7 Things Stroke Doctors Say You Should Never, Ever Do

 None of these are specific enough and my stroke was only preventable if my dads' doctor had told him to have his children tested for carotid plaque after he was diagnosed with 80% blockage

7 Things Stroke Doctors Say You Should Never, Ever Do

In the United States, strokes are a top cause of death and a major cause of disability, according to the American Stroke Association. This is a scary reality, especially since many of the stroke risk factors are pretty silent (like high cholesterol and high blood pressure) ― until they’re not.

But just because some of the risk factors aren’t always obvious doesn’t mean strokes can’t be controlled. In fact, it’s estimated that 80% of strokes are preventable through lifestyle changes like exercise, diet and more, according to the Centers for Disease Control and Prevention.

No one knows that more than the experts who treat the issue. Stroke doctors say they think a lot about the key ways to lower their risk (and their patients’ risk) of stroke.

“I like to think of it more proactively — what I could do to prevent stroke,” said Dr. Anthony Kim, a vascular neurologist and medical director of the University of California at San Francisco Stroke Center.

Below, stroke doctors share the habits they personally avoid ― and why you should avoid them, too.

Have A Sedentary Lifestyle

According to Dr. Arthur Wang, director of endovascular neurosurgery at Tulane University School of Medicine, one of the modifiable risk factors for stroke is having a sedentary lifestyle.

While there isn’t one across-the-board definition of a sedentary lifestyle, overall, it means spending too much time sitting or lying down and not enough time exercising or moving around.

“It’s been shown that regular physical activity helps keep your blood vessels clog-free. It stops the buildup of plaque in the arteries,” Wang said. “And so we generally recommend that people get probably 30 minutes of moderate exercise maybe five times a week.”

This could mean going for walks, runs, biking, gardening or joining a group workout class — there is no wrong way to get moving.

(Mine was anything but sedentary; three years post stroke at age 53 I had a pulse of 54, meaning I had the cardiovascular fitness of an athlete.  My doctor asked what I was doing to stay in shape; 'I've done nothing for the past three years!', she was amazed. Now 19 years later, I'm just average fitness for my age.)

Ignore High Blood Pressure

“It turns out that a lot of the same things that we would recommend for a healthy lifestyle also reduce the risk of both heart disease and stroke,” Kim said. “But if there’s one factor that is the most impactful it would be blood pressure, blood pressure, blood pressure.”

Elevated blood pressure, particularly over time, can lead to problems, he said: High blood pressure is the biggest modifiable stroke risk factor.

“If you took a magic wand and waved it and suddenly eliminated high blood pressure from the U.S. population, there would be 60% fewer strokes,” Kim said. “It’s by far the leading risk factor for stroke and we call it the silent killer because oftentimes, patients don’t feel it; you have to have it checked and monitored and treated.”

(My high blood pressure didn't occur until 10 years post stroke.)

“If you took a magic wand and waved it and suddenly eliminated high blood pressure from the U.S. population, there would be 60% fewer strokes.”

- Dr. Anthony Kim, University of California, San Francisco, Stroke Center

Skip Regular Check-Ups

“These risk factors oftentimes don’t have any real symptoms,” Wang said, which is a worrisome thing to think about. “A patient would never know that their blood pressure’s high, they wouldn’t know whether they have high cholesterol unless all of this is routinely tested or screened on a regular basis.”

This means it’s crucial that you visit your primary care doctor for the routine check-ups that they deem necessary. They’ll screen you for issues like high cholesterol and high blood pressure while checking other risk factors like your blood sugar and weight, too, he added.

“I think just being hyper-vigilant about those things, especially when these risk factors for stroke are very cryptic, meaning that they don’t manifest in any real symptoms, so it’s really important for patients to understand that so they take the actionable steps to see their doctor to get these routine screening tests,” Wang said.

Your doctor can also review any risk factors outside your control, like gender (strokes are more common in women, Wang said), race (they’re more common in Black people, he noted) and personal history.

“In terms of previous medical history, those who have had prior strokes in the past, or if one of their parents had a stroke in the past, are at a much higher risk of having a future stroke,” Wang said.

Smoke

According to both Kim and Wang, one of the habits that is high on a to-avoid list is smoking. 

“That definitely increases the risk of stroke, and heart disease, for that matter,” Kim said.

“And one of the ways that it does that is by causing the blood vessels to become narrowed over time, and that can ultimately lead to blockages in blood flow to part of the brain, which is essentially what a stroke is,” he explained.

