High-Resolution Digital Phenotypes From Consumer Wearables and Their Applications in Machine Learning of Cardiometabolic Risk Markers: Cohort Study.

BACKGROUND: Consumer-grade wearable devices enable detailed recordings of heart rate and step counts in free-living conditions. Recent studies have shown that summary statistics from these wearable recordings have potential uses for longitudinal monitoring of health and disease states. However, the relationship between higher resolution physiological dynamics from wearables and known markers of health and disease remains largely uncharacterized. OBJECTIVE: We aimed to derive high-resolution digital phenotypes from observational wearable recordings and to examine their associations with modifiable and inherent markers of cardiometabolic disease risk. METHODS: We introduced a principled framework to extract interpretable high-resolution phenotypes from wearable data recorded in free-living conditions. The proposed framework standardizes the handling of data irregularities; encodes contextual information regarding the underlying physiological state at any given time; and generates a set of 66 minimally redundant features across active, sedentary, and sleep states. We applied our approach to a multimodal data set, from the SingHEART study (NCT02791152), which comprises heart rate and step count time series from wearables, clinical screening profiles, and whole genome sequences from 692 healthy volunteers. We used machine learning to model nonlinear relationships between the high-resolution phenotypes on the one hand and clinical or genomic risk markers for blood pressure, lipid, weight and sugar abnormalities on the other. For each risk type, we performed model comparisons based on Brier scores to assess the predictive value of high-resolution features over and beyond typical baselines. We also qualitatively characterized the wearable phenotypes for participants who had actualized clinical events. RESULTS: We found that the high-resolution features have higher predictive value than typical baselines for clinical markers of cardiometabolic disease risk: the best models based on high-resolution features had 17.9% and 7.36% improvement in Brier score over baselines based on age and gender and resting heart rate, respectively (P<.001 in each case). Furthermore, heart rate dynamics from different activity states contain distinct information (maximum absolute correlation coefficient of 0.15). Heart rate dynamics in sedentary states are most predictive of lipid abnormalities and obesity, whereas patterns in active states are most predictive of blood pressure abnormalities (P<.001). Moreover, in comparison with standard measures, higher resolution patterns in wearable heart rate recordings are better able to represent subtle physiological dynamics related to genomic risk for cardiometabolic disease (improvement of 11.9%-22.0% in Brier scores; P<.001). Finally, illustrative case studies reveal connections between these high-resolution phenotypes and actualized clinical events, even for borderline profiles lacking apparent cardiometabolic risk markers. CONCLUSIONS: High-resolution digital phenotypes recorded by consumer wearables in free-living states have the potential to enhance the prediction of cardiometabolic disease risk and could enable more proactive and personalized health management.

Beyond fitness tracking: The use of consumer-grade wearable data from normal volunteers in cardiovascular and lipidomics research.

The use of consumer-grade wearables for purposes beyond fitness tracking has not been comprehensively explored. We generated and analyzed multidimensional data from 233 normal volunteers, integrating wearable data, lifestyle questionnaires, cardiac imaging, sphingolipid profiling, and multiple clinical-grade cardiovascular and metabolic disease markers. We show that subjects can be stratified into distinct clusters based on daily activity patterns and that these clusters are marked by distinct demographic and behavioral patterns. While resting heart rates (RHRs) performed better than step counts in being associated with cardiovascular and metabolic disease markers, step counts identified relationships between physical activity and cardiac remodeling, suggesting that wearable data may play a role in reducing overdiagnosis of cardiac hypertrophy or dilatation in active individuals. Wearable-derived activity levels can be used to identify known and novel activity-modulated sphingolipids that are in turn associated with insulin sensitivity. Our findings demonstrate the potential for wearables in biomedical research and personalized health.

The application of exercise stress cardiovascular magnetic resonance in patients with suspected dilated cardiomyopathy.

