Abstract 021: Greater Calcium Density of Coronary Artery Plaque is Protective for Cardiovascular Events. The Multi-Ethnic Study of Atherosclerosis

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Michael H Criqui
Keyword(s):  
Coronary Artery ◽  
Standard Deviation ◽  
Proportional Hazards Model ◽  
Hazard Ratio ◽  
Calcium Deposition ◽  
Agatston Score ◽  
Standard Deviation Increase ◽  
Density Score ◽  
Independent Association ◽  
Volume Score

Background— Coronary artery calcium (CAC) measured by computed tomography (CT) has strong predictive value for incident cardiovascular disease (CVD) events. The standard CAC score is the Agatston, which is the product of the within slice CAC plaque area and a plaque specific density factor of 1, 2, 3, or 4, summed for all CT slices. Thus, the Agatston score is weighted upward for greater CAC density. However, data from both observational studies and randomized trials suggest increased CAC density per se may be protective for CVD. Methods— In a multi-ethnic population of 3398 men and women with Agatston scores > 0 at baseline, we derived a formula using the individual Agatston scores and the volume scores to create a per participant CAC density score. We then analyzed the independent associations of CAC volume and CAC density with incident hard CVD, defined as MI, resuscitated cardiac arrest, cardiac death, stroke, or stroke death, Results— During a median of 7.6 years of follow-up, there were 265 hard CVD events, 175 of which were coronary heart disease (CHD) events. In a proportional hazards model including the General Framingham Risk Score (GFRS) and both the CAC volume and CAC density score, the CAC volume score showed a strong independent association with incident CVD, with a hazard ratio per natural log standard deviation increase of 1.62, p<.0001. Conversely, the CAC density score showed an independent association that was strongly protective for CVD, with a hazard ratio per standard deviation increase of 0.72, p<.0003. Multivariate quartile analyses showed that at any given volume score, a density score in the 4 th quartile (range 3.2 to 4.0) decreased the risk of a CVD event by 51%, p=.002. The density score showed no significant interactions with either sex or ethnicity. The addition of the volume score to the model containing the GFRS increased the area under the ROC curve (AUC) from 0.664 to 0.6869, p=.015, and further addition of the density score increased the AUC to .6994, p=.023. Separate analyses limited to CHD events showed similar results. Conclusions— At any given volume of CAC, increased density in calcified coronary plaques is protective for incident CVD, consistent with the concept that calcium deposition may increase the stability of atherosclerotic plaques. CAC scoring systems should be modified to weight downward for density rather than upward, and thus improve CVD risk prediction.

Periostin promotes arterial calcification through PPARγ-related glucose metabolism reprogramming

2021 ◽  
Author(s):  
Yi Zhu ◽  
Jing-Jing Ji ◽  
Xiao-Dong Wang ◽  
Xue-Jiao Sun ◽  
Min Li ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Ex Vivo ◽  
Matrix Gla Protein ◽  
Calcium Deposition ◽  
Arterial Calcification ◽  
Agatston Score ◽  
Respiratory Chain Complexes ◽  
Ecm Remodeling ◽  
Pparγ Agonist ◽  
Lactate Levels

Extracellular matrix (ECM) exerts a list of biological functions, contributing to almost 30% of the osteogenic process. Periostin is a secreted protein that can alter ECM remodeling in response to vascular injury. However, the functional role of periostin in vascular calcification has yet to be fully described. Ex vivo, recombinant periostin accelerated thoracic aortas calcification, increased the expression of glycolysis key enzymes, and disturbed the normal oxidative phosphorylation (OXPHOS), which could be alleviated by the peroxisome proliferation-activated receptor γ (PPARγ) agonist pioglitazone. In vascular smooth muscle cells (VSMCs), recombinant periostin promoted VSMC-osteoblastic phenotype transition and calcium deposition, and suppressed PPARγ expression. Mechanistically, recombinant periostin caused over-activation of glycolysis and mitochondrial dysfunction in VSMCs, as assessed by extracellular acidification rate (ECAR), oxygen consumption rate, and mitochondrial respiratory chain complexes activities. Targeted glycolysis inhibitors reduced mitochondrial calcium overload, apoptosis, and periostin-induced VSMCs calcification. PPARγ agonists preserved glycolysis and OXPHOS in the stimulated microenvironment, and reversed periostin-promoted VSMC calcification. Furthermore, plasma periostin, lactate, and matrix Gla protein levels were measured in 274 patients who underwent computed tomography to determine coronary artery calcium score (Agatston score). Plasma periostin and lactate levels were both linked to an Agatston score of more than zero in patients with coronary artery calcification. There is also a positive correlation between plasma periostin and lactate levels. This study suggests that downregulation of PPARγ is involved in the mechanism by which periostin accelerates arterial calcification, partly through excessive glycolysis activation and unbalanced mitochondrial homeostasis.

