Serum osteoprotegerin levels and long‐term prognosis in subjects with stable coronary artery disease

Summary. Background: Osteoprotegerin (OPG) is a secretory glycoprotein which belongs to the tumor necrosis factor receptor family. OPG immunoreactivity was demonstrated in normal blood vessels and in early atherosclerotic lesions. In a previous study, we showed that high serum OPG levels are associated with progression of coronary artery disease (CAD). Objectives: The present study was designed to assess the association between serum OPG level and long‐term prognosis in patients with stable coronary artery disease. Methods: We performed a prospective, observational cohort study in 225 subjects to examine whether serum OPG levels can predict cardiovascular mortality. The median OPG levels were 1.02 ng mL^?1 at baseline. Results: During the follow‐up (61 ± 25 months), 27 deaths occurred including 13 cardiovascular deaths. When the subjects were divided into three groups according to serum OPG level, the group with high serum OPG showed a higher risk for cardiovascular mortality. A Multivariate Cox proportional hazards model indicated that the higher risk of cardiovascular death in the high OPG level group remained significant (hazards ratio of 7.44, 95%CI 0.92–60.30, highest vs. lowest OPG tertile). In contrast, serum OPG levels were not associated with non‐cardiovascular mortality. Conclusions: Our data show that serum OPG levels are an independent predictor of cardiovascular mortality in patients with stable coronary artery disease.     

Mortality due to pulmonary embolism,myocardial infarction,and stroke among incident dialysis patients

See also Zoccali C, Mallamaci F. Pulmonary embolism in chronic kidney disease: a lethal, overlooked and research orphan disease. This issue, pp 2481–3. Summary. Background: It is has been suggested that dialysis patients have lower mortality rates for pulmonary embolism than the general population, because of platelet dysfunction and bleeding tendency. However, there is limited information whether dialysis is indeed associated with a decreased mortality risk from pulmonary embolism. Objective: The aim of our study was to evaluate whether mortality rate ratios for pulmonary embolism were lower than for myocardial infarction and stroke in dialysis patients compared with the general population. Methods: Cardiovascular causes of death for 130 439 incident dialysis patients registered in the ERA‐EDTA Registry were compared with the cardiovascular causes of death for the European general population. Results: The age‐ and sex‐standardized mortality rate (SMR) from pulmonary embolism was 12.2 (95% CI 10.2–14.6) times higher in dialysis patients than in the general population. The SMRs in dialysis patients compared with the general population were 11.0 (95% CI 10.6–11.4) for myocardial infarction, 8.4 (95% CI 8.0–8.8) for stroke, and 8.3 (95% CI 8.0–8.5) for other cardiovascular diseases. In dialysis patients, primary kidney disease due to diabetes was associated with an increased mortality risk due to pulmonary embolism (HR 1.9; 95% CI 1.0–3.8), myocardial infarction (HR 4.1; 95% CI 3.4–4.9), stroke (HR 3.5; 95% CI 2.8–4.4), and other cardiovascular causes of death (HR 3.4; 95% CI 2.9–3.9) compared with patients with polycystic kidney disease. Conclusions: Dialysis patients were found to have an unexpected highly increased mortality rate for pulmonary embolism and increased mortality rates for myocardial infarction and stroke.     

Effects of perioperative statins on patient outcomes after noncardiac surgery: a meta-analysis

Background: Cardiovascular complications are strongly correlated with a higher risk of mortality during follow-up after noncardiac surgery. However, controversy remains regarding whether perioperative administration of hydroxymethylglutaryl-CoA reductase inhibitors (statins) has a beneficial effect on patient outcomes.

Objective: We performed a meta-analysis to validate the hypothesis that perioperative statins improve patient outcomes after noncardiac surgery.

Methods: Electronic databases (PubMed, Web of Science, EMBASE, and the Cochrane Library) were searched for randomized controlled trials (RCTs) published up to 10 November 2017. RCTs were eligible for inclusion if they compared perioperative statin treatment with control treatment in patients scheduled for noncardiac surgery and reported data pertaining to clinical outcomes.

