Integrating essence of "time" for blood pressure control in nephrology care.

Controlling blood pressure (BP) is essential in the management of patients with chronic kidney disease. Reflecting the intrinsic variability of BP, several parameters of BP over time have been shown to predict adverse outcomes. Systolic BP time in target range has been recently proposed as a new promising parameter. Park et al. confirmed its prognostic value in patients with chronic kidney disease. We review the potential clinical usefulness and challenges of this parameter in nephrology care.

Premorbid physical activity and prognosis after incident myocardial infarction: The atherosclerosis risk in communities study.

BACKGROUND: High to moderate levels of physical activity (PA) are associated with low risk of incident cardiovascular disease. However, it is unclear whether the benefits of PA in midlife extend to cardiovascular health following myocardial infarction (MI) in later life. METHODS: Among 1,111 Atherosclerosis Risk in Communities study participants with incident MI during Atherosclerosis Risk in Communities follow-up (mean age 73 [SD 9] years at MI, 54% men, 21% Black), PA on average 11.9 (SD 6.9) years prior to incident MI (premorbid PA) was evaluated as the average score of PA between visit 1 (1987-1989) and visit 3 (1993-1995) using a modified Baecke questionnaire. Total and domain-specific PA (sport, nonsport leisure, and work PA) was analyzed for associations with composite and individual outcomes of mortality, recurrent MI, and stroke after index MI using multivariable Cox models. RESULTS: During a median follow-up of 4.6 (IQI 1.0-10.5) years after incident MI, 823 participants (74%) developed a composite outcome. The 10-year cumulative incidence of the composite outcome was lower in the highest, as compared to the lowest tertile of premorbid total PA (56% vs. 70%, respectively). This association remained statistically significant even after adjusting for potential confounders (adjusted hazard ratio [aHR] 0.80 [0.67-0.96] for the highest vs. lowest tertile). For individual outcomes, high premorbid total PA was associated with a low risk of recurrent MI (corresponding aHR 0.64 [0.44, 0.93]). When domain-specific PA was analyzed, similar results were seen for sport and work PA. The association was strongest in the first year following MI (e.g., aHR of composite outcome 0.66 [95% CI 0.47, 0.91] for the highest vs. lowest tertile of total PA). CONCLUSIONS: Premorbid PA was associated positively with post-MI cardiovascular health. Our results demonstrate the additional prognostic advantages of PA beyond reducing the risk of incident MI.

Guidelines for clinical evaluation of chronic kidney disease in early stages : AMED research on regulatory science of pharmaceuticals and medical devices.

BACKGROUND: For the development of pharmaceutical products in kidney field, appropriate surrogate endpoints which can predict long-term prognosis are needed as an alternative to hard endpoints, such as end-stage kidney disease. Though international workshop has proposed estimated glomerular filtration rate (GFR) slope reduction of 0.5-1.0 mL/min/1.73 m /year and 30% decrease in albuminuria/proteinuria as surrogate endpoints in early and advanced chronic kidney disease (CKD), it was not clear whether these are applicable to Japanese patients. METHODS: We analyzed J-CKD-DB and CKD-JAC, Japanese databases/cohorts of CKD patients, and J-DREAMS, a Japanese database of patients with diabetes mellitus to investigate the applicability of eGFR slope and albuminuria/proteinuria to the Japanese population. Systematic review on those endpoints was also conducted including the results of clinical trials published after the above proposal. RESULTS: Our analysis showed an association between eGFR slope and the risk of end-stage kidney disease. A 30% decrease in albuminuria/proteinuria over 2 years corresponded to a 20% decrease in the risk of end-stage kidney disease patients with baseline UACR ≥ 30 mg/gCre or UPCR ≥ 0.15 g/gCre in the analysis of CKD-JAC, though this analysis was not performed on the other database/cohort. Those results suggested similar trends to those of the systematic review. CONCLUSION: The results suggested that eGFR slope and decreased albuminuria/proteinuria may be used as a surrogate endpoint in clinical trials for early CKD (including diabetic kidney disease) in Japanese population, though its validity and cutoff values must be carefully considered based on the latest evidence and other factors.

