Predictor Of Incident Cardiovascular Disease Research Articles

The added value of device measured physical activity to the prediction of incident cardiovascular disease.

Abstract Background Conventional risk prediction models for Major Adverse Cardio/Cerebrovascular Events (MACCE) primarily rely on non-modifiable factors such as age, sex, and physiological measurements, including LDL/HDL cholesterol and blood pressure readings, that are prone to variations across medical practices and are often unavailable in many parts of the world. In this study, we investigate the potential of inexpensive wearable measurements of physical activity to enhance MACCE prediction when physiological measurements are unavailable. Purpose To assess the added value of physical activity measurements, collected via wrist-worn accelerometers, to established cardiovascular risk prediction models. Additionally, we seek to investigate whether physical activity measurements can substitute for common physiological measurements in established cardiovascular risk models. Methods We obtained accelerometer-measured physical activity over 7 days between 2013 and 2015 from 69,898 UK Biobank (UKB) participants without a prior history of MACCE, defined as death or hospitalisation due to (1) myocardial infarction, (2) heart failure, or (3) Stroke/transient ischaemic attack. We assessed the added value of daily step counts, sleep duration, and a deep learning-derived activity health score (Fig 1), calculated from complete 7-day accelerometer recordings, to established clinical risk models (SCORE2, QRISK3 and AHA) before and after excluding measurements of cholesterol and systolic blood pressure (SBP). The primary outcome was the first recorded MACCE within 6 years. Risk scores were developed in men and women using Cox proportional hazards models. We assessed predictive performance using Harrel’s C-index, net reclassification index (NRI), and net benefit at the recommended treatment threshold for each model. Results Of the 69,898 UKB participants in the study, 3,386 (4.8%) experienced a MACCE over a 6-year follow-up period. In place of HDL ratio and SBP, the addition of deep-learned activity health scores modestly improved performance in the best clinical baseline, QRISK3 for Female participants ΔC-index women:0.003 (95% CI 0.002-0.004); Δnet benefit 0.02(0.01-0.03); NRI 0.04, (0.02-0.07), and outperformed manually extracted steps and sleep measurements. We report no significant improvements for men. We find a greater increase in model performance when both HDL ratio and SBP, plus activity health scores, are included in the model. ΔC-index women:0.008, (0.007-0.009); men: 0.003 (0.002-0.004) (Fig 2). Conclusion Our findings indicate that in the absence of cholesterol and systolic blood pressure, the addition of device-measured physical activity modestly improves the performance of clinical risk scores among individuals without prior cardiovascular disease (CVD). These findings could further refine intervention strategies for targeted prevention of CVD, particularly in settings where physiological measurements may be unavailable.

THE METABOLIC SCORE FOR INSULIN RESISTANCE (METS-IR) PREDICTS CARDIOVASCULAR DISEASE AND ITS SUBTYPES IN PATIENTS WITH HYPERTENSION AND OBSTRUCTVE SLEEP APNEA

Objective: We aimed to evaluate the METS-IR (metabolic score for insulin resistance) index for the prediction of incident cardiovascular disease (CVD) and its subtypes (coronary artery disease and stroke) in patients with hypertension and obstructive sleep apnea (OSA). Design and method: A retrospective cohort study was conducted with 2031 adults with hypertension and OSA, participants from the Urumqi Research on Sleep Apnea and Hypertension study (UROSAH). The hazard ratios and 95% CIs (credibility interval) for CVD and its subtypes were estimated using multivariate Cox proportional hazards regression models. Results: After a median follow-up of 6.80 years (interquartile range: 5.90–8.00 years), a total of 317 (15.61%) participants developed new-onset CVD, including 198 (9.75%) incident coronary heart disease (CHD) and 119 (5.86%) incident stroke. After adjusting for as many relevant confounding factors as possible, each SD increase in METS-IR was associated with a 30% increased risk of new onset overall CVD events, a 32% increased risk of new onset CHD, and a 27% increased risk of new onset stroke. When METS-IR was assessed as tertiles, after adjustment for fully confounding factors, the highest tertiles versus the lowest tertiles were associated with a greater hazard of CVD (HR 2.05; 95% CI 1.52,-2.77), CHD (HR 1.96; 95% CI 1.35–2.84), and stroke (HR 2.24; 95% CI 1.35–3.72). The results of various subgroups and sensitivity analyses were similar. When METS-IR was added, CVD predictions were reclassified and identified more accurately than baseline models for the C-index, continuous net reclassification improvement, and integrated discrimination index. CHD and stroke showed similar results. Conclusions: METS-IR is a powerful predictor of CVD and its subtypes in patients with hypertension and OSA, which can facilitate the identification of high-risk individuals and provide individualized CVD prevention.