OBJECTIVES: The imaging features of dilated cardiomyopathy (DCM) overlap with physiological exercise-induced cardiac remodeling in active and otherwise healthy individuals. Distinguishing the two conditions is challenging. This study examined the diagnostic and prognostic roles of exercise stress imaging in asymptomatic patients with suspected DCM. METHODS: Exercise stress cardiovascular magnetic resonance (CMR) was performed in 60 asymptomatic patients with suspected DCM (dilated left ventricle and/or impaired systolic function on CMR), who also underwent DNA sequencing for DCM-causing genetic variants. Confirmed DCM was defined as genotype- and phenotype-positive (G+P+). Another 100 healthy subjects were recruited to establish normal exercise capacities (peak exercise cardiac index; PeakCI). The primary outcome was a composite of all-cause mortality, cardiac decompensation and ventricular arrhythmic events. RESULTS: No patients with confirmed G+P+ DCM had PeakCI exceeding the 35th percentile specific for age and sex. Applying this threshold in G-P+ patients, those with PeakCI below 35th percentile had characteristics similar to confirmed DCM while patients with higher PeakCI were younger, more active and higher longitudinal strain. Adverse cardiovascular events occurred only in patients with low exercise capacity (P = 0.004). CONCLUSIONS: In individuals with suspected DCM, exercise stress CMR demonstrates diagnostic and prognostic potential in distinguishing between pathological DCM and physiological exercise-induced cardiac remodeling.

Harnessing technology and molecular analysis to understand the development of cardiovascular diseases in Asia: a prospective cohort study (SingHEART).

BACKGROUND: Cardiovascular disease (CVD) imposes much mortality and morbidity worldwide. The use of "deep learning", advancements in genomics, metabolomics, proteomics and devices like wearables have the potential to unearth new insights in the field of cardiology. Currently, in Asia, there are no studies that combine the use of conventional clinical information with these advanced technologies. We aim to harness these new technologies to understand the development of cardiovascular disease in Asia. METHODS: Singapore is a multi-ethnic country in Asia with well-represented diverse ethnicities including Chinese, Malays and Indians. The SingHEART study is the first technology driven multi-ethnic prospective population-based study of healthy Asians. Healthy male and female subjects aged 21-69 years old without any prior cardiovascular disease or diabetes mellitus will be recruited from the general population. All subjects are consented to undergo a detailed on-line questionnaire, basic blood investigations, resting and continuous electrocardiogram and blood pressure monitoring, activity and sleep tracking, calcium score, cardiac magnetic resonance imaging, whole genome sequencing and lipidomic analysis. Outcomes studied will include mortality and cause of mortality, myocardial infarction, stroke, malignancy, heart failure, and the development of co-morbidities. DISCUSSION: An initial target of 2500 patients has been set. From October 2015 to May 2017, an initial 683 subjects have been recruited and have completed the initial work-up the SingHEART project is the first contemporary population-based study in Asia that will include whole genome sequencing and deep phenotyping: including advanced imaging and wearable data, to better understand the development of cardiovascular disease across different ethnic groups in Asia.

Fractal analysis of left ventricular trabeculations is associated with impaired myocardial deformation in healthy Chinese.

