiving therapy with aspirin and warfarin (p = 0.779). No significant correlation was observed between PMP and sP-selectin levels (p = 0.463), and the clinical characteristics that contribute to increased stroke risk in patients with AF. On stepwise multiple regression analysis in the combined cohort of AF patients plus disease control subjects, the presence/absence of AF was not an independent determinant of PMP and sP-selectin levels. CONCLUSION: There is evidence of platelet activation (ie, high PMP and sP-selectin levels) in AF patients, but this is likely to be due to underlying cardiovascular diseases rather than the arrhythmia per se.     

Procoagulant microparticles: disrupting the vascular homeostasis equation?

Apoptosis and vascular cell activation are main contributors to the release of procoagulant microparticles (MPs), deleterious partners in atherothrombosis. Elevated levels of circulating platelet, monocyte, or endothelial-derived MPs are associated with most of the cardiovascular risk factors and appear indicative of poor clinical outcome. In addition to being a valuable hallmark of vascular cell damage, MPs are at the crossroad of atherothrombosis processes by exerting direct effects on vascular or blood cells. Under pathological circumstances, circulating MPs would support cellular cross-talk leading to vascular inflammation and tissue remodeling, endothelial dysfunction, leukocyte adhesion, and stimulation. Exposed membrane phosphatidylserine and functional tissue factor (TF) are 2 procoagulant entities conveyed by circulating MPs. At sites of vascular injury, P-selectin exposure by activated endothelial cells or platelets leads to the rapid recruitment of MPs bearing the P-selectin glycoprotein ligand-1 and blood-borne TF, thereby triggering coagulation. Within the atherosclerotic plaque, sequestered MPs constitute the main reservoir of TF activity, promoting coagulation after plaque erosion or rupture. Lesion-bound MPs, eventually harboring proteolytic and angiogenic effectors are additional actors in plaque vulnerability. Pharmacological strategies aimed at modulating the release of procoagulant MPs appear a promising therapeutic approach of both thrombotic processes and bleeding disorders.     

Microparticles in atrial fibrillation: A link between cell activation or apoptosis,tissue remodelling and thrombogenicity

Microparticles (MPs) are small membrane vesicles that are shed from virtually all cells in response to stress. Widely described in atherothrombotic diseases, recent data suggest a role for circulating MPs in the hypercoagulable state associated with supraventricular tachyarrhythmia. During atrial fibrillation, several mechanisms, such as high ventricular heart rate, low or oscillatory shear stress, stretch, hypoxia, inflammation and oxidative stress, are potent inducers of apoptotic cell death, which leads to the shedding of procoagulant MPs within the vasculature. As key regulators of cell–cell cross-talk and important mediators of inflammatory, thrombogenic and proteolytic pathways, MPs directly or indirectly contribute to the amplification loops involved in atrial fibrillation. Because high levels of platelets and endothelial-derived MPs are identified during stroke and are associated with infarct size and clinical outcome, they are proposed to be a potent marker of ischaemic risk. During pulmonary vein isolation, the additional increases of platelet and leukocyte MP levels suggest the extent of tissue damage and reflect a transient activation of the coagulation cascade that could favour ischaemic stroke. Conversely, the observed decreases of several apoptotic markers some months after the restoration of sinus rhythm suggest that the extent of apoptotic processes is reversible and might enable restoration of haemostasis. In this review, we will summarise the current evidence supporting the roles of apoptosis and cell activation in the development of the prothrombotic state observed in atrial fibrillation, with a particular focus on procoagulant MPs.     

Serum androgens and risk of atrial fibrillation in older men: The Cardiovascular Health Study

Background

Decline in serum androgens is common among older men and has been associated with cardiovascular disease, although its role in risk of atrial fibrillation (AF) has not been well defined.

Hypothesis

Low serum androgens are associated with an increased risk of AF.

