American Heart Association

epidemiology and genetics

Diabetes Mellitus, But Not Prediabetes, Associated With Poorer Cognitive Performance After Stroke

Lina Palaiodimou, MD

Lo JW, Crawford JD, Samaras K, Desmond DW, Köhler S, Staals J, et al. Association of Prediabetes and Type 2 Diabetes With Cognitive Function After Stroke: A STROKOG Collaboration Study. Stroke. 2020.

Diabetes mellitus (DM) affects about 422 million people and is one of the leading causes of death worldwide (World Health Organization). More importantly, the burden of type 2 diabetes (T2D) has been rising relentlessly in all countries in the past three decades. However, it is estimated that a significant percentage of cases of T2D remain undiagnosed. DM is one of the major modifiable risk factors for stroke. In addition, it has been associated with adverse outcomes after stroke, including higher mortality, poorer neurological and functional outcomes, longer hospital stay, higher readmission rates, and stroke recurrence. Another outcome, the post-stroke cognitive function, and its relationship with DM, are being evaluated in the STROKOG collaboration study.

Lo et al. for the STROKOG collaboration present a meta-analysis of individual participant data (IPD) derived from seven international post-stroke cohorts with the aim to investigate the relationship between T2M and prediabetes with cognitive impairment after stroke.

What About Stroke Primary Prevention? Article Commentary on “Hypothetical Lifestyle Strategies in Middle-Aged Women and the Long-Term Risk of Stroke”

Grace Y. Kuo, MD, MS, BA

Jain P, Suemoto C, Rexrode K, Manson J, Robins J, Hernan M, et al. Hypothetical Lifestyle Strategies in Middle-Aged Women and the Long-Term Risk of Stroke. Stroke. 2020.

We are fortunate enough to be in an era in which we have multiple validated treatments for stroke care. However, with the decrease in overall stroke incidence and mortality, we are beginning to see a gender disparity in the disease of stroke. More women, particularly in the elderly populations, suffer from stroke than men. Although it may be due to longer life expectancy for women, it is still important to look for strategies to decrease this disparity. Prospective studies have found an inverse association between healthy lifestyles and strokes. However, as the natural history of the chronic conditions that lead to strokes occurs over decades, the actual effects of lifestyle interventions for primary prevention are difficult to study in randomized trials.

The article “Hypothetical Lifestyle Strategies in Middle-Aged Women and the Long-Term Risk of Stroke” is an attempt to understand the effects of dietary and non-dietary modifications on stroke risk by using longitudinal observational data in a hypothetical analysis to estimate the possible risk reduction of the interventions. Data was obtained from the Nurse’s Health Study (NHS), a database that was started in 1976 with 121,701 participants. In 1984, the participants were sent a food frequency questionnaire (FFQ), which was used as a basis for dietary pattern. Based on this survey, 59,727 participants were deemed eligible, after exclusion criteria of having pre-existing cardiovascular events (stroke, MI, angina, history of CABG) and cancer. Incomplete surveys or surveys with implausible responses were also excluded from analysis. 1986, the first follow-up year, was set as the baseline year to allow for adjustment for pre-baseline confounders. Every two years thereafter, participants were sent follow-up questionnaires. Participants were followed until their first diagnosis of stroke, death or June 2012.

Sleep Disturbances and Increased Risk of Atherosclerosis in the Young

Raffaele Ornello, MD

Zhao YY, Javaheri S, Wang R, Guo N, Koo BB, Stein JH, et al. Associations Between Sleep Apnea and Subclinical Carotid Atherosclerosis: The Multi-Ethnic Study of Atherosclerosis. Stroke. 2019;50:3340–3346.

Literature suggests that sleep disturbances, including sleep apnea (SA), are associated with an increased risk of stroke; however, the reasons for the association are unclear.

In their prospective observational study, the authors assessed the association between sleep disturbances and indirect markers of atherosclerosis, namely the carotid intima-media thickness (CIMT) and the presence of carotid plaque, in a multi-ethnic population of 1615 subjects aged 45-85 years. The authors found an association between SA and carotid plaque only in subjects younger than 68 years; on the other hand, decreased oxygen saturation during sleep was associated with an increase in CIMT, only in younger or black individuals.