BACKGROUND: Left ventricular (LV) non-compaction (LVNC) is defined by extreme LV trabeculation, but is measured variably. Here we examined the relationship between quantitative measurement in LV trabeculation and myocardial deformation in health and disease and determined the clinical utility of semi-automated assessment of LV trabeculations. METHODS: Cardiovascular magnetic resonance (CMR) was performed in 180 healthy Singaporean Chinese (age 20-69 years; males, n = 91), using balanced steady state free precession cine imaging at 3T. The degree of LV trabeculation was assessed by fractal dimension (FD) as a robust measure of trabeculation complexity using a semi-automated technique. FD measures were determined in healthy men and women to derive normal reference ranges. Myocardial deformation was evaluated using feature tracking. We tested the utility of this algorithm and the normal ranges in 10 individuals with confirmed LVNC (non-compacted/compacted; NC/C ratio > 2.3 and ≥1 risk factor for LVNC) and 13 individuals with suspected disease (NC/C ratio > 2.3). RESULTS: Fractal analysis is a reproducible means of assessing LV trabeculation extent (intra-class correlation coefficient: intra-observer, 0.924, 95% CI [0.761-0.973]; inter-observer, 0.925, 95% CI [0.821-0.970]). The overall extent of LV trabeculation (global FD: 1.205 ± 0.031) was independently associated with increased indexed LV end-diastolic volume and mass (sß = 0.35; p < 0.001 and sß = 0.13; p < 0.01, respectively) after adjusting for age, sex and body mass index. Increased LV trabeculation was independently associated with reduced global circumferential strain (sß = 0.17, p = 0.013) and global diastolic circumferential and radial strain rates (sß = 0.25, p < 0.001 and sß = -0.15, p = 0.049, respectively). Abnormally high FD was observed in all patients with a confirmed diagnosis of LVNC. Five out of 13 individuals with suspected LVNC had normal FD, despite NC/C > 2.3. CONCLUSION: This study defines the normal range of LV trabeculation in healthy Chinese that can be used to make or refute a diagnosis of LVNC using the fractal analysis tool, which we make freely available. We also show that increased myocardial trabeculation is associated with higher LV volumes, mass and reduced myocardial strain.

Assessing exercise cardiac reserve using real-time cardiovascular magnetic resonance.

BACKGROUND: Exercise cardiovascular magnetic resonance (ExCMR) has great potential for clinical use but its development has been limited by a lack of compatible equipment and robust real-time imaging techniques. We developed an exCMR protocol using an in-scanner cycle ergometer and assessed its performance in differentiating athletes from non-athletes. METHODS: Free-breathing real-time CMR (1.5T Aera, Siemens) was performed in 11 athletes (5 males; median age 29 [IQR: 28-39] years) and 16 age- and sex-matched healthy volunteers (7 males; median age 26 [interquartile range (IQR): 25-33] years). All participants underwent an in-scanner exercise protocol on a CMR compatible cycle ergometer (Lode BV, the Netherlands), with an initial workload of 25W followed by 25W-increment every minute. In 20 individuals, exercise capacity was also evaluated by cardiopulmonary exercise test (CPET). Scan-rescan reproducibility was assessed in 10 individuals, at least 7 days apart. RESULTS: The exCMR protocol demonstrated excellent scan-rescan (cardiac index (CI): 0.2 ± 0.5L/min/m2) and inter-observer (ventricular volumes: 1.2 ± 5.3mL) reproducibility. CI derived from exCMR and CPET had excellent correlation (r = 0.83, p < 0.001) and agreement (1.7 ± 1.8L/min/m2). Despite similar values at rest (P = 0.87), athletes had increased exercise CI compared to healthy individuals (at peak exercise: 12.2 [IQR: 10.2-13.5] L/min/m2 versus 8.9 [IQR: 7.5-10.1] L/min/m2, respectively; P < 0.001). Peak exercise CI, where image acquisition lasted 13-17 s, outperformed that at rest (c-statistics = 0.95 [95% confidence interval: 0.87-1.00] versus 0.48 [95% confidence interval: 0.23-0.72], respectively; P < 0.0001 for comparison) in differentiating athletes from healthy volunteers; and had similar performance as VO2max (c-statistics = 0.84 [95% confidence interval = 0.62-1.00]; P = 0.29 for comparison). CONCLUSIONS: We have developed a novel in-scanner exCMR protocol using real-time CMR that is highly reproducible. It may now be developed for clinical use for physiological studies of the heart and circulation.

Cardiovascular magnetic resonance reference ranges for the heart and aorta in Chinese at 3T.