Association between Statin use and Incident Peripheral Artery Disease According to Race, Age, and Presence of Depression in the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Peripheral artery disease (PAD) is associated with high morbidity and mortality and has been commonly described as a coronary heart disease equivalent. Statin medications are recommended for primary prevention of atherosclerotic cardiovascular disease (CVD) among other indications. Therefore, understanding the longitudinal relationship of incident PAD is necessary to inform future research on how to prevent the disease. Depression complicates CVD patients' ability to properly adhere to their medications, yet the effect of depression on the relationship between statin use and incident PAD is understudied. People with PAD have a higher incidence of depressive symptoms than people without PAD. Black American and Hispanic populations are disproportionately affected by both PAD and depression yet research on the modifying effect of either race or depression on the relationship between statin use and onset of PAD is minimal. While statin utilization is highest for ages 75-84 years, there is minimal evidence of favorable risk-benefit balance. Consequently, in this project, we examined the relationship between statin use and incident PAD and whether this relationship is modified by race/ethnicity, depressive symptoms, or age. METHODS: We used data on participants from the Multi-Ethnic Study of Atherosclerosis from visit 1 (2000) through study visit 6 (2020) who had three separate measurements of the ankle-brachial index (ABI) taken at visit 1, visit 3, and visit 5. Incident PAD was defined as 1) incident lower extremity amputation or revascularization or 2) ABI less than 0.90 coupled with ABI decrease greater than 0.15 over the follow-up period. Statin use was noted on the study visit prior to incident PAD diagnosis while depressive symptoms were measured at exam 1, visit 3, and visit 5. Propensity score matching was implemented to create balance between the participants in the two treatment groups, that is, statin-treated and statin-untreated groups, to reduce the problem of confounding by indication. Propensity scores were calculated using multivariate logistic regression model to estimate the probability of receiving statin treatment. We used Cox proportional hazards regression to investigate the relationship between time-dependent statin use as well as other risk factors with incident PAD, overall and stratified by 1) race, 2) depression status, and 3) age. RESULTS: A total of 4,210 participants were included in the final matched analytic cohort. There were 810 incident cases (19.3%) of PAD that occurred over an average (mean) of 11.3 years (SD = 5.7) of follow-up time. In the statin-treated group, and with an average follow-up time of 12.5 years (SD = 5.6), there were 281 cases (13.4%) of incident PAD with the average follow-up time of 10.1 years (SD = 5.5), whereas in the statin-untreated group, there were 531 cases (25.2%) (P < 0.001). Results demonstrate a lower risk of PAD event in the statin-treated group compared to the untreated group (hazard ratio [HR] = 0.45, 95% confidence interval [CI]: 0.33-0.62) over the span of 18.5 years. The interactions between 1) depression and 2) race with statin use for incident PAD were not significant. However, other risk factors which were significant included Black American race that had approximately 30% lower hazard of PAD compared to non-Hispanic White (HR = 0.70, 95% CI: 0.58-0.84); age-stratified models were also fitted, and stain use was still a significant treatment factor for ages 45-54 (HR = 0.45, 95% CI: 0.33-0.63), 55-64 (HR = 0.61, 95% CI: 0.46-0.79), and 65-74 years (HR = 0.61, 95% CI: 0.48-0.78) but not for ages 75-84 years. CONCLUSIONS: Statin use was associated with a decreased risk of incident PAD for those under the age of 75 years. Neither race nor depression significantly modified the relationship between statin use and incident PAD; however, the risk of incident PAD was lower among Black Americans. These findings highlight that the benefit of statin may wane for those over the age of 75 years. Findings also suggest that statin use may not be compromised in those living with depression.

On-demand mobile hypertension training for primary health care workers in Nigeria: a pilot study.

BACKGROUND: Only one out of every ten Nigerian adults with hypertension has their blood pressure controlled. Health worker training is essential to improve hypertension diagnosis and treatment. In-person training has limitations that mobile, on-demand training might address. This pilot study evaluated a self-paced, case-based, mobile-optimized online training to diagnose and manage hypertension for Nigerian health workers. METHODS: Twelve hypertension training modules were developed, based on World Health Organization and Nigerian guidelines. After review by local academic and government partners, the course was piloted by Nigerian health workers at government-owned primary health centers. Primary care physician, nurse, and community health worker participants completed the course on their own smartphones. Before and after the course, hypertension knowledge was evaluated with multiple-choice questions. Learners provided feedback by responding to questions on a Likert scale. RESULTS: Out of 748 users who sampled the course, 574 enrolled, of whom 431 (75%) completed the course. The average pre-test score of completers was 65.4%, which increased to 78.2% on the post-test (P < 0.001, paired t-test). Health workers who were not part of existing hypertension control programs had lower pre-test scores and larger score gains. Most participants (96.1%) agreed that the training was applicable to their work, and nearly all (99.8%) agreed that they enjoyed the training. CONCLUSIONS: An on-demand mobile digital hypertension training increases knowledge of hypertension management among Nigerian health workers. If offered at scale, such courses can be a tool to build health workforce capacity through initial and refresher training on current clinical guidelines in hypertension and other chronic diseases in Nigeria as well as other countries.

