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Highlighted articles October

Volume 265 Issue October 2017

By Simona Negrini and Arnold von Eckardstein (Editor–in-Chief).

Ischemic stroke is a major cause of mortality, morbidity, disability, and need of nursing care, which becomes more and more relevant as human life expectancy increases. Also because of its heterogeneous etiology, cardiovascular risk factors have different impact on stroke and coronary heart disease. This issue of Atherosclerosis contains several articles reporting on the associations of biochemical and genetic risk factors, as well as imaging biomarkers, with stroke or morphological signs of cerebral ischemia and damage.

Issue highlights


    Highlighted articles

    Association of high-density lipoprotein cholesterol concentration with different types of stroke and coronary heart disease: The Japan Public Health Center-based prospective (JPHC) study

    While low high-density lipoprotein (HDL) cholesterol concentration is an established risk factor for coronary heart disease (CHD), evidence regarding stroke and stroke subtypes is very limited in Asian populations.

    Saito et al. conducted a prospective study of 30,736 individuals from nine Japanese communities, with no history of cardiovascular disease (CVD). CHD and stroke (including its subtypes) were assessed, and sex-specific hazard ratios and 95% confidence intervals for outcomes were estimated according to quintiles of HDL cholesterol, using Cox proportional models adjusted for other CVD risk factors.

    296 CHD and 1712 stroke events were identified over a median 15-year follow-up. HDL cholesterol concentration showed an inverse association with CHD in men and women. A low HDL cholesterol concentration slightly raised the risk for total strokes in men, but not in women. When analyzed by subtypes, an inverse relationship between HDL cholesterol concentration and the incidence of lacunar infarction was observed. HDL cholesterol concentration was positively associated with the risk of intracerebral hemorrhage (ICH) in a linear manner in women, but not in men.

    The associations of HDL cholesterol concentration with lacunar infarction and ICH may be related to different functional properties of HDL rather than to its protective function against lipid-rich atherosclerosis.

    The impact of APOA5, APOB, APOC3 and ABCA1 gene polymorphisms on ischemic stroke: Evidence from a meta-analysis

    Au et al. conducted a meta-analysis to study the causal relationships of APOA5, APOB, APOC3 and ABCA1 gene polymorphisms with ischemic stroke risk.

    Data were extracted from all eligible studies retrieved from search in multiple databases until March 2017. The strength of the association between each studied polymorphism and ischemic stroke risk was measured as odds ratios and 95% confidence intervals, under fixed- and random-effect models.

    A total of 79 studies reporting on the association between the polymorphisms and ischemic stroke risk were identified. The pooled data indicated that all genetic models of APOA5 rs662799, allelic and over-dominant models of APOA5 rs3135506, APOB rs1801701 and APOB rs1042031 and the dominant model of ABCA1 rs2230806 were significantly associated with a higher risk of ischemic stroke. However, no significant associations were observed between ischemic stroke and ApoB (rs693) and APOC3 (rs4520, rs5128, rs2854116 and rs2854117), under any genetic model.

    Association of descending thoracic aortic plaque with brain atrophy and white matter hyperintensities: The Framingham Heart Study

    Aortic atherosclerosis is an aggregate marker of vascular risk factor exposure and has been associated with intracranial atherosclerosis and stroke. Aparicio et al. conducted this cross-sectional community-based study to investigate the hypothesis that atherosclerosis of the descending aorta (DAo) is a risk marker for brain aging and injury.

    1527 participants in the Framingham Offspring cohort, who underwent both aortic and brain MRI, were evaluated. Participants were free of clinical stroke, dementia, or other neurological illness at the time of MRI investigations. The authors related the prevalence and burden of aortic plaque to total cerebral brain volume (TCBV) and white matter hyperintensity volume (WMHV). An additional analysis compared incidence of stroke or transient ischemic attack (TIA) in participants with and without DAo plaques.

    The presence of thoracic DAo plaque was associated with decreased TCBV in sex-pooled analysis and with increased WMHV only in men. Similar associations of DAo plaque burden with TCBV and WMHV were also observed. In the prospective follow-up, 43 strokes and 11 TIAs were found. Presence of DAo plaque was not associated with subsequent stroke or TIA.

    In conclusion, DAo plaque is associated with accelerated brain aging. These data underscore the potential implications of incidentally identified subclinical aortic atherosclerosis and question whether targeted intervention in these high-risk individuals can modulate cognitive decline.

    In their editorial, van Agtmaal and Schram emphasize how this data provides additional evidence for an association of systemic atherosclerosis with structural brain changes. In view of the large impact that cognitive decline and dementia have on the personal, medical care and society level, the need for interventions that can effectively prevent cognitive decline is paramount.

    Cerebral white matter hyperintensity is associated with intracranial atherosclerosis in a healthy population

    Cerebral white matter hyperintensity (WMH) is commonly found in ischemic stroke patients, especially when accompanied by intracranial atherosclerosis (ICAS). However, the relationship between WMH and ICAS in a healthy population has not been evaluated so far.

    Nam et al. conducted a study on 3159 healthy subjects who underwent health checkups, including brain magnetic resonance imaging and angiography. ICAS was defined as an occlusion or more than 50% stenosis of intracranial vessels on magnetic resonance angiography. Volumes of WMH were quantitatively rated.

    In multivariate analysis, ICAS was significantly associated with WMH volumes after adjusting for confounders. Associations of age, hypertension, and diabetes were also significant, independently of ICAS. In the ICAS positive group hypertension, diabetes, and statin use were more prevalent than in the ICAS negative group.

    ICAS is associated with larger WMH volume in a healthy population. A close observation of this group and a strict control of vascular risk factors are needed.

    Impact of cystatin C and microalbuminuria on cognitive impairment in the population of community-dwelling Japanese

    Cognitive impairment affects our well-being, as such, early diagnosis is critical. Kono et al. investigated whether serum cystatin C and albuminuria are associated with cognitive impairment.

    The cognitive function of the study participants was evaluated by means of the mini-mental state examination (MMSE), a worldwide measurement of cognitive function, assessing orientation, concentration, language, praxis, and memory. In addition, levels of cystatin C in serum and albumin in urine were assessed by latex nephelometric immunoassays.

    Multivariate linear regression analyses adjusted for age and sex showed that MMSE was significantly associated with systolic blood pressure, cystatin C (inversely) and albuminuria (inversely). In multiple stepwise linear regression analysis, age, history of stroke, systolic blood pressure, serum cystatin C were independently associated with MMSE levels.

    In conclusion, cognitive function was significantly and inversely associated with cystatin C and albuminuria, in a relatively young general population.

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