Kunihiro Matsushita

BACKGROUND Older adults have markedly increased risks of heart failure (HF), specifically HF with preserved ejection fraction (HFpEF). Identifying novel biomarkers can help in understanding HF pathogenesis and improve at-risk population identification. This study aimed to identify metabolites associated with incident HF, HFpEF, and HF with reduced ejection fraction and examine risk prediction in older adults. METHODS Untargeted metabolomic profiling was performed in Black and White adults from the ARIC study (Atherosclerosis Risk in Communities) visit 5 (n=3719; mean age, 75 years). We applied Cox regressions to identify metabolites associated with incident HF and its subtypes. The metabolite risk score (MRS) was constructed and examined for associations with HF, echocardiographic measures, and HF risk prediction. Independent samples from visit 3 (n=1929; mean age, 58 years) were used for …

BackgroundRecent guidance suggests clinicians increase use of cystatin C for the estimation of GFR. Discrepant levels of creatinine-versus cystatin C–based eGFR (eGFRcr versus eGFRcys) can occur and might signify inaccurate estimation of GFR using creatinine alone. This study sought to enhance the knowledge of the risk factors and clinical implications of having a large eGFR discrepancy.MethodsParticipants in the Atherosclerosis Risk in Communities Study, a prospective cohort study of US adults, were followed over 25 years. eGFR discrepancy was measured at five clinical visits and defined as eGFRcys either 30% lower or higher than eGFRcr, the current clinical standard of care. The associations between eGFR discrepancies and kidney-related laboratory parameters were assessed using linear and logistic regression and long-term adverse outcomes, including kidney failure, AKI, heart failure, and death …

Aims Interleukin-6 (IL-6) and interleukin-18 (IL-18), important cytokines implicated in atherosclerosis and inflammaging, were assessed for associations with global cardiovascular disease (CVD), atrial fibrillation (AF), and death in older adults. Methods and results Participants from Atherosclerosis Risk in Communities study Visit 5 (mean age 75.4 ± 5.1 years) with IL-6 and IL-18 measurements were included (n = 5672). Cox regression models were used to assess associations of IL-6 and IL-18 with coronary heart disease (CHD), ischaemic stroke, heart failure (HF) hospitalization, global CVD (composite of CHD, stroke, and HF), AF, and all-cause death. Over a median follow-up of 7.2 years, there were 1235 global CVD events, 530 AF events, and 1173 deaths. Higher IL-6 [hazard ratio (HR) 1.57, 95% confidence interval (CI) 1.44–1.72 per log unit increase] and IL-18 (HR 1.13 …

Background Racial disparities in guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) have not been fully documented in a community setting. Methods In the ARIC Surveillance Study (2005–2014), we examined racial differences in GDMT at discharge, its temporal trends, and the prognostic impact among individuals with hospitalized HFrEF, using weighted regression models to account for sampling design. Optimal GDMT was defined as beta blockers (BB), mineralocorticoid receptor antagonist (MRA) and ACE inhibitors (ACEI) or angiotensin II receptor blockers (ARB). Acceptable GDMT included either one of BB, MRA, ACEI/ARB or hydralazine plus nitrates (H-N). Results Of 16,455 (unweighted n = 3,669) HFrEF cases, 47% were Black. Only ~ 10% were discharged with optimal …

ImportanceChronic kidney disease (low estimated glomerular filtration rate [eGFR] or albuminuria) affects approximately 14% of adults in the US.ObjectiveTo evaluate associations of lower eGFR based on creatinine alone, lower eGFR based on creatinine combined with cystatin C, and more severe albuminuria with adverse kidney outcomes, cardiovascular outcomes, and other health outcomes.Design, Setting, and ParticipantsIndividual-participant data meta-analysis of 27 503 140 individuals from 114 global cohorts (eGFR based on creatinine alone) and 720 736 individuals from 20 cohorts (eGFR based on creatinine and cystatin C) and 9 067 753 individuals from 114 cohorts (albuminuria) from 1980 to 2021.ExposuresThe Chronic Kidney Disease Epidemiology Collaboration 2021 equations for eGFR based on creatinine alone and eGFR based on creatinine and cystatin C; and albuminuria estimated as …

