Influence of the β-fibrinogen-455G/A polymorphism on development of ischemic stroke and coronary heart disease

Background

Ischemic stroke (IS) and coronary heart disease (CHD) are two vascular disorders that are a common cause of death worldwide. Several studies have assessed the association of the β-fibrinogen-455G/A (FGB-455G/A) polymorphism and risk of IS and CHD, but the results are still inconsistent. Our study aimed to investigate whether the FGB-455G/A polymorphism was associated with susceptibility to IS and CHD by using meta-analysis.

Methods

Relevant studies were identified from PubMed, Embase and four Chinese database up to July 2013.Data were analyzed and processed by Stata 11.2. A pooled OR with 95% CI was calculated to estimate the strength of the genetic association. Cumulative meta-analysis was performed to assess the tendency of pooled OR over time.

Results

45 studies based on a total of 7238 cases and 7395 controls were included in our meta-analysis. The results indicated that the FGB-455G/A polymorphism is associated with the risk of IS when compared with the dominant model (OR = 1.518, 95%CI = 1.279-1.802 for AA + GA vs. GG). In the subgroup analysis by ethnicity, significantly elevated risks were associated with the A allele in Asians (OR = 1.700, 95%CI = 1.417-2.040), but not in Caucasians (OR = 0.942, 95%CI = 0.813-1.091). Both the hypertension and non-hypertension subgroups reached significant results, but no significance was found when stratified according to sex or subtype of IS. Results indicate that the FGB-455G/A polymorphism is associated with CHD (OR = 1.802, 95%CI = 1.445-2.246).

Conclusion

Our meta-analysis suggests that the FGB-455G/A polymorphism contributes to susceptibility to IS and CHD.     

Alcohol consumption, types of alcoholic beverages and risk of venous thromboembolism - the Tromsø Study

Moderate alcohol consumption has been shown to protect against cardiovascular diseases. The association between alcohol consumption, especially types of alcoholic beverages, and venous thromboembolism (VTE) is less well described. The aim of this study was to investigate the impact of alcohol consumption and different alcoholic beverages on risk of VTE. Information on alcohol consumption was collected by a self-administrated questionnaire in 26,662 subjects, aged 25-97 years, who participated in the Troms? Study, in 1994-1995. Subjects were followed through September 1, 2007 with incident VTE as the primary outcome. There were 460 incident VTE-events during a median of 12.5 years of follow-up. Total alcohol consumption was not associated with risk of incident VTE. However, subjects consuming ≥ 3 units of liquor per week had 53% increased risk of VTE compared to teetotalers in analyses adjusted for age, sex, body mass index, smoking, diabetes, cancer, previous cardiovascular disease, physical activity and higher education (HR: 1.53, 95% CI: 1.00-2.33). Contrary, subjects with a wine intake of ≥ 3 units/week had 22% reduced risk of VTE (HR: 0.78, 95% CI: 0.47-1.30), further adjustment for liquor and beer intake strengthened the protective effect of wine (HR: 0.53, 95% CI: 0.30-1.00). Frequent binge drinkers (≥ 1/week) had a 17% increased risk of VTE compared to teetotallers (HR 1.17, 95% CI: 0.66-2.09), and a 47% increased risk compared to non-binge drinkers (HR 1.47, 95% CI: 0.85-2.54). In conclusion, liquor consumption and binge drinking was associated with increased risk of VTE, whereas wine consumption was possibly associated with reduced risk of VTE.     

Is cardiovascular disease a risk factor in the development of axonal polyneuropathy?