BACKGROUND: Cardiovascular magnetic resonance (CMR) reference ranges have not been well established in Chinese. Here we determined normal cardiac and aortic reference ranges in healthy Singaporean Chinese and investigated how these data might affect clinical interpretation of CMR scans. METHODS: In 180 healthy Singaporean Chinese (20 to 69 years old; males, n = 91), comprehensive cardiac assessment was performed using the steady state free precision technique (3T Ingenia, Philips) and images were analysed by two independent observers (CMR42, Circle Cardiovascular Imaging). Measurements were internally validated using standardized approaches: left ventricular mass (LVM) was measured in diastole and systole (with and without papillary muscles) and stroke volumes were compared in both ventricles. All reference ranges were stratified by sex and age; and "indeterminate/borderline" regions were defined statistically at the limits of the normal reference ranges. Results were compared with clinical measurements reported in the same individuals. RESULTS: LVM was equivalent in both phases (mean difference 3.0 ± 2.5 g; P = 0.22) and stroke volumes were not significantly different in the left and right ventricles (P = 0.91). Compared to females, males had larger left and right ventricular volumes (P < 0.001 for all). Indexed LVM was significantly higher in males compared to females (50 ± 7 versus 38 ± 5 g/m2, respectively; P < 0.001). Overall, papillary muscles accounted for only ~2% of the total LVM. Indexed atrial sizes and aortic root dimensions were similar between males and females (P > 0.05 for all measures). In both sexes, age correlated negatively with left and right ventricular volumes; and positively with aortic sinus and sinotubular junction diameters (P < 0.0001 for all). There was excellent agreement in indexed stroke volumes in the left and right ventricles (0.1±5.7 mL/m2, 0.7±6.2 mL/m2, respectively), LVM (0.6±6.4 g/m2), atrial sizes and aortic root dimensions between values reported in clinical reports and our measured reference ranges. CONCLUSIONS: Comprehensive sex and age-corrected CMR reference ranges at 3T have been established in Singaporean Chinese. This is an important step for clinical practice and research studies of the heart and aorta in Asia.

Segregation of neuronal and vascular retinal damage in patients with hypertension and diabetes.

This study aimed to examine the impact of diabetes and hypertension on retinal nerve fiber layer (RNFL) thickness components. Optical coherence tomography (OCT) measurements do not consider blood vessel contribution, which this study addressed. We hypothesized that diabetes and/or hypertension would lead to thinner RNFL versus controls due to the vascular component. OCT angiography was used to measure the RNFL in 121 controls, 50 diabetes patients, 371 hypertension patients, and 177 diabetes patients with hypertension. A novel technique separated the RNFL thickness into original (vascular component) and corrected (no vascular component) measurements. Diabetes-only (98 ± 1.7 µm; p = 0.002) and diabetes with hypertension (99 ± 0.8 µm; p = 0.001) patients had thinner original RNFL versus controls (102 ± 0.8 µm). No difference was seen between hypertension-only patients (101 ± 0.5 µm; p = 0.083) and controls. After removing the blood vessel component, diabetes/hypertension groups had thinner corrected RNFL versus controls (p = 0.024). Discrepancies in diabetes/hypertension patients were due to thicker retinal blood vessels within the RNFL thickness (p = 0.002). Our findings suggest that diabetes and/or hypertension independently contribute to neurodegenerative thinning of the RNFL, even in the absence of retinopathy. The differentiation of neuronal and vascular components in RNFL thickness measurements provided by the novel technique highlights the importance of considering vascular changes in individuals with these conditions.

Endothelial function and arterial stiffness assessment as early surrogate markers of vascular risk in patients with systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) are at risk of premature atherosclerosis. Conventional prediction risk equations do not adequately predict the cardiovascular risk of these patients because of the complex interaction of traditional and SLE specific risk factors and treatment effects, as well as, the dynamic insult to the vasculature. Non-invasive vascular assessment is able to evaluate the vascular damage accumulated over time. The aim of this review is to examine the role of non-invasive assessment of endothelial function and arterial stiffness as surrogate markers for vascular risk in SLE patients.

The Singapore National Precision Medicine Strategy.

