Traditional Vascular Risk Factors Research Articles

Genetic susceptibility to cerebrovascular disease.

Cerebrovascular disease (CeVD) remains a major cause of death and a leading cause of disability worldwide. CeVD is a complex and multifactorial disease caused by the interaction of vascular risk factors, environment, and genetic factors. In the present article, we discussed genetic susceptibility to CeVD, with particular emphasis on genetic studies of the associations between lipid traits and CeVD. Several animal and clinical studies clearly defined genetic predisposition to atherosclerosis and CeVD, and particularly to ischemic stroke. Recent evidence has shown that traditional vascular risk factors explain only a small proportion of variance in atherosclerosis, suggesting that additional nontraditional factors and novel genetic determinants impact CeVD. With the help of genome-wide technology, novel genetic variants have been implicated in CeVD and lipid metabolism such as those in protein convertase subtilisin/kexin type 9 (PCSK9) gene in stroke and familial hypercholesterolemia. These studies are important as they contribute to our understanding of the genetic mechanisms underlying CeVD and to developing more effective CeVD prevention strategies. CeVD is a complex and multifactorial disease and genetics likely plays an important role in its pathogenesis. The gene-gene and gene-environment interactions of genes involved in biology of vascular disease, including the lipid metabolism are important factors for individual susceptibility to CeVD. Accounting for individual variation in genes, environment and lifestyle will bring us closer to precision medicine, which is an emerging and recently introduced new approach for disease treatment and prevention in clinical practice.

Ischemic stroke in the young: Current perspectives on incidence, risk factors, and cardiovascular prognosis.

About one-fourth of ischemic strokes occur in working-aged individuals in the high-income countries, with worldwide increasing incidence in this age group from 1980s to present. Recent evidence suggests that traditional vascular risk factors are more prevalent than previously suggested in young adult stroke patients and they accumulate with age particularly in men. Accordingly, relatively high rates of atherosclerotic changes have been detected in these patients. The strength of association of vascular risk factors has gone poorly studied, however. Many young patients with ischemic stroke have, in turn, no traditional risk factors, while they may harbor other conditions with weak or uncertain association with the stroke alone. These individual conditions often represent a risk factor that may be strictly young-age specific, more prevalent in younger than older stroke patients (e.g. patent foramen ovale), or more prevalent among the young in the population. Despite high rates of vascular risk factors and atherosclerotic changes, these findings do not translate to higher frequencies of identified classical stroke mechanisms. In fact, cryptogenic causes are markedly common and even more frequent among the very young patients. Limited randomized trial evidence exists to support secondary prevention decision-making in patients, yet they face an increased risk of death and future vascular events for years to come-dependent on risk factor profile and cause of the stroke. This review provides an overview of recent data on epidemiology, risk factors, and their strength of association in ischemic stroke in the young. Furthermore, the relationship between with the risk factors and cardiovascular outcomes and key features on the evidence related to secondary prevention will be discussed.

Isolated asymptomatic pulmonary arteriovenous malformation presenting with ischaemic stroke

Young onset stroke is uncommon, and may be due to conditions other than traditional vascular risk factors. A 42-year-old woman with an ischaemic stroke was found to have left atrial bubble study positivity on transthoracic echocardiogram (TTE) suggestive of patent foramen ovale, however she also had low peripheral oxygen saturation. Investigation revealed an isolated pulmonary arteriovenous malformation (PAVM), visible on admission chest radiograph. This can cause embolic stroke and is an alternate cause of the TTE findings. The PAVM was able to be closed via endovascular intervention, removing the shunt and therefore removing her risk of recurrent stroke events. This is a rare cause of embolic stroke in young people which can be easily missed on investigation yet is amenable to treatment.