OBJECTIVES: To determine if cardiovascular disease may be a risk factor in the development of chronic idiopathic axonal polyneuropathy (CIAP). METHODS: In this incidence case-control study, the prevalence of cardiovascular disease and risk factors in 97 patients with CIAP (mean age 67.5 (SD 7.9) years) and the prevalence of neuropathic features in 97 patients with peripheral arterial disease (PAD) (mean age 67.1 (SD 7.3) years) were investigated. The results were compared with those for 96 age and sex matched controls without diagnosed PAD or polyneuropathy (mean age 67.5 (SD 9.1) years). In a randomly chosen subgroup of 23 patients with CIAP, 42 patients with PAD, and 48 controls, an electrodiagnostic investigation was performed. RESULTS: Patients with CIAP more often had manifest cardiovascular disease and cardiovascular risk factors than controls (stroke 18% v 6% of patients, odds ratio (OR) 3.2 (95% confidence interval (CI) 1.8 to 5.9); heart disease 29% v 15%, OR 2.4 (95% CI 1.2 to 4.9); family history of cardiovascular disease 42% v 21%, OR 2.8 (95% CI (1.5 to 5.2); hypertension 56% v 39%, OR 2.0 (95% CI 1.1 to 3.6); hypercholesterolaemia 46% v 21%, OR 3.3 (95% CI 1.5 to 7.3); current smoking 38% v 23%, OR 2.1 (95% CI 1.1 to 3.9)). The prevalence of cardiovascular disease and cardiovascular risk factors was lower than in patients with PAD. Patients with PAD more often had polyneuropathy than controls (15% v 5%, OR 3.3 (95% CI 1.1 to 10.0)). There was a trend towards lower nerve conduction velocities and lower amplitudes on electrodiagnostic investigation compared with controls. CONCLUSION: This study shows that cardiovascular disease and CIAP often coexist, and therefore cardiovascular disease may be a cofactor in the development of CIAP.     

Daytime sleepiness and risk of coronary heart disease and stroke: results from the Nurses’ Health Study II

ObjectiveThe objective of this study was to determine whether daytime sleepiness is independently associated with coronary heart disease (CHD) and stroke or whether the positive association is explained by short sleep duration, disturbed sleep, and circadian disruption, conditions that are associated with cardiometabolic risk factors for vascular events.MethodsLongitudinal analyses of data from the Nurses’ Health Study II comprising 84,003 female registered nurses aged 37–54 at baseline were conducted in 2001 with follow-up until 2009. Multivariate Cox regression was used to explore the relationship between reported daytime sleepiness and the incidence of either CHD or stroke (n = 500 cases).ResultsWomen who reported daytime sleepiness almost every day, compared with rarely/never, had an elevated adjusted risk of cardiovascular disease (CVD) (hazard ratio (HR) = 1.58, 95% confidence interval (CI) 1.15–2.17). Controlling for sleep variables (sleep duration, snoring, shift work, and sleep adequacy) or potential metabolic biological mediators of disrupted sleep (diabetes, hypercholesterolemia, and hypertension) appreciably attenuated the relationship (HR = 1.17, 95% CI 0.84–1.65; and HR = 1.34, 95% CI 0.97–1.85, respectively). Controlling for both sleep variables and metabolic risk factors eliminated an independent association (HR = 1.09, 95% CI 0.77–1.53). A similar pattern was observed for CHD and stroke individually.ConclusionsDaytime sleepiness was not an independent risk factor for CVD in this cohort of women, but rather, was associated with sleep characteristics and metabolic abnormalities that are risk factors for CVD.     

Going to the heart of the matter: do negative emotions cause coronary heart disease?

OBJECTIVE: Negative emotions, such as anger, anxiety, and depression, have emerged as potentially important risk factors for coronary heart disease. The purpose of this article is to consider the nature and function of emotions, to review epidemiological evidence for an association between the three negative emotions and coronary heart disease (CHD), to discuss briefly the mechanisms by which emotions may be linked to CHD, and to consider this evidence in light of theoretical insights provided by mainstream psychological research on emotions. METHODS: We collected articles published between 1980 and 1998 on the relationship between each negative emotion and CHD. We also collected review articles or chapters published during the same time period that considered mechanisms by which emotions may increase CHD risk. We used a qualitative approach to review the published literature. RESULTS: Evidence that anxiety is involved in the onset of CHD is strongest, whereas evidence for an association between anger and CHD is limited but suggestive. Although depression has consistently been linked to mortality following a myocardial infarction, evidence for its role in the onset of coronary disease is quite mixed. Numerous unresolved issues leave our current understanding of the emotion-health relationship incomplete. Psychological theories of emotion are considered to help address gaps in our knowledge. CONCLUSION: Growing evidence indicates that negative emotions may influence the development of CHD. The focused and specific consideration of negative emotions and their possible role in the etiology of CHD gives insight into current knowledge and suggests important directions for future research.     

