Mera, Robertino M.

Background: Information on the associations among arterial stiffness, carotid intima-media thickness (cIMT) and carotid plaques as biomarkers of atherosclerosis is limited. We aimed to assess whether aortic pulse wave velocity (PWV) - as a surrogate of arterial stiffness - is associated with increased cIMT and the presence of carotid plaques in a cohort of older adults of Amerindian ancestry. Methods: Atahualpa residents aged ≥60 years (n=320) underwent aortic PWV determinations, and carotid ultrasound for cIMT and plaque assessment. Multivariate models were fitted to assess the independent association between the aortic PWV, and cIMT and carotid plaques (as dependent variables), after adjusting for relevant confounders. Differences in risk factors across these biomarkers were investigated. Results: Mean values of aortic PWV were 10.3±1.8 m/s, and those of cIMT were 0.91±0.21 mm (24% had a cIMT >1 mm). Carotid plaques were observed in 118 (37%) subjects. In univariate analyses, risk factors associated with an increased aortic PWV included age, female gender, poor physical activity and high blood pressure. An increased cIMT was associated with age, male gender, poor diet, high blood pressure and severe edentulism. The presence of carotid plaques was associated with increasing age, poor physical activity and high blood pressure. A fully-adjusted generalized linear model showed a significant association between aortic PWV and cIMT (β: 0.028; 95% C.I.: 0.001 - 0.056; p =0.047). In contrast, a logistic regression model showed no association between aortic PWV and carotid plaques (OR: 1.14; 95% C.I.: 0.83 - 1.56; p =0.423), after adjusting for relevant confounders. Conclusions: This study shows an independent association between aortic PWV and cIMT but not with carotid plaques. These biomarkers may indicate distinct phenotypes for atherosclerosis.

AbstractStudy ObjectivesThis study assessed changes in sleep quality before and after the peak of the SARS-CoV-2 pandemic in community dwellers enrolled in the Atahualpa Project.MethodsAtahualpa residents aged ≥40 years were eligible if they had a Pittsburgh Sleep Quality Index (PSQI) 9 months before the pandemic and a lateral flow-based test for identification of SARS-CoV-2 antibodies during the peak of the pandemic. Six months later, individuals completed a follow-up PSQI. The independent relationship between SARS-CoV-2 infection and deterioration in sleep quality was assessed by fitting logistic mixed models for longitudinal data.ResultsOf 639 participants (mean age at baseline: 59 ± 12.8 years), 325 (51%) had SARS-CoV-2 antibodies. A total of 185 (29%) individuals at baseline and 311 (49%) at follow-up were poor sleepers (p < 0.001). Mixed logistic regression models demonstrated a significant increase in poor sleepers at follow-up (odds ratio [OR]: 2.85; 95% CI: 2.16 to 3.75), which was more marked among SARS-CoV-2 seropositive subjects (OR: 3.8; 95% CI: 2.48 to 5.81). The adjusted proportion of poor sleepers increased from 29% to 56.2% (95% CI: 50.9% to 61.6%) among SARS-CoV-2 seropositive individuals, but only to 40.7% (95% CI: 35.3% to 46.1%) in their seronegative counterparts (p < 0.001). Likewise, progression from a good to a poor sleeper status was higher among seropositive individuals than in their seronegative counterparts (38.1% vs 22.3%; p < 0.001), after adjusting for relevant covariates.ConclusionsThis study shows a deleterious effect of SARS-CoV-2 in sleep quality. An effect of SARS-CoV-2 in disrupting sleep-related pathways cannot be ruled out.Trial registrationThe Atahualpa Project has been registered at ClinicalTrials.gov; the identifier number is NCT01627600, and the date was: 10/02/2012 (https://clinicaltrials.gov/ct2/show/NCT01627600?cond=Atahualpa&draw=2&rank=1). The Sleep Disorders substudy has been registered at ClinicalTrials.gov; the identifier number is NCT01877616, and the date was: 06/13/2013 (https://clinicaltrials.gov/ct2/show/NCT01877616?cond=Atahualpa&draw=2&rank=4).