Methods

We examined the prospective associations between testosterone, its more active metabolite dihydrotestosterone (DHT), and sex hormone–binding globulin (SHBG) with risk of AF among 1019 otherwise healthy men with average age 76.3 ±4.9 years in the Cardiovascular Health Study.

Results

After median follow‐up of 9.5 years, 304 (30%) men developed AF. We detected a nonlinear association with risk of incident AF in both free and total DHT, in which subjects with the lowest levels had a higher risk of incident AF. After adjustment for demographics, clinical risk factors, left atrial diameter, and serum NT‐proBNP levels, men with free DHT <0.16 ng/dL were at increased risk compared with men with higher levels (hazard ratio: 1.48, 95% confidence interval: 1.01–2.17, P <0.05). Sensitivity analyses confirmed that the increased risk was not cutpoint‐specific, with a significant association noted up to cutpoints <~0.2 ng/dL. We also detected a complex nonlinear association between SHBG and incident AF, in which subjects in the middle quintile (52.9–65.3 nmol/L) had increased risk.

Conclusions

Among older men, low free DHT is associated with an increased risk of incident AF. Further studies are needed to explore mechanisms for this association.     

Serum N-terminal atrial natriuretic peptide in adult patients late after surgical repair of atrial septal defect

BACKGROUND: The purpose of surgical closure of atrial septal defect (ASD) is to relieve the cardiovascular system from a haemodynamic burden. Excessive amounts of atrial peptides are released in congestive heart failure, valvular diseases and congenital heart diseases. AIMS: To examine whether patients after surgical repair of ASD have higher concentrations of N-terminal atrial natriuretic peptide (ANP-N) than age-, sex- and body mass index (BMI)-matched control subjects. METHODS: Medical history, physical examination, standard 12-lead electrocardiogram, and ANP-N concentrations were obtained in 65 adult patients operated for ASD at the age of 21+/-13 years (mean+/-standard deviation), 21+/-6 years after surgical closure of ASD. Sixty-seven healthy subjects matched for age, sex and BMI served as controls. RESULTS: In the patients serum ANP-N was higher than in the control subjects 0.41+/-0.32 nmol/l, median 0.31 nmol/l, interquartile range (IQR) 0.21-0.49 nmol/l vs. 0.24+/-0.12 nmol/l, median 0.23 nmol/l, IQR 0.17-0.29 nmol/l, (P=0.0003). Patients with concomitant diseases had higher ANP-N concentrations (0.51+/-0.39 nmol/l, median 0.34, IQR 0.26-0.73 nmol/l) than ASD patients without any history or signs of disease (0.28+/-0.16 nmol/l, median 0.27, IQR 0.17-0.40 nmol/l, P=0.01). The 'healthy' ASD patients had higher hormone concentrations than age-, sex- and BMI-matched control subjects (0.28+/-0.16 median 0.27 nmol/l, IQR 0. 17-0.40 nmol/l and 0.21+/-0.07 nmol/l, median 0.20 nmol/l, IQR 0. 15-0.27 nmol/l, P=0.01). Multiple stepwise linear regression analysis showed that age at operation was strongly associated with the post-operative ANP-N concentration (r(2)=0.25, P=0.0002). CONCLUSION: ASD patients have higher ANP-N concentrations late after surgical repair. Hormone levels correlate with age at operation. Our finding supports the clinical praxis of operating on these patients in their childhood and adolescence.     