Never did.

T

Drink Too Much Alcohol

You’re probably aware that alcohol is not good for you. It’s linked to certain kinds of cancer, liver disease, and yes, stroke, too. Specifically, Kim said there is an “association between ... excessive alcohol use and heart disease and stroke risk.”

Alcohol recommendations vary by person, but, the CDC considers more than four drinks in one sitting for women or five drinks in one sitting for men to be excessive drinking. More than eight drinks per week for women and 15 drinks per week for men is also considered excessive drinking.

Generally, it’s accepted that women should not have more than one alcoholic drink a day and men should not have more than two, Kim said. These are also the recommendations put forth by the Dietary Guidelines for Americans.

(My alcohol use has expanded since my stroke because it lubricates my social connection which is going to prevent dementia. You doctors can shove your statements on alcohol.)

Ignore Your Diet

A proper diet is important for managing stroke risk, too. This means moderating foods that are full of saturated fats, sugar and salt, Wang said. (Additionally, Kim pointed out that there is a relationship between salt intake and high blood pressure, which, as we now know, is another stroke risk factor.)

When it comes to what you should eat, Kim points to the work of author and journalist Michael Pollan. This advice is “eat food, mostly plants, not too much,” Wang said. This means having a diet that’s rich in fruits and veggies with some meat added in.  

Dismiss Necessary Treatment

Since strokes are so common in this country (and this world), it’s important that you’re aware of the signs and get treated as soon as possible. Available stroke treatments work better the sooner they’re done, Kim said.

“Because many strokes aren’t painful, and the symptoms of stroke vary so much, it’s important to recognize symptoms of stroke,” he said.

And, there’s a useful acronym to help people remember the signs — and that acronym is FAST, Kim said. FAST stands for “facial drooping, arm weakness, speech difficulty and time to call 9-1-1,” according to the American Stroke Association website. 

“These are not the list of all potential stroke symptoms, but any one of those  [factors] raises the suspicion that it could be a stroke, especially if it happens suddenly,” Kim noted.

And, once again, it’s important to remember that getting treatment as fast as possible is vital, he said.

Tiny plastics in carotid plaque tied to elevated risk for heart attack, stroke, death

It is your doctor's and hospital's responsibility to contact stroke leadership and get research done to alleviate this problem. But I guess that is impossible since there is NO STROKE LEADERSHIP! So you're screwed.

Tiny plastics in carotid plaque tied to elevated risk for heart attack, stroke, death

Key takeaways:

• Patients who had microplastics or nanoplastics in their carotid plaque were more likely to die or have a heart attack or stroke than those who did not.
• The findings confirm prior in vitro and animal studies.

Perspective from Larry B. Goldstein, MD, FAAN, FANA, FAHA

Among patients with asymptomatic carotid artery disease who had carotid endarterectomy, those whose atheromas contained microplastics and/or nanoplastics had worse outcomes than those whose atheromas did not, researchers reported.

Risk for heart attack, stroke or all-cause death at nearly 3 years was more than fourfold higher in patients with carotid atheromas containing microplastics and/or nanoplastics (MNPs) than in those with no evidence of MNPs, the researchers wrote in The New England Journal of Medicine.

Data were derived from Marfella R, et al. N Engl J Med. 2024;doi:10.1056/NEJMoa2309822.

“Recent studies performed in preclinical models have led to the suggestion of MNPs as a new risk factor for cardiovascular diseases,” Raffaele Marfella, MD, PhD, from the department of advanced medical and surgical sciences at the University of Campania “Luigi Vanvitelli,” Naples, Italy, and colleagues wrote. “However, the clinical relevance of these findings is unknown. Evidence is lacking to show that MNPs infiltrate vascular lesions in humans or to support an association between the burden of MNPs and cardiovascular disease. To explore whether MNPs are detectable within atherosclerotic plaque and whether the burden of MNPs is associated with cardiovascular disease, we assessed the presence of these substances in surgically excised carotid artery plaque by means of pyrolysis-gas chromatography-mass spectrometry, stable isotope analysis and electronic microscopy. We then determined whether the presence of MNPs was associated with a composite endpoint of myocardial infarction, stroke or death from any cause.”

The researchers enrolled 304 patients with asymptomatic carotid artery disease undergoing carotid endarterectomy, of whom 257 completed follow-up of a mean of 33.7 months.

