American Heart Association

epidemiology and genetics

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.

Breath Well During Sleep; Have Less Risk for Recurrent Ischemic Strokes

Lina Palaiodimou, MD

Brown DL, Shafie-Khorassani F, Kim S, Chervin RD, Case E, Morgenstern LB, et al. Sleep-Disordered Breathing Is Associated With Recurrent Ischemic Stroke. Stroke. 2019;50:571–576.

The role of sleep-disordered breathing (SDB) is well established in the development of a first stroke or death from any cause. Previous studies have shown that SDB is associated with an increased incidence of stroke or death from any cause, and this association is independent of other cardiovascular and cerebrovascular risk factors. This condition appears both in prestroke patients and in poststroke patients, and is more often obstructive than central. An association between SDB and recurrent strokes is also being presumed, but there are no sufficient prospective data to demonstrate and support this association.

The study of Brown et al. is an attempt to enrich the scarce data regarding the interaction between SDB and recurrent strokes. More specifically, the primary endpoint of this study is to investigate the association between SDB and recurrent ischemic stroke and secondary endpoints are: possible association between SDB and all-cause poststroke mortality and possible influence of ethnicity on the interaction between SDB and outcome measures (recurrent stroke or mortality). For that purpose, the investigators designed a prospective study of 842 patients who suffered from an index ischemic stroke and underwent a sleep apnea study shortly after the event. Additionally, patients had to be above 45 years old and be a resident of Nueces County, as the study was limited in 7 acute care hospitals of this certain county. Demographics, stroke risk factors, clinical variables and the REI (which is the sum of apneas plus hypopneas per hour of sleep apnea study duration) were recorded. Patients were followed until the first recurrent stroke, death or the last follow-up date, whichever came first. Proportional hazard models were conducted, both unadjusted and adjusted, to assess the association between REI and recurrent stroke or death. Finally, the interaction of ethnicity, REI and each outcome was statistically analyzed.

Impact of Air Pollution on Stroke Mortality

Kristina Shkirkova, BSc

Chen G, Wang A, Li S, Zhao X, Wang Y, Li H, et al. Long-Term Exposure to Air Pollution and Survival After Ischemic Stroke. Stroke. 2019;50:563-570

The risk factors of stroke, a major contributor to the global burden of disability and mortality, include environmental exposure to air pollution. Pre-stroke long-term exposure to air pollution derived particulate matter is associated with higher mortality rates after ischemic stroke, the authors of the new study from China report.

The study by Chen et al. estimated the daily exposure of a cohort of 12291 ischemic stroke patients to air pollutants via a machine learning algorithm that accounted for temporal and spatial meteorological and satellite monitoring data for the geocoded location of patients’ home address. The authors looked at 3-year pre-stroke air levels of particulate matter with aerodynamic diameter ≤10 μm and nitrogen dioxide and the rates of mortality after ischemic stroke within 1 year follow up period between 2007 and 2008. Smaller coarse particles in the air mixture were the primary interest in this study, as they contain the most toxin and are able penetrate deeper through the respiratory system and cause an inflammatory response.