Contralateral differences in ankle SBP and pulse wave velocity: associations with incident heart failure and mortality.

BACKGROUND: Contralateral differences in brachial SBP are indicative of underlaying cardiovascular issues. OBJECTIVES: To examine the association of contralateral differences in ankle SBP, brachial-ankle pulse wave velocity (baPWV), and heart-ankle pulse wave velocity (haPWV) with incident heart failure and all-cause and cardiovascular mortality. METHODS: Cox proportional-hazards models were used to calculate hazard ratios and 95% confidence intervals (95% CIs) in 5077 participants (75 ±â€Š5 years) of the Atherosclerosis Risk in Communities study. RESULTS: Over a mean follow-up of 7.5 ±â€Š2.2 years, there were 457 heart failure events, 1275 all-cause and 363 cardiovascular deaths. Interankle SBP difference of at least 10 mmHg [hazard ratio = 1.12; confidence interval (CI) 1.00-1.28], at least 15 mmHg (hazard ratio = 1.21; CI 1.03-1.43), contralateral difference in baPWV more than 240 cm/s (hazard ratio = 1.22; CI 1.02-1.46), and haPWV more than 80 cm/s (hazard ratio = 1.24; CI 1.04-1.48) were each independently associated with all-cause mortality after adjustment for confounders. Contralateral differences in ankle SBP of at least 15 mmHg (hazard ratio = 1.56; CI 1.17-2.09), and haPWV more than 80 cm/s (hazard ratio = 1.42; CI 1.03-1.96) were both independently associated with cardiovascular mortality. Unadjusted analysis revealed that those with contralateral differences in ankle SBP of at least 10 and at least 15 mmHg, baPWV more than 240, and haPWV more than 80 cm/s had higher risks of heart failure (all P < 0.05). CONCLUSION: These results underscore the significance of evaluating contralateral differences in ankle SBP and PWV as potential markers of increased mortality risk among older adults.

Ankle-Brachial Index and Risk of Sudden Cardiac Death in the Community: The ARIC Study.

BACKGROUND: Sudden cardiac death (SCD) is a significant global public health problem accounting for 15% to 20% of all deaths. A great majority of SCD is associated with coronary heart disease, which may first be detected at autopsy. The ankle-brachial index (ABI) is a simple, noninvasive measure of subclinical atherosclerosis. The purpose of this study was to examine the relationship between ABI and SCD in a middle-aged biracial general population. METHODS AND RESULTS: Participants of the ARIC (Atherosclerosis Risk in Communities) study with an ABI measurement between 1987 and 1989 were included. ABI was categorized as low (≤0.90), borderline (0.90-1.00), normal (1.00-1.40), and noncompressible (>1.40). SCD was defined as a sudden pulseless condition presumed to be caused by a ventricular tachyarrhythmia in a previously stable individual and was adjudicated by a committee of cardiac electrophysiologists, cardiologists, and internists. Cox proportional hazards models were used to evaluate the associations between baseline ABI and incident SCD. Of the 15 081 participants followed for a median of 23.5 years, 556 (3.7%) developed SCD (1.96 cases per 1000 person-years). Low and borderline ABIs were associated with an increased risk of SCD (demographically adjusted hazard ratios [HRs], 2.27 [95% CI, 1.64-3.14] and 1.52 [95% CI, 1.17-1.96], respectively) compared with normal ABI. The association between low ABI and SCD remained significant after adjustment for traditional cardiovascular risk factors (HR, 1.63 [95% CI, 1.15-2.32]). CONCLUSIONS: Low ABI is independently associated with an increased risk of SCD in a middle-aged biracial general population. ABI could be incorporated into future SCD risk prediction models.

Peripheral artery disease, chronic kidney disease, and recurrent admissions for acute decompensated heart failure: The ARIC study.