Results: Twelve RCTs involving 4707 patients (2371 in the perioperative statin group and 2336 in the control group) were ultimately included in this meta-analysis. The incidences of postoperative myocardial infarction, composite of death/myocardial infarction/stroke and new cases of atrial fibrillation were all lower in patients treated with statins than in control group patients, as shown by the fixed-effects model (odds ratio (OR)?=?0.460, 95% confidence interval (CI)?=?0.324–0.653, p?=?0 for myocardial infarction; OR?=?0.617, 95% CI?=?0.476–0.801, p?=?0 for composite of death/myocardial infarction/stroke; OR?=?0.406, 95% CI?=?0.247–0.666, p?=?0 for new atrial fibrillation). No significant differences in the incidences of stroke or transient ischemic attack, all-cause mortality and cardiovascular mortality were observed between the statin and control arms.

Conclusions: This meta-analysis supports the hypothesis that perioperative statins effectively reduce the incidences of postoperative myocardial infarction, composite of death/myocardial infarction/stroke and new cases of atrial fibrillation in patients undergoing noncardiac surgery.

• Key Messages

• Cardiovascular complications are strongly correlated with a higher risk of mortality during follow-up after noncardiac surgery.

• We performed a meta-analysis to confirm the hypothesis that perioperative statins improve patient outcomes after noncardiac surgery.

     

Novel mutations in leukotriene C4 synthase and risk of cardiovascular disease based on genotypes from 50 000 individuals

Summary. Background: Atherosclerosis is an inflammatory condition where cysteinyl leukotrienes have been identified to play an important role. Furthermore, cysteinyl leukotrienes may also affect thrombus formation. Using prospective, cross‐sectional and case‐control designs, we tested the hypothesis that hitherto unknown genetic variation, likely to affect the function of leukotriene C₄ synthase, is associated with risk of venous thromboembolism, ischemic stroke and myocardial infarction. Methods and Results: Resequencing the gene coding for leukotriene C₄ synthase in an extreme risk population with more than 1500 individuals revealed 17 new mutations, of which four are likely to change protein function (211G>A (minor allele frequency, 0.0001), IVS3 + 1G>A (0.002), 374G>A (0.0006) and 451_453+10del (0.0007)). Based on genotyping 50 000 individuals, age and sex adjusted odds ratios for venous thromboembolism were 2.0 (95% CI, 1.3–3.5) for IVS3+1G>A heterozygotes vs. wild type, and 1.9 (1.5–2.7) for any mutation heterozygote vs. wild type. Corresponding values were 2.0 (1.3–3.2) and 1.5 (1.1–2.1) for ischemic stroke, and 1.0 (0.8–1.3) and 1.2 (1.0–1.4) for myocardial infarction. Conclusions: Four novel mutations that are likely to change the function of leukotriene C₄ synthase were associated with increased risk of venous thromboembolism and ischemic stroke. These findings need confirmation in other independent studies. In addition, the mechanism behind these findings deserves further investigation.     

Prothrombotic gene variation and new vascular events after cerebral ischemia of arterial origin

Summary. Background: Several genetic variants involved in hemostasis have been associated with ischemic stroke or myocardial infarction (MI). Stroke patients who carry a prothrombotic genotype may also be at increased risk for subsequent vascular events. Patients and methods: We included 887 patients with non‐disabling cerebral ischemia of arterial origin, who were referred to the University Medical Center Utrecht in the Netherlands between 1995 and 2005 and followed them for the occurrence of ischemic stroke, MI or death. The primary outcome was a composite of death from all vascular causes, non‐fatal ischemic stroke, non‐fatal MI, whichever happened first. We selected 22 prothrombotic variants in 14 genes that were previously associated with ischemic stroke or MI or had evidence of functionality. Results: During a 4.6‐year mean follow‐up period new vascular events occurred in 135 patients (annual event rate 3.3%). None of the 22 variants was associated with the occurrence of new vascular events. Eight additional analyses with secondary outcomes or among subgroups revealed four associations that were likely to be false positive after accounting for multiple testing. Conclusions: In this cohort, prothrombotic genetic variants do not affect the risk of new vascular events after cerebral ischemia of arterial origin. This study does not support the use of prothrombotic genetic variants to identify stroke patients at increased risk for new vascular events or to guide antithrombotic treatment.     

