Patrick Campbell

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Data published from researchers at the Wolfson Centre for Prevention of Stroke and Dementia at Oxford University suggests high blood pressure in midlife was linked to an increased risk of brain damage later in life. 

Results of the study, which examined both systolic and diastolic blood pressure before the age of 50 and brain damage later in life, revealed patients with higher blood pressure were more likely to have a higher volume of white matter hyperintensities as they grow older.

“The study showed that diastolic blood pressure in people in their 40s and 50s is associated with more extensive brain damage years later. This means that it is not just the systolic blood pressure, the first, higher number, but the diastolic blood pressure, the second, lower number, that is important to prevent brain tissue damage,” said Karolina Wartolowska, a clinical research fellow at the Centre for Prevention of Stroke and Dementia, University of Oxford, 

. “Many people may think of hypertension and stroke as diseases of older people, but our results suggest that if we would like to keep a healthy brain well into our 60s and 70s, we may have to make sure our blood pressure, including the diastolic blood pressure, stays within a healthy range when we are in our 40s and 50s.”

With an interest in the effect of blood pressure control on potential brain damage, Wartolowska and colleagues from Oxford University designed their analysis as a community-based cohort study using data from more than 35,000 patients in the UK Biobank Study. Patients included in the study were between 40-69 years of age, had data collected between March 2006 to October 2010, and underwent magnetic resonance imaging between August 2014 and October 2019.

Of note, patients were not eligible for inclusion if they had missing blood pressure data at baseline or missing MRI data. Patients were also deemed ineligible if they had previous diagnoses of conditions such as conditions, such as multiple sclerosis or other demyelinating disorders, cerebral infarction, encephalitis or brain abscess, brain tumor, or systemic lupus erythematosus.

For the purpose of analysis, investigators hoped to assess associations between white matter hyperintensities load and concurrent versus past blood pressure using models adjusted for factors including age, sex, cardiovascular risk factors, blood pressure source, assessment center, and time since baseline. Investigators pointed out associations adjusted for regression dilution bass were determined between median white matter hyperintensities and usual systolic or diastolic blood pressure, stratified by age and baseline blood pressure readings.

In total, 37,041 patients were deemed eligible for inclusion in the study and these patients had a median time between visits of 9.07 (4.28-13.49) years. Investigators noted these patients were similar to those in the overall UK Biobank population but did contain more active smokers and fewer people with a history of diabetes, angina, myocardial infarction, or antihypertensive medication use.

Upon analysis, results indicated white matter hyperintensities were more strongly associated with concurrent systolic blood pressure(DBP: ß=.064; 95% CI, 0.050–0.078; SBP: ß=.076; 95% CI, 0.062–0.090) but revealed the strongest association was for past diastolic blood pressure (DBP: ß=.087; 95% CI, 0.064-0.109; SBP: ß=.045; 95% CI, 0.022–0.069), especially those under 50 year of age (DBP: ß=.103; 95% CI, 0.055-0.152; SBP: ß=.012; 95% CI ,-0.044 to 0.069).

Additionally, because of the higher prevalence of elevated systolic blood pressure, investigators determined median white matter hyperintensities increased 1.126 (95% CI, 1.107–1.146) per 10 mmHg increase in usual systolic blood pressure and 1.106 (95% CI 1.090–1.122) per 5 mmHg increase in diastolic blood pressure. Results also suggested the population attributable fraction of white matter hyperintensities in the top decile was greater for elevated systolic blood pressure—19.1% for concurrent and 24.4% for past systolic blood pressure). Furthermore, results indicated any increase in blood pressure, even among patients with systolic blood pressure below 140 mmHg and diastolic blood pressure below 90 mmHg or those on antihypertensive medications, was associated with increased white matter intensities.

"Our results suggest that to ensure the best prevention of white matter hyperintensities in later life, control of diastolic blood pressure, in particular, may be required in early midlife, even for diastolic blood pressure below 90mmHg, whilst control of systolic blood pressure may be more important in late life,” Wartolowska added.