The authors’ results suggest that the mechanisms linking sleep disturbances to carotid plaques and to increased CIMT are different and both more pronounced in younger individuals. However, the most relevant result of the study is perhaps a negative one: Habitual snoring was not associated with any increased risk of carotid atherosclerosis. The study findings are in line with the recently released 2019 AHA/ASA guidelines for the management of acute ischemic stroke, which recommend against systematic screening for SA in all patients with acute ischemic stroke.

Article Commentary: “Stroke Incidence and Case Fatality According to Rural or Urban Residence: Results From the French Brest Stroke Registry”

Kristina Shkirkova, BSc

Grimaud O, Lachkhem Y, Gao F, Padilla C, Bertin M, Nowak E, et al. Stroke Incidence and Case Fatality According to Rural or Urban Residence: Results From the French Brest Stroke Registry. Stroke. 2019;50:2661–2667.

In this entry, I discuss a recent publication by Olivier Grimaud and colleagues regarding the stroke incidence and case fatality according to rural or urban residence. Although rural-urban disparities in stroke epidemiology research have received modest attention in recent years, localization of most stroke registries in large urban areas confounds exploration of stroke mortality as a function of urban/rural area.

There has been conflicting evidence regarding the association between stroke incidence and rural or urban residence status. Recent data in the United States suggests that rural residence location is associated with higher incidence of stroke than urban location of residence. Similarly, results from other high-income countries also report conflicting data. The authors of this study sought to examine the relationship between stroke incidence, case fatality, and residence location using the French Brest Stroke Registry.

Article Commentary: “Leveraging Human Genetics to Estimate Clinical Risk Reductions Achievable by Inhibiting Factor XI”

Alan C. Cameron, MB ChB, BSc (Hons), MRCP

Georgi B, Mielke J, Chaffin M, Khera AV, Gelis L, Mundl H, et al. Leveraging Human Genetics to Estimate Clinical Risk Reductions Achievable by Inhibiting Factor XI. Stroke. 2019.

In this recent article, Georgi and colleagues highlight coagulation factor XI (FXI) as a promising new target for antithrombotic therapy to prevent ischemic stroke without an increased risk of major bleeding. The authors analyzed data from the UK Biobank and two large genome wide association studies to formulate a genetic score standardized to a 30% increase in relative activated partial thromboplastin time, which is equivalent to effects achieved by pharmacological FXI inhibition compared to enoxaparin for the prevention of venous thromboembolism after total knee arthroplasty. 

The results herald what could potentially be a game-changer in antithrombotic therapy for stroke prevention. The authors demonstrate that genetic predisposition to lower FXI levels is associated with a 53% reduction in risk of ischemic stroke (OR 0.47, 95% CI 0.36–0.61; p=1.5×10−8) and a 90% reduction in risk of venous thrombosis (OR 0.1, 95% CI 0.07–0.14; p=3.03×10−43) without an increase in major bleeding (OR 0.69, 95% CI 0.45–1.04; p=0.0739). The reductions in risk of ischemic stroke are similar in patients with or without a history of atrial fibrillation (AF), suggesting that absolute risk reductions are higher in patients with AF. The authors went on to apply a calibration factor to estimate the effects of genetically lower FXI levels compared to placebo and demonstrate an estimated risk reduction of 56% (OR 0.44, 95% CI 0.31–0.62); this is broadly comparable to relative risk reductions observed with warfarin compared to placebo.

Do Long Work Hours Increase the Risk of Stroke? An Observational Study From the CONSTANCES Cohort

Anusha Boyanpally, MD

Fadel M, Sembajwe G, Gagliardi D, Pico F, Li J, Ozguler A, et al. Association Between Reported Long Working Hours and History of Stroke in the CONSTANCES Cohort. Stroke. 2019;50:1879–1882

Long working hours (LWH) may be a risk factor for cardiovascular diseases and stroke (1). There is limited evidence on the association of LWH and increased risk of stroke (2, 3). Fadel et al. have reported association of LWH and risk of stroke in a large French population-based cohort.

The study included randomly selected adults aged 18 to 69 years from the CONSTANCES cohort. Data was obtained from self-administered questionnaires, health examinations, and physician diagnosed stroke cases at affiliated health-screening centers. The authors have categorized working years of exposures as >1 year, 1 – <10 years, and ≥10 years. Variables included are; age, sex, smoking, occupation, history of stroke, age occurrence of stroke, diabetes, high blood pressure, dyslipidemia (both hypercholesteremia or hypertriglyceridemia), family history of cardiovascular events and body mass index. The study has excluded patients with part-time jobs, and history of stroke.