BACKGROUND AND AIMS: Peripheral artery disease (PAD) has not only been associated with recurrent hospitalization for acute decompensated heart failure (ADHF) but is also associated with chronic kidney disease (CKD), a known risk factor for worse heart failure outcomes. The interaction of CKD with PAD in post-discharge ADHF outcomes is not well known. METHODS: Since 2005, hospitalizations for ADHF were sampled from 4 US regions by the Atherosclerosis Risk in Communities (ARIC) study and classified by physician review. We examined the adjusted association of PAD with 1-year ADHF readmissions, in patients with and without CKD (defined by glomerular filtration rate [GFR] ≤60 mL/min/1.73 m2 [stage 3a or worse]). RESULTS: From 2005 to 2018, there were 1049 index hospitalizations for patients with ADHF (mean age 77 years, 66 % white) with creatinine data, who were discharged alive. Of these, 155 (15 %) had PAD and 66 % had CKD. In comparison to those without PAD, patients with PAD had more comorbid conditions and higher 1-year ADHF readmission rates, irrespective of CKD status. After adjustment, PAD was associated with a greater risk of 1-year ADHF readmissions, both for patients with concomitant CKD (HR, 1.70; 95 % CI: 1.29-2.24) and those without CKD (HR, 1.97; 95 % CI: 1.14-3.40); p-interaction = 0.8. CONCLUSION: Among patients hospitalized with ADHF, those with concurrent PAD have more prevalent cardiovascular comorbidities and higher likelihood of 1-year ADHF readmission, irrespective of CKD status. Integrating a more holistic approach in management of patients with concomitant heart failure, PAD and CKD may be an important strategy to improve the prognosis in this vulnerable population.

Risk of recurrent stroke and dementia following acute stroke by changes in kidney function: results from the Perindopril Protection Against Recurrent Stroke Study.

BACKGROUND: Limited data exist on the relationship between declining kidney function and cardiovascular events, dementia, and mortality in patients with a history of stroke.Thus the aims of the study were to investigate functional relationships between dynamic kidney function change and cardiovascular outcomes, and clarify whether adding kidney parameters to conventional cardiovascular risk factors improves model discrimination. METHODS: Post hoc analysis of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) clinical trial of blood pressure lowering for the secondary prevention of stroke. We examined the association between dynamic kidney function defined as percentage change (declines of >30%, and >0 to ≤30%, and increases of ≥0 to <30%, and ≥30%) in estimated glomerular filtration rate (eGFR) over 2 years and recurrent stroke, major cardiovascular events, dementia and all-cause death over the next 2 years using Cox proportional hazard models controlling for eGFR at registration and potential confounders. Restricted cubic splines were used to assess the functional relationships. C-statistics and Net Reclassification Improvement (NRI) at 2 years were used to assess model discrimination. RESULTS: In 4591 patients followed for a mean of approximately 2 years, 254 (5.5%) developed recurrent stroke, 391 (8.5%) had a major cardiovascular event, 221 (4.8%) developed dementia, and 271 (5.9%) died. Reverse J-like or U-like relationships were observed for percent declines in eGFR and outcomes. Using declines in eGFR of >0 to ≤30% as a reference, increased risks were evident for a greater decline (>30%) in relation to recurrent stroke [adjusted hazard ratio 1.85, 95% confidence interval (CI) 1.20-2.85], major cardiovascular event (2.24, 1.62-3.10) and all-cause death (2.09, 1.39-3.15). A larger increase (≥30%) in eGFR was also associated with a greater risk of all-cause death (1.96, 1.14-3.37). Improvements in the C-statistic were found by adding baseline eGFR and percent change compared with a model with conventional cardiovascular risk factors alone, for major cardiovascular events, dementia, and all-cause mortality. CONCLUSION: Declining kidney function following an incident cerebrovascular event is associated with additional risk of a major cardiovascular events, dementia, and 2-year mortality. However, a large increase in kidney function was also found to be associated with a higher risk of mortality.

Disruption of diabetes and hypertension care during the COVID-19 pandemic and recovery approaches in the Latin America and Caribbean region: a scoping review protocol.

