American Heart Association

epidemiology and genetics

Statins and Intracerebral Hemorrhage — Causation or Coincidence?

Kevin S. Attenhofer, MD

Gaist D, Goldstein LB, Cea Soriano L, García Rodríguez LA. Statins and the Risk of Intracerebral Hemorrhage in Patients With Previous Ischemic Stroke or Transient Ischemic Attack. Stroke. 2017

Statins are some of the most commonly prescribed drugs in the fields of cardio- and cerebrovascular disease. In the last two decades, randomized controlled trials have shown that statin therapy reduces the risk of major vascular events in high-risk populations. Definitions of these populations have changed over the years, but currently the AHA/ASA stroke guidelines recommend statins in all patients for secondary stroke prevention.

Despite the ubiquitous usage of statins, it has been noted that some data (from the Heart Protection Study (HPS) and the Stroke Prevention with Aggressive Reductions of Cholesterol Levels (SPARCL)) suggests that the benefits of high-dose atorvastatin treatment was partially offset by an increase in hemorrhagic stroke. The association of statins and intracerebral hemorrhage (ICH) has remained controversial ever since. Subsequent meta-analyses and case control studies — some of which included data from SPARCL — found no associated increase in the risk of ICH in patients on statin therapy.

Eating Healthy: Tips for Stroke Prevention

Rohan Arora, MD

Larsson SC. Dietary Approaches for Stroke Prevention. Stroke. 2017

This review by Susanna Larsson focuses on the current evidence from randomized controlled trials and prospective studies on dietary modifications that could help with stroke prevention.

The article is very important since diet is one of the modifiable factors that can help with reducing the risk of stroke and promote cardiovascular health. The stroke survivors or their family members are of utmost curiosity to change their diet after seeing a family member suffer from stroke.

Physical Activity and Stroke Risk: A Role for Moderate Physical Activity

Mark R. Etherton, MD, PhD

Willey JZ, Voutsina J, Sherzai A, Ma H, Bernstein L, Elkind MSV, et al. Trajectories in Leisure-Time Physical Activity and Risk of Stroke in Women in the California Teachers Study. Stroke. 2017

In this entry, I discuss a recent publication by Joshua Willey and colleagues regarding the protective effects of physical activity on stroke risk.

A beneficial role of physical activity in the prevention of cardiovascular disease and ischemic stroke has been consistently demonstrated. An outstanding question, however, is how changes in physical activity impact incident stroke risk. The authors of this manuscript, therefore, set out to investigate the association between changes in self-reported physical activity at two time points and incident stroke risk.

The authors used the California Teachers Study cohort, which is a large prospective cohort of female teachers in the state of California, and examined self-reported physical activity at two time points (1995 and 2005-6). In total, 61,256 participants were included in the analysis with notable exclusion criteria, including history of stroke or age less than 26 years old. Exercise was reported as moderate (e.g. brisk walking) or strenuous (e.g. swimming, running) and quantified as hours per week and months per year in the past 3 years. The authors used this data to then establish average minutes/week and dichotomized the measures by the AHA recommendations for moderate (150 minutes/week) or strenuous (75 minutes/week) activity. Using these metrics of physical activity, the authors assessed incident stroke risk.

Location of Brain Infarct and Gender is Associated with Risk of Dementia: A Review of AGES-Reykjavik Study

Shashank Shekhar, MD, MS

Sigurdsson S, Aspelund T, Kjartansson O, Gudmundsson EF, Jonsdottir MK, Eiriksdottir G, et al. Incidence of Brain Infarcts, Cognitive Change, and Risk of Dementia in the General Population: The AGES-Reykjavik Study (Age Gene/Environment Susceptibility-Reykjavik Study). Stroke. 2017

The recent published longitudinal study by Sigurdsson and colleagues highlights the types of infarction that are associated with cognitive decline, as well as the sex factor that can contribute to dementia after ischemic strokes.