Predicting incident cardiovascular disease among African-American adults: A deep learning approach to evaluate social determinants of health in the Jackson heart study.

The present study sought to leverage machine learning approaches to determine whether social determinants of health improve prediction of incident cardiovascular disease (CVD). Participants in the Jackson Heart study with no history of CVD at baseline were followed over a 10-year period to determine first CVD events (i.e., coronary heart disease, stroke, heart failure). Three modeling algorithms (i.e., Deep Neural Network, Random Survival Forest, Penalized Cox Proportional Hazards) were used to evaluate three feature sets (i.e., demographics and standard/biobehavioral CVD risk factors [FS1], FS1 combined with psychosocial and socioeconomic CVD risk factors [FS2], and FS2 combined with environmental features [FS3]) as predictors of 10-year CVD risk. Contrary to hypothesis, overall predictive accuracy did not improve when adding social determinants of health. However, social determinants of health comprised eight of the top 15 predictors of first CVD events. The social determinates of health indicators included four socioeconomic factors (insurance status and types), one psychosocial factor (discrimination burden), and three environmental factors (density of outdoor physical activity resources, including instructional and water activities; modified retail food environment index excluding alcohol; and favorable food stores). Findings suggest that whereas understanding biological determinants may identify who is currently at risk for developing CVD and in need of secondary prevention, understanding upstream social determinants of CVD risk could guide primary prevention efforts by identifying where and how policy and community-level interventions could be targeted to facilitate changes in individual health behaviors.

Can deep learning on retinal images augment known risk factors for cardiovascular disease prediction in diabetes? A prospective cohort study from the national screening programme in Scotland

AimsThis study’s objective was to evaluate whether deep learning (DL) on retinal photographs from a diabetic retinopathy screening programme improve prediction of incident cardiovascular disease (CVD). MethodsDL models were trained to jointly predict future CVD risk and CVD risk factors and used to output a DL score. Poisson regression models including clinical risk factors with and without a DL score were fitted to study cohorts with 2,072 and 38,730 incident CVD events in type 1 (T1DM) and type 2 diabetes (T2DM) respectively. ResultsDL scores were independently associated with incident CVD with adjusted standardised incidence rate ratios of 1.14 (P = 3 × 10−04 95 % CI (1.06, 1.23)) and 1.16 (P = 4 × 10−33 95 % CI (1.13, 1.18)) in T1DM and T2DM cohorts respectively. The differences in predictive performance between models with and without a DL score were statistically significant (differences in test log-likelihood 6.7 and 51.1 natural log units) but the increments in C-statistics from 0.820 to 0.822 and from 0.709 to 0.711 for T1DM and T2DM respectively, were small. ConclusionsThese results show that in people with diabetes, retinal photographs contain information on future CVD risk. However for this to contribute appreciably to clinical prediction of CVD further approaches, including exploitation of serial images, need to be evaluated.

The Metabolic Score for Insulin Resistance (METS-IR) Predicts Cardiovascular Disease and Its Subtypes in Patients with Hypertension and Obstructive Sleep Apnea.

We aimed to evaluate the METS-IR (metabolic score for insulin resistance) index for the prediction of incident cardiovascular disease (CVD) and its subtypes (coronary artery disease and stroke) in patients with hypertension and obstructive sleep apnea (OSA). A retrospective cohort study was conducted with 2031 adults with hypertension and OSA, participants from the Urumqi Research on Sleep Apnea and Hypertension study (UROSAH). The hazard ratios and 95% CIs (credibility interval) for CVD and its subtypes were estimated using multivariate Cox proportional hazards regression models. After a median follow-up of 6.80 years (interquartile range: 5.90-8.00 years), a total of 317 (15.61%) participants developed new-onset CVD, including 198 (9.75%) incident coronary heart disease (CHD) and 119 (5.86%) incident stroke. After adjusting for as many relevant confounding factors as possible, each SD increase in METS-IR was associated with a 30% increased risk of new onset overall CVD events, a 32% increased risk of new onset CHD, and a 27% increased risk of new onset stroke. When METS-IR was assessed as tertiles, after adjustment for fully confounding factors, the highest tertiles versus the lowest tertiles were associated with a greater hazard of CVD (HR 2.05; 95% CI 1.52,-2.77), CHD (HR 1.96; 95% CI 1.35-2.84), and stroke (HR 2.24; 95% CI 1.35-3.72). The results of various subgroups and sensitivity analyses were similar. When METS-IR was added, CVD predictions were reclassified and identified more accurately than baseline models for the C-index, continuous net reclassification improvement, and integrated discrimination index. CHD and stroke showed similar results. METS-IR is a powerful predictor of CVD and its subtypes in patients with hypertension and OSA, which can facilitate the identification of high-risk individuals and provide individualized CVD prevention.