Thrombin generation in patients with a first acute myocardial infarction

Summary. Background: Despite improved treatment options, myocardial infarction is still an important cause of morbidity and mortality. One of the contributing mechanisms in the acute myocardial infarction (AMI) is plasma hypercoagulability. Methods: We investigated hypercoagulability in 135 (first) patients with AMI using thrombin generation (TG) testing. TG testing was performed in plasmas, drawn upon admission and before medication administration, and subsequently after 4 days, 3 and 6 months. Further, we evaluated determinants of thrombin generation using multiple regression analysis of major coagulation proteins and inhibitors. Admission TG results were also related to 1‐year outcome: cardiovascular death, recurrent myocardial infarction, a second coronary intervention [percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)] and ischemic stroke. Results: At day 0, the TG parameters peak height, endogenous thrombin potential (ETP) and lag time were increased compared with a reference population. Peak height and lag time stayed persistently increased in patients. The lowest half of the ETP values was statistically not significantly associated with an occurrence of endpoints. The lowest half of the ETP values combined with the upper half of the D‐dimer values were associated with endpoints; odds ratio 5.8 (1.1–30.7). Tissue factor pathway inhibitor (TFPI) seems to be an important determinant of TG in AMI and healthy persons. Conclusions: TG reflects acute hypercoagulability during AMI and partly also in the 6‐month period after the acute event. TG shows a trend of an inverse association with risk of recurrent ischemic cardiovascular complications. Unraveling mechanisms in TG might improve our understanding of the pathophysiology of AMI and direct future improvements in medical care.     

Alcohol consumption reduces coronary heart disease even among men with hypertension

Evaluation of: Beulens JW, Rimm EB, Ascherio A, Spiegelman D, Hendriks HF, Mukamal KJ. Alcohol consumption and risk for coronary heart disease among men with hypertension. Ann. Intern. Med. 146(1), 10–19 (2007).

Beulens and colleagues evaluated 11,711 men with hypertension in a cohort study and found that moderate alcohol consumption was associated with a decreased risk of myocardial infarction in comparison with subjects who abstained from alcohol consumption. There were no significant differences in death from all causes, death due to cardiovascular disease, total stroke events and ischemic stroke between the two groups.     

Atrial fibrillation and upper limb thromboembolectomy: a national cohort study

Summary. Background: The risk factors associated with, and the incidence of systemic embolism in patients with atrial fibrillation (AF) are poorly understood. Objectives: We studied the association between AF and upper limb thromboembolectomy involving brachial, ulnar or radial artery in a national cohort study that included all individuals aged 40–99 years with incident AF. Methods: Data were retrieved from the Danish National Vascular Registry, the National Registry of Patients, the Danish Civil Registration System and Statistics Denmark. Results: In total, 131 476 patients (68 042 men and 63 434 women) with AF without previous thromboembolectomy in the upper limb were registered. In the study cohort, 130 men underwent upper limb thromboembolectomy over 220 890 person‐years of observation, whilst 275 women underwent thromboembolectomy over 197 777 patient‐years. The incidence per 100 000 person‐years was 58.9 (95% CI, 49.2–69.8) for men and 139.1 (95% CI, 123.1–156.5) for women. The relative risk of thromboembolectomy among patients with AF compared to the background population was 7.5 (95% CI, 6.3–8.9) for men, and 9.3 (95% CI, 8.3–10.5) for women. Women with AF had a relative thromboembolectomy risk of 1.8 (95% CI, 1.5–2.3) compared to men with AF. Among patients with AF, history of hypertension (HR 2.2–2.9), myocardial infarction (HR 2.9–3.9), heart failure (HR 1.6–1.9) and stroke (HR 2.2–3.8) were significantly associated with increased risk of thromboembolectomy in both men and women. Conclusions: AF substantially increases the risk of upper limb thromboembolectomy. This risk is higher with increasing age, female gender, and associated with hypertension, myocardial infarction, heart failure and stroke.     