Marfella and colleagues detected polyethylene in the atheromas of 58.4% of patients (mean level, 21.7 g/mg of plaque) and found that 12.1% of those patients also had measurable amounts of polyvinyl chloride in their atheromas (mean level, 5.2 g/mg of plaque). In those with MNPs, the mean age was 71 years and 77.3% were men. In those without MNPs, the mean age was 73 years and 73.8% were men.

Electron microscopy showed “visible, jagged-edged foreign particles” in plaque macrophages and scattered in external debris, and X-rays revealed that some of these particles also contained chlorine, the researchers wrote.

Compared with those who had no MNPs detected, patients who had MNPs detected were at more than fourfold risk for MI, stroke or death during follow-up (20% vs. 7.5%; HR = 4.53; 95% CI, 2-10.27; P < .001), according to the researchers.

“Our findings suggest that nanoplastics, rather than microplastics, might accumulate in sites of atherosclerosis,” the researchers wrote. “Indeed, the large majority of particles detected in the current study were also below the 200 nm threshold suggested for gut and other barriers and were visible in the extracellular space as scattered debris, which aligns with the notion that the absorption and distribution of MNPs increase as particle size decreases.”

Perspective

Back to Top

Larry B. Goldstein, MD, FAAN, FANA, FAHA

This is an important initial study showing an association between MNPs and cardiovascular outcomes. The primary finding is that patients with evidence of MNPs within atherosclerotic carotid artery plaques in asymptomatic persons were at higher risk of subsequent CV events. As pointed out by the authors, this does not necessarily mean that the two are causally linked because of the possibility of other unmeasured factors that could differ between those with and without MNPs. Preclinical data, however, provide some evidence of vascular effects of MNPs.

At this point, it is unclear what we can do to prevent events related to MNPs. MNPs are fairly ubiquitous. Because there appeared to be a relationship between the amount of MNPs and vascular events, developing strategies to reduce exposure on a population level may need to be considered.

This study was limited to patients who were treated for asymptomatic carotid artery atherosclerotic disease. Extending the observation to other populations would further support the association.

Larry B. Goldstein, MD, FAAN, FANA, FAHA

Healio | Cardiology Today Editorial Board Member

Ruth L. Works Professor and Chair, Department of Neurology

Associate Dean for Clinical Research, College of Medicine

Co-Director, Kentucky Neuroscience Institute

Co-Director, UK Neuroscience Research Priority Area

Interim Director, UK-Norton Stroke Care Network

KY Clinic - University of Kentucky

Disclosures: Goldstein reports no relevant financial disclosures.

Published by:

Sources/Disclosures

Collapse

Source:

Marfella R, et al. N Engl J Med. 2024;doi:10.1056/NEJMoa2309822.

Association of Carotid Plaque and Flow Velocity With White Matter Integrity in a Middle-aged to Elderly Population

I can't tell what this means. I had 80% carotid blockage that completely closed up post stroke(glad that occurred).

My doctor told me I had a bunch of white matter hyperintensities but never showed me them on any scan, so I don't know the size, location or any intervention needed, because my doctor knew nothing and did nothing.

 

Association of Carotid Plaque and Flow Velocity With White Matter Integrity in a Middle-aged to Elderly Population

David Leander Rimmele, Elina Larissa Petersen, View ORCID ProfileEckhard Schlemm, Simon S. Kessner, Marvin Petersen, Carola Mayer, Bastian Cheng, Tanja Zeller, Christoph Waldeyer, Christian-Alexander Behrendt, Christian Gerloff, Götz Thomalla

First published September 19, 2022, DOI: https://doi.org/10.1212/WNL.0000000000201297

 

Add to Cart ($39)

• Article
• Figures & Data
• Info & Disclosures
• CME Course

This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.

Abstract

Background and Objectives It is uncertain whether there is an association of carotid plaques (CPs) and flow velocities with peak width mean diffusivity (PSMD) and white matter hyperintensities (WMH) independent of shared risk factors. We aimed to study this association controlling for biomarkers of inflammation and cardiac dysfunction and typical cardiovascular risk factors and spatial distribution.