ImportanceFactors associated with the risk of dementia remain to be fully understood. Systemic infections are hypothesized to be such factors and may be targets for prevention and screening.ObjectiveTo investigate the association between hospitalization with infection and incident dementia.Design, Setting, and ParticipantsData from the community-based Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study, were used. Enrollment occurred at 4 research centers in the US, initiated in 1987 to 1989. The present study includes data up to 2019, for 32 years of follow-up. Data analysis was performed from April 2021 to June 2022.ExposuresHospitalizations with infections were identified via medical record review for selectedInternational Classification of Diseases, Ninth Revision(ICD-9) andInternational Statistical Classification of Diseases and Related Health Problems, Tenth Revision(ICD-10 …

Aims The 2021 European Society of Cardiology (ESC) guideline on cardiovascular disease (CVD) prevention categorizes moderate and severe chronic kidney disease (CKD) as high and very-high CVD risk status regardless of other factors like age and does not include estimated glomerular filtration rate (eGFR) and albuminuria in its algorithms, systemic coronary risk estimation 2 (SCORE2) and systemic coronary risk estimation 2 in older persons (SCORE2-OP), to predict CVD risk. We developed and validated an ‘Add-on’ to incorporate CKD measures into these algorithms, using a validated approach. Methods In 3,054 840 participants from 34 datasets, we developed three Add-ons [eGFR only, eGFR + urinary albumin-to-creatinine ratio (ACR) (the primary Add-on), and eGFR + dipstick proteinuria] for SCORE2 and SCORE2-OP. We validated C-statistics and net …

ImportanceClinical practice guidelines recommend selecting an appropriately sized cuff based on mid-arm circumference prior to measuring blood pressure (BP). To our knowledge, the effect of miscuffing on BP measurement when using an automated BP device has not been quantified.ObjectiveTo determine the effect of using a regular BP cuff vs an appropriately sized BP cuff on automated BP readings.Design, Setting, and ParticipantsThis randomized crossover trial of community-dwelling adults with a wide range of mid-arm circumferences took place between March 16 and October 25, 2021, in Baltimore, Maryland. Participants were recruited via BP screening events at a public food market and a senior housing facility, targeted mailings to prior research participants, placement of study brochures in hypertension clinics at Johns Hopkins University, and referrals from physicians providing hypertension care to …

Chronic kidney disease (CKD) is an asymptomatic disease associated with high morbidity and life-threatening complications that lead to decreased life expectancy. Worldwide prevalence of CKD is escalating at an alarming rate. Large population-based representative surveys have been reported in Western countries to estimate the prevalence of the disease. However, there is paucity of data as far as developing nations are concerned. Asia is the world's largest continent accommodating maximum number of under-developed and developing countries with an unclear picture of prevalence of CKD. Current review attempts to give an insight to the prevalence of CKD in this region by combining population-based surveys. This review will assist in estimating the burden of CKD in Asia, so that appropriate control measures could be designed.

Rationale & ObjectiveThe utility of conventional upper reference limits (URL) for N-terminal pro–brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hsTnT) in chronic kidney disease (CKD) remains debated. We analyzed the distribution of hsTnT and NT-proBNP in people with CKD in ambulatory settings to examine the diagnostic value of conventional URL in this population.Study DesignObservational study.Setting & ParticipantsWe studied participants of the Chronic Renal Insufficiency Cohort (CRIC) with CKD and no self-reported history of cardiovascular disease.ExposureEstimated glomerular filtration rate (eGFR).OutcomeNT-proBNP and hsTnT at baseline.Analytical ApproachWe described the proportion of participants above the conventional URL for NT-proBNP (125 pg/mL) and hsTnT (14 ng/L) overall and by eGFR. We then estimated 99th percentile URL for NT-proBNP and hsTnT …

BACKGROUND The purpose of this document is to provide clinicians with guidance, using expert consensus, to help summarize evidence and offer practical recommendations. METHODS Expert Consensus Documents are intended to provide guidance for clinicians in areas in which there are no clinical practice guidelines, especially for new and evolving tests such as arterial stiffness measurements, until any formal guidelines are released. RESULTS This expert consensus document is intended as a source of information for decision-making and to guide clinician–patient discussions in various clinical scenarios. CONCLUSIONS The goal is to help clinicians and patients make a more informed decision together.