Abstract TP222: Frequency of Intracranial Arterial Imaging and its Yield in Consecutive Patients with Non-lacunar Cryptogenic Ischemic Stroke: ESUS Global Registry

Background: Atherosclerotic stenosis of large IC arteries is an important cause of stroke. The prevalence of ICS in stroke population differs by ethnicity.We report the frequency of ICS among a global sample of patients with non-lacunar cryptogenic ischemic stroke (NLCIS) who did not have another identifiable cause for stroke i.e. cardioembolic, extracranial LAD, or other specific causes. Hypothesis: We hypothesized that the prevalence rates of ICS will differ according to global regions. Methods: Consecutive patients with recent ischemic stroke were retrospectively surveyed at 19 stroke centers in 19 countries to identify the frequency of IC imaging and its yield. Countries were grouped by World Bank regions. ICS was considered to be significant if there was >50% stenosis in the arteries proximal to the index stroke evidenced by MRA, CTA or TCD. Results: We identified a total of 2145 consecutive ischemic stroke patients among which 475 had NLCIS. IC arterial imaging was carried-out,on average, in 87% of patients. Of these 414 patients, 15% had stenosis proximal to the area of brain ischemia. The frequency of ICS among NLCIS patients was highest in East Asia (27%) and lowest in Pacific (4%). Patients with ICS in Latin America were significantly younger when compared to other 4 regions. Conclusion: IC arterial imaging is carried out in majority of stroke centers in patients with NLCIS, among whom the fraction of IS associated with ICS is substantial throughout the world, averaging about 15%. MRA / CTA had a higher yield than TCD. On average these patients have traditional vascular risk factors except for Latin American patients who are significantly younger with no vascular risk factors.

Cerebral vasoreactivity is impaired in treated, virally suppressed HIV-infected individuals.

To compare cerebral vasoreactivity, a measure of cerebrovascular endothelial function, between treated, virally suppressed HIV-infected individuals and HIV-uninfected controls and to evaluate the effect of HIV-specific factors on cerebral vasoreactivity. Cross-sectional study of 65 antiretroviral therapy-treated, virally suppressed HIV-infected individuals and 28 HIV-uninfected controls. Participants underwent noninvasive assessment of cerebral vasoreactivity using transcranial Doppler ultrasound and inhaled carbon dioxide (CO2). We used mixed effects multivariable linear regression to determine the association of HIV infection and HIV-specific factors with cerebral vasoreactivity. Mean age was 57.2 years for HIV-infected participants and 53.5 years for HIV-uninfected controls. Most participants (95%) were men. Twenty-six per cent of HIV-infected participants were nonwhite compared to 32% of controls. Among HIV-infected participants, mean CD4 cell count was 596 cells/μl, and mean duration of viral suppression was 7.8 years. Cerebral vasoreactivity in response to hypercapnia (cerebral VRhyper) was lower in HIV-infected individuals compared to uninfected controls (3.23 versus 3.81%, P = 0.010). After adjusting for demographic and vascular risk factors, HIV infection was independently associated with lower cerebral vasoreactivity (-0.86%, 95% CI -1.30 to -0.42%, P < 0.001). We did not find a statistically significant effect of recent or nadir CD4 cell count on cerebral vasoreactivity. There was a trend toward higher cerebral vasoreactivity for each additional year of viral suppression. Treated, virally suppressed HIV infection negatively impacted cerebral vasoreactivity even after adjustment for traditional vascular risk factors. These data highlight the potential contribution of cerebrovascular endothelial dysfunction to the elevated risk of stroke observed in HIV-infected individuals.

Acupuncture treatment for ischaemic stroke in young adults: protocol for a randomised, sham-controlled clinical trial

IntroductionStroke in young adults is not uncommon. Although the overall incidence of stroke has been recently declining, the incidence of stroke in young adults is increasing. Traditional vascular risk factors...

Influence of Age at Diagnosis and Time-Dependent Risk Factors on the Development of Diabetic Retinopathy in Patients with Type 1 Diabetes.