Dilated hypertrophic phenotype of the carotid artery is associated with accelerated age-associated central arterial stiffening.

Hypertrophic carotid geometric phenotypes (h-CGP) are predictors of incident cardiovascular disease (CVD). While arterial aging is hypothesized as a contributor to this associated risk, the association of CGPs with chronological age is not clear. In this manuscript we examine whether hypertrophic CGPs represent accelerated biological, rather than chronological, aging by examining their association with carotid-femoral pulse wave velocity (PWV), the hallmark of arterial aging. We analyzed data from 5516 participants of the SardiNIA study with a wide range of age at baseline (20-101years), and a median follow-up time of 13years (mean 11.5years; maximum 17.9years). Baseline CGPs were defined based on the common carotid lumen diameter, wall thickness, and their ratio. Subject-specific rates of change of PWV, blood pressure parameters, body mass index, glucose, and lipids were estimated using linear mixed effects models. Compared to those with typical(t-) CGP, those with dilated hypertrophy (dh-) CGP had a greater longitudinal increase in PWV; this increase was significantly greater among older individuals and men. The greater PWV longitudinal increase in dh-CGP remained significant after adjusting for baseline values and rates of change of covariates. Dilated hypertrophic CGP is independently associated with accelerated increase in age-associated arterial stiffening over time, with a strong association in men than in women. Future studies are needed to examine if this association mediates the increased risk for CVD observed in individuals with hypertrophic cardiac remodelling and the role of retarding it to reduce this risk. HIGHLIGHTS: • Individuals with dilated hypertrophic geometric phenotypes of the common carotid artery (increased age- and sex-specific wall thickness and lumen diameter) have greater future central arterial stiffening, independently of other determinants of arterial stiffening. • The dilated hypertrophic phenotype group has a greater age-specific arterial dilation, wall thickening, and stiffness (the arterial aging triad). This suggests that this phenotype is a form of accelerated aging that might explain the worse clinic outcomes observed in this group. • Understanding the natural history of the carotid geometric phenotype across the lifespan and the determinants of the deleterious progression towards the dilated hypertrophic phenotype are needed to develop interventions that reduce the adverse clinical outcomes associated with it.

Association between remnant cholesterol and arterial stiffness in a Chinese community-based population: A cross-sectional study.

As a surrogate of arterial stiffness, the brachial-ankle pulse wave velocity (baPWV) is a good predictor of incident cardiovascular disease. Remnant cholesterol (RC) is a proven independent risk factor for cardiovascular disease. However, the relationship between RC and baPWV is unknown. The present study was performed to explore this relationship. Cross-sectional study. This study involved 8,028 participants of a community-based atherosclerosis cohort from China. Community residents aged ≥40 years were enrolled by responding to detailed research recruitment posters or by phone invitation. The participants comprised 2,938 (36.60%) men, and their mean age was 56.57 ± 9.04 years. The baPWV was measured with a standard protocol using the Omron Colin BP-203RPE III device (Omron Healthcare, Kyoto, Japan). RC was calculated as follows: RC = TC - LDL-C - HDL-C. The mean baPWV was 1,646.85 ± 374.11 cm/s. The median RC concentration was 0.56 (0.41-0.74) mmol/L. In the multivariate logistic regression analyses, the concentrations of RC, triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C) were all positively and independently associated with baPWV. The baPWV was higher in the fourth than first lipid profile quartile. The HDL-C concentration was inversely associated with baPWV. When RC was forced into the model with other lipid profile indices simultaneously, only the RC and TG concentrations remained significantly associated with baPWV. Lipids are independently associated with baPWV. The RC and TG concentrations have stronger associations with arterial stiffness than other lipid indices in the Chinese community-based population.

Timing and Predictors of Incident Cardiovascular Disease in Systemic Lupus Erythematosus: Risk Occurs Early and Highlights Racial Disparities.