scholarly journals Association of cardiovascular disease risk factors with coronary artery calcium volume versus density

Heart ◽  
2017 ◽  
Vol 104 (2) ◽  
pp. 135-143 ◽  
Author(s):  
Isac C Thomas ◽  
Brandon Shiau ◽  
Julie O Denenberg ◽  
Robyn L McClelland ◽  
Philip Greenland ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Coronary Artery ◽  
Coronary Artery Calcium ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Density Score ◽  
Volume Score

ObjectivesRecently, the density score of coronary artery calcium (CAC) has been shown to be associated with a lower risk of cardiovascular disease (CVD) events at any level of CAC volume. Whether risk factors for CAC volume and CAC density are similar or distinct is unknown. We sought to evaluate the associations of CVD risk factors with CAC volume and CAC density scores.MethodsBaseline measurements from 6814 participants free of clinical CVD were collected for the Multi-Ethnic Study of Atherosclerosis. Participants with detectable CAC (n=3398) were evaluated for this study. Multivariable linear regression models were used to evaluate independent associations of CVD risk factors with CAC volume and CAC density scores.ResultsWhereas most CVD risk factors were associated with higher CAC volume scores, many risk factors were associated with lower CAC density scores. For example, diabetes was associated with a higher natural logarithm (ln) transformed CAC volume score (standardised β=0.44 (95% CI 0.31 to 0.58) ln-units) but a lower CAC density score (β=−0.07 (−0.12 to −0.02) density units). Chinese, African-American and Hispanic race/ethnicity were each associated with lower ln CAC volume scores (β=−0.62 (−0.83to −0.41), −0.52 (−0.64 to −0.39) and −0.40 (−0.55 to −0.26) ln-units, respectively) and higher CAC density scores (β= 0.41 (0.34 to 0.47), 0.18 (0.12 to 0.23) and 0.21 (0.15 to 0.26) density units, respectively) relative to non-Hispanic White.ConclusionsIn a cohort free of clinical CVD, CVD risk factors are differentially associated with CAC volume and density scores, with many CVD risk factors inversely associated with the CAC density score after controlling for the CAC volume score. These findings suggest complex associations between CVD risk factors and these components of CAC.

C-reactive protein, insulin resistance and risk of cardiovascular disease: a population-based study

2008 ◽  
Vol 15 (5) ◽  
pp. 594-598 ◽  
Author(s):  
Jørgen Jeppesen ◽  
Tine W. Hansen ◽  
Michael H. Olsen ◽  
Susanne Rasmussen ◽  
Hans lbsen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Standard Deviation ◽  
Population Based ◽  
Hazard Ratio ◽  
C Reactive Protein ◽  
Standard Deviation Increase ◽  
Population Based Study ◽  
Reactive Protein

Background C-reactive protein (CRP), a marker of inflammation, and insulin resistance (IR), a metabolic disorder, are closely related. CRP and IR have both been identified as significant risk factors of cardiovascular disease (CVD) after adjustment for conventional CVD risk factors. It is not clear whether CRP predicts CVD independent of IR. Design Prospective population-based study. Methods Two thousand three hundred and fifty-seven Danish men and women, recruited from the general population, aged 41–72 years, without major CVD at baseline were studied. Traditional and new risk factors were recorded at baseline. CRP was determined by a high-sensitivity assay, and IR was determined by the homoeostasis model assessment (HOMA-IR) method. Results Over a median follow-up of 9.4 years, the incidence of the prespecified CV event, defined as the composite event of CV death, nonfatal ischaemic heart disease and nonfatal stroke, amounted to 222 cases. In Cox proportional-hazard models, adjusted for age, sex, smoking habit, total cholesterol, waist circumference, levels of triglycerides and high-density lipoprotein-cholesterol, systolic and diastolic blood pressures, physical activity and HOMA-IR, the hazard ratio (95% confidence interval) of a CV event was 1.33 (1.14–1.55; 0.001) per standard deviation increase in log-transformed CRP level. In the same model, the hazard ratio of a CV event was 1.11 (1.02–1.21; P < 0.05) per standard deviation increase in HOMA-IR level. Conclusion In a general Danish population free of major CVD at baseline, both CRP and IR were significantly related to risk of CVD.

