American Heart Association

epidemiology and genetics

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.

Rising Incidence of Stroke in Pregnancy: What’s to Blame?

Kara Jo Swafford, MD

Liu S, Chan W-S, Ray JG, Kramer MS, Joseph KS, and for the Canadian Perinatal Surveillance System (Public Health Agency of Canada). Stroke and Cerebrovascular Disease in Pregnancy: Incidence, Temporal Trends, and Risk Factors. Stroke. 2018;50:13–20.

Stroke is the most common cause of long-term disability in women after pregnancy. In Canada, the incidence of stroke at delivery was 4.8 per 100,000 deliveries between 2003-2007, with an associated case fatality of 9.4%. In the United States, the rate of stroke during the antepartum period increased from 15 to 22 per 100,000 deliveries between 1994-1995 and 2006-2007, with the rate during the postpartum period increasing from 12 to 22 per 100,000 deliveries over the same time period.

Liu et al. investigated the incidence, trends and risk factors associated with stroke in pregnancy in Canada by performing a retrospective population-based cohort study including antenatal, delivery and postpartum admissions within 42 days between 2003-2016. Stroke incidence was 13.4 cases per 100,000 deliveries between 2003-2016; 60% hemorrhagic and 30% ischemic stroke, with a 7.4% case fatality rate. Over half (51.7%) of cases occurred during the postpartum period. The rate of stroke increased from 10.8 to 16.6 cases per 100,000 deliveries between 2003-2004 and 2015-2016. Risk increased with increasing gestational duration, advanced maternal age, gestational hypertension, preeclampsia, eclampsia, connective tissue disorders, sepsis, postpartum hemorrhage requiring blood transfusion, congenital heart disease, HIV infection and thrombophilia. Several potential confounders, such as smoking, body mass index, ethnicity and socio-economic status, were not available.

Article Commentary: “Long-Term Exposure to Particulate Matter Air Pollution Is a Risk Factor for Stroke”

Burton J. Tabaac, MD

Scheers H, Jacobs L, Casas L, Nemery B, Nawrot TS. Long-Term Exposure to Particulate Matter Air Pollution Is a Risk Factor for Stroke: Meta-Analytical Evidence. Stroke. 2018

A study in 2010, published in INTERSTROKE, detailed the risk factors for stroke in 22 countries. It was shown that 90% of all ischemic and hemorrhagic strokes can be attributed to 10 major risk factors, hypertension and current smoking being the most prominent.1 This current meta-analytical article, written by Scheers et al, analyzed the Pubmed citation database to quantify the pooled association between stroke incidence and mortality with long-term exposure to particulate matter. This meta-analysis suggests a statistically significant effect of recent particulate matter exposure and the risk of stroke.

The article incorporates 20 publications, including more than 10 million people, and more than 200,000 stroke events to reveal that the association between long-term particulate matter exposure and stroke event was positive in North America and Europe (but not statistically significant for the latter) and null in Asia. The authors are keen to differentiate recent and long-term exposure to particulate matter, as they are different pathophysiological concepts. The study focus regarding short-term exposure asks when strokes are most likely to occur, whereas the consideration pertaining to long-term exposure focuses on where people are at risk.