Aim. To determine the influence of age at onset of type 1 diabetes and of traditional vascular risk factors on the development of diabetic retinopathy, in a cohort of patients who have been followed up after onset. Methods. Observational, retrospective study. The cohort consists of 989 patients who were followed up after diagnosis for a mean of 10.1 (SD: 6.8) years. The influence of age at diagnosis, glycemic control, duration of diabetes, sex, blood pressure, lipids, BMI, and smoking is analyzed using Cox univariate and multivariate models with fixed and time-dependent variables. Results. 135 patients (13.7%) developed diabetic retinopathy. The cumulative incidence was 0.7, 5.9, and 21.8% at 5-, 10-, and 15-year follow-up, respectively. Compared to the group with onset at age <10 years, the risk of retinopathy increased 2.5-, 3-, 3.3-, and 3.7-fold in the groups with onset at 10–14, 15–29, 30–44, and >44 years, respectively. During follow-up we also observed an association between diabetic retinopathy and HbA1c levels, HDL-cholesterol, and diastolic blood pressure. Conclusion. The rate of diabetic retinopathy is higher in patients who were older at type 1 diabetes diagnosis. In addition, we confirmed the influence of glycemic control, HDL-cholesterol, and diastolic blood pressure on the occurrence of retinopathy.

Determinants of atherosclerosis in an Egyptian cohort of systemic sclerosis: Relation to disease activity and severity

BackgroundSystemic sclerosis (SSc) is a rare multi-system autoimmune disease characterized by vascular abnormalities with an increased prevalence of macrovascular disease. Aim of the workTo evaluate macro-vascular disease (atherosclerosis) in SSc patients and determine its relation to the disease activity and severity. Patients and methodsTwenty-five SSc patients and 20 matched controls were included. The modified Rodnan skin score (mRss) and disease severity by Medsger’s severity score were assessed. Carotid intima-media thickness (IMT) and flow mediated vasodilatation (FMD) of the brachial artery were measured. Traditional vascular risk factors were assessed by thorough history taking and laboratory investigations. ResultsThe age of the patients ranged from 15 to 60years and they were 22 females and 3 males. 15 had limited and 10 diffuse cutaneous SSc. All SSc patients had an increased IMT (1.24±0.29mm) which was normal in the control subjects (0.77±0.09mm) (p<0.0001). SSc patients had significantly lower HDL, thickened IMT and lower FMD than controls (p=0.005, p<0.0001 and p<0.0001 respectively). The younger age of disease onset was significantly associated with more FMD impairment (r=−0.4, p=0.04) and Medsger’s severity score (r=0.5, p=0.009). The mRss and Medsger’s severity score significantly correlated with the IMT (r=0.84, p=0.01 and r=0.56, p=0.003 respectively). A significant negative correlation was found between FMD and IMT (r=−0.77, p<0.0001). Medsger’s severity score significantly correlated with FMD (r=−0.44, p=0.02). ConclusionSSc is associated with an increased risk of atherosclerosis when compared to age and sex-matched controls. Determinants of this include; younger age of disease onset and more sever disease and low levels of HDL.

Emerging Vascular Risk Factors in Women: Any Differences from Men?

Gender differences have been reported for traditional vascular risk factors such as smoking, obesity, diabetes, hypertension, dyslipidemia, age and family history of premature coronary heart disease. The prevalence, severity, associations and response to treatment of several emerging cardiovascular disease (CVD) risk factors may also differ between men and women. Such CVD risk factors include certain inflammatory and hemostatic markers, endothelial dysfunction, homocysteine, lipid disorders, microalbuminuria/proteinuria, coronary artery calcium score, arterial stiffness, periodontitis, inflammatory bowel syndrome, obstructive sleep apnea, impaired glucose metabolism, metabolic syndrome and non-alcoholic fatty liver disease. Further larger prospective studies are needed to establish these relationships. Hormone replacement therapy may also affect vascular risk. These data should be taken into consideration when assessing and treating CVD risk in women.

Correlation between Carotid Intima–Media Thickness and Early-Stage Chronic Kidney Disease: Results from Asymptomatic Polyvascular Abnormalities in Community Study