Methods We included participants from the population-based Hamburg City Health Study, recruiting citizens between 45 and 74 years of age. Medical history was obtained from structured interviews and extended laboratory tests, physical examinations, MRI of the head, echocardiography, and abdominal and carotid ultrasound were performed. We performed multivariable regression analysis with PSMD and periventricular, deep, and total volume of WMH (pWMH, dWMH, tWMH) as dependent variables. PSMD was calculated as the difference between the 95th and 5th percentiles of MD values on the white skeleton in standard space. Volumes of WMH were determined by the application of a manually trained k-nearest neighbor segmentation algorithm. WMH measured within a distance of 1 cm from the surface of the lateral ventricles were defined as pWMH and above 1 cm as dWMH.

Results Two thousand six hundred twenty-three participants were included. The median age was 65 years, and 56% were women. Their median tWMH was 946 mm³(IQR:419, 2,164), PSMD 2.24 mm²/s × 10⁻⁴ (IQR: 2.04, 2.47), peak systolic velocity (PSV) of internal carotid arteries 0.70m/second (IQR:0.60, 0.81), and 35% had CPs. Adjusted for age, sex, high-sensitive CRP, NT-proBNP, and commonly measured cardiovascular risk and systemic hemodynamic factors, both CPs (B = 0.15; CI: 0.04, 0.26; p = 0.006) and low PSV (B = −0.49; CI: −0.87, −0.11; p = 0.012) were significantly associated with a higher tWMH and PSMD. Low PSV (B = −0.48; CI: −0.87, −0.1; p = 0.013) was associated with pWMH and the presence of CP with pWMH (B = 0.15; CI: 0.04, 0.26; p = 0.008) and dWMH (B = 0.42; CI: 0.11, 0.74; p < 0.009).

Discussion Low PSV and CP are associated with WMH and PSMD independent of cardiovascular risk factors and biomarkers of inflammation and cardiac dysfunction. This points toward pathophysiologic pathways underlying both large and small vessel disease beyond the common cardiovascular risk profile.

Trial Registration Information The trial was submitted at clinicaltrials.gov, under NCT03934957 on January 4, 2019. The first participant was enrolled in February 2016.

Complicated carotid artery plaques present underrecognized risk for recurrent stroke

So WHOM is going to solve and prevent this problem from occurring? If we had ANY STROKE LEADERSHIP AT ALL, we could ask them to assign researchers to this. But we have nada. 

Complicated carotid artery plaques present underrecognized risk for recurrent stroke

By Regina Schaffer

Source/Disclosures

ADD TOPIC TO EMAIL ALERTS

Among patients with cryptogenic stroke, ipsilateral complicated carotid artery plaque detected by MRI was associated with elevated risk for recurrent ischemic stroke or transient ischemic attack, data show.

“To our knowledge, there are no studies that have related the presence of complicated carotid artery plaques or intraplaque hemorrhage as assessed in the first days after stroke to recurrent ischemic stroke or TIA,” Martin Dichgans, MD, professor of neurology and director of the Institute for Stroke and Dementia Research at the Medical Center of the University of Munich, and colleagues wrote in the Journal of the American College of Cardiology. “Such information is needed, particularly for patients with nonstenosing carotid artery plaques and no recognizable cause of stroke (cryptogenic stroke), to optimize strategies for risk prediction and potentially also for stratifying patients into future secondary prevention trials.”

Source: Adobe Stock

Prospective stroke data

Dichgans and colleagues analyzed data from 196 patients aged 49 years or older enrolled in CAPIAS, an observational, prospective study conducted in four tertiary care centers in Germany that recruited patients with ischemic stroke restricted to a single carotid artery. Complicated carotid artery plaques, defined as American Heart Association lesion type VI, were assessed by multisequence, contrast-enhanced carotid MRI obtained within 10 days from stroke onset. Recurrent events were assessed after 3, 12, 24 and 36 months. The primary outcome was recurrent ischemic stroke or TIA.

Within the cohort, 104 patients had cryptogenic stroke and nonstenosing carotid artery plaque. During a mean follow-up of 30 months, 16 patients experienced recurrent ischemic stroke and five patients experienced TIA.

The 3-year incidence rate for the primary outcome was higher among patients with ipsilateral complicated carotid artery plaque (9.5 per 100 patient-years) compared with patients without ipsilateral complicated carotid artery plaque (3.61 per 100 patient-years; log-rank P = .025).

In models adjusted for age and sex, ipsilateral complicated carotid artery plaques were associated with a 2.5-fold increased risk for recurrent ischemic stroke or TIA over 3 years (HR = 2.51; 95% CI, 1.03-6.11; P =.043). Results persisted after restricting analyses to ipsilateral recurrent ischemic stroke or TIA (HR = 3.37; 95% CI, 1.21-9.38; P = .02).