Myocardial infarction and cerebrovascular accident following non-cardiac surgery: differences in postoperative temporal distribution and risk factors

Summary. Background: Myocardial infarction and stroke after non‐cardiac surgery are two ominous cardiovascular complications believed to share similar pathophysiological processes. However, the differences in the temporal distribution between them have not been adequately investigated in a large cohort of patients. Methods and Results: The preoperative clinical features and daily occurrence of myocardial infarction and stroke were routinely recorded in 36 634 consecutive patients following elective non‐cardiac, non‐carotid surgery . The preoperative characteristics and postoperative daily distribution of postoperative myocardial infarction and stroke were compared using exponential and linear regressions models. Myocardial infarction and stroke occurred in 122 (0.33%) and 126 (0.34%) patients, respectively, during the first 30 days after surgery. More patients with myocardial infarction had diabetes mellitus and cardiac disease (P = 0.041 and <0.0001, respectively) whereas more patients with stroke were older and female (P = 0.003 and 0.038, respectively). The peak incidence of myocardial infarction was on the day of surgery (43%) and declined exponentially thereafter (F = 725.4, P < 0.0001). However, postoperative stroke best fitted a linear regression with almost even daily distribution (F = 15.9, P = 0.0004). The median time to myocardial infarction was one day [95% confidence interval (95% CI) = 0–2 days] compared with nine days (95% CI = 7–11 days) for stroke. Conclusions: The peak incidence of postoperative myocardial infarction is early after non‐cardiac surgery and declines exponentially thereafter, as opposed to stroke, which occurs at a constant rate during the postoperative period. Myocardial infarction and cerebrovascular accident following non‐cardiac surgery differ in their preoperative risk factors, and in the postoperative time‐line of their occurrence.     

A 32-year longitudinal study of alcohol consumption in Swedish women: Reduced risk of myocardial infarction but increased risk of cancer

Objective. To assess associations between the intake of different types of alcoholic beverages and the 32-year incidence of myocardial infarction, stroke, diabetes, and cancer, as well as mortality, in a middle-aged female population. Design. Prospective study. Setting. Gothenburg, Sweden, population about 430 000. Subjects. Representative sample of a general population of women (1462 in total) aged 38 to 60 years in 1968–1969, followed up to the ages of 70 to 92 years in 2000–2001. Main outcome measures. Associations between alcohol intake and later risk of mortality and morbidity from myocardial infarction, stroke, diabetes, and cancer, studied longitudinally. Results. During the follow-up period, 185 women developed myocardial infarction, 162 developed stroke, 160 women became diabetic, and 345 developed cancer. Women who drank beer had a 30% lower risk (hazards ratio (HR) 0.70, 95% confidence interval (CI) 0.50–0.95) of developing myocardial infarcion and almost half the risk (HR 0.51 CI 0.33–0.80). A significant association between increased risk of death from cancer and high spirits consumption was also shown (hazards ratio [HR] 1.47, CI 1.06–2.05). Conclusions. Women with moderate consumption of beer had a reduced risk of developing myocardial infarction. High spirits consumption was associated with increased risk of cancer mortality.     

ABO genotype and risk of thrombotic events and hemorrhagic stroke

Summary. Background: The non‐O alleles of the ABO genotype have been associated with an increased risk of thrombosis. Risk associated with the specific A¹, A² or B alleles is not well defined. Objectives: To examine the association of the ABO genotype with myocardial infarction (MI), ischemic stroke, hemorrhagic stroke, and venous thrombosis (VT). Patients and methods: We used data from two ongoing population‐based case–control studies of MI, stroke, and VT. Cases included hypertensive adults and postmenopausal women with incident non‐fatal MI (n = 1063), ischemic stroke (n = 469), and hemorrhagic stroke (n = 91), and postmenopausal women with incident non‐fatal VT (n = 504). Controls were frequency matched to cases on age, sex, hypertension status, and year of identification. ABO genotypes were determined using single‐nucleotide polymorphisms, and subjects were grouped by diplotype according to the presence of O¹, O², A¹¹, A² and B alleles. Logistic regression was used to test the association of diplotypes with risk of each outcome. Results: As compared with the O¹O¹ group, the A¹¹ allele was associated with an increased risk of VT [odds ratio (OR) 1.79; 95% confidence interval (CI) 1.41–2.26] and MI (OR 1.23; 95% CI  1.05–1.44). The B allele was associated with an increased risk of VT (OR 1.82; 95% CI  1.29–2.57) and ischemic stroke (OR 1.59; 95% CI  1.17–2.17). The AB diplotype category was associated with a 2.7‐fold risk of VT (OR 2.70; 95% CI  1.73–4.21). No other associations reached significance. Conclusions: The VT and MI findings are confirmatory, and the ischemic stroke finding with the B allele is a novel finding and needs replication.     