Circulating procoagulant microparticles in cancer patients

Accumulating evidence indicates that microparticles (MPs) are important mediators of the interaction between cancer and the hemostatic system. We conducted a large prospective cohort study to determine whether the number of circulating procoagulant MPs is elevated in cancer patients and whether the elevated MP levels are predictive of occurrence of venous thrombembolism (VTE). We analyzed plasma samples of 728 cancer patients from the ongoing prospective observational Vienna Cancer and Thrombosis Study. Study endpoint was the occurrence of symptomatic VTE. Sixty-five age- and sex-matched healthy controls were recruited for defining the cut-off point for elevated MPs (4.62 nanomolar phosphatidylserine [nM PS]), which was set at the 95th percentile of MP levels in healthy controls. The measurement of MPs was performed after capture onto immobilized annexin V, and determination of their procoagulant activity was quantified with a prothrombinase assay. During a median observation period of 710 days, 53 patients developed VTE. MP levels (nM PS) were significantly higher in cancer patients than in healthy controls (median [25th–75th percentile], 3.95 [1.74–7.96] vs. 1.19 [0.81–1.67], p < 0.001). Multivariate analysis including age, sex, surgery, chemo- and radiotherapy showed no statistically significant association of the hazard ratio of elevated MPs with VTE (0.95 [95% CI, 0.55–1.64], p = 0.856). In conclusion, MP levels were elevated in cancer patients compared to healthy individuals in this study. However, elevated MP levels were not predictive of VTE.     

几丁质酶-3样蛋白-1在心房颤动发病机制中的作用

目的探讨几丁质酶-3样蛋白-1（ehitinase-3．1ike-1protein,YKL-40）在心房颤动（房颤）发病机制中的作用。方法选择在广州市番禺区何贤纪念医院心内科住院的房颤患者71例（其中阵发性房颤组22例,持续性房颤组30例．永久性房颤组19例）为研究对象。另外,选择同期年龄匹配的健康体检者20名为对照组。采用酶联免疫吸附试验（ELISA）方法检测各组血浆YKL-40浓度并进行比较。结果各组间基线资料比较,差异无统计学意义（P〉0。05）。永久性房颤组、持续性房颤组及阵发性房颤组血浆YKL-40浓度均显著高于对照组,差异有统计学意义[（4．21±0．62）μg／L、（3．72±0．63）μg／L、（3．29＋0．75）μg／Lus（2．79±0．56）μg／L,P〈0．05];持续性及永久性房颤组血浆YKL-40浓度高于阵发性房颤组,差异有统计学意义（P〈0．05）;永久性房颤组YKL-40浓度高于持续性房颤组．差异有统计学意义（P〈0．05）。结论YKL-40可能参与房颤的发生、发展。     

Platelet microparticles and vascular cells interactions: a checkpoint between the haemostatic and thrombotic responses

Described 40 years ago as cell dust, microparticles (MPs) are now considered a key component in the haemostatic response. Owing to their plasma membrane reactivity, platelets are believed to constitute the main source of circulating procoagulant microparticles and behave as true sensors for the haemostatic response. Erythrocytes, leukocytes and endothelial cells are also able to shed MPs in the blood flow, their respective contribution varying with the pathophysiologic circumstances and extent of the cellular damage. The catalytic properties of MPs rely on a procoagulant anionic phospholipid, phosphatidylserine, made accessible at the outer leaflet following plasma membrane remodelling and on the eventual presence of tissue factor (TF). Under resting conditions, most membrane-bound TF is encrypted. Although able to bind to FVIIa, it does not trigger blood coagulation. Under prothrombotic conditions, TF decryption would occur through intricate pathways involving platelets, monocytes, endothelial cells and derived MPs. P-selectin/P-selectin glycoprotein Ligand-1 (PSGL-1) interactions and reactive oxygen species would promote TF decryption in cell-MP aggregates. At sites of endothelium injury, the swift recruitment of TF+-MPs through P-selectin/PSGL-1 interactions enables the concentration of TF activity above a threshold allowing coagulation to be triggered. Another crucial feature in the initiation of blood coagulation, possibly tuned by MPs, is the balance between TF and TFPI. In specific pathophysiologic contents with elevated levels of circulating TF+-MPs, accessible TFPI at the MP surface would be overwhelmed. Beyond their procoagulant properties demonstrated in vitro, a number of pieces of evidence points to procoagulant MPs as efficient effectors in the haemostatic response, and as pathogenic markers of thrombotic disorders and vascular damage. This review will focus on the pathophysiological significance of platelet-derived MPs and their interaction with vascular cells.     