DNA-polymorphisms and plasma levels of vascular disease risk factors in Greenland Inuit--is there a relation with the low risk of cardiovascular disease in the Inuit?

Greenland Inuit are a population with a low risk of cardiovascular disease. Recently, we stated that frequencies of potentially high risk alleles of the apolipoproteins, fibrinogen, factor V, glycoprotein IIIa and factor VII (FVII) genes have different allele frequencies in the Inuit when compared with Caucasian populations. We have extended this study and evaluated whether or not this was also true for the genetic polymorphisms of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), angiotensin-converting enzyme (ACE) and angiotensinogen in a group of 133 Greenland Inuit, aged 30-34 gamma. In addition, we compared the plasma levels of these factors and those of C-reactive protein (CRP) and D-Dimer in Inuit and in Danes, comparable for age and gender. Frequencies (f) were assessed of the alleles that are known as the potential high risk alleles in Caucasians. In the Inuit, the f(insertion allele) of the t-PA intron8ins311 polymorphism was 0.37 (CI 0.32-0.43), the f(4G allele) of the PAI-1 promoter polymorphism was 0.88 (CI 0.83-0.91), the f(deletion allele) of the ACE intron16ins287 polymorphism was 0.40 (CI 0.33-0.47) and the f(M-allele) of the angiotensinogen M/T353 polymorphism was 0.30(CI 0.25-0.38). As for fibrinogen and FVII polymorphisms, these frequencies are all significantly different from what is reported for Caucasian populations. In the Inuit, plasma levels of fibrinogen and D-Dimer were higher than in the Danes, the PAI-1 levels were lower and FVII, t-PA and CRP levels were comparable. The observed allele frequencies of the polymorphisms of t-PA, fibrinogen, FVII, ACE, angiotensinogen and the plasma levels of PAI-1 and D-Dimer were in accordance with the low CVD risk in the Inuit, considering the observed associations between these measures and CVD risk in Caucasian populations, but for other measures this was not the case (allele frequencies of the PAI-1 polymorphism, and plasma levels of fibrinogen, FVII and t-PA). In conclusion there are clear differences in genetic background and plasma levels of risk factors in Greenland Inuit compared with Caucasian populations, and these differences were sometimes, but not always, in accordance with the observed low cardiovascular disease risk of the Inuit population.     

The definition of posttraumatic stress disorder in alcoholic Vietnam veterans. Are the DSM-III criteria necessary and sufficient?

The authors evaluated the validities of the DSM-III elements defining posttraumatic stress disorder (PTSD) in alcoholic Vietnam veterans by studying the relationships of each to qualification for a PTSD diagnosis under DSM-III standards, the history of a major stressor (3 or more months of combat), and the presence/absence of enough other problems to meet the symptomatic DSM-III requirements for this diagnosis. Elements dealing with the reexperiencing of traumas, diminished pleasure, detachment from others, hyperalertness, sleep disturbance, guilt over behaviors required for survival, and avoidance of stimuli reminiscent of traumas showed substantial correlations with eligibility for a PTSD diagnosis. However, items dealing with emotional expressiveness, response to intimacy, survival guilt, impaired memory, and trouble concentrating either failed to correlate with qualification for a PTSD diagnosis or yielded marginal results. One ("lacking direction") of 10 additional symptoms sometimes termed as "post-Vietnam syndrome" behaviors correlated with eligibility for a PTSD diagnosis as well. The present results and those described in earlier studies suggest that several modifications in the DSM-III definition of PTSD are desirable.     

Are there differences in cortical excitability between akinetic-rigid and tremor-dominant subtypes of Parkinson's disease?