Impact of vascular disease in predicting stroke and death in patients with atrial fibrillation: the Danish Diet,Cancer and Health cohort study

Summary. Background: The presence of vascular disease (peripheral artery disease [PAD] and/or myocardial infarction [MI]) may impact on the risk of stroke and death among patients with incident atrial fibrillation (AF). To test this hypothesis, we analyzed data from a large Danish prospective cohort, the Danish Diet, Cancer and Health (DCH) study, to assess the risk of stroke or death among those who developed AF according to concomitant presence of vascular disease. Methods: A prospective cohort study of 57 053 persons (27 178 men and 29 876 women, respectively), aged between 50 and 64 years. The risk of stroke or death for patients with vascular disease was assessed amongst 3315 patients with incident AF (mean age, 67.1 years; 2130 men, 1185 women) using Cox proportional hazard models, after a median follow‐up of 4.8 years. Results: Of the subjects with AF, 417 (12.6%) had ‘vascular disease’ (PAD and/or prior MI). The risk of the primary endpoint (stroke or death) was significantly higher in patients with vascular disease at 1‐year follow‐up (crude hazard ratio [HR] 2.51 [1.91–3.29]), with corresponding crude HRs for PAD and MI being 3.51 (2.40–5.13), and 1.99 (1.46–2.72), respectively. For the secondary endpoints of death or stroke individually, these risk estimates were similar (crude HR 2.48 [1.89–3.26] and 1.77 [1.18–2.66], respectively). After adjustment for risk factors within the CHADS₂ score, the adjusted HR for the primary endpoint (stroke or death) in patients with vascular disease was 1.91 (1.44–2.54), which was also significant for death (1.97 [1.48–2.62]). Conclusion: Vascular disease (prior MI and PAD) is an independent risk factor for the primary endpoint of ‘stroke or death’ in patients with AF, even after adjustment for the CHADS₂ risk score, although this is driven by the impact on mortality. This reaffirms that patients with vascular disease represent a ‘high‐risk’ population, which necessitates proactive management of all cardiovascular risk factors and effective thromboprophylaxis (i.e. oral anticoagulation), which has been shown to significantly reduce the risk of stroke and death in AF.     

Statins after recent stroke reduces recurrence and improves survival in an aging Mediterranean population without known coronary heart disease

