Summary Background Carotid intima-media thickness (cIMT) is related to the risk of cardiovascular events in the general population. An association between changes in cIMT and cardiovascular risk is ...frequently assumed but has rarely been reported. Our aim was to test this association. Methods We identified general population studies that assessed cIMT at least twice and followed up participants for myocardial infarction, stroke, or death. The study teams collaborated in an individual participant data meta-analysis. Excluding individuals with previous myocardial infarction or stroke, we assessed the association between cIMT progression and the risk of cardiovascular events (myocardial infarction, stroke, vascular death, or a combination of these) for each study with Cox regression. The log hazard ratios (HRs) per SD difference were pooled by random effects meta-analysis. Findings Of 22 eligible studies, 16 with 36 984 participants were included. During a mean follow-up of 7·0 years, 1519 myocardial infarctions, 1339 strokes, and 2028 combined endpoints (myocardial infarction, stroke, vascular death) occurred. Yearly cIMT progression was derived from two ultrasound visits 2–7 years (median 4 years) apart. For mean common carotid artery intima-media thickness progression, the overall HR of the combined endpoint was 0·97 (95% CI 0·94–1·00) when adjusted for age, sex, and mean common carotid artery intima-media thickness, and 0·98 (0·95–1·01) when also adjusted for vascular risk factors. Although we detected no associations with cIMT progression in sensitivity analyses, the mean cIMT of the two ultrasound scans was positively and robustly associated with cardiovascular risk (HR for the combined endpoint 1·16, 95% CI 1·10–1·22, adjusted for age, sex, mean common carotid artery intima-media thickness progression, and vascular risk factors). In three studies including 3439 participants who had four ultrasound scans, cIMT progression did not correlate between occassions (reproducibility correlations between r =−0·06 and r =−0·02). Interpretation The association between cIMT progression assessed from two ultrasound scans and cardiovascular risk in the general population remains unproven. No conclusion can be derived for the use of cIMT progression as a surrogate in clinical trials. Funding Deutsche Forschungsgemeinschaft.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Atherosclerosis is an inflammatory chronic disease affecting arterial vessels and leading to vascular diseases, such as stroke and myocardial infarction. The relationship between atherosclerosis and ...risk of neurodegeneration has been established, in particular with vascular cognitive impairment and dementia (VCID). Systemic atherosclerosis increases the risk of VCID by inducing cerebral infarction, or through systemic or local inflammatory factors that underlie both atherosclerosis and cognition. Omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) are involved in inflammatory processes, but with opposite roles. Specifically, omega-3 PUFAs exert anti-inflammatory properties by competing with omega-6 PUFAs and displacing arachidonic acid in membrane phospholipids, decreasing the production of pro-inflammatory eicosanoids. Experimental studies and some clinical trials have demonstrated that omega-3 PUFA supplementation may reduce the risk of different phenotypes of atherosclerosis and cardiovascular disease. This review describes the link between atherosclerosis, VCID and inflammation, as well as how omega-3 PUFA supplementation may be useful to prevent and treat inflammatory-related diseases.
Biologic sex influences many variables that are important to brain health in general, and to stroke or cerebral ischemia in particular, such as general health status, cerebrovascular anatomy and ...function, unique risk factors such as pregnancy and preeclampsia, symptomatology, and therapeutic response. A more complete understanding of the scale and depth of sexual dimorphism in the brain and the role of more general sex-based factors is crucial to reducing the burden of stroke in women and men. This focused review highlights recent findings in stroke, including sex differences in epidemiology, risk factor reduction, comparative use of stroke therapeutics in both sexes, the importance of frailty in women, and the biologic basis for sex differences in stroke. Such findings show tremendous promise for the future of personalized medicine in stroke prevention and treatment.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Aims
Global longitudinal strain (GLS) assessed by speckle‐tracking echocardiography has been proposed as a parameter able to reflect early changes in left ventricular systolic function at a stage ...when left ventricular ejection fraction (LVEF) is still normal. This study aimed at assessing prevalence and prognostic value of left ventricular systolic dysfunction (LVSD) assessed by echocardiographic speckle‐tracking GLS in a community‐based cohort.