Systemic lupus erythematosus (SLE) affects Black people 2 to 3 times more frequently than non-Black people and is associated with higher morbidity and mortality. In total, 4 studies with predominantly non-Black SLE cohorts highlighted that cardiovascular disease (CVD) is no longer primarily a late complication of SLE. This study assessed the timing and predictors of incident CVD in a predominantly Black population-based SLE cohort. Incident SLE cases from the population-based Georgia Lupus Registry were validated as having a CVD event through review of medical records and matching with the Georgia Hospital Discharge Database and the National Death Index. The surveillance period for an incident CVD event spanned a 15-year period, starting from 2 years prior to SLE diagnosis. Among 336 people with SLE, 253 (75%) were Black and 56 (17%) had an incident CVD event. The frequency of CVD events peaked in years 2 and 11 after SLE diagnosis. There was a 7-fold higher risk of incident CVD over the entire 15-year period; this risk was 19-fold higher in the first 12 years in Black people as compared to non-Black people with SLE. Black people with SLE (P < 0.001) and those with discoid rash (hazard ratio 3.2, 95% CI 1.4-7.1) had a higher risk of incident CVD events. The frequency of incident CVD events peaked in years 2 and 11 after SLE diagnosis. Being Black or having a discoid rash were strong predictors of an incident CVD event. Surveillance for CVD and preventive interventions, directed particularly toward Black people with recent SLE diagnoses, are needed to reduce racial disparities.

Circulating cardiac biomarkers improve risk stratification for incident cardiovascular disease in community dwelling populations.

SummaryBackgroundPlasma cardiac markers may assist in prediction of incident cardiovascular disease.MethodsThe incremental value of cardiac Troponins (T and I) and NT-proBNP added to risk factors in the PREDICT score for incident cardiovascular disease (CVD) in primary care, was assessed in 4102 asymptomatic participants in a randomised controlled trial of Vitamin D (ViDA). Findings were corroborated in 2528 participants in a separate community-based observational registry of CVD-free volunteers (HVOLS).FindingsHazard ratios for first cardiovascular events adjusted for PREDICT risk factors, comparing fifth to first quintiles of marker plasma concentrations, were 2.57 (95% CI 1.47-4.49); 3.01 (1.66-5.48) and 3.38 (2.04-5.60) for hs-cTnI, hs-cTnT and NT-proBNP respectively. The C statistic for discrimination of the primary endpoint increased from 0.755 to 0.771 (+0.016, p = 0.01). Cardiac marker data correctly reclassified risk upwards in 6.7% of patients and downwards in 3.3%. These findings were corroborated by results from HVOLS.InterpretationIncrements in plasma cardiac biomarkers robustly and reproducibly predicted increased hazard of incident CVD, independent of established risk factors, in two community-dwelling populations. Cardiac markers may augment risk assessment for onset of CVD in primary care.FundingViDA was funded by the Health Research Council of New Zealand (grant 10/400) and the Accident Compensation Corporation. HVOLS was funded by the Health Research Council of NZ Programme Grants (grants 02/152 and 08/070) and by grants from the Heart Foundation of NZ and the Christchurch Heart Institute Trust. Roche Diagnostics provided in-kind support for NT-proBNP and hs-cTnT assays and Abbott Laboratories for hs-cTnI assays.

Diet quality in an ethnically diverse population of older men in Australia.

To compare the Australian Dietary Guideline Index (DGI-2013) and the Pyramid-based Mediterranean Diet Score (pyrMDS) as measures of diet quality in an ethnically diverse group of older men. Seven hundred and ninety-four older men aged ≥75 participated in wave 3 (2012-2013) of the Concord Health and Ageing in Men Project. Dietary intake was assessed using a validated diet history questionnaire. Ethnicity was based on self-reported country of birth and categorised as Australian-born (418 men), Italian or Greek migrants (188), and other migrants (188). Incident cardiovascular outcomes until March 2018 were measured using the composite of major adverse cardiovascular events (MACE), which comprises all-cause mortality, acute myocardial infarction, congestive cardiac failure, coronary revascularisation and/or ischaemic stroke. Ability to predict incident cardiovascular outcomes and all-cause mortality were compared between standardised DGI-2013 pyrMDS scores by comparison of hazard ratios, discrimination (Harrell's C-statistic) and calibration (calibration plots). Italian and Greek migrant men had significantly lower DGI-2013 scores (91.7 vs. 93.9; p = 0.01) but significantly higher pyrMDS scores (8.8 vs. 8.2; p < 0.0001) than Australian-born men. In the whole sample (794 men), the pyrMDS was a better predictor of both MACE (age-adjusted HR = 0.84; 95% CI = 0.75-0.94 vs. HR = 0.92; 95% CI = 0.82-1.03 for DGI-2013) and all-cause mortality (age-adjusted HR = 0.69; 95% CI = 0.60-0.80 vs. HR = 0.86; 95% CI = 0.74-0.99). The pyrMDS also demonstrated superior discrimination for predicting all-cause mortality and superior calibration for MACE and all-cause mortality. The DGI-2013 appears to underestimate diet quality in older Italian and Greek migrant men. The pyrMDS appears superior to the DGI-2013 for prediction of incident cardiovascular disease and mortality regardless of ethnic background.