INTRODUCTION: The COVID-19 pandemic significantly disrupted primary healthcare globally, with particular impacts on diabetes and hypertension care. This review will examine the impact of pandemic disruptions of diabetes and hypertension care services and the evidence for interventions to mitigate or reverse pandemic disruptions in the Latin America and Caribbean (LAC) region. METHODS AND ANALYSES: This scoping review will examine care delivery disruption and approaches for recovery of primary healthcare in the LAC region during the COVID-19 pandemic, focusing on diabetes and hypertension awareness, detection, treatment and control. Guided by Arksey and O'Malley's scoping review methodology framework, this protocol adheres to the Joanna Briggs Institute guidelines for scoping review protocols and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance for protocol development and scoping reviews. We searched MEDLINE, CINAHL, Global Health, Embase, Cochrane, Scopus, Web of Science and LILACS for peer-reviewed literature published from 2020 to 12 December 2022 in English, Spanish or Portuguese. Studies will be considered eligible if reporting data on pandemic disruptions to primary care services within LAC, or interventions implemented to mitigate or reverse pandemic disruptions globally. Studies on COVID-19 or acute care will be excluded. Two reviewers will independently screen each title/abstract for eligibility, screen full texts of titles/abstracts deemed relevant and extract data from eligible full-text publications. Conflicts will be resolved through discussion and with the help of a third reviewer. Appropriate analytical techniques will be employed to synthesise the data, for example, frequency counts and descriptive statistics. Quality will be assessed using the Newcastle Ottawa Quality Assessment Scale. ETHICS AND DISSEMINATION: No ethics approval was needed as this is a scoping review of published literature. Results will be disseminated in a report to the World Bank and the Pan American Health Organization, in peer-reviewed scientific journals, and at national and international conferences.

Associations of Dietary Calcium and Phosphorus With Vascular and Valvular Calcification: The ARIC Study.

Background: High dietary calcium and phosphorus may accelerate vascular calcification, but epidemiological data are inconsistent. Most of those studies assessed diet at one point and have not been systematically evaluated. Objectives: The purpose of this study was to assess the associations of dietary calcium and phosphorus intakes in middle age with coronary artery and extra-coronary calcification at older age. Methods: We studied 1,914 participants from the ARIC (Atherosclerosis Risk In Communities) study (mean age 80.5 years) without coronary heart disease who underwent chest computed tomography scans at visit 7 (2018-2019) and completed a 66-item food frequency questionnaire at 2 earlier visits (visit 1 [1987-1989] and visit 3 [1993-1995]). Dietary calcium and phosphorus intakes were averaged between these 2 visits. Calcification was quantified by the Agatston score in coronary artery, ascending aorta, descending aorta, aortic valve ring, aortic valve, and mitral valve. Results: Dietary calcium intake was inversely associated with coronary artery and ascending aorta calcification, whereas the association was not significant for other measures of extra-coronary calcification. For example, the highest vs lowest quartile of calcium intake showed an adjusted OR of 0.66 (95% CI: 0.45-0.98) for coronary artery calcification (Agatston score ≥75th percentile). Dietary phosphorus intake demonstrated similar results, but the magnitude of the association was weaker than dietary calcium intake. Conclusions: Dietary calcium and phosphorus intakes at middle age were not positively associated with vascular and valvular calcification at over 75 years old. Our findings did not support the link between a calcium or phosphorus-rich diet and vascular and valvular calcification.

Identification of Fatigue Subtypes and Their Correlates in Prevalent Heart Failure: A Secondary Analysis of the Atherosclerosis Risk in Communities Study.

BACKGROUND: Among patients with heart failure (HF), fatigue is common and linked to quality of life and functional status. Fatigue is hypothesized to manifest as multiple types, with general and exertional components. Unique subtypes of fatigue in HF may require differential assessment and treatment to improve outcomes. We conducted this study to identify fatigue subtypes in persons with prevalent HF in the ARIC study (Atherosclerosis Risk in Communities) and describe the distribution of characteristics across subtypes. METHODS: We performed a cross-sectional analysis of 1065 participants with prevalent HF at ARIC visit 5 (2011-2013). We measured exertional fatigue using the Modified Medical Research Council Breathlessness scale and general fatigue using the Patient Reported Outcomes Measurement Information System fatigue scale. We used latent class analysis to identify subtypes of fatigue. Number of classes was determined using model fit statistics, and classes were interpreted and assigned fatigue severity rating based on the conditional probability of endorsing survey items given class. We compared characteristics across classes using multinomial regression. RESULTS: Overall, participants were 54% female and 38% Black with a mean age of 77. We identified 4 latent classes (fatigue subtypes): (1) high general/high exertional fatigue (18%), (2) high general/low exertional fatigue (27%), (3) moderate general/moderate exertional fatigue (20%), and (4) low/no general and exertional fatigue (35%). Female sex, Black race, lower education level, higher body mass index, increased depressive symptoms, and higher prevalence of diabetes were associated with higher levels of general and exertional fatigue. CONCLUSIONS: We identified unique subtypes of fatigue in patients with HF who have not been previously described. Within subtype, general and exertional fatigue were mostly concordant in severity, and exertional fatigue only occurred in conjunction with general fatigue, not alone. Further understanding these fatigue types and their relationships to outcomes may enhance our understanding of the symptom experience and inform prognostication and secondary prevention efforts for persons with HF.