scholarly journals Pharmacogenetic Polygenic Risk Score for Bronchodilator Response in Children and Adolescents with Asthma: Proof-of-Concept

2021 ◽  
Vol 11 (4) ◽  
pp. 319
Author(s):  
Joanne E. Sordillo ◽  
Sharon M. Lutz ◽  
Michael J. McGeachie ◽  
Jessica Lasky-Su ◽  
Scott T. Weiss ◽  
...  
Keyword(s):  
Standard Deviation ◽  
Risk Score ◽  
Association Studies ◽  
Polygenic Risk Score ◽  
Genome Wide Association Studies ◽  
Linear Regression Models ◽  
Standard Deviation Increase ◽  
Polygenic Risk ◽  
Bronchodilator Response ◽  
Children With Asthma

Genome-wide association studies (GWAS) of response to asthma medications have primarily focused on Caucasian populations, with findings that may not be generalizable to minority populations. We derived a polygenic risk score (PRS) for response to albuterol as measured by bronchodilator response (BDR), and examined the PRS in a cohort of Hispanic school-aged children with asthma. We leveraged a published GWAS of BDR to identify relevant genetic variants, and ranked the top variants according to their Combined Annotation Dependent Depletion (CADD) scores. Variants with CADD scores greater than 10 were used to compute the PRS. Once we derived the PRS, we determined the association of the PRS with BDR in a cohort of Hispanic children with asthma (the Genetics of Asthma in Costa Rica Study (GACRS)) in adjusted linear regression models. Mean BDR in GACRS participants was5.6% with a standard deviation of 10.2%. We observed a 0.63% decrease in BDR in response to albuterol for a standard deviation increase in the PRS (p = 0.05). We also observed decreased odds of a BDR response at or above the 12% threshold for a one standard deviation increase in the PRS (OR = 0.80 (95% CI 0.67 to 0.95)). Our findings show that combining variants from a pharmacogenetic GWAS into a PRS may be useful for predicting medication response in asthma.

scholarly journals Diagnostic and prognostic value of coronary artery calcium score of zero: is it time for guidelines to change?

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
E Arbas Redondo ◽  
D Tebar Marquez ◽  
I.D Poveda Pinedo ◽  
R Dalmau Gonzalez-Gallarza ◽  
S.C Valbuena Lopez ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Coronary Angiography ◽  
Coronary Artery Calcium ◽  
Cardiac Ct ◽  
Invasive Coronary Angiography ◽  
Agatston Score ◽  
Non Invasive ◽  
Artery Disease

Abstract Introduction Cardiac computed tomography (CT) use has progressively increased as the preferred initial test to rule out coronary artery disease (CAD) when clinical likelihood is low. Coronary artery calcium (CAC) detected by CT is a well-established marker for cardiovascular risk. However, it is not recommended for diagnosis of obstructive CAD. Absence of CAC, defined as an Agatston score of zero, has been associated to good prognosis despite underestimation of non-calcified plaques. Purpose To evaluate whether zero CAC score could help ruling out obstructive CAD in a safely manner. Methods Observational study based on a prospective database of patients (pts) referred to cardiac CT between 2017 and 2019. Pts with an Agatston score of zero were selected. Results We included 176 pts with zero CAC score and non-invasive coronary angiography performed. The median duration of follow-up was 23.9 months. Baseline characteristics of the population are shown in Table 1. In 117 pts (66.5%), cardiac CT was indicated as part of their chest pain evaluation. Mean age was 57.2 years old, 68.2% were women and only and 9.4% were active smokers. Normal coronary arteries were found in 173 pts (98.3%). Obstructive CAD, defined as ≥50% luminal diameter stenosis of a major vessel, was present in 1/176 (0.6%); while non-obstructive atherosclerotic plaques were found in 2 pts (1.1%). During follow-up, one patient died of out-of-hospital cardiac arrest. None either suffered from myocardial infarction or needed coronary revascularization. Conclusions In our cohort, a zero CAC score detected by cardiac CT rules out obstructive coronary artery disease in 98.3%, with only 1.7% of non-calcified atherosclerosis plaques and 0.6% of major adverse events. Although further research on this topic is needed, these results support the fact that non-invasive coronary angiography could be avoided in patients with low clinical likelihood of CAD and zero CAC score, facilitating the management of the increasing demand for coronary CT and reduction of radiation dose. Funding Acknowledgement Type of funding source: None