What is known and Objective: The effect of a statin‐based medical intervention on prevention of fatal and non‐fatal stroke recurrence and the incidence of all‐causes mortality have been explored previously in aging populations within the scope of clinical trials research. However, such evidence needs to be explored under conditions of routine clinical practice. The objective of this study was to determine whether statin therapy in patients with a first stroke episode reduces the incidence of 6‐year recurrent fatal or non‐fatal stroke and all‐cause mortality in an aging Mediterranean population without known coronary heart disease followed in routine medical practice. Methods: A retrospective study was carried out using records on death, hospitalizations owing to stroke and history of statin therapy included in the Badalona Serveis Assistencials (BSA) database. The cohort studied consisted of consecutive patients covered by the BSA health provider plan with a first‐ever acute stroke episode during January 2003 until December 2008, for whom there was available information covering the 6‐year follow‐up period. Recurrence rate (RR) and incidence rate (IR) of fatal/non‐fatal stroke and all‐causes mortality were computed. Association with statin therapy was assessed by means of calculation of relative risk (RR) and hazard ratio (HR) using multivariate logistic regression and Cox proportional hazards models controlling for confounding covariates. Results and Discussion: The cohort comprised a series of 601 consecutive patients [57% men, 75·9 (12·4) years old (88% >60 years)]. Of these, 32% received statins, which were associated with lower fatal/non‐fatal recurrent stroke RR; 7% vs. 18% [adjusted RR = 0·32 (CI: 0·16–0·61), P = 0·001] and lower IR; 16·78 vs. 45·22 events/year‐1000 subjects [adjusted HR = 0·35 (0·19–0·64), P = 0·001]. Similarly, observed all‐causes mortality was lower in the cohort receiving statins; 11% vs. 16% [adjusted RR = 0·29 (CI: 0·08–1·12), P = 0·072], and also mortality rate; 26·09 vs. 36·25 deaths/year‐1000 subjects [adjusted HR = 0·23 (0·08–0·67), P = 0·007]. What is new and Conclusions:  Statin therapy in patients with first‐ever acute stroke lowers the risk of 6‐year stroke recurrence and improves survival in an aging Mediterranean cohort. These results add additional evidence in routine clinical practice to the observed effects of statins in clinical trials.     

Relation between serum osteoprotegerin and carotid intima media thickness in a general population – the Tromsø Study

Summary. Background: Previous studies have reported conflicting results on the relation between serum osteoprotegerin (OPG) concentration and carotid intima media thickness (CIMT). Patients/methods: The present study was conducted to investigate the relations between OPG, risk factors for cardiovascular diseases (CVD) and carotid intima media thickness (CIMT) in a large cross‐sectional study including 6516 subjects aged 25–85 years who participated in a population‐based health survey. Results: CIMT increased significantly across tertiles of OPG after adjustment for traditional cardiovascular risk factors such as age, gender, smoking, total cholesterol, high‐density lipoprotein (HDL) cholesterol, C‐reactive protein (CRP), body mass index (BMI), systolic blood pressure, CVD and diabetes mellitus (P < 0.0001). There was a significant interaction between age and OPG (P = 0.026). The risk of being in the uppermost quartile of CIMT was reduced (OR 0.52, 95% CI 0.30–0.88) with each standard deviation (SD) higher level of OPG in subjects < 45 years (n = 444), whereas subjects ≥ 55 years of age (n = 4884) had an increased risk of being in the uppermost quartile of CIMT (OR 1.19, 95% CI 1.10–1.29) after adjustment for traditional CVD risk factors. Conclusions: Age has a differential impact on the association between OPG and CIMT in a general population. The present findings may suggest that increased serum OPG does not promote early atherosclerosis in younger subjects.     

High blood hemoglobin concentration as risk factor of major atherosclerotic cardiovascular events in 114,159 healthy men and women in the Apolipoprotein MOrtality RISk study (AMORIS)

Abstract

Background. Few studies have tested differences in relationships between hemoglobin (Hb) and long-term risk of major cardiovascular diseases according to age and gender in healthy subjects as opposed to anemia.

Aims. Such relationships were examined and risk-tested in relation to Hb values in the Apolipoprotein MOrtality RISk (AMORIS) Study.

Methods. Using data from AMORIS and the Swedish hospital discharge and mortality registers, a prospective cohort study of 114,159 subjects with mean follow-up of 11.8 years, the association between Hb and risk of acute myocardial infarction (AMI), ischemic stroke (IS), and congestive heart failure (CHF) by Cox regression analysis according to age and gender was studied.

Results. Elevated Hb levels were associated to acute myocardial infarction (AMI) (HR 1.10 (1.06–1.13) per SD change), mostly confined to men and younger subjects but with greater sex similarity trends for CHF. Slightly increased risks were seen for the lowest Hb levels in the elderly and in females. IS risk was positively and more linearly associated to Hb.