Doppler transmitral flow indexes and risk of atrial fibrillation (the Framingham Heart Study)

Atrial fibrillation (AF) is characterized by structural remodeling and atrial systolic failure. It is unclear if atrial filling abnormalities precede the onset of AF. We evaluated 942 Framingham Study subjects (587 women; mean age 75 years) who underwent Doppler echocardiographic evaluation at a routine examination and who did not have a history of AF. We used multivariable Cox regression models (stratified by gender and prevalent cardiovascular disease) to examine the relations of Doppler transmitral flow indexes (ratio of the velocity-time integrals of the early [E] and late [A] diastolic filling waves [VTI E/A], a correlate of atrial conduit function; E-wave deceleration time; the atrial filling fraction, an index of atrial systolic function; and peak A wave velocity) to the incidence of AF. At follow-up (mean 7 years), 85 subjects (41 women) developed AF. In models adjusting for established risk factors for AF (including left atrial size) at baseline, and for heart failure and myocardial infarction on follow-up, a 1 SD increment in VTI E/A was associated with a 28% increase in risk of AF (hazards ratio 1.28, 95% confidence interval 1.02 to 1.59). A 1 SD decrease in the atrial filling fraction was associated with a 28% higher risk of AF (hazards ratio 1.28, 95% confidence interval 0.98 to 1.67). There was a U-shaped relation between peak A-wave velocity and risk of AF. Thus, in our elderly community-based sample, increased VTI E/A and a low atrial filling fraction were markers of increased risk of AF, suggesting that altered atrial filling may antedate AF.     

Circulating procoagulant microparticles in obesity

AIM: Obesity is a risk factor for cardiovascular diseases and venous thromboembolism. Circulating procoagulant microparticles (MP) have been described in various clinical situations associated with thrombosis and in diabetic patients. The aim of this preliminary study was to evaluate the presence of MP in obese patients without any other vascular risk factor in particular diabetes. METHODS: Fifty-eight obese women <50 year-old without other cardiovascular risk factors were recruited from a single out-patient nutrition clinic. They were compared to 45 age-matched healthy normal weight controls. Main outcome was MP levels in patients and controls. Relationships between MP concentrations and parameters reflecting insulin resistance in patients were also studied. RESULTS: Obese patients were 33.3 +/- 1.2 years old and had a mean BMI of 42.4 +/- 0.9 kg/m2. There vas a greater proportion of smokers in the obese group (34.5 vs 15.6%). Mean MP levels were markedly higher in obese patients compared to controls (10.6 +/- 0.5 vs 3.2 +/- 0.3 nMPSeq, P < 0.001). There was no difference in MP concentrations between smokers and non smokers. In the obese group, there was a negative correlation between MP and BMI (r = -0.265, P < 0.05) but no relationship could be established between MP concentrations and markers of insulin resistance. CONCLUSION: This increase in circulating MP levels reflects cell activation and could account for the increased risk of thrombotic complications in obesity. Further studies are ongoing to explore the relationships between MP levels and coagulation markers and to assess the effect of weight reduction.     

Cellular mechanisms underlying the formation of circulating microparticles

Microparticles (MPs) derived from platelets, monocytes, endothelial cells, red blood cells, and granulocytes may be detected in low concentrations in normal plasma and at increased levels in atherothrombotic cardiovascular diseases. The elucidation of the cellular mechanisms underlying the generation of circulating MPs is crucial for improving our understanding of their pathophysiological role in health and disease. The flopping of phosphatidylserine (PS) to the outer leaflet of the plasma membrane is the key event that will ultimately lead to the shedding of procoagulant MPs from activated or apoptotic cells. Research over the last few years has revealed important roles for calcium-, mitochondrial-, and caspase-dependent mechanisms leading to PS exposure. The study of Scott cells has unraveled different molecular mechanisms that may contribute to fine-tuning of PS exposure and MP release in response to a variety of specific stimuli. The pharmacological modulation of MP release may have a substantial therapeutic impact in the management of atherothrombotic vascular disorders. Because PS exposure is a key feature in pathological processes different from hemostasis and thrombosis, the most important obstacle in the field of MP-modulating drugs seems to be carefully targeting MP release to relevant cell types at an optimal level, so as to achieve a beneficial action and limit possible adverse effects.     