This study is based on the longitudinal data gathered from an Icelandic population-based cohort of men and women from 2002 to 2006, in which 5764 participants were examined. A total of 3316 patients were followed up from 2007 to 2011. The study utilized the MRI to get the baseline and follow-up imaging to define the location of the stroke. All types of infarcts were included and categorized into Cortical infarcts, subcortical infarcts, and cerebellar infarction. Of 3316 participants from the follow-up, 2612 participants (1070 male and 1542 female) were included. Rejection of the rest was based on exclusion criteria. Cognition was assessed regarding memory, processing speed, and executive function. The cognitive screening was done with mini-mental and digital symbol substitution test and later confirmed using a diagnostic battery of neuropsychological tests. For each infarction type, the sample was categorized into four groups based on a combination of incidence and prevalence to find gender-based differences.

Reducing Recurrent Strokes with Secondary Risk-Factor Modification — Reflections from Temporal Trends in a Population-Based Study

Gurmeen Kaur, MBBS

Bergström L, Irewall AL, Söderström L, Ögren J, Laurell K, Mooe T. One-Year Incidence, Time Trends, and Predictors of Recurrent Ischemic Stroke in Sweden From 1998 to 2010: An Observational Study. Stroke. 2017

The risk of recurrent stroke has been on a decline as per estimates from different countries, including Italy, Taiwan and the “Western world.” Rikstroke is the Swedish Stroke Register where all Swedish hospital admissions because of stroke are recorded. The authors describe an excellent longitudinal study design where patients with ischemic strokes were followed up from 1998 to 2009. From the year 1998, all Swedish hospitals and rehab centers report their admissions to the Rikstroke registry, which had an astounding 85% coverage in the year 2009.

The recurrence of ischemic stroke events was calculated by amalgamating the Rikstroke registry with the Swedish National Inpatient Register (IPR), which contains data about diagnoses and dates of discharge from hospitalizations in Sweden.

Understanding Changing Temporal Trends in Dementia — Does Improving Vascular Health Have a Role?

Gurmeen Kaur, MBBS

Pase MP, Satizabal C, Seshadri S. Role of Improved Vascular Health in the Declining Incidence of Dementia. Stroke. 2017

It is projected that 13.8 million Americans will have dementia by the year 2050, making it a major public health epidemic. While the overall prevalence is on a rise, every individual’s chance of developing dementia per year is decreasing. The authors used the Framingham Heart Study (FHS) to demonstrate nearly a 20% decrease in developing dementia by a specific age over the past 30 years and have explored the temporal trends of this change.

Improved cardiovascular health and better management of stroke and vascular risk factors may be the reason for this observed decrease. Vascular risk factors have also been implicated in the pathophysiology of both vascular dementia and Alzheimer’s type dementia. A meta-analysis of 14,730 adults, including 862 with a history of stroke and 13,868 controls, demonstrated that a history of stroke increased the risk of AD dementia by 59%. Leukoariosis or increased burden of small vessel disease suggests silent ischemia. Many large databases show that the incidence of strokes is decreasing, which may be a contributing factor to decreased rates of dementia.

Heart Failure Associated With All Types of Strokes at Long-term Follow Up

Peggy Nguyen, MD

Adelborg K, Szépligeti S, Sundbøll J, Horváth-Puhó E, Henderson VW, Ording A, et al. Risk of Stroke in Patients With Heart Failure: A Population-Based 30-Year Cohort Study. Stroke. 2017

Heart failure has previously been identified in association with ischemic stroke, with previous literature citing thrombus formation, hypercoagulable state, endothelial dysfunction and impaired cerebral autoregulation as possible mechanisms underlying ischemia. Additionally, heart failure and stroke share several common etiological conditions, including hypertension and dyslipidemia (Stroke. 2011;42:2977-2982). However, the association between heart failure and hemorrhagic stroke, and the long-term implications of heart failure on all-stroke risk, remained to be clearly elucidated. Here, patients with heart failure (n = 289,353) were compared to an age and gender matched control group (n = 1,446,765), for the outcomes of ischemic stroke, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) evaluated at 30 days, 1 year, and 30 years, providing a far more extensive follow up than previous studies.

Calorie-free, But Perhaps Not Risk-free: Artificial Sweeteners and the Risk of Stroke and Dementia

Neal S. Parikh, MD

Pase MP, Himali JJ, Beiser AS, Aparicio HJ, Satizabal CL, Vasan RS, et al. Sugar- and Artificially Sweetened Beverages and the Risks of Incident Stroke and Dementia: A Prospective Cohort Study. Stroke.