scholarly journals Assessing the Role of Pericardial Fat as a Biomarker Connected to Coronary Calcification—A Deep Learning Based Approach Using Fully Automated Body Composition Analysis

2021 ◽  
Vol 10 (2) ◽  
pp. 356
Author(s):  
Lennard Kroll ◽  
Kai Nassenstein ◽  
Markus Jochims ◽  
Sven Koitka ◽  
Felix Nensa
Keyword(s):  
Adipose Tissue ◽  
Deep Learning ◽  
Coronary Artery ◽  
Cardiac Ct ◽  
Coronary Calcification ◽  
Risk Scores ◽  
Agatston Score ◽  
Composition Analysis ◽  
Significance Level ◽  
Tissue Quantification

(1) Background: Epi- and Paracardial Adipose Tissue (EAT, PAT) have been spotlighted as important biomarkers in cardiological assessment in recent years. Since biomarker quantification is an increasingly important method for clinical use, we wanted to examine fully automated EAT and PAT quantification for possible use in cardiovascular risk stratification. (2) Methods: 966 patients with intermediate Framingham risk scores for Coronary Artery Disease referred for coronary calcium scans were included in clinical routine retrospectively. The Coronary Artery Calcium Score (CACS) was extracted and tissue quantification was performed by a deep learning network. (3) Results: The Computed Tomography (CT) segmentations predicted by the network indicated no significant correlation between EAT volume and EAT radiodensity when compared to Agatston score (r = 0.18, r = −0.09). CACS 0 category patients showed significantly lower levels of total EAT and PAT volumes and higher EAT and PAT densities than CACS 1–99 category patients (p < 0.01). Notably, this difference did not reach significance regarding EAT attenuation in male patients. Women older than 50 years, thus more likely to be postmenopausal, were shown to be at higher risk of coronary calcification (p < 0.01, OR = 4.59). CACS 1–99 vs. CACS ≥100 category patients remained below significance level (EAT volume: p = 0.087, EAT attenuation: p = 0.98). (4) Conclusions: Our study proves the feasibility of a fully automated adipose tissue analysis in clinical cardiac CT and confirms in a large clinical cohort that volume and attenuation of EAT and PAT are not correlated with CACS. Broadly available deep learning based rapid and reliable tissue quantification should thus be discussed as a method to assess this biomarker as a supplementary risk predictor in cardiac CT.

scholarly journals Evaluation of an AI-based, automatic coronary artery calcium scoring software

2019 ◽  
Vol 30 (3) ◽  
pp. 1671-1678 ◽  
Author(s):  
Mårten Sandstedt ◽  
Lilian Henriksson ◽  
Magnus Janzon ◽  
Gusten Nyberg ◽  
Jan Engvall ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Coronary Artery ◽  
Coronary Artery Calcium ◽  
Rank Test ◽  
Agatston Score ◽  
Risk Category ◽  
Automatic Method ◽  
Calcium Scoring ◽  
Excellent Correlation ◽  
Automatic Software