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Data from more than 37k patients in the UK Biobank study suggests hypertension in midlife was linked to an increased risk of white matter hyperintensities later in life.

Midlife Hypertension Linked to Increased Risk of Later Life Brain Damage

This content was originally published on Practical Cardiology, a sister publication of NeurologyLive. To view the original post, 

A recently published analysis of coronavirus disease 2019 (COVID-19) data from more than 1400 patients with stroke offers a new view of outcome predictors for this closely watched patient population.

All told, the data suggest that having COVID-19 at onset of stroke is associated with more than twice the rate of mortality of other patients with stroke and worse outcomes, as well as that individuals of Asian descent may be at higher risk of COVID-19-associated strokes than other groups.

"Our findings suggest that in some people, COVID-19 may influence stroke risk through its effect on excessive blood clotting or inflammation, and may also influence the characteristics and outcome of the stroke, including greater severity with a higher chance of multiple large vessel blood clots,” said study investigator David Werring, PhD, professor and consultant neurologist, Queen Square Institute of Neurology, University College London (UCL), and National Hospital for Neurology and Neurosurgery, in a statement.

Werring added that the data offer support for testing individuals for COVID-19 when they present to the hospital with a stroke, and noted that “further research is needed to determine whether treatments (such as the use of early full dose anticoagulation) should differ depending on this test result.”

With a knowledge gap related to characteristics and outcomes of stroke in patients with COVID-19, Werring and team of colleagues from the University College of London sought to provide clinicians with an updated overview of trends in this area. The (Service Evaluation of The Impact of COVID-19 On Stroke (SETICOS) project, which is currently being conducted in 13 stroke centers in England and Scotland, was designed to fill this hole.

Overall Stroke Risk Appears Low With COVID-19 Infection

Using data from SETICOS, investigators created a case-control study with patients admitted for stroke between March 9 and July 5, 2020. From a search of this time period, investigators identified 86 patients with stroke and evidence of COVID-19 at time of onset. For their analysis, investigators compared the characteristics and outcomes of these patients to those of the 1384 stroke patients admitted during the same time period without evidence of COVID-19.

Of the 86 patients with strokes and COVID-19, 81 were ischemic strokes and 5 were intracerebral hemorrhages. This group had a median age of 74.5 years (range, 67–84), and 54.7% were men, 71.6% were white, 9.5% were black, and 17.6% were Asian. Of the 1834 stroke patients in the control group, 1193 ischemic strokes and 191 were intracerebral hemorrhages. This group had a median age of 73 years (range, 61–82), 52.8% were men, 82.3% were white, 9.1% were black, and 7.3% were Asian.

In comparison to controls with ischemic stroke, those with ischemic stroke and COVID-19 were more likely to have multiple large vessel occlusions (17.9% vs 8.1%; 

<.03) and were more severe (median National Institutes of Health Stroke Scale [NIHSS] score, 8 vs 5; 

Additionally, those with COVID-19 and ischemic stroke were associated with higher log10 D-dimer levels (COVID-19: 3.4; controls: 3.0; 

<.01), as well as higher variance (standard deviation 0.83 vs. 0.63; 

 <.03), indicating there was a broader distribution of D-dimers in those with COVID-19. As well, those with COVID-19 were associated with more severe disability on discharge (median modified Rankin Scale (mRS) score, 4 vs 3; 

 <.0001) and inpatient death (19.8% vs 9.6%; 

Additionally, in the 44 instances in which ischemic stroke and COVID-19 were present with both symptom onset dates recorded, COVID-19-relevant symptoms—fever, cough, or dyspnea—occurred a median of 6 days before the stroke onset. For the 3 individuals with intracerebral hemorrhage who had both dates recorded, the COVID-19 symptoms occurred a median of 4 days after the stroke onset. “Although the numbers are small, the difference between these two medians was significant (

With regard to outcomes, 19.8% of ischemic strokes among patients with COVID-19 resulted in death compared to 9.6% of patients in the control group (

 <.00003). Additionally, the investigators pointed out that the recurrence of stroke during admission was very rare among those with COVID-19 (2.3%) and the control group (1.0%).