Chronic kidney disease (CKD) might be a potential independent risk factor for increased carotid intima-media thickness (IMT). Our aim is to determine whether mild to moderate kidney dysfunction is associated with increased carotid IMT. We employed 3629 subjects free from clinical cardiovascular diseases at the baseline visit of the Asymptomatic Polyvascular Abnormalities in Community Study. Kidney function was evaluated in terms of estimated glomerular filtration rate (eGFR) calculated by the Chronic Kidney Disease Epidemiology Collaboration China equation. The mean of the maximal internal and common carotid IMT was measured by means of high-resolution B-mode ultrasound. Univariable linear regressions and multivariate logistic regressions were used to evaluate the independent association between kidney function and carotid IMT. In the unadjusted linear analysis, carotid IMT showed a significant negative correlation with eGFR in both male (r = -.346, P < .001) and female (r = -.253, P < .001) subjects. After adjustment for age, traditional vascular risk factors (smoking, diabetes, systolic blood pressure, diastolic blood pressure, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, and antihypertensive drug use), and nontraditional risk factors (C-reactive protein and homocysteine), the association remained significant. The odds ratio for increased IMT was 1.299 (95% confidence interval [CI], 1.062-1.588) in the group with an eGFR of 60-89 mL/minute/1.73 m(2) and 1.789 (95% CI, 1.203-2.660) in the group with an eGFR of 30-59 mL/minute/1.73 m(2). Increased IMT is associated with early-stage CKD. This association is independent of traditional and nontraditional cardiovascular risk factors. Early detection of kidney dysfunction is important to improve risk stratification of atherosclerotic disease.

Acute Ischemic Stroke on Cancer Patients, a Distinct Etiology? A Case-Control Study.

It is still unclear whether the etiology of ischemic stroke differs between cancer and non-cancer patients. Stroke and cancer share common modifiable risk factors but evidence suggests that cancer patients have specific conditions that increase the risk of stroke. Our goal was to compare the etiology of ischemic stroke in cancer and non-cancer patients. Case-control study conducted in patients admitted to a stroke unit between January 2007 and December 2012. Cases had a concomitant diagnosis of cancer and acute ischemic stroke, controls of only stroke. Age, gender, vascular risk factors and etiology were compared between groups. Fifty-six cases were identified; 64.3% were men with a mean age of 71 years; 21 patients had evidence of active cancer. Gastrointestinal cancer (25.9%) was the most common; 151 controls were included matched for gender and age. Common modifiable vascular risk factors, between groups (cases versus controls) were not significantly different, except for diabetes mellitus, more frequent in the control group (16.1% vs 33.8%, p = 0.02). Previous thrombotic events were more frequent in the cancer cohort (8.9% vs 0.7%, p = 0.007). Other determined etiology subtype (TOAST classification) was more frequent in cancer patients when compared to controls (13.0% vs 0.8%, p < 0.01), and a hypercoagulable state was significantly more prevalent in active cancer patients. In our case-control study two subsets of cancer patients were delineated. In a subgroup, cancer and stroke co-exist, sharing traditional vascular risk factors. In another subset of patients, stroke appears to be directly related to the presence of a malignancy, where hypercoagulopathy turns out to be a decisive mechanism. In clinical grounds, hypercoagulopathy as stroke etiology should prompt the physician to screen the patient for occult cancer.

Infarctus cérébral du sujet jeune

Ischemic stroke is not rare in young adults since one in ten stroke patients are less than 50years old. This incidence increased over the past last years, mainly due to the rise in the prevalence of traditional vascular risk factors in this sub-group of age but also of illegal drug use. Even though both survival and functional outcome of young stroke patients are better than those observed in older patients, socio-economic and quality of life consequences make this disease a main objective in terms of primary and secondary prevention. Identifying the cause of ischemic stroke in young adults is of major importance to prevent stroke recurrence. However, given the wide variety of potential underlying causes, the etiologic work-up of stroke in young adults requires a different approach from that in the elderly. In this context, a sequential diagnostic work-up is needed in order to optimize the yield of diagnostic tests, to reduce their cost and risks for the patient. Arterial dissection is the most frequent cause of stroke in young adults but other less frequent causes are numerous. Despite a comprehensive work-up, about one third of cases remains unexplained leading to the diagnosis of cryptogenic ischemic stroke.

Comment: Spice, reversible cerebral vasoconstriction, and intracranial hemorrhage.

There is a view prevalent in society that cannabis and its synthetic analogues are safe. However, there are increasing reports of ischemic stroke coming on during or soon after the use of cannabis and its synthetic analogues.1,2 Patients tend to be younger and without traditional vascular risk factors. A number of mechanisms have been proposed, including cardiac embolism, reversible vasoconstriction, and cerebral arteriopathy.

Prevalence and Risk Factors of Acute Incidental Infarcts.