Plasma adenosine levels and platelet activation in patients with atrial fibrillation

Platelet activation is observed in patients with atrial fibrillation (AF). P-selectin, which is expressed on platelet activation, plays an important role in the formation of thromboemobli. Because adenosine is known to attenuate platelet activation, we evaluated adenosine levels and 2 indicators of platelet activation, i.e., expression of P-selectin on platelets and plasma levels of beta-thromboglobulin, in 28 patients with AF (20 men and 8 women, age range 64+/-2 years) with sex- and age-matched (+/-2 years) subjects with sinus rhythm. The incidence of risk factors for stroke except for coronary heart disease and in echocardiographic parameters did not differ between the 2 groups. Plasma adenosine levels were lower (p <0.05) in patients with AF than in controls (mean [interquartile range] 13.4 [19.3-9.3] vs 19.1 [30.8-11.9] nmol/L). The expression of P-selectin on platelets (6.8% [13.6-3.4] vs 4.0% [8.8-1.8]) and plasma levels of beta-thromboglobulin were higher (p <0.05) in patients with AF. Flow cytometric analysis revealed that an antagonist of adenosine receptors, 8-sulfophenyltheophylline, increased the expression of P-selectin on platelets in a dose-dependent manner in the in vitro study. These results suggest that decreased plasma levels of adenosine were associated with platelet activation in patients with AF. Substitution of adenosine may provide a strategy for preventing platelet activation in these patients.     

Platelet surface CD62P and CD63, mean platelet volume, and soluble/platelet P-selectin as indexes of platelet function in atrial fibrillation: a comparison of "healthy control subjects" and "disease control subjects" in sinus rhythm.

OBJECTIVES: The aim of this work was to comprehensively study the role of platelets in atrial fibrillation (AF), in relation to the underlying cardiovascular diseases and type of AF, and to analyze the effect of antithrombotic treatment on different aspects of platelet activation. BACKGROUND: Platelet activation is present in nonvalvular AF, but there is debate whether this is due to AF itself and/or to underlying cardiovascular diseases. METHODS: A total of 121 AF patients were compared with 65 "healthy control subjects" and 78 "disease control subjects" in sinus rhythm. Platelet activation was assessed using 4 different aspects of platelet pathophysiology: 1) platelet surface expression of CD62P (P-selectin) and CD63 (a lysosomal glycoprotein) (by flow cytometry); 2) mean platelet volume (MPV) (by flow cytometry); 3) plasma levels of soluble P-selectin (sP-selectin, enzyme-linked immunoadsorbent assay); and 4) total amount of P-selectin per platelet (pP-selectin) ("platelet lysis" assay). RESULTS: Both AF patients and "disease control subjects" had higher levels of CD62P (p < 0.001), CD63 (p < 0.001), and sP-selectin (p < 0.001) compared with "healthy control subjects," with no difference between AF patients and "disease control subjects." Patients with permanent AF had higher levels of sP-selectin (p = 0.014) and MPV (p = 0.025) compared with those with paroxysmal AF. The presence of AF independently affected the levels of CD62P expression, while "high-risk" AF patients (CHADS score > or =2) had higher levels of CD62P compared with those with "low risk." Introducing warfarin resulted in a reduction of pP-selectin (p = 0.013). CONCLUSIONS: There is a degree of excess of platelet activation in AF compared with "healthy control subjects," but no significant difference between AF patients and "disease control subjects" in sinus rhythm. Platelet activation may differ according to the subtype of AF, but this is not in excess of the underlying comorbidities that lead to AF. Platelet activation in AF may be due to underlying cardiovascular diseases, rather than due to AF per se.     