Clinical significance of nocturnal home blood pressure monitoring and nocturnal hypertension in Asia.

Nocturnal home blood pressure (BP) monitoring has been used in clinical practice for ~20 years. The authors recently showed that nocturnal systolic BP (SBP) measured by a home BP monitoring (HBPM) device in a Japanese general practice population was a significant predictor of incident cardiovascular disease (CVD) events, independent of office and morning home SBP levels, and that masked nocturnal hypertension obtained by HBPM (defined as nocturnal home BP ≥ 120/70 mmHg and average morning and evening BP < 135/85 mmHg) was associated with an increased risk of CVD events compared with controlled BP (nocturnal home BP < 120/70 mmHg and average morning and evening BP < 135/85 mmHg). This evidence revealed that (a) it is feasible to use a nocturnal HBPM device for monitoring nocturnal BP levels, and (b) such a device may offer an alternative to ambulatory BP monitoring, which has been the gold standard for the measurement of nocturnal BP. However, many unresolved clinical problems remain, such as the measurement schedule and conditions for the use of nocturnal HBPM. Further investigation of the measurement of nocturnal BP using an HBPM device and assessments of the prognostic value are thus warranted. Asians are at high risk of developing nocturnal hypertension due to high salt sensitivity and salt intake, and the precise management of their nocturnal BP levels is important. Information and communication technology‐based monitoring devices are expected to facilitate the management of nocturnal hypertension in Asian populations.

Skin autofluorescence predicts new cardiovascular disease and mortality in people with type 2 diabetes

BackgroundSkin autofluorescence (SAF) is a non-invasive marker of tissue accumulation of advanced glycation endproducts (AGE). Recently, we demonstrated in the general population that elevated SAF levels predict the development of type 2 diabetes (T2D), cardiovascular disease (CVD) and mortality. We evaluated whether elevated SAF may predict the development of CVD and mortality in individuals with T2D.MethodsWe included 2349 people with T2D, available baseline SAF measurements (measured with the AGE reader) and follow-up data from the Lifelines Cohort Study. Of them, 2071 had no clinical CVD at baseline. 60% were already diagnosed with diabetes (median duration 5, IQR 2–9 years), while 40% were detected during the baseline examination by elevated fasting blood glucose ≥7.0 mmol/l) and/or HbA1c ≥6.5% (48 mmol/mol).ResultsMean (±SD) age was 57 ± 12 yrs., BMI 30.2 ± 5.4 kg/m2. 11% of participants with known T2D were treated with diet, the others used oral glucose-lowering medication, with or without insulin; 6% was using insulin alone. Participants with known T2D had higher SAF than those with newly-detected T2D (SAF Z-score 0.56 ± 0.99 vs 0.34 ± 0.89 AU, p < 0.001), which reflects a longer duration of hyperglycaemia in the former group. Participants with existing CVD and T2D had the highest SAF Z-score: 0.78 ± 1.25 AU. During a median follow-up of 3.7 yrs., 195 (7.6%) developed an atherosclerotic CVD event, while 137 (5.4%) died. SAF was strongly associated with the combined outcome of a new CVD event or mortality (OR 2.59, 95% CI 2.10–3.20, p < 0.001), as well as incidence of CVD (OR 2.05, 95% CI 1.61–2.61, p < 0.001) and death (OR 2.98, 2.25–3.94, p < 0.001) as a single outcome. In multivariable analysis for the combined endpoint, SAF retained its significance when sex, systolic blood pressure, HbA1c, total cholesterol, eGFR, as well as antihypertensive and statin medication were included. In a similar multivariable model, SAF was independently associated with mortality as a single outcome, but not with incident CVD.ConclusionsMeasuring SAF can assist in prediction of incident cardiovascular disease and mortality in individuals with T2D. SAF showed a stronger association with future CVD events and mortality than cholesterol or blood pressure levels.

Pulse Pressure, Prognosis, and Influence of Sacubitril/Valsartan in Heart Failure With Preserved Ejection Fraction.