ObjectiveTo assess by transcranial magnetic stimulation (TMS) the excitability of various cortical circuits in akinetic-rigid and tremor-dominant subtypes of Parkinson's disease (PD).MethodsThe study included 92 patients with PD according to UK Brain Bank criteria, with akinetic-rigid (n = 64) or tremor-dominant (n = 28) subtype. Cortical excitability study, including resting and active motor thresholds (rMT and aMT), input—output curve of motor evoked potentials, contralateral and ipsilateral silent periods (cSP and iSP), short and long-interval intracortical inhibition (SICI and LICI), and intracortical facilitation (ICF) were measured. The results obtained were compared to a control group of 30 age- and sex-matched healthy subjects.ResultsThe patients in the tremor group had significantly lower rMT and aMT compared to controls and akinetic-rigid patients and significantly shorter iSP duration compared to akinetic-rigid patients, while iSP latency tended to be longer in akinetic-rigid patients compared to controls. There were no significant differences between the two PD subgroups regarding other cortical excitability parameters, including paired-pulse TMS parameters.ConclusionsOnly subtle differences of cortical excitability were found between patients with akinetic-rigid vs. tremor-dominant subtype of PD.SignificanceThe clinical heterogeneity of PD patients probably has an impact on cortical excitability measures, far beyond the akinetic-rigid versus tremor-dominant profile.     

The prevalence of metabolic risk factors of atherosclerotic cardiovascular disease in Williams syndrome,Prader–Willi syndrome,and Down syndrome

Background Risk for atherosclerotic cardiovascular disease (CVD) and association with abdominal obesity have not been extensively studied in genetic syndromes associated with intellectual disability.

Methods A cross-sectional study was conducted in individuals aged 20–43 years with Williams syndrome (WS; n?=?21), Prader–Willi syndrome (PWS; n?=?20), and Down syndrome (DS; n?=?31). Established metabolic risk factors of CVD were assessed.

Results High prevalence of hypertension and type 2 diabetes was seen in the group with PWS, whereas low prevalence rates were found in the group with DS. In the group with WS, we found a high prevalence of hypertension and a trend towards increased risk of type 2 diabetes, combined with better blood lipid profile. Abdominal obesity was prevalent in all 3 subgroups and was associated with an increased risk of hypertension and metabolic syndrome.

Conclusion PWS and WS had increased risk of CVD. In order to prevent CVD in these groups, regular assessments of the known risk factors are recommended.     

Are there gender differences in the severity and consequences of sleep disordered in children?

ObjectivesIn adults there is a distinct gender difference in the prevalence and severity of sleep disordered breathing (SDB), however there have been limited studies examining the effects of gender in children with SDB. We aimed to compare the effects of gender on severity of SDB, blood pressure, sleep and respiratory characteristics, quality of life, behavior and executive function.MethodsWe included 533 children aged 3–18 years, who underwent standard pediatric overnight polysomnography (PSG) between 2004 and 2016. Blood pressure was recorded prior to each study. Quality of life, behavior and executive function were assessed with parental questionnaires. Children were grouped by gender and SDB severity based on their obstructive apnea hypopnea index (OAHI) into non-snoring controls, Primary Snoring (PS) (OAHI≤1 event/h), Mild obstructive sleep apnea (OSA) (OAHI>1-≤5 events/h) and moderate/severe (MS) OSA (OAHI>5 events/h) and data compared with 2-way ANOVA.ResultsA total of 298 boys and 235 girls were studied. There were no differences in age, BMI z-score, SDB severity sleep characteristics or blood pressure between genders. Diastolic blood pressure was elevated in females with MS OSA compared to males (P < 0.05). Quality of life, behavior and executive function scores were all elevated in the SDB groups compared to controls. Females with MS OSA exhibited more internalizing behavioral problems compared to males (59.2 ± 2.4 vs. 51.4 ± 2.3, P < 0.05).ConclusionsIn contrast to studies in adults, we identified no gender differences in the severity or consequences of SDB in children, other than females with moderate-severe OSA exhibiting more internalizing problems and higher diastolic blood pressure.     