Permanent atrial fibrillation in patients without structural heart disease is not associated with signs of infection by Chlamydia pneumoniae and Helicobacter pylori

OBJECTIVE: The objective of this study was to explore the role of Chlamydia pneumoniae and Helicobacter pylori infections in patients with idiopathic permanent atrial fibrillation. METHODS AND RESULTS: Sera from 72 patients with permanent atrial fibrillation without structural heart disease (mean age 69.6 years, 23 women) were analysed for IgG antibodies against Chlamydia pneumoniae and Helicobacter pylori and compared in a I:I age- and sex-matched case:control manner with those pooled from a healthy reference population of 72 individuals from the same geographical area. After excluding patients with other possible or definite factors known either to cause atrial fibrillation or to affect the prevalence of seropositivity to these agents, the frequency of seropositivity due to one or both of the infectious agents was compared. Serum C-reactive protein (CRP) level was assessed using immunoturbidimetry technique. Both agents were equally common in men and women. Neither seropositivity to Chlamydia pneumoniae (76% vs. 83%, patients vs. control subjests, ns) nor to Helicobacter pylori (57% contra 55%, patients vs. controls, ns) alone reached significance in the comparisons between patients with atrial fibrillation and control subjects. Serum CRP was higher in patients with AF (5.3 mg/L vs. 2.8 mg/L, P < 0.001). CONCLUSIONS: Though presence of permanent AF is associated with elevated CRP levels, this elevation is not the result of earlier infections with Chlamydia pneumoniae or Helicobacter pylori or their combination.     

Does location of epicardial adipose tissue correspond to endocardial high dominant frequency or complex fractionated atrial electrogram sites during atrial fibrillation?

Background- Although increased epicardial adipose tissue (EAT) volume is known to be associated with increased prevalence of atrial fibrillation (AF), the exact mechanisms are unclear. Therefore, we investigated whether EAT locations were associated with high dominant frequency (DF) sites or complicated fractionated atrial electrogram sites during AF. Methods and Results- Three-dimensional reconstruction computed tomography images depicting EAT volumes (obtained by 320-detector-row multislice computed tomography) were merged with NavX-based DF and complicated fractionated atrial electrogram maps obtained during AF for 16 patients with paroxysmal AF and for 18 patients with persistent AF. Agreement between locations of the EAT, especially EAT surrounding the left atrium, and of high DF or complicated fractionated atrial electrogram sites was quantified. In addition, serum biomarker levels were determined. EAT surrounding the left atrium volumes was significantly greater in patients with persistent AF than in patients with paroxysmal AF (52.9 cm(3) [95% CI, 44.2-61.5] versus 34.8 cm(3) [95% CI, 26.6-43.0]; P=0.007). Serum high-sensitivity C-reactive protein and interleukin-6 levels were significantly higher in persistent AF patients than in paroxysmal AF patients (median high-sensitivity C-reactive protein, 969 ng/mL [interquartile range, 307-1678] versus 320 ng/mL [interquartile range, 120-660]; P=0.008; median interleukin-6, 2.4 pg/mL [interquartile range, 1.7-3.2] versus 1.3 [interquartile range, 0.8-2.4] pg/mL; P=0.017). EAT locations were in excellent agreement with high DF sites (κ=0.77 [95% CI, 0.71-0.82]) but in poor agreement with complicated fractionated atrial electrogram sites (κ=0.22 [95% CI, 0.13-0.31]). Conclusions- Increased EAT volume and elevation of inflammatory biomarkers are noted in persistent AF rather than paroxysmal AF patients. High DF sites are located adjacent to EAT sites. Thus, EAT may be involved in the maintenance of AF.     

Atrial fibrillation and left atrial enlargement: cause or effect?