Arterial stiffness is increased with increasing age, and pulse pressure (PP), a marker of arterial stiffness, is a predictor of incident cardiovascular disease and mortality. However, the prognostic relevance of PP in heart failure (HF) with preserved ejection fraction has not been fully understood. We studied 4796 patients with HF with preserved ejection fraction from the PARAGON-HF trial. All patients underwent sequential run-in phases of valsartan and sacubitril/valsartan before randomization. We categorized patients by PP quartile and evaluated the influence of baseline PP on the PARAGON-HF primary end point (total HF hospitalizations and cardiovascular death). At screening, the median PP was 58 mm Hg (interquartile range, 50-69 mm Hg). There was a nonlinear, J-shaped association between PP and outcomes. Multivariable Cox proportional hazards models showed that patients in the highest PP quartile had a higher risk of the primary end point (adjusted hazard ratio, 1.39 [95% CI, 1.14-1.69]; P=0.001), total HF hospitalizations (adjusted hazard ratio, 1.43 [95% CI, 1.15-1.79]; P=0.001), and myocardial infarction (adjusted hazard ratio, 1.54 [95% CI, 1.06-2.23]; P=0.022) compared with those in the second (lowest risk) PP quartile. Reductions in PP during sacubitril/valsartan run-in were associated with a decreased risk of the primary end point and total HF hospitalizations. One year after randomization, PP was significantly lower in the sacubitril/valsartan group compared with the valsartan group (3.0 mm Hg decrease [95% CI, 2.4-3.5]; P<0.001). In conclusion, PP was an independent predictor of cardiovascular events in patients with HF with preserved ejection fraction enrolled in PARAGON-HF. Sacubitril/valsartan lowered PP compared with valsartan.

Concealed Coronary Atherosclerosis In Idiopathic Paroxysmal Atrial Fibrillation is Associated with Imminent Cardiovascular Diseases.

Previous research showed a significant difference in the presence of subclinical coronary artery disease (CAD) on cardiac CT angiography (CTA) between patients with idiopathic paroxysmal atrial fibrillation (iAF) versus a matched sinus rhythm population (iSR). Here we present 5-year follow-up data and the consequences of subclinical CAD on baseline CTA on the development of cardiovascular disease in iAF. In 99 iAF patients (who underwent CTA as part of work-up for pulmonary vein isolation) and 221 matched iSR controls (who underwent CTA for CAD assessment), the incidence of hypertension, diabetes and major cardiovascular events (MACCE) during follow-up was obtained. Multivariable Cox regression analysis was used to reveal predictors of incident cardiovascular disease in the iAF group. During a follow-up of 68±11 months, over one third of patients developed cardiovascular disease, with no difference between iAF and iSR (log-rank p=0.56), and comparable low rates of MACCE (4.0% vs 5.0%,p=0.71). Within the iAF group, age (HR1.12(1.03-1.20);p=0.006), left atrial diameter (HR1.16(1.03-1.31);p=0.01), Segment Involvement Score (total number of coronary segments with atherosclerotic plaque; HR1.43(1.09-1.89);p=0.01) and the number of calcified plaques on CTA (HR0.53(0.30-0.92);p=0.01) were independent predictors of incident cardiovascular disease. Subclinical coronary disease on CTA may be useful to identify the subset of patients with iAF that harbour concealed cardiovascular risk factors and need intensive clinical follow-up to ensure timely initiation of appropriate therapy once CV disease develops, including anticoagulation and vascular prophylactic therapy.

The association between indices of blood pressure waveforms (PTC1 and PTC2) and incident heart failure.

The radial artery pulse waveform is a continuous measure of pressure throughout the cardiac cycle, and thus can provide more information than just systolic and diastolic blood pressures. New indices based on a Windkessel model of the waveform, PTC1 and PTC2, are related to arterial compliance and add information for prediction of incident cardiovascular disease (coronary heart disease, stroke, myocardial infarction) but their association with heart failure is unknown. Among 6229 adults (mean age 62 years) from four race/ethnic groups who were initially free of clinical cardiovascular disease and heart failure in 2000-2002, we evaluated the associations of baseline PTC1 and PTC2 with incident heart failure. Mean ± standard deviation PTC1 and PTC2 were 394 ± 334 and 94 ± 46 ms, respectively. During a median of 15.7 years follow-up, there were 357 heart failure events (148 with reduced, 150 with preserved, and 59 with unknown ejection fraction). After adjustment for traditional risk factors, the hazard ratio for heart failure per 1 standard deviation higher PTC2 was 0.73 (95% confidence interval: 0.63--0.85). Higher PTC2 was also significantly associated with lower risk of heart failure with reduced ejection fraction (hazard ratio = 0.67; 95% confidence interval: 0.56--0.80). There was no evidence of a significant association between PTC2 and heart failure with preserved ejection fraction or between PTC1 and heart failure. The PTC2 measure of the radial artery pulse waveform may represent a novel phenotype related to heart failure, especially heart failure with reduced ejection fraction.

Incorporating kidney disease measures into cardiovascular risk prediction: Development and validation in 9 million adults from 72 datasets.