Background Inability to encircle the neck by hands (neck grasp) has been proposed as an indicator of obstructive sleep apnea (OSA) that would be useful for recognition of candidates for polysomnography (PSG). We assessed the value of neck grasp for predicting OSA in community-dwelling older adults of Amerindian ancestry. Methods Neck grasp was evaluated in individuals aged ≥60 years undergoing PSG. The association between neck grasp and OSA was assessed by logistic regression models adjusted for relevant covariates. Mediation analysis was used to establish the proportion of the effect of the association between neck grasp and OSA, which is mediated by the neck circumference (a well-known OSA biomarker). Receiver operator characteristics curve analysis was used to estimate diagnostic accuracy of neck grasp for predicting OSA. Results Of 201 individuals undergoing PSG, 167 (83%) had the neck grasp test. The remaining 34 could not perform the test because of different factors. Neck grasp was positive in 127 (76%) cases, and 114 (68%) individuals had OSA (apnea-hypopnea index ≥5). Multivariate logistic regression models disclosed a significant association between neck grasp and OSA. The neck circumference was the single covariate remaining independently significant in these models. Neck grasp was not efficient at predicting OSA (sensitivity: 83.3%, specificity: 39.6%, positive predictive value: 0.75 and negative predictive value: 0.53). The area under the curve disclosed only a moderate predictive capability (61.5%) of neck grasp. Conclusion Results do not support the use of neck grasp as an independent predictor of OSA in the study population.

Abstract Introduction Evidence of the relationship between periodic limb movements during sleep (PLMS) and cerebral small vessel disease (cSVD) is limited and inconsistent. Here, we aimed to assess the independent association between PLMS and the different neuroimaging signatures of cSVD. Methods Community dwelling adults aged ≥60 years enrolled in the Atahualpa Project undergoing PSG and MRI with time intervals ≤6 months were included. MRI readings focused on white matter hyperintensities (WMH) of presumed vascular origin, deep cerebral microbleeds (CMB), silent lacunar infarcts (LI), and >10 enlarged basal ganglia-perivascular spaces (BG-PVS). Data from single-night polysomnograms were interpreted according to recommendations of the American Academy of Sleep Medicine. Associations between the PLMS index and neuroimaging signatures of cSVD (as dependent variables) were assessed by means of logistic regression models, adjusted for relevant confounders. Results A total of 146 individuals (mean age: 71.4 ± 7.5 years; 64% women) were included. A PLMS index ≥15/hour were noted in 48 (33%) participants. Moderate-to-severe WMH were present in 33 individuals (23%), deep CMB in 9 (6%), silent LI in 16 (11%), and >10 BG-PVS in 44 (30%). In univariate analyses, silent LI (p=0.035) and the presence of >10 enlarged BG-PVS (p=0.034) were significantly higher among participants with a PLMS index ≥15/hour. However, fully-adjusted multivariate models showed no significant association between PLMS index ≥15/hour and any of the neuroimaging signatures of cSVD. Conclusion This study shows no independent association between the PLMS index and neuroimaging signatures of cSVD in stroke-free community-dwelling older adults. Support This study was supported by Universidad Espíritu Santo - Ecuador.