In a blinded controlled study, 58 consecutive patients with definite left atrial enlargement (M-mode dimension of at least 45 mm) were followed up after 1-2 years. The aim of the study was to examine the following: (a) the prospective risk of developing atrial fibrillation (AF); and (b) the effect of the heart rhythm on the left atrial size. Of 36 patients in sinus rhythm, one developed paroxysmal AF and one developed persistent AF during a median follow-up period of 20 months. Thus the incidence of new AF was 5% per year. Eighteen patients died before scheduled echocardiographic follow-up, but in the remaining subjects the left atrial dimension did not change significantly: the median increment was 1 mm in 20 patients who sustained sinus rhythm vs 2 mm in 16 patients with chronic AF (P greater than 0.05). Although left atrial dilatation may cause AF and vice versa, this study demonstrated that the incidence of new AF is low, despite the fact that the left atrial dimension is substantially increased. Similarly, AF per se does not appear to have any major impact on the left atrial dimension.     

内皮功能对阵发性房颤患者心血管事件的影响

目的 旨在探讨阵发性房颤患者内皮功能受损与心血管事件的关系。方法 选择291例阵发性房颤患者为观察组,选择无房颤病史窦性心律者40例作为对照组。对观察组进行肱动脉血流介导的血管舒张功能（flowmediated vasodilation,FMD）测定,并根据FMD水平将房颤患者分为低FMD房颤组（n=97,FMD<5.9%）和高FMD房颤组（n=194,FMD≥5.9%）。进行30个月的临床随访,首要终点事件定义为复合心血管事件（心血管死亡、非致死性心肌梗死、卒中和需住院的心力衰竭）。结果 低FMD房颤组平均年龄较对照组增高（P<0.05）,也较高FMD房颤组增高（P<0.05）。低FMD房颤组CHA2DS2-VASc积分较高FMD房颤组显著增加（P<0.05）。同时心脏超声数据显示低FMD房颤组左房末径值较对照组增高（P<0.01）、也较高FMD房颤组增高（P<0.05）;高FMD组左房末径值较对照组也明显升高（P<0.01）。与对照组比较,低FMD房颤组心血管事件发生率增加（P<0.01）,高FMD房颤组亦增加（P<0.05）;...     

Serum 25-hydroxyvitamin D concentration, established and emerging cardiovascular risk factors and risk of myocardial infarction before the age of 60 years

ObjectiveWe examined the relationships of serum 25-hydroxyvitamin D (25(OH)D) concentration to established and emerging cardiovascular risk factors and risk of myocardial infarction (MI) in a population-based case–control study of MI before the age of 60 years.MethodsA total of 387 survivors of a first MI and 387 sex- and age-matched controls were included. Fasting blood samples drawn three months after the MI in cases and at the same time in the matched controls were used for biochemical analyses.ResultsSerum concentrations of 25(OH)D, adjusted for seasonal variation, were lower in cases than controls (55.0 (40.0–71.0) nmol/L vs 60.5 (47.0–75.0) nmol/L; median (interquartile range); standardized odds ratio (OR) for MI with 95% confidence interval in univariable analysis: 0.80 (0.69–0.93); p = 0.003). The 25(OH)D association with MI disappeared after adjustment for established and emerging risk factors (OR: 1.01 (0.82–1.25)). Current smoking and plasma levels of proinsulin and PAI-1 activity were independently associated with 25(OH)D in controls, whereas waist circumference, plasma triglycerides, proinsulin, PAI-1 activity and cystatin C, and non-Nordic ethnicity were independently associated with 25(OH)D in patients. Serial measurements of 25(OH)D (samples drawn <4 h and 3 months after the onset of MI) in 57 patients showed no systematic differences between sampling times.ConclusionVitamin D insufficiency, which is associated with a multitude of metabolic, procoagulant and inflammatory perturbations, is not independently related to premature MI. This suggests that vitamin D insufficiency either constitutes an epiphenomenon or increases the risk of MI by promoting established risk factor mechanisms that predispose to atherothrombosis.     