BackgroundChronic kidney disease (CKD) measures (estimated glomerular filtration rate [eGFR] and albuminuria) are frequently assessed in clinical practice and improve the prediction of incident cardiovascular disease (CVD), yet most major clinical guidelines do not have a standardized approach for incorporating these measures into CVD risk prediction. “CKD Patch” is a validated method to calibrate and improve the predicted risk from established equations according to CKD measures.MethodsUtilizing data from 4,143,535 adults from 35 datasets, we developed several “CKD Patches” incorporating eGFR and albuminuria, to enhance prediction of risk of atherosclerotic CVD (ASCVD) by the Pooled Cohort Equation (PCE) and CVD mortality by Systematic COronary Risk Evaluation (SCORE). The risk enhancement by CKD Patch was determined by the deviation between individual CKD measures and the values expected from their traditional CVD risk factors and the hazard ratios for eGFR and albuminuria. We then validated this approach among 4,932,824 adults from 37 independent datasets, comparing the original PCE and SCORE equations (recalibrated in each dataset) to those with addition of CKD Patch.FindingsWe confirmed the prediction improvement with the CKD Patch for CVD mortality beyond SCORE and ASCVD beyond PCE in validation datasets (Δc-statistic 0.027 [95% CI 0.018–0.036] and 0.010 [0.007–0.013] and categorical net reclassification improvement 0.080 [0.032–0.127] and 0.056 [0.044–0.067], respectively). The median (IQI) of the ratio of predicted risk for CVD mortality with CKD Patch vs. the original prediction with SCORE was 2.64 (1.89–3.40) in very high-risk CKD (e.g., eGFR 30–44 ml/min/1.73m2 with albuminuria ≥30 mg/g), 1.86 (1.48–2.44) in high-risk CKD (e.g., eGFR 45–59 ml/min/1.73m2 with albuminuria 30–299 mg/g), and 1.37 (1.14–1.69) in moderate risk CKD (e.g., eGFR 60–89 ml/min/1.73m2 with albuminuria 30–299 mg/g), indicating considerable risk underestimation in CKD with SCORE. The corresponding estimates for ASCVD with PCE were 1.55 (1.37–1.81), 1.24 (1.10–1.54), and 1.21 (0.98–1.46).InterpretationThe “CKD Patch” can be used to quantitatively enhance ASCVD and CVD mortality risk prediction equations recommended in major US and European guidelines according to CKD measures, when available.FundingUS National Kidney Foundation and the NIDDK.

Advanced fibrosis is associated with incident cardiovascular disease in patients with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular disease. It is not well understood, however, which individuals with NAFLD are at highest risk for cardiovascular disease. To determine the factors associated with incident cardiovascular events in a prospective cohort of individuals with biopsy-proven NAFLD without pre-existing cardiovascular disease. From 2011 to 2018, adults with biopsy-proven NAFLD without cardiovascular disease were enrolled in a tissue repository and were followed prospectively to the first recorded date of incident cardiovascular disease, death or the end of follow-up (11/1/2018). Competing risks analysis was performed to identify predictors of incident cardiovascular disease. After a median follow-up time of 5.2years, 26/285 (9.1%) individuals experienced an incident cardiovascular event. Advanced fibrosis (stage 3-4) on biopsy was a significant predictor of incident cardiovascular disease, and this persisted on multivariable analysis (SHR 2.86, 95% CI 1.36-6.04) after considering relevant covariates, including cardiovascular risk scores, which were not independent predictors. Of the non-invasive indicators of fibrosis, the NAFLD fibrosis score was the only independent predictor of cardiovascular disease. Other histologic features, including steatohepatitis, were not associated with incident cardiovascular disease. In adults with biopsy-proven NAFLD, advanced fibrosis on biopsy and higher NAFLD fibrosis score were significant and independent predictors of incident cardiovascular disease, even after considering traditional risk factors and cardiovascular risk scores. These findings should be considered when evaluating NAFLD patients for primary prevention of cardiovascular disease, and further evaluation into the link between advanced fibrosis and cardiovascular disease is needed.

Insomnia as an Independent Predictor of Incident Cardiovascular Disease in HIV: Data From the Veterans Aging Cohort Study.