The study of silent stroke has been limited to imaging of chronic infarcts; acute incidental infarcts (AII) detected on brain magnetic resonance imaging have been less investigated. This study aims to describe prevalence and risk factors of AII in a community and a clinic-based population. Subjects were drawn from 2 ongoing studies: Epidemiology of Dementia in Singapore study, which is a subsample from a population-based study, and a clinic-based case-control study. Subjects from both studies underwent similar clinical and neuropsychological assessments and brain magnetic resonance imaging. Prevalence of AII from these studies was determined. Subsequently, risk factors of AII were examined using multivariable logistic regression models. AII were seen in 7 of 623 (1.2%) subjects in Epidemiology of Dementia in Singapore (mean age, 70.9±6.8 years; 45% men) and in 12 of 389 (3.2%) subjects (mean age, 72.1±8.3 years; 46% men) in the clinic-based study. AII were present in 0.8% of subjects with no cognitive impairment, 1.9% of those with cognitive impairment not dementia, and 4.2% of subjects with dementia. Significant association of AII was found with cerebral microbleeds (≥5) in the Epidemiology of Dementia in Singapore (odds ratio, 6.76; 95% confidence interval, 1.28-35.65; P=0.02) and in the clinic-based cohort (odds ratio, 4.65; 95% confidence interval, 1.39-15.53; P=0.01). There was no association of AII with hypertension, diabetes mellitus, or hyperlipidemia. AII are more likely to be present in those with cognitive impairment. Although a cause-effect relationship between the presence of AII and cognitive impairment is plausible, the association may be because of under-reporting of symptoms by individuals with cognitive impairment. The association between AII and cerebral microbleeds may indicate cerebral vasculopathy, independent of traditional vascular risk factors.

Intima-Media Thickness and Cognitive Function in Stroke-Free Middle-Aged Adults: Findings From the Coronary Artery Risk Development in Young Adults Study.

The relationship between carotid artery intima-media thickness (IMT) and cognitive function in midlife remains relatively unexplored. We examined the association between IMT and cognitive function in a middle-aged epidemiological cohort of 2618 stroke-free participants. At the year 20 visit (our study baseline), participants from the Coronary Artery Risk Development in Young Adults study had IMT measured by ultrasound at the common carotid artery. Five years later, participants completed a cognitive battery consisting of the Rey Auditory-Verbal Learning Test of verbal memory, the Digit Symbol Substitution Test of processing speed, and the Stroop test of executive function. We transformed cognitive scores into standardized z scores, with negative values indicating worse performance. Mean age at baseline was 45.3 years (SD, 3.6). Greater IMT (per 1 SD difference of 0.12 mm) was significantly associated with worse performance on all cognitive tests (z scores) in unadjusted linear regression models (verbal memory, -0.16; 95% confidence interval [CI], -0.20 to -0.13; processing speed, -0.23; 95% CI, -0.27 to -0.19; and executive function, -0.17; 95% CI, -0.20 to -0.13). In models adjusted for sociodemographics and vascular risk factors that lie earlier in the causal pathway, greater IMT remained negatively associated with processing speed (-0.06; 95% CI, -0.09 to -0.02; P, 0.003) and borderline associated with executive function (-0.03; 95% CI, -0.07 to 0.00; P, 0.07) but not with verbal memory. We observed an association between greater IMT and worse processing speed-a key component of cognitive functioning-at middle age above and beyond traditional vascular risk factors. Efforts targeted at preventing early stages of atherosclerosis may modify the course of cognitive aging.

Do traditional risk stratification models for cerebrovascular events apply in irradiated head and neck cancer patients?