Doubts, fears and misconceptions. What is the future of thrombolysis in acute stroke?

Alteplase for acute ischemic stroke may be the first stroke intervention to have a significant public health impact. In February 1999, this therapy was conditionally licensed in Canada for acute ischemic stroke within three hours of symptom onset. However, considerable controversy exists regarding its safety, its wider applicability outside clinical trials, and its ultimate availability. In this article we review the thrombolytic literature, attempt to answer many of the concerns, provide new guidelines for its use, and cite the need for more information about whom we should and should not be treating with this therapy.     

The anxious heart in whose mind? A systematic review and meta-regression of factors associated with anxiety disorder diagnosis,treatment and morbidity risk in coronary heart disease

ObjectiveTo (1) report the prognostic association between anxiety disorder subtypes and major adverse cardiac events (MACE), (2) report anxiety disorder prevalence in coronary heart disease (CHD), and (3) report the efficacy of anxiety disorder treatments in CHD.MethodsA comprehensive electronic database search was performed in November 2013 for studies reporting anxiety disorder prevalence according to structured interview in CHD samples or MACE, and randomized controlled trials (RCTs) comparing anxiety disorder treatment with placebo or usual care. From 4041 articles 42 samples were selected for extraction (8 for MACE prognosis, 39 for prevalence, no RCTs were eligible).ResultsFive generalized anxiety disorder (GAD) studies reported 883 MACE events (combined n = 2851). There was a non-significant association between GAD and MACE (risk ratio = 1.20, 95% CI .86–1.68, P = .28) however the effect size was highly significant in outpatient samples (adjusted hazard ratio = 1.94, 95% CI 1.45–2.60, P < .001). No other anxiety disorder subtype was associated with MACE. Prevalence data showed high comorbidity with depression (49.06%; 95% CI 34.28–64.01) and substantial heterogeneity between studies. Panic disorder prevalence was higher in psychiatrist/psychologist raters (9.92% vs. 4.74%) as was GAD (18.45% vs. 13.01%). Panic and GAD estimates were also heterogeneous according to DSM-III-R versus DSM-IV taxonomies.ConclusionsThe paucity of extant anxiety disorder RCTs, alongside MACE risk for GAD outpatients, should stimulate further anxiety disorder intervention in CHD populations. Research should focus on depression and anxiety, thereby unraveling disorder specific and more generic pathways.     

UK research expenditure on dementia,heart disease,stroke and cancer: are levels of spending related to disease burden?

Background and purpose: A UK government review recommended that the impact of disease on the population and economy should be assessed to inform health research priorities. This study aims to quantify UK governmental and charity research funding for dementia, cancer, coronary heart disease (CHD) and stroke in 2007/08 and assess whether the levels of research expenditure are aligned with disease and economic burden. Methods: We identified UK governmental agencies and charities providing health research funding and determined their levels of funding for dementia, cancer, CHD and stroke. Research funding levels were compared to the number of cases, disability‐adjusted life years (DALYs) and economic burden. Economic costs were estimated using data on morbidity, mortality, health and social care use, private costs and other related indicators. Results: Research funding to the four diseases was £833 million, of which £590 million (71%) was devoted to cancer, £169 million (20%) to CHD, £50 million (6%) to dementia and £23 million (4%) to stroke. Cancer received £482 in research funding per 1000 DALYs lost, CHD received £266, dementia received £166, with stroke receiving £71. In terms of economic burden, for every £1 million of health and social care costs attributable to each disease, cancer received £129 269 in research funding, CHD received £73 153, stroke received £8745 and dementia received £4882. Conclusions: Most health research funding in the UK is currently directed towards cancer. When compared to their burden, our analysis suggests that research spending on dementia and stroke is severely underfunded in comparison with cancer and CHD.     

Weekday distribution of alcohol consumption in Norway: influence on the occurrence of epileptic seizures and stroke?