Insomnia is associated with increased cardiovascular disease (CVD) risk in the general population and is highly prevalent in people with HIV. The CVD risk conferred by insomnia in the HIV population is unknown. Using the Veterans Aging Cohort Study Survey Cohort, insomnia symptoms were measured and dummy coded with the item, "Difficulty falling or staying asleep?" (5-point scale from no difficulty to bothers a lot). Incident CVD event ICD-9 codes (acute myocardial infarction, stroke, or coronary artery revascularization) were identified with the Department of Veterans Affairs (VA) and Medicare administrative data and VA fee-for-service data. Those with baseline CVD were excluded. HIV-infected (N = 3108) veterans had a median follow-up time of 10.8 years, during which 267 CVD events occurred. Compared to HIV-infected veterans with no difficulty falling or staying asleep, HIV-infected veterans bothered a lot by insomnia symptoms had an increased risk of incident CVD after adjusting for demographics [hazard ratio (HR) = 1.64, 95% confidence interval (CI): 1.16 to 2.31, P = 0.005], CVD risk factors (HR = 1.62, 95% CI: 1.14 to 2.30, P = 0.007), additional potential confounders (hepatitis C infection, renal disease, anemia, alcohol use, and cocaine use; HR = 1.70, 95% CI: 1.19 to 2.43, P = 0.003), and HIV-specific factors (HIV-1 RNA, CD4 T-cell count, and antiretroviral therapy; HR = 1.66, 95% CI: 1.16 to 2.37, P = 0.005). Additional adjustment for nonbenzodiazepine sleep medication (HR = 1.62, 95% CI: 1.13 to 2.32, P = 0.009) did not attenuate the association; however, it fell short of significance at P < 0.01 after adjustment for depressive symptoms (HR = 1.51, 95% CI: 0.98 to 2.32, P = 0.060) or antidepressant medication (HR = 1.51, 95% CI: 1.04 to 2.19, P = 0.031). Highly bothersome insomnia symptoms were significantly associated with incident CVD in HIV-infected veterans, suggesting that insomnia may be a novel, modifiable risk factor for CVD in HIV.

Obstructive Sleep Apnea With or Without Excessive Daytime Sleepiness: Clinical and Experimental Data-Driven Phenotyping.

Introduction: Obstructive sleep apnea (OSA) is a serious and prevalent medical condition with major consequences for health and safety. Excessive daytime sleepiness (EDS) is a common—but not universal—accompanying symptom. The purpose of this literature analysis is to understand whether the presence/absence of EDS is associated with different physiopathologic, prognostic, and therapeutic outcomes in OSA patients.Methods: Articles in English published in PubMed, Medline, and EMBASE between January 2000 and June 2017, focusing on no-EDS OSA patients, were critically reviewed.Results: A relevant percentage of OSA patients do not complain of EDS. EDS is a significant and independent predictor of incident cardiovascular disease (CVD) and is associated with all-cause mortality and an increased risk of metabolic syndrome and diabetes. Male gender, younger age, high body mass index, are predictors of EDS. The positive effects of nasal continuous positive airway pressure (CPAP) therapy on blood pressure, insulin resistance, fatal and non-fatal CVD, and endothelial dysfunction risk factors have been demonstrated in EDS-OSA patients, but results are inconsistent in no-EDS patients. The most sustainable cause of EDS is nocturnal hypoxemia and alterations of sleep architecture, including sleep fragmentation. These changes are less evident in no-EDS patients that seem less susceptible to the cortical effects of apneas.Conclusions: There is no consensus if we should consider OSA as a single disease with different phenotypes with or without EDS, or if there are different diseases with different genetic/epigenetic determinants, pathogenic mechanisms, prognosis, and treatment.The small number of studies focused on this issue indicates the need for further research in this area. Clinicians must carefully assess the presence or absence of EDS and decide accordingly the treatment. This approach could improve combination therapy targeted to a patient's specific pathology to enhance both efficacy and long-term adherence to OSA treatment and significantly reduce the social, economic, and health negative impact of OSA.

Endogenous testosterone does not improve prediction of incident cardiovascular disease in a community-based cohort of adult men: results from the Tehran Lipid and Glucose Study

Introduction: To explore the predictive value of testosterone added to the Framingham Risk Score (FRS) for cardiovascular disease (CVD).Methods: Among 816 men, 30–70 years/old, without prevalent CVD, from a community-based cohort (Tehran Lipid and Glucose Study), we assessed the predictive value of testosterone with incident CVD, using three multivariate Cox proportional-hazards models. Model I: FRS variables; model II: Model I plus total testosterone; model III: Model II plus Systolic blood pressure (SBP) * total testosterone (the best fit interaction-term between testosterone and FRS variables). Discriminations and goodness-of-fit were assessed by the C-statistic and the approach of Grønnesby, respectively. p Value <.05 was significant.Results: During 12 years of follow-up, 121 CVD events occurred. In all models, age, treated SBP, smoking, and diabetes were associated with increased CVD (p values <.05). Neither testosterone (models II and III), nor SBP * testosterone (model III) were associated with CVD (p values >.05). The C-statistics for models I, II, and III were 0.819, 0.820, and 0.821, respectively, indicating no significant improvement in the discrimination power. The models’ goodness-of-fit did not improve compared with the FRS.Conclusion: Testosterone could not add to the predictive value of FRS for CVD in men, either directly, or through interactions with FRS variables.