Researchers also found that the presence of a ruptured fibrous cap at baseline (HR = 4.91; 95% CI, 1.31-18.45; P = .018) and intraplaque hemorrhage (HR = 4.37; 95% CI, 1.2-15.97; P = .026) were the largest drivers of increased risk for recurrent events in patients with cryptogenic stroke.

The researchers noted that study participants were selected for the presence of carotid artery plaque and were mildly affected, as reflected by the NIH Stroke Scale score at baseline.

“This, together with the relatively large CIs for recurrence rates, emphasizes the need for additional studies,” the researchers wrote. “We envision the next step to be a multicenter study determining the precise prevalence of intraplaque hemorrhage and associated recurrence rates in unselected patients with anterior circulation stroke. Such a study would enable analyses in relevant subgroups to prepare for future prevention trials.”

Role of vulnerable carotid plaque

In a related editorial, Joshua Z. Willey, MD, MS, of the department of neurology at Columbia University Irving Medical Center, and Gerard Pasterkamp, MD, of the Central Laboratory of Diagnostics at University Medical Center Utrecht, the Netherlands, wrote that the study highlights the importance of considering substenotic atherosclerotic plaques as a cause of ischemic stroke and the subsequent risk for recurrence.

“Whether these patients require different medical treatment and whether a subsequent cardioembolic source does not need to be as extensively ruled out with higher-cost cardiac imaging or implantable loop recorders remain to be answered by future studies,” Willey and Pasterkamp wrote.

Read next

Shorter door-to-needle times improve long-term outcomes in ischemic stroke
THALES: Ticagrelor plus aspirin reduces 30-day recurrent stroke, death vs. aspirin alone

Reference:

• Willey JZ, et al. J Am Coll Cardiol. 2022;doi:10.1016/j.jacc.2022.04.004.

 

Morphological Subtypes of Intracranial Internal Carotid Artery Arteriosclerosis and the Risk of Stroke

 

My doctors never found the 80% blockage in my right carotid artery even though they told me that artery had dissected and thrown a clot into my brain. So they left me with a risk of further strokes until 3 years later when that artery completely closed up.

Morphological Subtypes of Intracranial Internal Carotid Artery Arteriosclerosis and the Risk of Stroke

Tim C. van den Beukel

,

Janine E. van der Toorn

,

Meike W. Vernooij

,

Maryam Kavousi

,

Ali C. Akyildiz

,

Pim A. de Jong

,

Aad van der Lugt

,

M. Kamran Ikram

,

Daniel Bos

Originally published22 Nov 2021https://doi.org/10.1161/STROKEAHA.121.036213Stroke. 2021;0:STROKEAHA.121.036213

Abstract

Background and Purpose:

Accumulating evidence highlights the existence of distinct morphological subtypes of intracranial carotid arteriosclerosis. So far, little is known on the prevalence of these subtypes and subsequent stroke risk in the general population. We determined the prevalence of morphological subtypes of intracranial arteriosclerosis and assessed the risk of stroke associated with these subtypes.

Methods:

Between 2003 and 2006, 2391 stroke-free participants (mean age 69.6, 51.7% women) from the population-based Rotterdam Study underwent noncontrast computed tomography to visualize calcification in the intracranial carotid arteries as a proxy for intracranial arteriosclerosis. Calcification morphology was evaluated according to a validated grading scale and categorized into intimal, internal elastic lamina (IEL), or mixed subtype. Follow-up for stroke was complete until January 1, 2016. We used multivariable Cox regression to assess associations of each subtype with incident stroke.

Results:

The prevalence of calcification was 82% of which 39% had the intimal subtype, 48% IEL subtype, and 13% a mixed subtype. During a median follow-up of 10.4 years, 155 participants had a stroke. All 3 subtypes were associated with a higher risk of stroke (adjusted hazard ratio [95% CI] for intimal: 2.11 [1.07–4.13], IEL: 2.66 [1.39–5.11], and mixed subtype 2.57 [1.18–5.61]). The association of the IEL subtype with stroke was strongest among older participants. The association of the intimal subtype with stroke was noticeably stronger in women than in men.

Conclusions:

Calcification of the IEL was the most prevalent subtype of intracranial arteriosclerosis. All 3 subtypes were associated with an increased risk of stroke, with noticeable age and sex-specific differences.