Abstract Objectives To evaluate an artificial intelligence (AI)–based, automatic coronary artery calcium (CAC) scoring software, using a semi-automatic software as a reference. Methods This observational study included 315 consecutive, non-contrast-enhanced calcium scoring computed tomography (CSCT) scans. A semi-automatic and an automatic software obtained the Agatston score (AS), the volume score (VS), the mass score (MS), and the number of calcified coronary lesions. Semi-automatic and automatic analysis time were registered, including a manual double-check of the automatic results. Statistical analyses were Spearman’s rank correlation coefficient (⍴), intra-class correlation (ICC), Bland Altman plots, weighted kappa analysis (κ), and Wilcoxon signed-rank test. Results The correlation and agreement for the AS, VS, and MS were ⍴ = 0.935, 0.932, 0.934 (p < 0.001), and ICC = 0.996, 0.996, 0.991, respectively (p < 0.001). The correlation and agreement for the number of calcified lesions were ⍴ = 0.903 and ICC = 0.977 (p < 0.001), respectively. The Bland Altman mean difference and 1.96 SD upper and lower limits of agreements for the AS, VS, and MS were − 8.2 (− 115.1 to 98.2), − 7.4 (− 93.9 to 79.1), and − 3.8 (− 33.6 to 25.9), respectively. Agreement in risk category assignment was 89.5% and κ = 0.919 (p < 0.001). The median time for the semi-automatic and automatic method was 59 s (IQR 35–100) and 36 s (IQR 29–49), respectively (p < 0.001). Conclusions There was an excellent correlation and agreement between the automatic software and the semi-automatic software for three CAC scores and the number of calcified lesions. Risk category classification was accurate but showing an overestimation bias tendency. Also, the automatic method was less time-demanding. Key Points • Coronary artery calcium (CAC) scoring is an excellent candidate for artificial intelligence (AI) development in a clinical setting. • An AI-based, automatic software obtained CAC scores with excellent correlation and agreement compared with a conventional method but was less time-consuming.

scholarly journals Atrial fibrillation progression risk factors and associated cardiovascular outcome in well-phenotyped patients: data from the AF-RISK study

EP Europace ◽  
2019 ◽  
Vol 22 (3) ◽  
pp. 352-360 ◽  
Author(s):  
Ruben R De With ◽  
Ernaldo G Marcos ◽  
Elton A M P Dudink ◽  
Henri M Spronk ◽  
Harry J G M Crijns ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Standard Deviation ◽  
Left Atrial ◽  
Left Atrial Volume ◽  
Plasminogen Activator Inhibitor 1 ◽  
Atrial Volume ◽  
Standard Deviation Increase ◽  
Recent Onset ◽  
Pai 1

Abstract Aims Atrial fibrillation (AF) is a progressive disease, but identifying patients at risk for AF progression is challenging. We aimed to identify factors associated with AF progression. Methods and results Atrial fibrillation progression was assessed in 392 patients with recent-onset paroxysmal or persistent AF included in the prospective, observational, multicentre identification of a risk profile to guide atrial fibrillation (AF-RISK) study. Progression of AF was assessed by Holter monitoring and 2-week event recorder at baseline and 1-year follow-up. AF progression was defined as: (i) doubling in AF burden at 1 year compared to baseline with a minimum AF burden of 10% in paroxysmal AF; or (ii) transition from paroxysmal to persistent or permanent AF; or (iii) persistent to permanent AF. Age was 60 ± 11 years, 62% were men, and 83% had paroxysmal AF. At 1 year, 52 (13%) had AF progression (11% in paroxysmal; 26% in persistent AF). Multivariable logistic regression showed that left atrial volume [odds ratio (OR) per 10 mL 1.251, 95% confidence interval (CI) 1.078–1.450; P &lt; 0.001], N-terminal pro-B-type natriuretic peptide (NT-proBNP; OR per standard deviation increase 1.583, 95% CI 1.099–2.281; P = 0.014), and plasminogen activator inhibitor-1 (PAI-1; OR per standard deviation increase 0.660, 95% CI 0.472–0.921; P = 0.015) were associated with AF progression. In an additional follow-up of 1.9 (0.9–3.3) years patients with AF progression developed more cardiovascular events and all-cause mortality (12.4%/year vs. 2.3%/year, P &lt; 0.001). Conclusion Atrial fibrillation progression occurred in 13% of patients with recent-onset AF during 1-year follow-up. Left atrial volume, NT-proBNP, and PAI-1 were associated with AF progression. Patients with AF progression had a higher event rate. Trial registration number Clinicaltrials.gov NCT01510210.

scholarly journals Plasma F2-Isoprostanes and Coronary Artery Calcification: The CARDIA Study

2005 ◽  
Vol 51 (1) ◽  
pp. 125-131 ◽  
Author(s):  
Myron Gross ◽  
Michael Steffes ◽  
David R Jacobs ◽  
Xinhua Yu ◽  
Linda Lewis ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Early Development ◽  
Coronary Artery Calcification ◽  
Continuous Variable ◽  
Oxidation Products ◽  
Gas Chromatography Mass Spectrometry ◽  
Agatston Score ◽  
Reactive Protein ◽  
Increased Risk ◽  
Coronary Artery Atherosclerosis