Primary radical radiotherapy (RT) for head and neck cancer (HNC) often results in significant radiation dose to the carotid arteries. We assessed whether HNC patients are at increased risk of a cerebrovascular event primarily due to RT or other risk factors for atherosclerosis by (i) risk-stratifying patients according to validated QRISK-2 and QSTROKE scores and (ii) comparing the prevalence of carotid artery stenosis (CAS) in irradiated and unirradiated carotid arteries. HNC patients treated with an RT dose >50 Gy to one side of the neck ≥2 years previously were included. QRISK-2 (2014) and Q-STROKE (2014) scores were calculated. We compared the prevalence of CAS in segments of the common carotid artery on the irradiated and unirradiated sides of the neck. Fifty patients (median age of 58 years (interquartile range (IQR) 50-62)) were included. The median QRISK-2 score was 10% (IQR 4.4-15%) and the median QSTROKE score was 3.4% (IQR 1.4-5.3%). For both scores, no patient was classified as high risk. Thirty-eight patients (76%) had CAS in one or both arteries. There was a significant difference in the number of irradiated arteries with stenosis (N = 37) compared with unirradiated arteries (N = 16) (P < 0.0001). There were more plaques on the irradiated artery compared with the unirradiated side - 64/87 (73.6%) versus 23/87 (26.4%), respectively (P < 0.001). Traditional vascular risk factors do not play a role in radiation-induced carotid atherosclerosis. Clinicians should be aware that traditional risk prediction models may under-estimate stroke risk in these patients.

The impact of concomitant diffuse idiopathic skeletal hyperostosis on the achievement of minimal disease activity in subjects with psoriatic arthritis.

Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by ossification of different entheses. Psoriatic arthritis (PsA) is a seronegative spondyloarthritis associated with psoriasis. Given the possible overlap of the two diseases, we assessed whether DISH presence may affect PsA clinical outcomes. Also, predictors of DISH presence in the cohort were investigated. Consecutive PsA patients from two Italian Rheumatology Research Units were enrolled. Subjects were splitted into two groups, according to the current treatment (TNF-α blockers or traditional DMARDs). All patients underwent a rheumatologic examination, blood sample collections and spine radiographs. Information about traditional vascular risk factors was recorded. In each patient, the presence of minimal disease activity was evaluated and the presence of DISH was established according to the Resnick and Niwayama criteria. Among the 80 enrolled subjects (57.5% men, mean age 56.5±11.1years), the overall prevalence of DISH was 30.0%. Patients with DISH were older, with higher BMI and waist circumference. DISH subjects showed worsen BASMI, HAQ and ESR. In a multivariate regression model, BASMI was a significant predictor of DISH presence (OR 3.027, 95% CI 1.449-6.325, p=0.003). The prevalence of MDA was lower in DISH patients than in no-DISH (16.7 vs 41.1%, p=0.041), and the presence of DISH was a predictor of not achieving MDA (OR 3.485, 95% CI 1.051-11.550, p=0.041). PsA subjects with DISH showed worsen indices of spine mobility and articular function and lower prevalence of minimal disease activity than no-DISH patients.

221 Comparing Erectile Dysfunction with Traditional Vascular Risk Factors in the Prediction of Coronary Artery Disease in Patients Presenting with Chest Pain

<h3>Introduction</h3> Erectile dysfunction (ED) is the persistent inability to attain or maintain an erection and affects up to 52% of men between the ages of 40 and 70. ED is an independent predictor of clinically overt cardiovascular (CV) events, coronary artery disease (CAD), stroke and all-cause mortality, preceding these by 2–5 years. ED has not been evaluated in patients referred to a rapid access chest pain clinic (RACPC) for suspected CAD. <h3>Purpose</h3> To prospectively investigate ED in patients referred to the RACPC and to assess ED as an independent predictor of CAD in these patients. <h3>Methods</h3> All male patients attending RACPC between October 2012 and February 2014 were eligible. ED was measured using a well validated 5-item International Index of Erectile function (IIEF-5) questionnaire, with ED being defined as IIEF-5 of ≤21 out of 25. ED was further categorised into mild-moderate (IIEF-5: 11–21) and severe (IIEF-5: ≤10). All patients underwent an exercise tolerance test (ETT) according to Bruce protocol where appropriate as a first line investigation. When this was not possible, patients underwent a functional imaging (stress echocardiography [SE] or myocardial perfusion scintigraphy [MPS]). Patients with positive or inconclusive studies went on to have coronary angiography (CA). Patients were considered to have CAD if they had a positive ETT, SE, MPS or CA. Results were analysed using Chi-squared test for categorical data and one-way ANOVA for continuous data. Stepwise Binary logistic regression model was used to determine the contribution of traditional risk factors and the presence of ED to the prediction of CAD. P-value less than 0.05 was considered significant. <h3>Results</h3> Our study cohort constituted 181 patients. Of these, 26 (14%) could not complete IIEF-5. Of the remaining 155 participants, 53 (34%) had normal erectile function (IIEF-5: ≥22). Of 102 (66%) ED patients, 55 (36%) had mild-moderate ED and 47 (30%) had severe ED. Patients with ED reported more risk factors than patients without ED, including smoking (68% vs. 55%, p = 0.004), diabetes (9% vs. 23%, p = 0.029), and hypertension (30% vs. 56%, p = 0.002). More patients with ED had CAD (47% vs. 25%, p = 0.014). Using stepwise Binary logistic regression including hypertension, hypercholesterolemia, smoking, diabetes, family history and ED as covariates, hypercholesterolemia (p = 0.045) and ED (p = 0.007) were significant independent predictors of CAD (r2=0.135, p = 0.001). <h3>Conclusions</h3> ED may be a more powerful predictor of CAD in male patients with chest pain when compared to traditional vascular risk factors.