Binge drinking at weekends is considered to be a predominant feature of alcohol consumption in the Nordic countries. Neurological diseases, such as seizures and stroke, have been reported to occur in temporal relation to alcohol intoxication and withdrawal. We wanted to investigate weekday variances in alcohol consumption in relation to the onset of neurological symptoms in these disorders. Consecutive patients admitted for epileptic seizures (n = 142) and ischemic strokes (n = 91) were included in the study. Control groups were consecutively hospitalized sciatica patients (n = 181), outpatients with epilepsy (n = 91), and healthy subjects (n = 254). The day-by-day alcohol intake during the 8 days prior to hospital admission was recorded. Seizures occurring in subjects with hazardous alcohol consumption, operationally defined by a score > or =8 in the Alcohol Use Disorders Identification Test (AUDIT-positive) were considered to be related to alcohol use. Binge drinkers were identified by an alcohol intake, on at least 1 of the last 3 days, of > or =6 standard units in men, or > or =4 standard units in women. Thirty-five percent of seizure patients were AUDIT-positive, in contrast to 18% and 16% of stroke and sciatica patients, and 12% and 13% of epilepsy outpatients and healthy controls. Twenty-three percent of seizure patients were binge drinkers whereas in the other groups, this proportion did not exceed 10%. In all groups, alcohol consumption peaked on Saturdays. More seizures occurred on Mondays compared to Saturdays, with a diminishing trend through the week. However, AUDIT-negative seizure patients, of which binge drinking occurred in only 5%, caused this difference. AUDIT-positive seizure patients had a higher and more evenly distributed alcohol intake through the week, and the occurrence of seizures in this group did not differ significantly between days of the week. Alcohol consumption peaked 2 days prior to the onset of withdrawal seizures. The weekend drinking pattern was confirmed for all the study groups. Hazardous alcohol consumption preceded every third acute seizure, but was found in only one of eight outpatients with epilepsy. AUDIT-negative patients caused a peak of seizure admissions on Mondays, compared to Saturdays, with a diminishing trend through the week.     

High-sensitivity C-reactive protein in stroke patients – The importance in consideration of influence of multiple factors in the predictability for disease severity and death

High sensitivity C-reactive protein (hsCRP) has been evaluated as a biomarker in stroke and relevant pathological diseases. While its predictive values in several pathological phenotypes have been confirmed, controversy exists among different studies. This review summarizes reports of the predictive values of hsCRP for the diagnosis, etiology, prognosis and mortality of stroke diseases. The current literature suggests that CRP expression is influenced by multiple factors, such as polymorphisms, the genomic backgrounds and gender. However, few reported studies analyzed data based on all these multiple factors. Future studies should focus on comprehensive analysis based on multiple factors.     

Structural and functional alterations of the heart in Parkinson’s disease

Parkinson’s disease (PD) patients have most frequently heart failure. The cause of this increased prevalence is not known. We designed a study to assess the cardiac function and cardiac structure in patients with PD compared to a control group.

Methods: Cross-sectional study with 50 PD patients and 50 healthy matched controls. We performed electro and echocardiograms to all patients and controls. The measurements were blind. In addition, we performed a neurological assessment.

Results: PD patients had higher left ventricular mass index (114.2 ± 38.4 vs. 94.1 ± 26.4 g/m²; P = 0.003) and higher left atrial volume (30.1 ± 7.9 vs. 26.7 ± 6.2 ml/m²; P = 0.01). PD was an independent risk factor for elevated left ventricular filling pressures (OR = 2.7, CI 95% 2.2–6.3; P = 0.004). Concentric remodeling and left ventricular hypertrophy were associated with more advanced Hoehn and Yahr stages. Moreover, patients with more dysautonomia symptoms showed more left ventricular hypertrophy. Finally, PD group had longer QT interval than control group regardless of the drugs.

Conclusions: PD is significantly associated with increased concentric left ventricular hypertrophy and diastolic dysfunction. Advanced stages of PD are associated with a more severe cardiac affection. These findings can explain the increase of heart failure in PD patients. Cardiomyopathy could be a non-motor parkinsonian symptom.