Abstract Background: Oxidation of lipids in lipoproteins and cells may initiate and enhance the early development of cardiovascular disease. Method and Results: We assayed F2-isoprostanes, oxidation products of arachidonic acid, by gas chromatography–mass spectrometry in a biracial cohort of 2850 young healthy adult men and women. Coronary artery calcification (CAC), a component of coronary artery atherosclerosis, was detectable in 10% of the cohort and appeared to be in its initial stages (Agatston scores &lt;20 in 47% and &lt;100 in 83% of CAC-positive participants). After adjusting for sex, clinical site, age, and race, the presence of any CAC was 24% more likely among those with high vs low concentrations of F2-isoprostanes [odds ratio (OR) = 1.24 per 92.2 pmol/L (32.7 ng/L; 1 SD of F2-isoprostanes); 95% confidence interval (CI), 1.09–1.41]. The OR was only slightly attenuated [1.18 per 92.2 pmol/L (32.7 ng/L); CI, 1.02–1.38] after further adjustment for body mass index, smoking, serum lipids, C-reactive protein, antioxidant supplementation use, diabetes, and blood pressure. As a continuous variable, the Agatston score increased by 6.9% per 92.2 pmol/L (32.7 ng/L) of F2-isoprostane concentration (P &lt;0.01). Whereas CAC prevalence was lower in women than men, mean (SD), F2-isoprostanes were higher in women {190 (108.9) pmol/L [67.4 (38.6) ng/L]} than in men {140.4 (55.6) pmol/L [49.8 (19.7) ng/L]}. Nevertheless, F2-isoprostanes were associated with an increased risk of CAC in both sexes. Conclusion: This association between increased concentrations of circulating F2-isoprostanes and CAC in young healthy adults supports the hypothesis that oxidative damage is involved in the early development of atherosclerosis.

scholarly journals Midlife Plasma Aβ and Late-Life Risk of Cognitive Impairment: The Atherosclerosis Risk in Communities Study

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 251-252
Author(s):  
Kevin Sullivan ◽  
Chad Blackshear ◽  
A Richey Sharrett ◽  
Rebecca Gottesman ◽  
David Knopman ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Standard Deviation ◽  
Sex Education ◽  
Lower Risk ◽  
Late Life ◽  
Cognitive Status ◽  
Cognitive Outcomes ◽  
Effective Population ◽  
Standard Deviation Increase ◽  
Cerebral Amyloidosis

Abstract Plasma-based biomarkers of amyloid beta (Aβ), a neuropathological hallmark of Alzheimer’s disease, show promise in predicting cognitive impairment and mapping onto cerebral amyloidosis, but little is known about how midlife plasma Aβ associates with late-life cognitive outcomes. Midlife plasma variants Aβ42 and Aβ40 were measured using a fluorimetric bead-based immunoassay in a subsample of visit 3 ARIC participants (1993-95; n=2585, mean age=59.4±5.2, 57% female, 23% African American). We investigated the relationship between midlife plasma Aβ and late-life mild cognitive impairment (MCI; n=923) and dementia (n=628) diagnosed from 2011-19. Multinomial logistic regressions estimated relative risk ratios (RRR) of MCI, dementia, and death vs normal cognitive status as a function of:(1) Aβ42:Aβ40 ratio, (2) Aβ42 and Aβ40 included as separate terms, and (3) Protected Aβ group (participants with Aβ42≥46 pg/ml and Aβ40 &lt;233 pg/ml). Adjusters included age, sex, education, site-race, and APOE4. Every doubling of midlife plasma Aβ42:Aβ40 up to a threshold of 0.20 was associated with 41% lower risk of developing MCI/dementia in comparison to cognitively normal (RRR=0.59 [95% CI:0.42, 0.82]), with no association for ratio values ≥0.20. Every standard deviation increase in plasma Aβ42 was associated with 17% lower risk of dementia (RRR=0.83 [0.70, 0.99]), whereas every standard deviation increase in plasma Aβ40 was associated with 16% higher risk of MCI (RRR=1.16 [1.02, 1.31]). The protected midlife plasma Aβ group had 86% lower risk of late-life dementia vs all others (RRR=0.14 [0.04, 0.47]). Early measurement of plasma Aβ may prove an accessible and effective population screener for future cognitive impairment.

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