Biomarkers May Help Predict Ischemic Stroke Risk

Anything in here that tests for stiff arteries?  What about for hemorrhagic strokes? 

Biomarkers May Help Predict Ischemic Stroke Risk

Patients with high levels of four blood biomarkers may be more likely to have an ischemic stroke than those with low rates of the markers, researchers reported.
In an observational study, natural logarithmic statistical transformation of markers of inflammatory, endothelial, and oxidative stress – C-reactive protein (CRP), tumor necrosis factor 2 (TNF2), total homocysteine (tHcy), and vascular endothelial growth factor (VEGF) – were each tied to a greater risk of incident ischemic stroke, Ashkan Shoamanesh, MD, of McMaster University, and colleagues reported online in Neurology.
"Identification of persons at high risk of stroke allows for development of targeted interventions to reduce the burden of stroke at the individual and population levels," study co-author Jose Romero, MD, of Boston University, told MedPage Today.
Using the biomarkers also helped better predict the risk of a stroke over the more traditionally used Framingham Stroke Risk Study, Romero said.
However, given that the study was observational, the results don't mean that elevation of these markers causes strokes, "nor do we provide thresholds for clinicians to consider increased risk," Romero noted.
Additionally, while the study doesn't suggest that these markers should be measured routinely in clinical practice, it does shed light on additional markers to identify those at a greater risk of a stroke, he said.
For their study, the researchers measured the levels of 15 biomarkers associated with inflammation in the blood of those from the Framingham Heart Study Offspring Cohort who'd never had a stroke. The 3,224 participants averaged 61 years of age at the study's onset and were observed for an average of nine years. During that period, 98 had a stroke.
In a model adjusted for age and sex, four of the 15 biomarkers were linked to an increased stroke risk, they found:

• CRP: HR 1.28, 95% CI 1.04 to 1.56
• TNFR2: HR 1.33, 95% CI 1.09 to 1.63
• tHcy: HR 1.32, 95% CI 1.11 to 1.58
• VEGF: HR 1.25, 95% CI 1.07 to 1.46

Three of the biomarkers remained significantly associated with stroke risk in a model adjusted for systolic blood pressure, hypertension treatment, current smoking, diabetes, cardiovascular disease, and atrial fibrillation. Only CRP was no longer significant, the researchers said.
Adding the four biomarkers to the Framingham Stroke Risk Profile improved the ability to predict which patients would be at greatest risk for ischemic stroke, they reported.
They also found in exploratory analyses a significant relationship between CRP and a subtype of ischemic stroke: atherosclerotic brain infarction (HR 1.31, 95% CI 1.06 to 1.33). They also saw a relationship between cerebral embolism and both interleukin 6 (HR 1.11, 95% CI 1.06 to 1.33) and fibrinogen (HR 1.40, 95% CI 1.06 to 1.86).
The study was limited by the fact that conditions that may affect vascular and systemic inflammation, such as chronic inflammatory diseases and infections, and long-term use of medications that have anti-inflammatory properties, were unaccounted for. Also, the biomarkers were measured at single time points and not repeated over time, the researchers said.
Deepak Gulati, MD, of the Ohio State University who wasn't involved in the study, called it "preliminary" in terms of establishing any solid evidence of an association between the biomarkers and ischemic stroke, but said it "brings about this important concept that needs to be explored further."
Gulati said that biomarkers must be accurately and reproducibly measurable, clinically feasible, cost effective, and prospectively validated in randomized clinical trials.
"Biomarkers are interesting, but nothing has yet been validated in terms of an ischemic stroke," he said.
Romero said future research could abet the development of "clinically meaningful thresholds" that may be used in practice and the testing of treatments and drugs in clinical trials that incorporate these markers to assess their benefit in treatment decisions for stroke risk reduction.
In an accompanying editorial, Stephen Williams, PhD, of the University of Virginia, and Svetlana Lorenzano, MD, PhD, of Sapienza University in Rome, agreed that the study "helped refine a well-established stroke risk clinical model ... and helped enhance individual stroke risk prediction," but similarly cautioned that it "should be further assessed in prospective investigations."
As of now, added Romero, stroke prevention should continue to focus on the assessment and treatment of modifiable risk factors as suggested by current stroke prevention guidelines.