Precision medicine promises to transform healthcare for groups and individuals through early disease detection, refining diagnoses and tailoring treatments. Analysis of large-scale genomic-phenotypic databases is a critical enabler of precision medicine. Although Asia is home to 60% of the world's population, many Asian ancestries are under-represented in existing databases, leading to missed opportunities for new discoveries, particularly for diseases most relevant for these populations. The Singapore National Precision Medicine initiative is a whole-of-government 10-year initiative aiming to generate precision medicine data of up to one million individuals, integrating genomic, lifestyle, health, social and environmental data. Beyond technologies, routine adoption of precision medicine in clinical practice requires social, ethical, legal and regulatory barriers to be addressed. Identifying driver use cases in which precision medicine results in standardized changes to clinical workflows or improvements in population health, coupled with health economic analysis to demonstrate value-based healthcare, is a vital prerequisite for responsible health system adoption.

The ARIC predictive model reliably predicted risk of type II diabetes in Asian populations.

BACKGROUND: Identification of high-risk individuals is crucial for effective implementation of type 2 diabetes mellitus prevention programs. Several studies have shown that multivariable predictive functions perform as well as the 2-hour post-challenge glucose in identifying these high-risk individuals. The performance of these functions in Asian populations, where the rise in prevalence of type 2 diabetes mellitus is expected to be the greatest in the next several decades, is relatively unknown. METHODS: Using data from three Asian populations in Singapore, we compared the performance of three multivariate predictive models in terms of their discriminatory power and calibration quality: the San Antonio Health Study model, Atherosclerosis Risk in Communities model and the Framingham model. RESULTS: The San Antonio Health Study and Atherosclerosis Risk in Communities models had better discriminative powers than using only fasting plasma glucose or the 2-hour post-challenge glucose. However, the Framingham model did not perform significantly better than fasting glucose or the 2-hour post-challenge glucose. All published models suffered from poor calibration. After recalibration, the Atherosclerosis Risk in Communities model achieved good calibration, the San Antonio Health Study model showed a significant lack of fit in females and the Framingham model showed a significant lack of fit in both females and males. CONCLUSIONS: We conclude that adoption of the ARIC model for Asian populations is feasible and highly recommended when local prospective data is unavailable.

Relationship of Quantitative Retinal Capillary Network and Myocardial Remodeling in Systemic Hypertension.

Background This study examined the associations between quantitative optical coherence tomography angiography (OCTA) parameters and myocardial abnormalities as documented on cardiovascular magnetic resonance imaging in patients with systemic hypertension. Methods and Results We conducted a cross-sectional study of 118 adults with hypertension (197 eyes). Patients underwent cardiovascular magnetic resonance imaging and OCTA (PLEX Elite 9000, Carl Zeiss Meditec). Associations between OCTA parameters (superficial and deep retinal capillary density) and adverse cardiac remodeling (left ventricular mass, remodeling index, interstitial fibrosis, global longitudinal strain, and presence of left ventricular hypertrophy) were studied using multivariable linear regression analysis with generalized estimating equations. Of the 118 patients with hypertension enrolled (65% men; median [interquartile range] age, 59 [13] years), 29% had left ventricular hypertrophy. After adjusting for age, sex, systolic blood pressure, diabetes, and signal strength of OCTA scans, patients with lower superficial capillary density had significantly higher left ventricular mass (ß=-0.150; 95% CI, -0.290 to -0.010), higher interstitial volume (ß=-0.270; 95% CI, -0.535 to -0.0015), and worse global longitudinal strain (ß=-0.109; 95% CI, -0.187 to -0.032). Lower superficial capillary density was found in patients with hypertension with replacement fibrosis versus no replacement fibrosis (16.53±0.64 mm-1 versus 16.96±0.64 mm-1; P=0.003). Conclusions We showed significant correlations between retinal capillary density and adverse cardiac remodeling markers in patients with hypertension, supporting the notion that the OCTA could provide a non-invasive index of microcirculation alteration for vascular risk stratification in people with hypertension.