Association between serum free thyroxine concentration and atrial fibrillation

BACKGROUND: Previous studies have suggested that minor changes in thyroid function are associated with risk of atrial fibrillation (AF). Our objective was to determine the relationship between thyroid function and presence of atrial fibrillation (AF) in older subjects. METHODS: A population-based study of 5860 subjects 65 years and older, which excluded those being treated for thyroid dysfunction and those with previous hyperthyroidism. Main outcome measures included tests of thyroid function (serum free thyroxine [T(4)] and thyrotropin [TSH]) and the presence of AF on resting electrocardiogram. RESULTS: Fourteen subjects (0.2%) had previously undiagnosed overt hyperthyroidism and 126 (2.2%), subclinical hyperthyroidism; 5519 (94.4%) were euthyroid; and 167 (2.9%) had subclinical hypothyroidism and 23 (0.4%), overt hypothyroidism. The prevalence of AF in the whole cohort was 6.6% in men and 3.1% in women (odds ratio, 2.23; P<.001). After adjusting for sex, logistic regression showed a higher prevalence of AF in those with subclinical hyperthyroidism compared with euthyroid subjects (9.5% vs 4.7%; adjusted odds ratio, 2.27; P=.01). Median serum free T(4) concentration was higher in those with AF than in those without (1.14 ng/dL; interquartile range [IQR], 1.05-1.27 ng/dL [14.7 pmol/L; IQR, 13.5-16.4 pmol/L] vs 1.10 ng/dL; IQR, 1.00-1.22 ng/dL [14.2 pmol/L; IQR, 12.9-15.7 pmol/L]; P<.001), and higher in those with AF when analysis was limited to euthyroid subjects (1.13 ng/dL; IQR, 1.05-1.26 ng/dL [14.6 pmol/L; IQR, 13.5-16.2 pmol/L] vs 1.10 ng/dL; IQR, 1.01-1.21 ng/dL [14.2 pmol/L; IQR, 13.0-15.6 pmol/L]; P=.001). Logistic regression showed serum free T(4) concentration, increasing category of age, and male sex all to be independently associated with AF. Similar independent associations were observed when analysis was confined to euthyroid subjects with normal TSH values. CONCLUSIONS: The biochemical finding of subclinical hyperthyroidism is associated with AF on resting electrocardiogram. Even in euthyroid subjects with normal serum TSH levels, serum free T(4) concentration is independently associated with AF.     

阵发性房颤随访情况和阵发性房颤进展的危险因素

目的 观察阵发性房颤的随访情况和分析阵发性房颤进展的危险因素。方法 对216例阵发性房颤患者进行随访,观察其主要结局（是否发生房颤进展）和临床事件（卒中、心力衰竭、再住院和出血事件）,再按是否房颤进展分为房颤进展组（n=87）和房颤未进展组（n=129）。采用巢式病例对照研究方法,进行单因素分析和多因素分析（采用多因素Logistic回归模型）,分析影响房颤进展的危险因素。结果 216例阵发性房颤患者经过3.45年（中位数）随访发生房颤进展者87例,其发生进展率为40.2%,年进展率为11.7%。房颤进展组脑卒中、心力衰竭、房颤相关的再住院发生率均显著高于房颤未进展组（分别17% vs. 6%,18% vs. 5%,37% vs. 17%, 分别P<0.05,P<0.01和P<0.01）;两组间病死率及出血发生率差异未达到显著水平。多因素分析显示,年龄(OR 1.082,95%CI 1.016-1.392,P<0.05)、左房内径>45 mm(OR 2.339,95%CI 1.445-3.785,P<0.05)、CHADS2评分>3分(OR 1.382,95%CI 1.081-1.987,P<0.05)以及超敏C反应蛋白（hs-CRP）水平(OR 1.124,95%CI 1.005-2.345,P<0.05 )是房颤进展的独立危险因素。结论 阵发性房颤进展的年发生率为11.6%。影响房颤进展的独立危险因素为年龄、左房内径、hs-CRP水平及CHADS2评分。