Association of Segment-Specific Pulse Wave Velocity With Vascular Calcification: The ARIC (Atherosclerosis Risk in Communities) Study.

BACKGROUND: Pulse wave velocity (PWV) is a noninvasive measure of arterial stiffness and predictor of cardiovascular disease. However, the association between PWV and vascular calcification across different vascular beds has not been fully investigated. This study aimed to quantify the association between PWV and multiterritory calcification and to explore whether PWV can identify individuals with vascular calcification beyond traditional risk factors. METHODS AND RESULTS: Among 1351 older adults (mean age, 79.2 years [SD, 4.1]) from the ARIC (Atherosclerosis Risk in Communities) study, we measured segment-specific PWVs: heart-carotid, heart-femoral, carotid-femoral, heart-ankle, brachial-ankle, and femoral-ankle. Dependent variables were high calcium score (≥75th percentile of Agatston score) across different vascular beds: coronary arteries, aortic valve ring, aortic valve, mitral valve, ascending aorta, and descending aorta. Quartiles of carotid-femoral, heart-femoral, heart-ankle, and brachial-ankle PWV were significantly associated with coronary artery calcium (eg, adjusted odds ratio [OR] for the highest versus lowest quartile of carotid-femoral PWV, 1.84 [95% CI, 1.24-2.74]). Overall, PWVs were most strongly associated with descending aorta calcification, with significant results for carotid-femoral, heart-femoral, heart-ankle, and brachial-ankle PWV (eg, adjusted OR for the highest versus lowest quartile of carotid-femoral PWV, 3.99 [95% CI, 2.61-6.17]). In contrast, femoral-ankle PWV was inversely associated with descending aorta calcification. Some PWVs improved the discrimination of coronary artery calcium and descending aorta calcification beyond traditional risk factors. CONCLUSIONS: The associations of PWV with vascular calcification varied substantially across segments, with descending aorta calcification most closely linked to PWVs. Our study suggests that some PWVs, especially carotid-femoral PWV, are helpful to identify individuals with coronary artery calcium and descending aorta calcification.

Universal Risk Prediction for Individuals With and Without Atherosclerotic Cardiovascular Disease.

BACKGROUND: American College of Cardiology/American Heart Association guidelines recommend distinct risk classification systems for primary and secondary cardiovascular disease prevention. However, both systems rely on similar predictors (eg, age and diabetes), indicating the possibility of a universal risk prediction approach for major adverse cardiovascular events (MACEs). OBJECTIVES: The authors examined the performance of predictors in persons with and without atherosclerotic cardiovascular disease (ASCVD) and developed and validated a universal risk prediction model. METHODS: Among 9,138 ARIC (Atherosclerosis Risk In Communities) participants with (n = 609) and without (n = 8,529) ASCVD at baseline (1996-1998), we examined established predictors in the risk classification systems and other predictors, such as body mass index and cardiac biomarkers (troponin and natriuretic peptide), using Cox models with MACEs (myocardial infarction, stroke, and heart failure). We also evaluated model performance. RESULTS: Over a follow-up of approximately 20 years, there were 3,209 MACEs (2,797 for no prior ASCVD). Most predictors showed similar associations with MACE regardless of baseline ASCVD status. A universal risk prediction model with the predictors (eg, established predictors, cardiac biomarkers) identified by least absolute shrinkage and selection operator regression and bootstrapping showed good discrimination for both groups (c-statistics of 0.747 and 0.691, respectively), and risk classification and showed excellent calibration, irrespective of ASCVD status. This universal prediction approach identified individuals without ASCVD who had a higher risk than some individuals with ASCVD and was validated externally in 5,322 participants in the MESA (Multi-Ethnic Study of Atherosclerosis). CONCLUSIONS: A universal risk prediction approach performed well in persons with and without ASCVD. This approach could facilitate the transition from primary to secondary prevention by streamlining risk classification and discussion between clinicians and patients.

Carotid Ultrasound-Based Plaque Score for the Allocation of Aspirin for the Primary Prevention of Cardiovascular Disease Events: The Multi-Ethnic Study of Atherosclerosis and the Atherosclerosis Risk in Communities Study.