The Application of Optical Coherence Tomography Angiography in Systemic Hypertension: A Meta-Analysis.

Objective: Multiple studies have compared various optical coherence tomography angiography (OCTA) parameters in participants with systemic hypertension vs. controls and have presented discordant findings. We conducted a meta-analysis to pool together data from different studies to generate an overall effect size and find out whether OCTA parameter(s) significantly differed in participants with systemic hypertension as compared to controls. Methods: We conducted a literature search through a search of electronic databases to identify studies before 19 June 2021, which compared OCTA parameters in non-diabetic participants with systemic hypertension vs. controls. If the OCTA parameter had a minimum number of 3 studies that analyzed it, the mean difference between participants with systemic hypertension and controls were analyzed using a random-effects model. Results: We identified 11 eligible studies. At the macula, 9 studies analyzed vessel density at the superficial capillary plexus (SVD), 7 analyzed vessel density at the deep capillary plexus (DVD), and 6 analyzed the area of the superficial foveal avascular zone (FAZ). Participants with systemic hypertension had significantly lower SVD (standardized mean difference [SMD], -0.50 [-0.70, -0.30], P < 0.00001, I 2 = 63%), lower DVD (SMD, -0.38 [-0.64, -0.13], P = 0.004, I 2 = 67%) and larger superficial FAZ (SMD, 0.32 [0.04, 0.61], P = 0.020, I 2 = 77%). Conclusion: The eyes of people with systemic hypertension have robustly lower superficial and deep vascular densities at the macula when compared to control eyes. Our results suggest that OCTA can provide information about pre-clinical microvascular changes from systemic hypertension.

Choriocapillaris microvasculature dysfunction in systemic hypertension.

We examined the choriocapillaris microvasculature using a non-invasive swept-source optical coherence tomography angiography (SS-OCTA) in 41 healthy controls and 71 hypertensive patients and determined possible correlations with BP and renal parameters. BP levels, serum creatinine and urine microalbumin/creatinine ratio (MCR) specimens were collected. The estimated glomerular filtration rate (eGFR) was calculated based on CKD-EPI Creatinine Equation. The main outcome was choriocapillaris flow deficits (CFD) metrics (density, size and numbers). The CFD occupied a larger area and were fewer in number in the hypertensive patients with poor BP control (407 ± 10 µm2; 3260 ± 61) compared to the hypertensives with good BP control (369 ± 5 µm2; 3551 ± 41) and healthy controls (365 ± 11 µm2; 3581 ± 84). Higher systolic BP (ß = 9.90, 95% CI, 2.86-16.93), lower eGFR (ß = - 0.85; 95% CI, - 1.58 to - 0.13) and higher urine MCR (ß = 1.53, 95% CI, 0.32-2.78) were associated with larger areas of CFD. Similar significant associations with systolic BP, eGFR and urine MCR were found with number of CFD. These findings highlight the potential role of choriocapillaris imaging using SS-OCTA as an indicator of systemic microvascular abnormalities secondary to hypertensive disease.

A Systematic Quality Scoring Analysis to Assess Automated Cardiovascular Magnetic Resonance Segmentation Algorithms.