Association of Sleep Apnea and Snoring With Incident Atrial Fibrillation in the Multi-Ethnic Study of Atherosclerosis.

The association between sleep apnea and atrial fibrillation (AF) has not been examined in a multiethnic adult population in prospective community-based studies. We prospectively (2000-2011) investigated the associations of physician-diagnosed sleep apnea (PDSA), which is considered more severe sleep apnea, and self-reported habitual snoring without PDSA (HS), a surrogate for mild sleep apnea, with incident AF in white, black, and Hispanic participants in the Multi-Ethnic Study of Atherosclerosis (MESA) who were free of clinical cardiovascular disease at baseline (2000-2002). Cox proportional hazards models were used to assess the associations, with adjustment for socioeconomic status, traditional vascular disease risk factors, race/ethnicity, body mass index, diabetes, chronic kidney disease, alcohol intake, and lipid-lowering therapy. Out of 4,395 respondents to a sleep questionnaire administered in MESA, 181 reported PDSA, 1,086 reported HS, and 3,128 reported neither HS nor PDSA (unaffected). Over an average 8.5-year follow-up period, 212 AF events were identified. As compared with unaffected participants, PDSA was associated with incident AF in the multivariable analysis, but HS was not (PDSA: hazard ratio = 1.76, 95% confidence interval: 1.03, 3.02; HS: hazard ratio = 1.02, 95% confidence interval: 0.72, 1.44). PDSA, a marker of more severe sleep apnea, was associated with higher risk of incident AF in this analysis of MESA data.

50 years forward: mechanisms of hyperglycaemia-driven diabetic complications

The advent of insulin treatment in 1923 meant fewer diabetes deaths from acute metabolic deterioration and sepsis and a progressive increase in the burden of disease caused by end-organ damage. These diabetic complications are the major cause of morbidity and premature mortality among diabetic subjects. Over the last 50 years it has become apparent that diabetic complications in disparate tissues may result from a combination of common pathological processes. Pathways activated by initial metabolic insults are promoted by co-factors such as renin-angiotensin-aldosterone system activation, hyperinsulinaemia, underlying genetic susceptibility, and traditional vascular risk factors, particularly hypertension and lipids. These common pathways include AGE formation, reactive oxygen species overproduction, protein kinase C activation, mitochondrial dysfunction and activation of proinflammatory and profibrotic signalling cascades. Once established, these interlinked pathways become self-perpetuating. Many drugs acting against individual downstream targets in these pathways have failed due to lack of efficacy or adverse effects. Gains in the future may be made by better control of existing risk factors, more sophisticated modulation of tissue glucose and insulin signalling, and interventions to improve mitochondrial function and reduce oxidative stress. Epigenetic and microRNA research may lead to methods to disrupt the mechanisms whereby pathological pathways are perpetuated. Expansion in capacity and expertise in biomarker measurement and analysis may allow better targeting of therapies to patients who are most likely to benefit. This is one of a series of commentaries under the banner '50 years forward', giving personal opinions on future perspectives in diabetes, to celebrate the 50th anniversary of Diabetologia (1965-2015).