Methods and Results
Participants from the community‐based prospective Northern Manhattan Study underwent two‐dimensional transthoracic echocardiography as part of the Cardiovascular Abnormalities and Brain Lesions study. Left ventricular systolic function was assessed by LVEF and speckle‐tracking GLS. Subjects were followed annually (mean = 4.8 ± 1.5 years) and incident vascular events (ischaemic stroke, myocardial infarction, and vascular death) were reviewed and adjudicated. Of the 708 study participants, 114 (16.1%) had abnormal GLS but normal LVEF (GLS‐LVSD), 30 (4.2%) had abnormal LVEF (LVEF‐LVSD), and 564 (79.7%) had normal GLS and LVEF (no‐LVSD). In multivariate analysis, risk of events was significantly greater in GLS‐LVSD adjusted hazard ratio (HR) = 2.39, 95% confidence interval (CI) = 1.20–4.77 and in LVEF‐LVSD (adjusted HR = 3.51, 95% CI = 1.25–9.88) compared with no‐LVSD. Among participants with normal LVEF, lower GLS was significantly associated with events (adjusted HR/unit decrease = 1.15, 95% CI = 1.03–1.28) whereas LVEF was not (adjusted HR/unit decrease = 1.01, 95% CI = 0.94–1.07). The GLS prognostic value was incremental to risk factors and LVEF both in the overall population (chi‐square change = 7.406, P = 0.006) and in participants with normal LVEF (chi‐square change = 6.357, P = 0.012).
Conclusion
In a community‐based cohort, GLS‐LVSD was four times more frequent than LVEF‐LVSD. GLS‐LVSD was a powerful and independent predictor of cardiovascular events. Left ventricular function assessment by GLS may improve cardiovascular risk stratification in subjects with normal LVEF.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Left atrial (LA) maximum volume (LAV(max)) is an indicator of left ventricular (LV) diastolic function. However, LAV(max) is also influenced by systolic events, whereas the LA minimum volume ...(LAV(min)) is directly exposed to LV pressure. The authors hypothesised that LAV(min) may be a better correlate of LV diastolic function than LAV(max).
Cross-sectional.
University hospital.
357 participants from a community-based cohort study.
LA volumes and reservoir function, measured as total LA emptying volume (LAEV) and LA emptying fraction (LAEF), were assessed by real-time three-dimensional echocardiography. LV diastolic function was assessed by trans-mitral early (E) and late (A) Doppler velocities and mitral early diastolic velocity by tissue-Doppler (e'). LV systolic function was assessed by LV ejection fraction (LVEF) and global longitudinal strain (GLS) by speckle-tracking.
LAV(min) significantly increased with worsening diastolic dysfunction (p<0.001), whereas the increase in LAV(max) was less pronounced (p=0.07). LAEV and LAEF decreased with worsening diastolic dysfunction (both p<0.001). In linear regressions, LAV(min) and LAV(max) were significant predictors of E/e', with higher parameter estimates for LAV(min). In multivariate models, LAV(min) resulted strongly associated with E/e' (β=0.45, p<0.001), whereas LAV(max) was not (β=-0.16, p=0.08). LA reservoir function was better associated with GLS than LVEF. In multivariate analyses, GLS was significantly associated with LAV(max) (β=-0.15, p=0.002), LAEV (β=-0.37, p<0.001) and LAEF (β=-0.28, p<0.001) but not with LAV(min).
LAV(min) is a better correlate of LV diastolic function than LAV(max). The impact of LV longitudinal systolic function on LA reservoir function might explain the weaker relation between LAV(max) and LV diastolic function.
Pulsatile hemodynamics are associated with brain small perivascular spaces (SPVS). It is unknown whether the stiffness of intermediary arteries connecting the aorta and brain modifies this ...association. Participants from the Northern Manhattan Study were assessed for SPVS (defined as ≤3 mm T1 voids) and white matter hyperintensity volume (WMH) using MRI. Middle (MCA) and anterior cerebral arterial (ACA) diameters (measured on time-of-flight MRA) and CCA strain (assessed by ultrasound) were used as surrogates of stiffness. Brachial and aortic pulse pressure (PP) and aortic augmentation index (Aix, assessed by applanation tonometry) were used as markers of pulsatility. We tested whether stiffness in intermediary arteries modifies the association between extracranial pulsatility with SPVS and WMH. We found that among 941 participants (mean age 71 ± 9 years, 60% women, 66% Hispanic), the right MCA/ACA diameter was associated with right anterior SPVS (B = 0.177, P = 0.002). Brachial PP was associated with right anterior SPVS (B = 0.003, P = 0.02), and the effect size was bigger with right MCA/ACA diameter in the upper tertile (P = 0.001 for the interaction). The association between right CCA strain and ipsilateral SPVS was modified by MCA/ACA diameter, with the largest effect size in those with ipsilateral MCA/ACA diameter in the upper tertile (P = 0.001 for the interaction). Similar dose-effects and statistical interactions were replicated using aortic AIx or aortic PP. We found no evidence of effect modification between pulsatile measures and WMH by stiffness measures. In summary, pulsatile hemodynamics relate to brain SPVS, and the association is the strongest among individuals with dilated brain arteries.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Prior studies suggest that exposure to the natural environment may be important for optimal mental health. The present study examines the association between block-level greenness (vegetative ...presence) and mental health outcomes, in a population-based sample of 249,405 U.S. Medicare beneficiaries aged ≥65 years living in Miami-Dade County, Florida, USA, whose location did not change from 2010 to 2011. Multilevel analyses examined relationships between greenness, as measured by mean Normalized Difference Vegetation Index from satellite imagery at the Census block level, and each of two mental health outcomes; Alzheimer's disease and depression, respectively, after statistically adjusting for age, gender, race/ethnicity, and neighborhood income level of the individuals. Higher block-level greenness was linked to better mental health outcomes: There was a reduced risk of Alzheimer's disease (by 18%) and depression (by 28%) for beneficiaries living in blocks that were 1 SD above the mean for greenness, as compared to blocks that were 1 SD below the mean. Planned post-hoc analyses revealed that higher levels of greenness were associated with even greater mental health benefits in low-income neighborhoods: An increase in greenness from 1 SD below to 1 SD above the mean was associated with 37% lower odds of depression in low-income neighborhoods, compared to 27% and 21% lower odds of depression in medium- and high-income neighborhoods, respectively. Greenness may be effective in promoting mental health in older adults, particularly in low-income neighborhoods, possibly as a result of the increased opportunities for physical activity, social interaction, or stress mitigation.