Interpretation. In AMORIS the highest AMI and CHF risks were found in the upper region of the distribution, but different shapes of relationships according to age and gender were found. IS associated positively with Hb. Key words:     

Atrial fibrillation hospitalization is not increased with short-term elevations in exposure to fine particulate air pollution

Background: Previous studies have observed that short‐term exposure to elevated concentrations of particulate matter (PM) air pollution increases risk of acute ischemic heart disease events and heart failure hospitalization, alters cardiac autonomic function, and increases risk of arrhythmias. This study explored the potential associations between short‐term elevations in PM exposure and atrial fibrillation (AF). Methods and Results: A case‐crossover study design was used to explore associations between fine PM (PM2.5, particles with an aerodynamic diameter ≤2.5 μm) and 10,457 AF hospitalizations from 1993 to 2008 of patients who lived on Utah's Wasatch Front. Patients were hospitalized at Intermountain Healthcare facilities with a primary diagnosis of AF. Concurrent day exposure and cumulative lagged exposures for up to 21 days were explored and the data were stratified by sex, age, and previous or subsequent admission for myocardial infarction. Although the estimated associations between PM2.5 and AF hospitalizations for the various lag structures and strata were consistently positive suggestive of risk, they were not statistically significant and they were extremely small compared to previously observed associations with ischemic heart disease events and heart failure hospitalizations. Further, we observed no additive risk between PM2.5 and AF hospitalization in those with respiratory disease or sleep apnea. Conclusions: Unlike previously observed associations with ischemic heart disease events and heart failure hospitalizations using similar study design and approaches, this study found that hospitalization for AF was not significantly associated with elevations in short‐term exposure to fine PM air pollution. (PACE 2011; 34:1475–1479)     

Severe vascular events in migraine patients

OBJECTIVE: To estimate rates of vascular events in relation to dispensing of triptans and ergot alkaloids among migraineurs, and to compare these rates with those of nonmigraineurs. CONTEXT: It has been speculated that the use of triptans or ergot alkaloid drugs might increase risk of ischemic events through vasoconstriction. Design: A retrospective cohort study of 130,411 migraineurs and 130,411 age-, sex-, and health plan-matched nonmigraineurs who were members of UnitedHealthcare during 1995 through 1999. The data source for this study was Ingenix's research database containing pharmacy and medical claims for UnitedHealthcare members, and the National Death Index. MAIN OUTCOME MEASURES: Incidence of cardiovascular and cerebrovascular events and mortality. RESULTS: Migraineurs and nonmigraineurs had identical rates of myocardial infarction: 1.4 per 1000 person-years. Migraineurs were 67% more likely to suffer a stroke than nonmigraineurs (adjusted relative risk [RR] 1.67, 95% confidence interval [CI] 1.31-2.13), and had higher rates of unstable angina and transient ischemic attacks. There was no increase in risk of myocardial infarction with current (adjusted RR 0.80, 95% CI 0.58-1.11) or recent (adjusted RR 1.15, 95% CI 0.71-1.87) triptan use. Neither current (adjusted RR 0.90, 95% CI 0.64-1.26) nor recent (adjusted RR 0.84, 95% CI 0.46-1.55) triptan use was associated with risk of stroke. Current users of ergot alkaloids were somewhat more likely to have a stroke than other migraineurs (adjusted RR 1.49, 95% CI 0.93-2.41), but there was no dose-response relationship. CONCLUSIONS: Use of triptans is not associated with increased risk of any ischemic events, including myocardial infarction and stroke, or mortality. Consistent with previous studies, migraineurs in general have an elevated risk of stroke, but not myocardial infarction, compared with nonmigraineurs.     

Prospective study of circulating soluble CD40 ligand concentrations and the incidence of cardiovascular disease in a nested prospective case–control study of older men and women