“By comparing characteristics and outcomes of strokes experienced by people with and without COVID-19, we found that there were differences between the groups, suggesting that COVID-19 exerts an influence over the presentation of stroke,” added Richard Perry, PhD, neurologist,  Queen Square Institute of Neurology, UCL, and National Hospital for Neurology and Neurosurgery, in the aforementioned statement.

 "Some of the differences relate to what other studies are uncovering about COVID-19, in that it might make blood stickier and more likely to clot.”

REFERENCES
1. Perry RJ, Smith CJ, Roffe C, et al. Characteristics and outcomes of COVID-19-associated stroke: a UK multicentre case-control study. 

. Published November 5, 2020. doi: 10.1136/jnnp-2020-324927
2. COVID-19 linked to worse stroke outcomes. News release. University College London. November 5, 2020. Accessed November 9, 2020. https://www.eurekalert.org/pub_releases/2020-11/ucl-clt110520.php

An analysis from English and Scottish stroke centers provides physicians a new view of the trends and outcomes of patients with COVID-19 who experience stroke.

COVID-19 Diagnosis at Stroke Onset Linked to Worse Outcomes

 on MDMag.com, part of the HCPLive Network.

Findings from a study presented at the American Stroke Association’s 

 suggests that an LDL-C of less than 70 mg/dL in caucasian patients lowers the risk of major vascular events following ischemic stroke. 

Data from the French cohort (n = 1073) of the Treat Stroke to Target (TST) trial indicated that the aggressive cholesterol target could prevent 1 in 4 major vascular events in the population.

The TST trial was a multicenter trial that randomized 2860 patients who recently experienced an atherothrombotic ischemic stroke in the past 3 months or transient ischemic attack (TIA) in 1:1 ratio to an LDL-C target of less than 70 mg/dL or an LDL of 100±10 mg/dL using statins or ezetimibe. The French cohort data presented at ISC 20 examined 1073 patients with a follow-up of 5.3 years, which was almost 2 years more than the 3.5 years of follow-up from the AHA 2019 presentation.

The trial had a composite endpoint of nonfatal ischemic stroke or myocardial infarction, news symptoms requiring urgent coronary or carotid revascularization, and vascular death. In the entire TST study cohort, the endpoint was achieved in 8.5% of patients in those with a target of less than 70 mg/dL and in 10.9% in the 100±10 mg/dL group (HR 0.78, 95% CI, 0.61-0.98; P = .036).

Of the 2860 patients, 1073 were randomized to a target of less than 70 mg/dL and 1075 were randomized to the 100±10 mg/dL group—mean LDL-C achieved after a median 5.3 years of follow-up was 66 mg/dL and 96 mg/dL, respectively. In the entire TST cohort, the mean LDL-C achieved for the groups was 65 mg/dL and 96 mg/dL.

In the French cohort, the primary outcome occurred in 9.6% of patients in the lower target group and 12.9% of patients in the 100±10 mg/dL group (HR 0.74, 95% CI, 0.75-0.94; P = .019). Investigators also pointed out cerebral infarction and urgent carotid revascularization following TIA was reduced by 27% (P = .046) and cerebral infarction or intracranial hemorrhage was reduced by 28% (P = .023) in patients with a target of less than 70 mg/dL.

When examining the primary outcome or intracranial hemorrhage, results indicated a 25% in these type of events (P = .022). An association was observed between a lower target LDL-C and intracranial hemorrhages—with 13 patients experiencing such an event in the lower target group versus 11 patients in the higher target group (HR 1.17, 95% CI, 0.53-2.62, P = .70). This is similar to an effect seen in the entire TST cohort (1.3% versus 0.9%; HR 1.38, 95% CI 0.68-2.82).

Results of an NNT analysis indicated a target LDL-C of less than 70 mg/dL avoided 1 subsequent major vascular event in 4 (NNT=30) in a Caucasian population.