In this entry, I discuss a recent publication by Matthew Pase and colleagues regarding the risks of stroke and dementia associated with the consumption of sugar-sweetened and artificially sweetened beverages.

Citing conflicting data, the authors sought to examine the association of sugar- or artificially sweetened soft drink intake with incident stroke and dementia in the Framingham Heart study.

Inverse Relationship between HDL2-C Subfraction and Carotid Intima-Media Thickness

Alexander E. Merkler, MD 

Increased carotid-intima media thickness (cIMT) is associated with future cerebrovascular events. Although previous data has shown an inverse relationship between high density lipoprotein cholesterol (HDL-C) and future cerebrovascular events, this association has been challenged in recent trials; therefore, it is uncertain whether HDL-C subfractions have differential effects on cerebrovascular risk.

Using the Northern Manhattan Study (NOMAS), Dr. Tiozzo et al. evaluate the relationship between HDL-C subfractions and cIMT. NOMAS is a prospective cohort study designed to determine stroke incidence and risk factors in a multiethnic urban population in Manhattan.

Nine hundred eighty-eight stroke-free participants with available data on HDL-C subfractions and cIMT measurements using high-resolution ultrasound were evaluated. HDL-C was assessed as HDL2-C and HDL3-C subfractions, and total HDL. cIMT was calculated as the composite measure of the near and the far wall of IMT in the common, internal, and bifurcation of the carotid artery on both sides of the neck. After controlling for demographics, vascular risk factors, LDL, and triglyceride levels, both HDL2-C and total HDL-C were inversely associated with cIMT; the association was even more robust among patients with diabetes. No association was found between HDL3-C and cIMT.

The main limitation is the lack of temporality between HDL-C subfraction measurement and cIMT assessment.

Overall, the results suggest an inverse relationship between total HDL and HDL2-C and cIMT, but not between HDL3-C and cIMT. If confirmed, these results may lead to HDL subfraction targeted therapies to reduce the risk of cerebrovascular disease.

Heart Rate Variability and Incident Stroke Risk in the Atherosclerosis Risk in Communities Study

Neal S. Parikh, MD
In this issue of Stroke, Amber Fyfe-Johnson and colleagues describe their investigation of the association between heart rate variability (HRV) and incident stroke risk in the Atherosclerosis Risk in Communities (ARIC) Study cohort.

They argue that autonomic nervous system (ANS) dysfunction, as reflected by HRV, may be associated with cardiovascular mortality, coronary heart disease, and mortality in stroke survivors. ANS dysfunction may be associated with dysregulated cerebrovascular autoregulation and blood pressure.

ARIC participants were assessed by EKG for HRV by four measures at visit 1 (1987-1989) and followed through December 31, 2011 for incident stroke by telephone ascertainment, hospital discharge diagnosis review, and state death registry review. Covariates, collected at the index visit and again at visit 4 (1996-1998), included: age, sex, race, smoking/alcohol use, physical activity, body mass index, blood pressure, blood lipids, and diabetes. Patients taking medications that modify HRV (beta-blockers, anti-arrythmics, calcium channel blockers, digoxin) and those with prevalent stroke, coronary disease, or heart failure were excluded.  

Cox proportional hazards models were used to calculate hazard ratios for the relationship between each quintile of HRV measures and stroke.

Of 12,550 ARIC participants, 816 (6.5%) had stroke. Crude cumulative stroke incidence was higher in patients with the lowest HRV quintile (compared to the highest quintile). However, after adjustment for covariates, associations between HRV and stroke risk were attenuated and did not meet statistical significance. In analyses restricted to participants with diabetes, stroke risk was higher in the lowest HRV quintile, but this association was only statistically significant when testing one of four HRV measures (HR 2.0, 95% confidence interval, 1.1-4.0).

The authors conclude that there may be an association between low HRV and incident stroke in populations already at risk – patients with diabetes. Whether this association would withstand adjustment for an expanded list of cardiovascular risk factors in a modern cohort is unclear. However, the importance of identifying simple indicators of stroke risk such as HRV cannot be overstated.