Neither the researchers nor the editorialists reported any financial relationships with industry.

• Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College

• Primary Source

  Neurology

  Source Reference: Shoamanesh A, et al "Circulating biomarkers and incident ischemic stroke in the Framingham Offspring Study" Neurology 2016; 87: 1-6.

• Secondary Source

  Neurology

  Source Reference: Williams SR, Lorenzano S "Seeking the 'holy grail' of biomarkers to improve stroke risk prediction of clinical scores" Neurology 2016; 87: 1-2.

Elevated Total Homocysteine Levels in Acute Ischemic Stroke Are Associated With Long-Term Mortality

You'll have to see what your doctor does with this information to reduce your risk of dying.
An updated stroke protocol on not dying would be the best.
http://stroke.ahajournals.org/content/46/9/2419.abstract

1. Zhihong Shi, MD, PhD;
2. Yalin Guan, MD, MS;
3. Ya Ruth Huo, BA, MD;
4. Shuling Liu, RN, MS;
5. Meilin Zhang, PhD;
6. Hui Lu, MD, MS;
7. Wei Yue, MD, MS;
8. Jinhuan Wang, MD, PhD;
9. Yong Ji, MD, PhD

+ Author Affiliations

1. From the Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases (Z.S., Y.G., S.L., H.L., W.Y., J.W., Y.J.), Department of Neurology (Z.S., Y.G., S.L., H.L., W.Y., Y.J.), and Department of Neurosurgery (J.W.), Tianjin Huanhu Hospital, Tianjin, China; School of Medicine, University of New South Wales, Kensington, NSW, Australia (Y.R.H.); and Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin, China (M.Z.).

1. Correspondence to Yong Ji, MD, PhD, Department of Neurology, Tianjin Huanhu Hospital, Qixiangtai Rd 122, Hexi, Tianjin 300060, China. E-mail jiyongusa@126.com

Abstract

Background and Purpose—Total homocysteine (tHcy) levels are associated with secondary vascular events and mortality after stroke. The aim of this study was to investigate whether tHcy levels in the acute phase of a stroke contribute to the recurrence of cerebro-cardiovascular events and mortality.

Methods—A total of 3799 patients were recruited after hospital admission for acute ischemic stroke. Levels of tHcy were measured within 24 hours after primary admission. Patients were followed for a median of 48 months.

Results—During the follow-up period, 233 (6.1%) patients died. After adjustment for age, smoking status, diabetes mellitus, and other cardiovascular risk factors, patients in the highest tHcy quartile (>18.6 μmol/L) had a 1.61-fold increased risk of death (adjusted hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.03–2.53) compared with patients in the lowest quartile (≤10 μmol/L). Further subgroup analysis showed that this correlation was only significant in the large-artery atherosclerosis stroke subtype (adjusted HR, 1.80; 95% CI, 1.05–3.07); this correlation was not significant in the small-vessel occlusion subtype (adjusted HR, 0.80; 95% CI, 0.30–2.12). The risk of stroke-related mortality was 2.27-fold higher for patients in the third tHcy quartile (adjusted HR, 2.27; 95% CI, 1.06–4.86) and 2.15-fold more likely for patients in the fourth quartile (adjusted HR, 2.15; 95% CI, 1.01–4.63) than for patients in the lowest tHcy quartile. The risk of cardiovascular-related mortality and the risk of recurrent ischemic stroke were not associated with tHcy levels.

Conclusions—Our findings suggest that elevated tHcy levels in the acute phase of an ischemic stroke can predict mortality, especially in stroke patients with the large-vessel atherosclerosis subtype.