Summary. Background: CD40 ligand(CD40L) is implicated in atherosclerotic plaque formation. Objectives: We investigated prospective associations between circulating soluble CD40L and myocardial infraction (MI) or stroke in an older general population cohort, accounting for established and novel cardiovascular risk factors. Methods: Baseline serum CD40L (sCD40L) was measured in incident MI (n = 368) and stroke (n = 304) cases and two controls per case, ‘nested’ in prospective UK studies of 4252 men and 4286 women aged 60–79 years, sampled from general practices in Britain in 1998–2000, with 7‐year follow‐up for fatal and non‐fatal MI and stroke. Results: sCD40L was higher in smokers and negatively associated with lung function and positively associated with total cholesterol and markers of inflammation, but not with other established cardiovascular disease (CVD) risk factors. Geometric mean sCD40L levels did not differ between MI cases and controls (5.94 ng mL^?1 vs. 5.82 ng mL^?1; P = 0.5) or between stroke cases and controls (5.61 ng mL^?1 vs. 5.28 ng mL^?1, P = 0.1). There was no strong evidence for elevated risk of MI or stroke in multivariable models comparing participants in the top to those in the bottom third of sCD40L. Age‐adjusted odds ratios (ORs) were 1.39 [95% confidence interval (CI) 0.98, 1.96] for MI and 1.16 (0.78, 1.73) for stroke. These attenuated to 1.24 (95% CI 0.86, 1.79) and 1.18 (0.78, 1.78), respectively, after adjustment for established and novel CVD risk factors. Conclusions: sCD40L is associated with other inflammatory markers but is not itself a strong independent risk marker for either stroke or MI.     

Lower Extremity Arterial Disease as a Predictor of Incident Atrial Fibrillation and Cardiovascular Events

ObjectiveTo evaluate the relationship between peripheral arterial disease (PAD) and incident atrial fibrillation (AF) and its clinical and pathophysiologic implications on ischemic stroke and all-cause mortality.Patients and MethodsWe identified all adult patients in the Mayo Clinic Health System without a previous diagnosis of AF undergoing ankle-brachial index (ABI) testing for any indication from January 1, 1996, to June 30, 2018. Retrospective extraction of ABI data and baseline echocardiographic data was performed. The primary outcome of interest was incident AF. The secondary outcomes of interest were incident ischemic stroke and all-cause mortality.ResultsA total of 33,734 patients were included in the study. After adjusting for demographic and comorbidity variables, compared with patients who had normal ABI (1.0 to 1.39), there was an increased risk of incident AF in patients with low ABI (<1.0) (adjusted hazard ratio, 1.14; 95% CI, 1.06 to 1.22) and elevated ABI (≥1.4) (adjusted hazard ratio, 1.18; 95% CI, 1.06 to 1.31). The risk was greater in patients with increasing severity of PAD. Patients with abnormal ABIs had an increased risk of ischemic stroke and all-cause mortality. We found that patients with PAD and incident AF have certain baseline echocardiographic abnormalities.ConclusionIn this large cohort of ambulatory patients undergoing ABI measurement, patients with PAD were at increased risk for incident AF, ischemic stroke, and mortality. In these high-risk patients with abnormal ABI, particularly severe PAD and cardiac structural abnormalities, routine monitoring for AF and management of cardiovascular risk factors may be warranted.     

Platelets oxidative stress in Indian patients with ischemic heart disease

Background: Oxidative stress has been implicated in the development of atherosclerosis and vascular tissue injury. Both platelet activation and lipid peroxidation are known to play major role in ischemic heart disease. The purpose of this study was to investigate the status of platelets oxidative stress in Indian patients with ischemic heart disease. Methods: We measured platelets aggregation, malonyldialdehyde (MDA), plasma‐ionized Ca²⁺, and antioxidant enzymes, i.e., glutathione peroxidase and superoxide dismutase in healthy volunteers and patients with myocardial infarction, unstable and stable angina 40 subjects each. Results: Platelets aggregation, MDA, and plasma‐ionized Ca²⁺ have increased significantly across the patients groups compared with controls, this increase was accompanied by an overall decrease in the antioxidant enzymes activity; except for the slight increases in the glutathione peroxidase levels among the myocardial infarction patients. Conclusions: The current results suggest that platelet lipid peroxidation as marked by increased MDA level is augmented in ischemic heart diseases. The increased oxidative stress seen in these patients was accompanied by platelet activation and impaired antioxidant enzymes activity. J. Clin. Lab. Anal. 24:49–54, 2010. © 2010 Wiley‐Liss, Inc.