BACKGROUND: Coronary artery calcium testing using noncontrast cardiac computed tomography is a guideline-indicated test to help refine eligibility for aspirin in primary prevention. However, access to cardiac computed tomography remains limited, with carotid ultrasound used much more often internationally. We sought to update the role of aspirin allocation in primary prevention as a function of subclinical carotid atherosclerosis. METHODS AND RESULTS: The study included 11 379 participants from the MESA (Multi-Ethnic Study of Atherosclerosis) and ARIC (Atherosclerosis Risk in Communities) studies. A harmonized carotid plaque score (range, 0-6) was derived using the number of anatomic sites with plaque from the left and right common, bifurcation, and internal carotid artery on ultrasound. The 5-year number needed to treat and number needed to harm as a function of the carotid plaque score were calculated by applying a 12% relative risk reduction in atherosclerotic cardiovascular disease (ASCVD) events and 42% relative increase in major bleeding events related to aspirin use, respectively. The mean age was 57 years, 57% were women, 23% were Black, and the median 10-year ASCVD risk was 12.8%. The 5-year incidence rates (per 1000 person-years) were 5.5 (4.9-6.2) for ASCVD and 1.8 (1.5-2.2) for major bleeding events. The overall 5-year number needed to treat with aspirin was 306 but was 2-fold lower for individuals with carotid plaque versus those without carotid plaque (212 versus 448). The 5-year number needed to treat was less than the 5-year number needed to harm when the carotid plaque score was ≥2 for individuals with ASCVD risk 5% to 20%, whereas the presence of any carotid plaque demarcated a favorable risk-benefit for individuals with ASCVD risk >20%. CONCLUSIONS: Quantification of subclinical carotid atherosclerosis can help improve the allocation of aspirin therapy.

Maintenance of Normal Blood Pressure From Middle to Older Age: Results From the Atherosclerosis Risk in Communities Study.

BACKGROUND: It is unknown whether maintaining normal blood pressure (BP) from middle to older age is associated with improved health outcomes. METHODS: We estimated the proportion of Atherosclerosis Risk in Communities study participants who maintained normal BP from 1987 to 1989 (visit 1) through 1996 to 1998 and 2011 to 2013 (over 4 and 5 visits, respectively). Normal BP was defined as systolic BP <120 mm Hg and diastolic BP <80 mm Hg, without antihypertensive medication. We estimated the risk of cardiovascular disease, dementia, and poor physical functioning after visit 5. In exploratory analyses, we examined participant characteristics associated with maintaining normal BP. RESULTS: Among 2699 participants with normal BP at baseline (mean age 51.3 years), 47.1% and 15.0% maintained normal BP through visits 4 and 5, respectively. The hazard ratios comparing participants who maintained normal BP through visit 4 but not visit 5 and through visit 5 versus those who did not maintain normal BP through visit 4 were 0.80 (95% CI, 0.63-1.03) and 0.60 (95% CI, 0.42-0.86), respectively, for cardiovascular disease, and 0.85 (95% CI, 0.71-1.01) and 0.69 (95% CI, 0.54-0.90), respectively, for poor physical functioning. Maintaining normal BP through visit 5 was more common among participants with normal body mass index versus obesity at visit 1, those with normal body mass index at visits 1 and 5, and those with overweight at visit 1 and overweight or normal body mass index at visit 5, compared with those with obesity at visits 1 and 5. CONCLUSIONS: Maintaining normal BP was associated with a lower risk of cardiovascular disease and poor physical functioning.