• Download figure
• Download PowerPoint

 

Carotid Plaques From Symptomatic Patients Are Characterized by Local Increase in Xanthine Oxidase Expression

But what about asymptomatic patients? I had zero symptoms until my stroke and yet carotid plaque tore loose which caused a clot to form and them break off and lodge someplace in my middle cerebral artery on my right side. My doctor never told me where  it lodged or what parts of the brain were damaged. In my opinion he was totally fucking useless, knew nothing, did nothing.

 

Carotid Plaques From Symptomatic Patients Are Characterized by Local Increase in Xanthine Oxidase Expression

Morsaleh Ganji

,

Valentina Nardi

,

Megha Prasad

,

Kyra L. Jordan

,

Melanie C. Bois

,

Federico Franchi

,

Xiang Y. Zhu

,

Hui Tang

,

Melissa D. Young

,

Lilach O. Lerman

,

Amir Lerman

Originally published10 Jun 2021https://doi.org/10.1161/STROKEAHA.120.032964Stroke. 2021;52:2792–2801

Abstract

• Download figure
• Download PowerPoint

Background and Purpose:

XO (xanthine oxidase) is a key enzyme of uric acid metabolism and is thought to contribute to oxidative pathways that promote atherosclerotic plaque progression, yet its role in plaque destabilization is not well elucidated. We hypothesized that XO is expressed in carotid plaque from symptomatic patients in association with cardiovascular risk factors.

Methods:

Patients were stratified by symptoms, defined as presentation with an ipsilateral cerebral ischemic event. Carotid atherosclerotic plaques were obtained from 44 patients with symptomatic plaque and 44 patients without ischemic cerebral events. Protein expression of XO was evaluated by immunohistochemical staining and the percentage of cells expressing XO and CD68 (macrophage marker) compared between the groups. Biochemical and demographic cardiometabolic risk factors of study participants also were measured.

Results:

Carotid atherosclerotic plaques from symptomatic patients were associated with significantly higher XO expression versus asymptomatic plaque (median [interquartile range]: 1.24 [2.09] versus 0.16 [0.34]; P<0.001) and with significantly higher circulating uric acid levels (mean±SD: 7.36±2.10 versus 5.37±1.79 mg/dL; P<0.001, respectively). In addition, XO expression in atherosclerotic carotid plaque was inversely associated with serum high-density lipoproteins cholesterol levels (P=0.010, r=−0.30) and directly with circulating uric acid levels (P<0.001, r=0.45). The average percentage of macrophages that expressed XO was significantly higher in symptomatic versus asymptomatic plaques (median [interquartile range]: 93.37% [25] versus 46.15% [21], respectively; P<0.001).

Conclusions:

XO overexpression in macrophages is associated with increased serum uric acid and low high-density lipoproteins cholesterol levels and may potentially have a mechanistic role in carotid plaque destabilization. The current study supports a potential role for uric acid synthesis pathway as a target for management of carotid atherosclerosis in humans.

 

Warfarin Treatment Is Associated to Increased Internal Carotid Artery Calcification

You'll need your doctor to monitor this. In my case I was only on it for 2 months, later on they say the median duration was 1.6 years, so I guess I was ok.

Warfarin Treatment Is Associated to Increased Internal Carotid Artery Calcification

 

Krista Nuotio^1,2*, Suvi M. Koskinen^2,3, Laura Mäkitie^1,2, Jarno Tuimala⁴, Petra Ijäs^1,2, Hanna M. Heikkilä², Jani Saksi², Pirkka Vikatmaa⁵, Pia Sorto², Sonja Kasari², Ilari Paakkari⁶, Heli Silvennoinen³, Leena Valanne³, Mikko I. Mäyränpää⁷, Lauri Soinne^1,2, Petri T. Kovanen⁸ and Perttu J. Lindsberg^1,2

• ¹Neurology, Neurocenter, Helsinki University Hospital, Helsinki, Finland
• ²Clinical Neurosciences, Clinicum, University of Helsinki, Helsinki, Finland
• ³Medical Imaging Center, Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
• ⁴Independent Researcher, Helsinki, Finland
• ⁵Abdominal Center, Vascular Surgery, Helsinki University Hospital, Helsinki, Finland
• ⁶Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland
• ⁷Pathology, Helsinki University and Helsinki University Hospital, Helsinki, Finland
• ⁸Wihuri Research Institute, Biomedicum Helsinki 1, Helsinki, Finland

Background: Long-term treatment with the vitamin K antagonist warfarin is widely used for the prevention of venous thrombosis and thromboembolism. However, vitamin K antagonists may promote arterial calcification, a phenomenon that has been previously studied in coronary and peripheral arteries, but not in extracranial carotid arteries. In this observational cohort study, we investigated whether warfarin treatment is associated with calcification of atherosclerotic carotid arteries.