BACKGROUND: The quantitative measures used to assess the performance of automated methods often do not reflect the clinical acceptability of contouring. A quality-based assessment of automated cardiac magnetic resonance (CMR) segmentation more relevant to clinical practice is therefore needed. OBJECTIVE: We propose a new method for assessing the quality of machine learning (ML) outputs. We evaluate the clinical utility of the proposed method as it is employed to systematically analyse the quality of an automated contouring algorithm. METHODS: A dataset of short-axis (SAX) cine CMR images from a clinically heterogeneous population (n = 217) were manually contoured by a team of experienced investigators. On the same images we derived automated contours using a ML algorithm. A contour quality scoring application randomly presented manual and automated contours to four blinded clinicians, who were asked to assign a quality score from a predefined rubric. Firstly, we analyzed the distribution of quality scores between the two contouring methods across all clinicians. Secondly, we analyzed the interobserver reliability between the raters. Finally, we examined whether there was a variation in scores based on the type of contour, SAX slice level, and underlying disease. RESULTS: The overall distribution of scores between the two methods was significantly different, with automated contours scoring better than the manual (OR (95% CI) = 1.17 (1.07-1.28), p = 0.001; n = 9401). There was substantial scoring agreement between raters for each contouring method independently, albeit it was significantly better for automated segmentation (automated: AC2 = 0.940, 95% CI, 0.937-0.943 vs manual: AC2 = 0.934, 95% CI, 0.931-0.937; p = 0.006). Next, the analysis of quality scores based on different factors was performed. Our approach helped identify trends patterns of lower segmentation quality as observed for left ventricle epicardial and basal contours with both methods. Similarly, significant differences in quality between the two methods were also found in dilated cardiomyopathy and hypertension. CONCLUSIONS: Our results confirm the ability of our systematic scoring analysis to determine the clinical acceptability of automated contours. This approach focused on the contours' clinical utility could ultimately improve clinicians' confidence in artificial intelligence and its acceptability in the clinical workflow.

Inter-relationship between ageing, body mass index, diabetes, systemic blood pressure and intraocular pressure in Asians: 6-year longitudinal study.

BACKGROUND: To investigate the biological effect of ageing on intraocular pressure (IOP) and risk factors in a population-based cohort study of Malay and Indian adults. METHODS: Participants aged 40-80 years were recruited for baseline and 6-year follow-up visits between 2004-2009 and 2010-2015, respectively. Blood pressure (BP) was measured with an automatic BP monitor and IOP were obtained by Goldmann applanation tonometry. Main outcome was change in IOP, defined as the difference between the 6-year IOP and the baseline IOP. Linear regression models were used to investigate the association of changes in IOP with risk factors. RESULTS: Participants without a history of glaucoma or cataract surgery at baseline were included (n = 3188; mean age: 54±9 years) . Their average IOP was reduced (-0.5±3.1 mm Hg), except for those who developed hypertension at follow-up (0.0±3.1 mm Hg). After adjusting for covariates, changes in IOP were negatively associated with age (ß=-0.07, 95% CI -0.13 to -0.01) and positively associated with body mass index, diabetes, hypertension (normotensive as reference group; newly developed hypertensive (ß=0.67, 95% CI 0.39 to 0.95) and chronic hypertensive (ß=0.46, 95% CI 0.22 to 0.70)), baseline systolic BP (SBP) (ß=0.20, 95% CI 0.14 to 0.26) and diastolic BP (DBP) (ß=0.33, 95% CI 0.22 to 0.44), as well as with 6-year increases in SBP (ß=0.27, 95% CI 0.21 to 0.33) and DBP (ß=0.52, 95% CI 0.41 to 0.63). CONCLUSIONS: Normal ageing and reduced systemic BP are associated with reduced IOP in Malay and Indian adults. Given that high IOP is a risk factor for glaucoma, our finding highlights the importance of controlling hypertension in older adults, where hypertension and glaucoma incidences are on a rise.

Impact of hypertension on retinal capillary microvasculature using optical coherence tomographic angiography.