Amarenco P, Kim JS, Labreuche J, et al; on behalf of the Treat Stroke to Target investigators. Benefit of Targeting a LDL Cholesterol Less than 70 mg/dL after an Ischemic Stroke of Atherosclerotic Origin. The 5-year Results of the French Part of the TST Trial. Presented at: 2020 International Stroke Conference. February 19-21, 2020; Los Angeles, CA. Abstract LB9.

The composite primary end point of the study occurred in 9.6% of patients in the lower-target LDL-C group compared with 12.9% in the higher target group.

Lower LDL-C Target May Help Prevent Vascular Events Following Ischemic Stroke

 on MDMag.com, part of the HCPLive Network. 

 suggest that the shingles vaccine may help reduce stroke risk in older people. 

Data revealed a 16% reduced risk of stroke in older adults who received the zoster vaccine live, conveying an additional benefit beyond shingles prevention. 

"Our study results may encourage people ages 50 and older to follow the recommendation and get vaccinated against shingles,” said Quanhe Yang, PhD, lead investigator and senior scientist at the CDC in Atlanta, GA, in a statement. “You are reducing the risk of shingles, and at the same time you may be reducing your risk of stroke."

While previous research has linked herpes zoster to an increased risk of stroke in older patients, no studies had established a definitive link between the Zoster Vaccine Live and the risk of stroke in this population group. To perform such as assessment, Yang and a team of CDC colleagues performed a retrospective analysis using the Medicare health records of more than 1.3 million Medicare fee-for-service beneficiaries.

For inclusion in the analysis, patients were required to be 66 years of age or older, have no stroke history, and must have received the Zoster Vaccine Live between 2008-2014. A total of 1,382,051 individuals were identified for inclusion and investigators proceeded to match this cohort with 1,382,051 controls to control for age, gender, race, medications, and comorbidities.

Cox proportional hazards models were used to examine the association between the vaccine and a composite endpoint of fatal and nonfatal incident stroke outcomes. Additional analyses were performed examining the effectiveness of the vaccine and stroke reduction stratified by different age groups.

During follow-up, which had a median length of 3.9 years, a total of 42,267 stroke events occurred over 5,890,113 person-years among those who received the vaccine. Of the 42,267 events, 33,510 were acute ischemic strokes and 4318 were hemorrhagic strokes.

Among matched controls, 48,139 total stroke events occurred over 5,693,943 person-years. Of the 48,139 events, 39,334 were acute ischemic strokes and 4713 were hemorrhagic strokes.

When comparing the groups, lower incidence rates per 1000 person-years were observed among those who received the Zoster Live Vaccine than those who did not for all stroke events (7.18 vs 8.45), acute ischemic stroke (5.40 vs 6.53), and for hemorrhagic stroke (0.73 vs 0.82; P <.001 for difference). Results of the Cox proportional hazards models indicated receiving the vaccine decreased risk of stroke by 16%, risk of ischemic stroke by approximately 18%, and risk of hemorrhagic stroke by 12%.

Of note, results indicate the beneficial impact on stroke risk appeared to be greater in patients 79 years of age and younger than in the older patients examined. Additionally, investigators pointed out the study examined a time period when the Zoster Vaccine Live was the only shingles vaccine available.

Yang Q, Chang A, Tong X, Merritt R. Herpes Zoster Vaccine Live And Risk For Stroke Among Medicare Beneficiaries: Population Based Matched Cohort Study. Presented at: 2020 International Stroke Conference. February 19-21, 2020; Los Angeles, CA. Abstract TP493.

The beneficial impact on stroke risk appeared to be greater in patients age 79 and younger than in the older patients examined.

Patrick Campbell

Articles

Midlife Hypertension Linked to Increased Risk of Later Life Brain Damage

COVID-19 Diagnosis at Stroke Onset Linked to Worse Outcomes

Lower LDL-C Target May Help Prevent Vascular Events Following Ischemic Stroke

Shingles Vaccine Linked to Lower Risk of Stroke