Methods: Overall, 500 consecutive patients underwent carotid endarterectomy, 82 of whom had received long-term warfarin therapy. The extent of calcification was assessed with preoperative computed tomography angiography, and both macroscopic morphological grading and microscopic histological examination of each excised carotid plaque were performed after carotid endarterectomy.

Results: Compared with non-users, warfarin users had significantly more computed tomography angiography-detectable vascular calcification in the common carotid arteries (odds ratio 2.64, 95% confidence interval 1.51–4.63, P < 0.001) and even more calcification in the internal carotid arteries near the bifurcation (odds ratio 18.27, 95% confidence interval 2.53–2323, P < 0.001). Histological analysis revealed that the intramural calcified area in plaques from warfarin users was significantly larger than in plaques from non-users (95% confidence interval 3.36–13.56, P = 0.0018).

Conclusions: Long-lasting warfarin anticoagulation associated with increased calcification of carotid atherosclerotic plaques, particularly in locations known to be the predilection sites of stroke-causing plaques. The clinical significance of this novel finding warrants further investigations.

Introduction

An atherosclerotic lesion in the internal carotid artery is a major cause of cerebral ischemic stroke. Although many elements of the underlying pathological processes of atherosclerosis, e.g., lipid accumulation and the inflammatory component, have been well-characterized in developing atherosclerotic lesions (1), the multifaceted roles of calcification in atherosclerotic lesions are still debated and under investigation (2–5).

Atrial fibrillation (AF), the most common sustained arrhythmia (6) poses a significant risk for cerebral embolism, which is most effectively prevented by anticoagulants (7–9). Both warfarin and modern oral anticoagulants are available and neurologists are frequently deciding on anticoagulation on patients with AF, often with simultaneous large artery atherosclerosis.

Warfarin has been claimed to have harmful effects on the arterial wall. Evidence from experimental animals has demonstrated that treatment with warfarin is linked to vascular calcification (10, 11), with similar findings from preliminary human studies (12–14). Human studies have suggested that exposure to warfarin may increase calcification in coronary arteries (15, 16), peripheral arteries (17), aorta (18), and aortic valve leaflets (19).

However, there are only a few studies that have investigated the association of warfarin and vascular calcification in carotid arteries (20, 21), and none of them has studied vascular calcification in extracranial carotid arteries. Hence, the present clinical investigation was undertaken to evaluate the hypothesis that chronic warfarin use is associated with vascular calcification in atherosclerotic carotid artery disease. We examined the preoperative computed tomography angiography (CTA) results, macroscopic calcification of the dissected carotid specimens, and histopathology of the plaques to determine the potential presence of calcification, and the extent of different types of calcification. The results obtained in users and non-users of warfarin therapy were compared.

Carotid Plaques From Symptomatic Patients Are Characterized by Local Increase in Xanthine Oxidase Expression

But what about asymptomatic patients? I had zero symptoms until my stroke and yet carotid plaque tore loose which caused a clot to form and them break off and lodge someplace in my middle cerebral artery on my right side. My doctor never told me where  it lodged or what parts of the brain were damaged. In my opinion he was totally fucking useless, knew nothing, did nothing.

Carotid Plaques From Symptomatic Patients Are Characterized by Local Increase in Xanthine Oxidase Expression

Morsaleh Ganji

,

Valentina Nardi

,

Megha Prasad

,

Kyra L. Jordan

,

Melanie C. Bois

,

Federico Franchi

,

Xiang Y. Zhu

,

Hui Tang

,

Melissa D. Young

,

Lilach O. Lerman

,

Amir Lerman

Originally published10 Jun 2021https://doi.org/10.1161/STROKEAHA.120.032964Stroke. ;0:STROKEAHA.120.032964

Abstract

Background and Purpose:

XO (xanthine oxidase) is a key enzyme of uric acid metabolism and is thought to contribute to oxidative pathways that promote atherosclerotic plaque progression, yet its role in plaque destabilization is not well elucidated. We hypothesized that XO is expressed in carotid plaque from symptomatic patients in association with cardiovascular risk factors.

