EVT Will Save Millions of Lives From Stroke. Eventually.

Ischemic Heart Disease

Ischaemic or ischemic heart disease (IHD), or myocardial ischaemia, is a disease characterized by ischaemia (reduced blood supply) of the heart muscle, usually due to coronary artery disease (atherosclerosis of the coronary arteries). Its risk increases with age, smoking, hypercholesterolaemia (high cholesterol levels), diabetes, and hypertension (high blood pressure), and is more common in men and those who have close relatives with ischaemic heart disease.

Symptoms of stable ischaemic heart disease include angina (characteristic chest pain on exertion) and decreased exercise tolerance. Unstable IHD presents itself as chest pain or other symptoms at rest, or rapidly worsening angina. Diagnosis of IHD is with an electrocardiogram, blood tests (cardiac markers), cardiac stress testing or a coronary angiogram. Depending on the symptoms and risk, treatment may be with medication, percutaneous coronary intervention (angioplasty) or coronary artery bypass surgery (CABG).

It is the most common cause of death in most Western countries, and a major cause of hospital admissions. There is limited evidence for population screening, but prevention (with a healthy diet and sometimes medication for diabetes, cholesterol and high blood pressure) is used both to prevent IHD and to decrease the risk of complications.

The medical history distinguishes between various alternative causes for chest pain (such as dyspepsia, musculoskeletal pain, pulmonary embolism). As part of an assessment of the three main presentations of IHD, risk factors are addressed. These are the main causes of atherosclerosis (the disease process underlying IHD): age, male sex, hyperlipidaemia (high cholesterol and high fats in the blood), smoking, hypertension (high blood pressure), diabetes, and the family history.

Study Finds U-shaped Association Between LDL-C And Mortality Risk In Acute Ischemic Stroke Patients

The general perception supports the mantra of "lower is better" for low-density lipoprotein cholesterol (LDL-C) levels in cardiovascular disease. However, during the acute stage of ischemic stroke, it is unclear how to interpret different LDL-C levels accurately. The evidence on clinical implication of LDL-C levels was mainly derived from long-term follow-up studies. The pathophysiological features of patients under the acute stage of ischemic stroke are different from the chronic stage. Concerns exist over whether low LDL-C levels may lead to adverse outcomes, such as increased mortality risk due to infection. The crosstalk between LDL-C and infection is also garnering increasing amounts of interest.

A new study has aimed to evaluate the association between LDL-C levels, post-stroke infection and all-cause mortality. In total, 804,855 ischemic stroke patients were enrolled. Associations between LDL-C levels, infection, and mortality risk were estimated by multivariate logistic regression models. Mediation analysis was performed under counterfactual framework to elucidate the mediation effect of post-stroke infection.

The work is published in Science Bulletin.

The study found a U-shaped association between LDL-C and mortality risk in acute ischemic stroke patients. The lowest mortality risk was at an LDL-C level of 2.67 mmol/L. The association between LDL-C and all-cause mortality was 38.20% mediated by infection. Sensitivity analysis showed that after excluding patients with increasing numbers of cardiovascular risk factors, the U-shaped association remained consistent but the LDL-C interval with the lowest mortality risk increased progressively, where infection maintained prominent mediation effects.

Subgroup analysis showed a consistent U-shaped association between LDL-C levels and mortality risk. The mediation effects of infection were largely consistent in subgroups of age ≥65 years, female, body mass index <25 kg/m2, and National Institutes of Health Stroke Scale ≥16.

Despite the known adverse effects of high LDL-C levels, in ischemic stroke patients, this study revealed that low LDL-C levels also indicate an increased risk of all-cause mortality during hospitalization, where post-stroke infection is an important mediating mechanism, indicating a potential causal chain of low LDL-C-infection-mortality in the acute stage of ischemic stroke. Further research is warranted to explore the risk-benefit relationship of approaches for rapid and substantial LDL-C reduction during the acute stage of ischemic stroke.

More information: Zi-Mo Chen et al, U-shaped association between low-density lipoprotein cholesterol levels and risk of all-cause mortality mediated by post-stroke infection in acute ischemic stroke, Science Bulletin (2023). DOI: 10.1016/j.Scib.2023.05.028

Citation: Study finds U-shaped association between LDL-C and mortality risk in acute ischemic stroke patients (2023, June 27) retrieved 29 June 2023 from https://medicalxpress.Com/news/2023-06-u-shaped-association-ldl-c-mortality-acute.Html

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Inflammatory Bowel Disease Linked With Increased Stroke Risk

Patients with inflammatory bowel disease (IBD) were 13% more likely to suffer a stroke than the general population, even decades after their diagnosis, according to a large national cohort study.