Article Commentary: “Disparities and Temporal Trends in the Use of Anticoagulation in Patients With Ischemic Stroke and Atrial Fibrillation”

Wayneho Kam, MD

Sur NB, Wang K, Di Tullio MR, Gutierrez CM, Dong C, Koch S, et al. Disparities and Temporal Trends in the Use of Anticoagulation in Patients With Ischemic Stroke and Atrial Fibrillation. Stroke. 2019;50:1452-1459.

Race-ethnic and sex disparities in stroke incidence and stroke-related death and disability are well-documented and persist in the modern health care system. The factors that contribute to these disparities are many, and stem from the biosocial complexities of the disease and the prevailing inequalities that exist in the continuum of stroke care.

The study by Sur et al., published in the June issue of Stroke, sought to examine yet another potential disparity in stroke care: differences in oral anticoagulant prescription pattern between blacks vs whites and women vs men for secondary stroke prevention. Data was drawn from the Florida-Puerto Rico Collaboration to Reduce Stroke Registry, which included 24040 patients with ischemic stroke and atrial fibrillation (AF).

Ischemic Stroke Incidence in Young Adults

Kathryn S. Hayward, PhD, PT

Aparicio HJ, Himali JJ, Satizabal CL, Pase MP, Romero JR, Kase CS, et al. Temporal Trends in Ischemic Stroke Incidence in Younger Adults in the Framingham Study. Stroke. 2019;50:1558–1560.

Stroke incidence has been decreasing over time. It is acknowledged that a reduction is occurring in older adults (age >65 years), but trends in younger adults remain less clear. Long-term cohort studies, such as the Framingham Study, provide the opportunity to characterize trends in rates of ischemic stroke. Such work can inform prevention efforts, both nationally and internationally. 

In this paper, Aparicio and colleagues report on the trends in 10-year incidence of ischaemic stroke among participants of the Framingham Heart Study. They divided participants into 35 to 54 years of age (younger adults) and ≥55 years of age (older adults). Individuals that attended exams at the Study clinic during four epochs from 1962 through 2005 were included.

Artificially Sweetened Beverages: Sweet Taste with Sour Consequences

Kristina Shkirkova, BSc

Mossavar-Rahmani Y, Kamensky V, Manson JE, Silver B, Rapp SR, Haring B et al. Artificially Sweetened Beverages and Stroke, Coronary Heart Disease, and All-Cause Mortality in the Women’s Health Initiative. Stroke. 2019;50(3):555-562

Consumption of Artificially Sweetened Beverages (ASB) has been associated with cardiovascular disease risks. In a cohort of postmenopausal US women from the Women’s Health Initiative Observational Study authors of the new study examined the association between ASB consumption and incidence of cardiovascular disease, including coronary heart disease, stroke, and mortality.

From among 93,676 women who were part of the Women’s Health Initiative Observational Study (WHI-OS) between 1993 and 1998, the study included 81,714 women, age 50 to 79, who provided information in their estimated ASB consumption. The mean follow-up period of all study participants was 11.9 years from the day of WHI-OS enrollment.

What’s Behind Childhood Arterial Ischemic Stroke?

Alejandro Fuerte, MD

McCrea N, Fullerton HJ, Ganesan V. Genetic and Environmental Associations With Pediatric Cerebral Arteriopathy: Insights Into Disease Mechanisms. Stroke. 2019;50:257–265.

Childhood arterial ischemic stroke (AIS) occurs by interaction between rare genetic risk factors and common environmental exposures. In this article, McCrea et al. expose these mechanisms relying mainly on the results of the VIPS study (Vascular Effects of Infection in Paediatric Stroke).

Genetic Associations

From a genetic point of view, it is important to highlight moyamoya arteriopathy and Neurofibromatosis type 1 (NF1). Moyamoya is a rare artery disease that consists of a progressive stenosis of the internal carotid artery and its main branches. Children with moyamoya are at risk of AIS, whereas adults are more prone to haemorrhagic stroke. NF1 is an autosomal dominant tumour-suppressor syndrome, caused by mutations in the gene encoding for neurofibromin, a RAS pathway inhibitor (chromosome 17). Children with NF1 have an increased risk of stroke, with odds ratios of 8.1 for haemorrhagic stroke and 3.4 for AIS.