Association of Cumulative Systolic Blood Pressure With Left Atrial Function in the Setting of Normal Left Atrial Size: The Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Lower left atrial (LA) function is associated with increased risk for cardiovascular disease events; data on risk factors for impaired LA function are limited. We evaluated the effect of cumulative systolic blood pressure (cSBP) from midlife to older age on LA strain in adults with normal LA size. METHODS: We included participants in the Atherosclerosis Risk in Communities study with LA strain measured on the visit 5 echocardiogram (2011-13), excluding those with atrial fibrillation and LA volume index >34 mL/m2. The cSBP was calculated from visit 1 (1987-89) through visit 5. Linear regression models were used to evaluate associations between cSBP and LA strain measures. RESULTS: A total of 3,859 participants with a mean (SD) age of 75.2 (5.0) years were included in the analysis; 725 (18.8%) were Black and 2,342 (60.7%) were women. After adjusting for demographics, cardiovascular disease risk factors, heart failure, and coronary heart disease, each 10 mm Hg increase in cSBP was associated with 0.32% (95% CI, -0.52%, -0.13%) and 0.37% (95% CI, -0.51%, -0.22%) absolute reduction in LA reservoir and conduit strain, respectively. Associations were attenuated after adjustment for left ventricular (LV) systolic and diastolic function and mass (-0.12%: 95% CI, -0.31, 0.06 for reservoir strain; and -0.24%: 95% CI -0.38%, -0.10% for conduit strain). In subgroup analyses, the association of cSBP with conduit strain was statistically significant among those with normal LV systolic and diastolic function. CONCLUSIONS: Cumulative exposure to elevated blood pressure from midlife to late life was modestly associated with lower LA reservoir and conduit strain in older adults with normal LA size, mostly related to the effect of blood pressure on LV function and mass. However, the association of cSBP and LA conduit strain in subgroups with normal LV function suggests that LA remodeling in response to hypertension occurs before LV dysfunction is detected on echocardiography.

Association of central arterial stiffness with atrial myopathy: the Atherosclerosis Risk in Communities (ARIC) study.

Atrial myopathy-defined as abnormal left atrial (LA) size and function-is associated with an increased risk of atrial fibrillation, heart failure, and dementia. Central arterial stiffness is associated with increased atrial afterload and fibrosis and may be a risk factor for atrial myopathy. We examined the association of carotid-femoral pulse wave velocity (cfPWV) with LA function and assessed potential causal relationships. We included 2825 Atherosclerosis Risk in Communities (ARIC) study participants from Visit 5 (2011-2013). cfPWV was related to echocardiographic LA function continuously per 1-SD and categorically in quartiles. Mendelian randomization (MR) analysis was performed using U.K. Biobank-derived genetic variants associated with arterial stiffness index and cardiac magnetic resonance measures of LA function. When analyzed per SD increment (297.6 cm/s), higher cfPWV was significantly associated with lower LA reservoir and conduit strain (ß = -0.53%, 95% CI [-0.81, -0.25] and ß = -0.46%, 95% CI [-0.68, -0.25], respectively) after adjusting for demographics, clinical characteristics, systolic blood pressure, and left ventricular (LV) morphology and function. In MR analyses there was a non-significant inverse association of arterial stiffness index with LA total, passive, and active emptying fractions. Higher cfPWV is associated with lower LA reservoir and conduit strain, independent of systolic blood pressure and LV morphology and function. No evidence for a causal relationship between arterial stiffness index and alterations in LA function was found. Future studies should examine the prospective association of central arterial stiffness with LA function alterations.

Chest symptoms and long-term risk of incident cardiovascular disease.

BACKGROUND: We sought to evaluate the associations of chest pain and dyspnea with the long-term risk of cardiovascular disease including coronary disease, heart failure, atrial fibrillation, and stroke. METHODS: In 13,200 participants without cardiovascular disease in the Atherosclerosis Risk in Communities study (1987-1989), chest pain was categorized into definite angina, possible angina, non-anginal chest pain, and no chest pain using the Rose questionnaire. Dyspnea was categorized into grades 3-4, 2, 1, and 0 by the modified Medical Research Council scale. The associations of chest pain and dyspnea with incident myocardial infarction, heart failure, atrial fibrillation, and stroke over a median follow-up of ∼27 years were quantified with multivariable Cox models. RESULTS: Definite angina and possible angina were associated with myocardial infarction (adjusted hazard ratios [HR] 1.80 [95%CI 1.45-2.13] and 1.65 [1.27-2.15]). Although lesser magnitude than myocardial infarction, both definite and possible angina were associated with heart failure. For atrial fibrillation, possible angina showed higher HR than definite angina. Dyspnea showed similar HRs for myocardial infarction and heart failure in grades 3-4 (2.00 [1.61-2.49] and 1.94 [1.62-2.32]). Stroke was least associated with chest symptoms. Chest pain and dyspnea significantly improved the discrimination of cardiovascular disease except stroke, beyond traditional risk factors. CONCLUSIONS: In individuals without cardiovascular disease, chest pain and dyspnea were independently associated with incident cardiovascular disease for about three decades, suggesting the need for evaluating chest pain from a broader perspective of cardiovascular disease beyond coronary disease and the importance of dyspnea for cardiovascular risk assessment including myocardial infarction.