The study included all biopsy-confirmed IBD patients in Sweden from 1969 to 2019, representing approximately 85,000 individuals. The incidence rate of stroke in these patients was 32.6 per 10,000 person-years, compared with 27.7 for matched controls (HR 1.13, 95% CI 1.08-1.17), Jiangwei Sun, PhD, of the Karolinska Institutet in Stockholm, and colleagues reported in Neurology.

The risk remained elevated 25 years after diagnosis and corresponded to one additional stroke per 93 IBD patients. "Our study is the largest with the longest follow-up so far to investigate stroke risk in IBD patients," the researchers wrote. "These findings highlight the need for clinical vigilance about the long-term excess risk of cerebrovascular events in IBD patients."

The excess risk was mainly driven by ischemic stroke (HR 1.14, 95% CI 1.09-1.18) rather than hemorrhagic stroke (HR 1.06, 95% CI 0.97-1.15), and was significantly higher across IBD subtypes. The risk increase was 19% for Crohn's disease (95% CI 1.10-1.29), 9% for ulcerative colitis (95% CI 1.04-1.16), and 22% for unclassified IBD (95% CI 1.08-1.37), the study found.

Possible underlying mechanisms for stroke risk in IBD patients, the researchers said, include chronic systemic inflammation and a shifted microbiota-gut-brain axis. Chronic inflammation induces endothelial dysfunction, promotes plaque formation as well as platelet activation and aggregation, and contributes to atherosclerosis and arterial stiffness, the team explained.

Furthermore, disruptions in the microbiota-gut-brain-axis have been linked to neurodevelopmental disorders, neurodegenerative diseases, and stroke through various processes including modulated blood-brain barrier formation, myelination, microglia maturation, and neuroinflammation. Finally, IBD patients can be at higher risk for blood clots due to surgeries, immobilization due to fractures, and steroid therapy, the researchers noted.

The study found a higher relative risk for stroke in women with IBD (HR 1.20, 95% CI 1.14-1.27) than in men (HR 1.06, 95% CI 1.01-1.12). This could be explained by differences in risk factor profiles, sex hormone-dependent mechanisms, and stroke pathophysiology, the researchers said.

Sun and colleagues also reported a much higher relative risk of stroke in younger patients. For those with IBD onset at age 17 or younger, the risk was more than doubled (HR 2.35, 95% CI 1.52-3.62). Risk gradually decreased with age, suggesting that in older patients traditional cardiovascular risk factors become more prevalent and may outweigh the risk associated with IBD. In addition, more severe disease activity in younger-onset IBD patients could contribute to this trend, the study authors said.

Regarding implications, the team explained, "screening and management of traditional stroke risk factors in IBD patients could be more urgent than in the general population to prevent fatal CVD complications."

In addition, "for individuals with traditional CVD risk factors, optimal anti-inflammatory therapy aiming at clinical response and remission or even endoscopic healing but with less adverse cardiovascular effects should be encouraged to reduce the excess risk of ischemic stroke," Sun and co-authors advised.

They identified biopsy-confirmed patients with IBD in the ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) cohort. The team also identified stroke patients and analyzed medical records data in the Swedish National Patient Register. The researchers matched the IBD patients with up to five reference individuals randomly selected from the general population.

The primary outcome was incident overall stroke; secondary outcomes were ischemic and hemorrhagic stroke. The researchers estimated hazard ratios with flexible parametric survival models, adjusting for factors including hypertension, diabetes, obesity, dyslipidemia, chronic kidney disease, and chronic obstructive pulmonary disease. The investigators also performed an analysis comparing stroke risk in the IBD patients with their IBD-free siblings, in order to assess any familial factors. The sibling comparison confirmed the main findings, Sun and co-authors said.

Study limitations, the team said, included that there was a lack of complete data on lifestyle factors that can contribute to stroke risk, such as smoking and alcohol use. The diagnostic criteria for IBD and stroke also changed during the study period, which may have affected associations. In addition, the study lacked information on inflammatory markers such a C-reactive protein. The researchers also cautioned that the findings may not be able to be extrapolated to other settings due to differences in the incidence and prevalence of IBD and stroke across countries, regions, and ethnicities and the fact that the Swedish healthcare system offers universal access "practically free of charge."

Jeff Minerd is a freelance medical and science writer based in Rochester, NY.

Disclosures

The study was supported by the Swedish Research Council.

Sun reported no relevant conflicts of interest.

Primary Source

Neurology

Source Reference: Sun N, et al "Long-term risk of stroke in patients with inflammatory bowel disease: a population-based, sibling-controlled cohort study, 1969–2019" Neurology 2023; DOI: 10.1212/WNL.0000000000207480.

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