The goal of this study was to determine the retinal blood flow rate (BFR) and blood flow velocity (BFV) of pre-capillary arterioles and post-capillary venules in patients with mild cognitive ...impairment (MCI) and Alzheimer's disease (AD). Forty patients (20 AD and 20 MCI) and 21 cognitively normal (CN) controls with a similar age range (± 5 yrs) were recruited. A retinal function imager (RFI) was used to measure BFRs and BFVs of arterioles and venules in the macular region. The thickness of the ganglion cell-inner plexiform layer (GCIPL) was measured using Zeiss Cirrus optical coherence tomography. Macular BFRs in AD group were 2.64 ± 0.20 nl/s (mean ± standard deviation) in arterioles and 2.23 ± 0.19 nl/s in venules, which were significantly lower than in MCI and CN groups (P < 0.05). In addition, BFRs in MCI were lower than in CN in both arterioles and venules (P < 0.05). The BFV of the arterioles was 3.20 ± 1.07 mm/s in AD patients, which was significantly lower than in CN controls (3.91 ± 0.77 mm/s, P = 0.01). The thicknesses of GCIPL in patients with AD and MCI were significantly lower than in CN controls (P < 0.05). Neither BFV nor BFR in arterioles and venules was related to age, GCIPL thickness, mini mental state examination (MMSE) score and disease duration in patients with AD and MCI (P > 0.05). The lower BFR in both arterioles and venules in AD and MCI patients together with the loss of GCIPL were evident, indicating the impairment of the two components in the neurovascular-hemodynamic system, which may play a role in disease progression.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
OBJECTIVETo determine whether high CSF levels of neurogranin (Ng) predict longitudinal decline in memory and executive function during early-stage Alzheimer disease (AD).
METHODSBaseline levels of ...CSF Ng were studied in relation to cross-sectional and longitudinal cognitive performance over 8 years. Data were obtained from the Alzheimerʼs Disease Neuroimaging Initiative database, and participants with normal cognition (n = 111) and mild cognitive impairment (MCI) (n = 193) were included.
RESULTSHigh levels of CSF Ng were associated with poor baseline memory scores (β = −0.21, p < 0.0001). CSF Ng predicted both memory and executive function decline over time (β = −0.0313, p = 0.0068 and β = −0.0346, p = 0.0169, respectively) independently of age, sex, education, and APOE ε4 status. When the rate of decline by tertiles was examined, CSF Ng was a level-dependent predictor of memory function, whereby the group with highest levels of Ng showed the fastest rates of decline in both memory and executive function. When examined separately, elevated Ng was associated with cognitive decline in participants with MCI but not in those with normal cognition. The levels of CSF Ng were not associated with cognitive measures when tau and amyloid 42 (Aβ42) were controlled for in these analyses.
CONCLUSIONSHigh CSF Ng associates with poor memory scores in participants with MCI cross-sectionally and with poor memory and executive function longitudinally. The association of Ng with cognitive measures disappears when tau and Aβ42 are included in the statistical models. Our findings suggest that CSF Ng may serve as a biomarker of cognition. Synaptic dysfunction contributes to cognitive impairment in early-stage AD.
Patients with minor stroke or transient ischemic attack (TIA), characterized as a brief episode of neurologic dysfunction caused by focal cerebral ischemia without infarction, have the least amount ...of disability and the most to lose should they have a stroke. Patients with vanishing symptoms may slip through our systems for detecting acute stroke owing either to patients’ delays in seeking medical attention or clinicians’ assessments that urgent treatment is not needed. This lost opportunity is even more worrisome given the tremendous improvements in the quality of primary and secondary stroke prevention that include evidence-based treatments with antiplatelet and oral anticoagulation . . .
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