Objective Information on the associations among arterial stiffness, carotid intima-media thickness (cIMT) and carotid plaques as biomarkers of atherosclerosis is limited in diverse populations. We aimed to assess whether aortic pulse wave velocity (aPWV) – as a surrogate of arterial stiffness – is associated with increased cIMT and the presence of carotid plaques in a cohort of older adults of Amerindian ancestry. Methods Atahualpa residents aged ≥60 years ( n = 320) underwent aPWV determinations, and carotid ultrasounds for cIMT and plaque assessment. Multivariate models were fitted to assess the independent association between the aPWV, and cIMT and carotid plaques, after adjusting for relevant confounders. Differences in risk factors across these biomarkers were investigated. Results Mean values of aPWV were 10.3 ± 1.8 m/s, and those of cIMT were 0.91 ± 0.21 mm (24% had a cIMT >1 mm). Carotid plaques were observed in 118 (37%) subjects. In univariate analyses, risk factors associated with an increased aPWV included age, female gender, poor physical activity and high blood pressure. An increased cIMT was associated with age, male gender, a poor diet, high blood pressure and severe tooth loss. The presence of carotid plaques was associated with increasing age, poor physical activity and high blood pressure. Multivariate models showed a significant association between aPWV and cIMT (β: 0.028; 95% C.I.: 0.001–0.056; p = 0.047) but not between aPWV and carotid plaques (OR: 1.14; 95% C.I.: 0.83–1.56; p = 0.423). Conclusions This study shows an independent association between aPWV and cIMT but not with carotid plaques. These biomarkers may indicate distinct phenotypes for atherosclerosis.

Background and Purpose— The apnea-hypopnea index (AHI) is associated with cerebral small vessel disease (cSVD), but pathogenesis of this association is elusive. We aimed to assess the effect of nighttime heart rate variability (HRV)—as a proxy of sympathetic upregulation—on the aforementioned association. Methods— Atahualpa residents aged ≥60 years undergoing brain magnetic resonance imaging, polysomnography, and 24-hour Holter monitoring (N=176) were included. The presence of moderate-to-severe white matter hyperintensities, deep cerebral microbleeds, lacunar infarcts, and >10 enlarged basal ganglia perivascular spaces were added for estimating the cSVD score. Interaction models were fitted to assess the effect modification of nighttime HRV in the association between the AHI and the cSVD score, and mediation analysis was utilized to assess the proportion of total effect by nighttime HRV on this association. Results— Generalized linear models showed a significant association between the AHI and the cSVD score ( P =0.025), as well as a significant inverse association between nighttime HRV and the cSVD score ( P =0.002), but no association between daytime HRV and the cSVD score ( P =0.097). Interaction models showed a significant interaction of nighttime HRV on the association between AHI and the cSVD score ( P =0.001), and mediation analysis found that the percent of total effect between AHI and cSVD score mediated by HRV was 30.8%. Predictive marginal means of the cSVD score were highly significant when the 10th percentile of nighttime HRV was compared across categories of 10th and 90th percentiles of the AHI (cSVD score margins, 0.61 [95% CI, 0.37–0.86] versus 1.67 [95% CI, 1.26–2.09]). Contour plots showed the effect of nighttime (but not daytime) HRV on the association between AHI and the cSVD score. Conclusions— This study shows an important effect of nighttime HRV on the association between the AHI and the cSVD score and provides further support for the role of sympathetic overactivity on this association.

There is limited information on participants’ adherence and reasons for declining consent in observational cohort studies conducted in remote rural communities. We aimed at sharing lessons learned during the Atahualpa Project, a population-based cohort study conducted in a rural Ecuadorian village. Atahualpa residents aged ≥40 years identified during door-to-door surveys who signed a consent form were enrolled. Annual surveys were conducted to assess the number of participants who moved out of the village, as well as those who died, declined consent, and newly entered the study. Reasons for declining consent were tabulated. Abstracted data included age, sex, education, disability, time between enrollment and declining consent, and reasons for withdrawal. We also counted participants who, despite expressing their willingness to continue in the study, refused specific procedures. After five years of follow-up, 54 (6.3%) of 863 enrolled individuals declined consent. Increasing age and disability had no impact on declining consent. In contrast, refusal was higher among relatives or neighbors of a given participant declining consent. Most people who declined consent did so after one or two years of enrollment. Less than 20% of enrolled individuals refused certain procedures. “Fear of the needle” was the most frequent reason for refusing blood tests, and common reasons for declining complimentary exams were lack of interest and time constraints. Cohort retention in the Atahualpa Project is high. Main reasons for this adherence include adequate selection of the village, detailed planning of procedures, assurance of sponsorship, and field personnel who continuously engage with study participants. This trial is registered with NCT01627600.