Methods:

Patients were stratified by symptoms, defined as presentation with an ipsilateral cerebral ischemic event. Carotid atherosclerotic plaques were obtained from 44 patients with symptomatic plaque and 44 patients without ischemic cerebral events. Protein expression of XO was evaluated by immunohistochemical staining and the percentage of cells expressing XO and CD68 (macrophage marker) compared between the groups. Biochemical and demographic cardiometabolic risk factors of study participants also were measured.

Results:

Carotid atherosclerotic plaques from symptomatic patients were associated with significantly higher XO expression versus asymptomatic plaque (median [interquartile range]: 1.24 [2.09] versus 0.16 [0.34]; P<0.001) and with significantly higher circulating uric acid levels (mean±SD: 7.36±2.10 versus 5.37±1.79 mg/dL; P<0.001, respectively). In addition, XO expression in atherosclerotic carotid plaque was inversely associated with serum high-density lipoproteins cholesterol levels (P=0.010, r=−0.30) and directly with circulating uric acid levels (P<0.001, r=0.45). The average percentage of macrophages that expressed XO was significantly higher in symptomatic versus asymptomatic plaques (median [interquartile range]: 93.37% [25] versus 46.15% [21], respectively; P<0.001).

Conclusions:

XO overexpression in macrophages is associated with increased serum uric acid and low high-density lipoproteins cholesterol levels and may potentially have a mechanistic role in carotid plaque destabilization. The current study supports a potential role for uric acid synthesis pathway as a target for management of carotid atherosclerosis in humans.

• Download figure
• Download PowerPoint

 

Carotid plaque vulnerability on magnetic resonance imaging and risk of future ischemic events: a systematic review and meta-analysis

The only thing that would have caught mine is if my Dad's doctor had told him to have any children tested for carotid blockage after he was diagnosed with 80% blockage. But he didn't so as a result I had a stroke. For non-symptomatic people like me there will never be any MRI scans. So you'll have to come up with something easier than that doesn't require a MRI scan

 

Carotid plaque vulnerability on magnetic resonance imaging and risk of future ischemic events: a systematic review and meta-analysis</

>

Asim Rizvi  ^{1   2   3} , Seyed M Seyedsaadat  ⁴ , Muayad Alzuabi  ⁵ , Mohammed H Murad  ⁵ , John Huston 3rd  ⁴ , Vance T Lehman  ⁴ , Giuseppe Lanzino  ⁶ , Luca Saba  ⁷ , Waleed Brinjikji  ^{4   8}

Affiliations

• PMID: 33236863
• DOI: 10.23736/S0390-5616.20.04959-0

Abstract

Introduction: Magnetic resonance imaging (MRI) can characterize carotid plaque features, including intraplaque hemorrhage (IPH), lipid-rich necrotic core (LRNC), and thin/ruptured fibrous cap (TRFC), that have increased tendency to cause future cerebrovascular ischemic events. We performed a systematic review and meta-analysis of studies evaluating association of MRI-identified high-risk plaque features, including IPH, LRNC, and TRFC, with risks of subsequent ischemic events of stroke, transient ischemic attack (TIA), or amaurosis fugax (AF) over follow-up duration of ≥3 months.

Evidence acquisition: Multiple databases were searched for relevant publications between January 2000 and March 2020. Studies reporting outcomes of future ischemic events of stroke, TIA, or AF for individual MRI-identified high-risk carotid plaque features over follow-up duration of ≥3 months were included. Random effects meta-analysis was performed to estimate odds ratios (OR) and 95% confidence intervals (CI) comparing outcomes between MRI-positive and MRI-negative groups.

Evidence synthesis: Fifteen studies including 2350 patients were included. The annual rate of future ischemic events was 11.9% for MRI-positive IPH, 5.4% for LRNC, and 5.7% for TRFC. IPH, LRNC, and TRFC were associated with increased risk of future ischemic events (OR 6.37; 95% CI, 3.96 to 10.24), (OR 4.34; 95% CI, 1.65 to 11.42), and (OR 10.60, 95% CI 3.56 to 31.58), respectively.

Conclusions: The current study findings strengthen the assertion that MRI-positive "high-risk" or "vulnerable" plaque features, including IPH, LRNC, and/or TRFC can predict risks of future ischemic events of stroke, TIA, or AF.