Markers of early vascular aging are not associated with cryptogenic ischemic stroke in the young: A case-control study

Nicolas Martinez-Majander; Daniel Gordin; Lotta Joutsi-Korhonen; Titta Salopuro; Krishna Adeshara; Gerli Sibolt; Sami Curtze; Jani Pirinen; Ron Liebkind; Lauri Soinne; Tiina Sairanen; Satu Suihko; Mika Lehto; Juha Sinisalo; Per-Henrik Groop; Turgut Tatlisumak; Jukka Putaala

doi:10.1016/j.jstrokecerebrovasdis.2022.106647

Markers of early vascular aging are not associated with cryptogenic ischemic stroke in the young: A case-control study

J Stroke Cerebrovasc Dis. 2022 Sep;31(9):106647. doi: 10.1016/j.jstrokecerebrovasdis.2022.106647. Epub 2022 Jul 15.

Authors

Nicolas Martinez-Majander¹, Daniel Gordin², Lotta Joutsi-Korhonen³, Titta Salopuro³, Krishna Adeshara⁴, Gerli Sibolt⁵, Sami Curtze⁵, Jani Pirinen⁶, Ron Liebkind⁵, Lauri Soinne⁵, Tiina Sairanen⁵, Satu Suihko⁷, Mika Lehto⁷, Juha Sinisalo⁷, Per-Henrik Groop⁸, Turgut Tatlisumak⁹, Jukka Putaala⁵

Affiliations

¹ Department of Neurology, Helsinki University Hospital and Clinical Neurosciences, University of Helsinki, Finland. Electronic address: nicolas.martinez-majander@hus.fi.
² Abdominal Center Nephrology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland; Joslin Diabetes Center, Harvard Medical School, Boston, MA, United States.
³ Department of Clinical Chemistry, HUSLAB, HUS Diagnostic Centre, Helsinki University Hospital, Helsinki, Finland.
⁴ Abdominal Center Nephrology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland; Clinical and Molecular Metabolism, Faculty of Medicine Research Programs, University of Helsinki, Helsinki, Finland.
⁵ Department of Neurology, Helsinki University Hospital and Clinical Neurosciences, University of Helsinki, Finland.
⁶ Department of Neurology, Helsinki University Hospital and Clinical Neurosciences, University of Helsinki, Finland; HUS Helsinki University Hospital, Porvoo Hospital Area, Internal Medicine, Finland; Department of Clinical Physiology and Nuclear Medicine, HUS Medical Imaging Center, Helsinki University Central Hospital and University of Helsinki, Finland.
⁷ Department of Cardiology, Heart and Lung Center, Helsinki University Hospital and University of Helsinki, Finland.
⁸ Abdominal Center Nephrology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
⁹ Department of Neurology, Helsinki University Hospital and Clinical Neurosciences, University of Helsinki, Finland; Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, and Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden.

PMID: 35849915
DOI: 10.1016/j.jstrokecerebrovasdis.2022.106647

Abstract

Background and purpose: We aimed to assess the association between covert atherosclerosis, arterial stiffness, and early-onset cryptogenic ischemic stroke (CIS) in a prospective case-control study.

Methods: We enrolled 123 young CIS patients (median age 41 years; 42% women) and 123 age- and sex-matched controls. Carotid intima-media thickness (CIMT), Augmentation Index (AIx), central pulse wave velocity (PWV), and subendocardial viability ratio (SEVR) were compared between patients and controls. Conditional logistic regression was used adjusting for age, systolic blood pressure, diastolic blood pressure, current smoking, total cholesterol/high-density lipoprotein cholesterol (Total-C/HDL-C) ratio, and glycated albumin to assess the independent association between CIMT, arterial stiffness and CIS.

Results: Patients with higher CIMT and PWV were older, more often men and they had more frequently well-documented risk factors, lower HDL and higher Total-C/HDL-C ratio compared to other tertiles. In univariate comparisons, we found no differences between patients and controls regarding CIMT, AIx, or PWV. In the entire cohort, patients had a significantly lower SEVR compared to controls (146.3%, interquartile range [IQR] 125.7-170.3 vs. 158.0%, IQR 141.3-181.0, P=0.010). SEVR was lower also in women compared to their controls (132.0%, IQR 119.4-156.1 vs. 158.7%, IQR 142.0-182.8, P=0.001) but no significant difference appeared between male patients and male controls. However, after adjusting for comorbidities and laboratory values these significant differences were lost (odds ratio [OR] 1.52, 95% confidence interval [CI] 0.47-4.91) in the entire cohort and OR 3.89, 95% CI 0.30-50.80 in women).

Conclusions: Higher CIMT and PWV were associated to higher age, male sex, and several well-documented cardiovascular risk factors. However, in this study we could not prove that either covert atherosclerosis or arterial stiffness contribute to pathogenesis of early-onset CIS.

Keywords: Arterial stiffness; Atherosclerosis; Brain infarction; Cryptogenic stroke; Intima-media thickness; Ischemic stroke; Risk factors; Young adults.

MeSH terms

Adult
Aging
Atherosclerosis*
Biomarkers
Carotid Intima-Media Thickness
Case-Control Studies
Cholesterol, HDL
Female
Humans
Ischemic Stroke*
Male
Pulse Wave Analysis
Risk Factors
Vascular Stiffness* / physiology

Substances

Biomarkers
Cholesterol, HDL