OBJECTIVE: Reduction in capillary density or rarefaction is a hallmark of essential hypertension. We measured the retinal capillary density using noninvasive optical coherence tomographic angiography (OCT-A) in adults with treated systemic hypertension and determined possible correlations with ambulatory blood pressure (BP) and renal parameters. METHODS: This observational cross-sectional study consisted of 153 normal eyes from 77 nondiabetic hypertensive adults [mean (SD) age, 58 (9) years; 49% women; 23% poorly controlled BP]. Data on 24-h ambulatory BP monitoring, serum creatinine, and urine microalbumin/creatinine ratio (MCR) were collected. Estimated glomerular filtration rate (eGFR) was calculated based on CKD-EPI Creatinine Equation. Retinal capillary density measured with the OCT-A (AngioVue) at superficial (SVP) and deep vascular plexuses (DVP). Linear regression was used to investigate the association of risk factors with capillary density. RESULTS: Retinal capillary density (percentage) at DVP was reduced in patients with poorly controlled BP (SBP = 148 ±â€Š8 mmHg; 27.2 ±â€Š13.0) compared with those with well controlled BP (SBP = 125 ±â€Š9 mmHg; 34.7 ±â€Š11.3). In the multivariable analysis, poorly controlled BP [ß = -6.49, 95% confidence interval (CI), -12.39 to -0.59], higher SBP (ß = -0.23, 95% CI -0.44 to -0.02) and lower eGFR (ß = 6.42, 95% CI 1.25-11.60) were associated with sparser retinal capillary density. Systemic factors were not associated with capillary density at SVP (all P > 0.05). CONCLUSION: In adults with treated systemic hypertension, retinal capillary density reduced with higher BP and poorer eGFR. These findings highlight the potential role of OCT-A to study early microvascular changes because of systemic hypertension.

Impact of systemic vascular risk factors on the choriocapillaris using optical coherence tomography angiography in patients with systemic hypertension.

We investigated the characteristics of the choriocapillaris flow voids using optical coherence tomography angiography (OCTA) in 85 patients (164 eyes) with hypertension (mean ± SD age, 56 ± 11 years; 45% women; 20% poorly controlled BP; 16% diabetes) who are without ocular diseases and determined possible correlations with systemic vascular risk factors. Data on 24-hour ambulatory blood pressure (BP), serum creatinine, and urine microalbumin/creatinine ratio (MCR) were collected. Estimated glomerular filtration rate (eGFR) was calculated based on CKD-EPI Creatinine Equation. OCTA imaging (6 × 6 mm scans; AngioVue) with quantitative microvascular analysis of the choriocapillaris was performed. Linear regression was used to investigate the association of systemic risk factors with area (percentage), size (pixels) and number of choriocapillaris flow voids. Diabetes (ß = 0.33; 95% CI, 0.02 to 0.63) and daytime systolic BP (ß = -0.13; 95% CI, -0.24 to -0.02) were associated with areas of flow voids. Age (ß = 0.21; 95% CI, 0.06 to 0.36) and daytime diastolic BP (ß = -0.18; 95% CI, -0.34 to -0.02) were associated with size of flow voids. Age (ß = -21.21; 95% CI, -31.79 to -10.63) and nighttime diastolic BP (ß = 13.89; 95% CI, 0.61 to 27.17) were associated with number of flow voids. Kidney parameters were not associated with any features of flow voids. In patients with hypertension, a higher BP appeared to increase blood flow in the choriocapillaris which needs to be considered when using the OCTA to study eye diseases in hypertensives.

Digital phenotyping by consumer wearables identifies sleep-associated markers of cardiovascular disease risk and biological aging.

Sleep is associated with various health outcomes. Despite their growing adoption, the potential for consumer wearables to contribute sleep metrics to sleep-related biomedical research remains largely uncharacterized. Here we analyzed sleep tracking data, along with questionnaire responses and multi-modal phenotypic data generated from 482 normal volunteers. First, we compared wearable-derived and self-reported sleep metrics, particularly total sleep time (TST) and sleep efficiency (SE). We then identified demographic, socioeconomic and lifestyle factors associated with wearable-derived TST; they included age, gender, occupation and alcohol consumption. Multi-modal phenotypic data analysis showed that wearable-derived TST and SE were associated with cardiovascular disease risk markers such as body mass index and waist circumference, whereas self-reported measures were not. Using wearable-derived TST, we showed that insufficient sleep was associated with premature telomere attrition. Our study highlights the potential for sleep metrics from consumer wearables to provide novel insights into data generated from population cohort studies.