Background The association of periodontal disease with atherosclerotic cardiovascular diseases is well known, but not specifically with incident peripheral artery disease (PAD). Therefore, we studied the associations of periodontal disease with incident PAD in a population‐based setting. Methods Among 9,793 participants (aged 53–75 years) without prevalent PAD, self‐reported history of periodontal disease was ascertained. Of these, 5,872 participants underwent full‐mouth examinations from which periodontal status was defined using the US Centers for Disease Control and Prevention‐American Academy of Periodontology (CDC‐AAP) definition. We quantified the association of periodontal disease with incident PAD (defined by hospital admission diagnosis or procedures) using multivariable Cox regression models. Results During a median follow‐up of 20.1 years, 360 participants (3.6%) developed PAD …

Background Low socioeconomic status (SES) is associated with a higher risk of heart failure (HF). The contribution of individual and neighborhood SES to the prognosis and quality of care for HF with reduced ejection fraction is not clear yet has important implications. Methods and Results We examined 728 participants of the ARIC (Atherosclerosis Risk in Communities) study (mean age, 78.2 years; 34% Black participants; 46% women) hospitalized with HF with reduced ejection fraction (ejection fraction <50%) between 2005 and 2018. We assessed associations between education, income, and area deprivation index with mortality and HF readmission using multivariable Cox models. We also evaluated the use of guideline‐directed medical therapy (optimal: ≥3 of ß‐blockers, mineralocorticoid receptor antagonist, angiotensin‐converting enzyme inhibitors, or angiotensin receptor blockers; acceptable: at least 2 …

Rationale & ObjectiveEvaluating repeated measures of estimated glomerular filtration rate (eGFR) and urinary protein-creatinine ratio (UPCR) over time may enhance our ability to understand the association between changes in kidney parameters and cardiovascular disease risk.Study DesignProspective cohort study.Setting & ParticipantsAnnual visit data from 2,438 participants in the Chronic Renal Insufficiency Cohort (CRIC).ExposuresAverage and slope of eGFR and UPCR in time-updated, 1-year exposure windows.OutcomesIncident heart failure, atherosclerotic cardiovascular disease events, death, and a composite of incident heart failure, atherosclerotic cardiovascular disease events, and death.Analytical ApproachA landmark analysis, a dynamic approach to survival modeling that leverages longitudinal, iterative profiles of laboratory and clinical information to assess the time-updated 3-year risk of adverse …

Background Although heart failure (HF) risk and cardiac structure/function reportedly differ according to race and gender, limited data exist in late life when risk of HF is highest. Objectives The goal of this study was to evaluate race/gender–based differences in HF risk factors, cardiac structure/function, and incident HF in late life. Methods This analysis included 5,149 HF-free participants from ARIC (Atherosclerosis Risk In Communities), a prospective epidemiologic cohort study, who attended visit 5 (2011-2013) and underwent echocardiography. Participants were subsequently followed up for a median 5.5 years for incident HF/death. Results Patients’ mean age was 75 ± 5 years, 59% were women, and 20% were Black. Male gender and Black race were associated with lower mean left ventricular ejection fraction. Black race was also associated with greater left ventricular wall thickness and concentricity …

Background Limited data exist to characterize novel measures of left atrial (LA) structure and function in older adults without prevalent heart failure (HF). Objectives The aim was to assess reference range of LA measures, their associations with N-terminal pro–B-type natriuretic-peptide (NT-proBNP) and the related risk for incident HF or death. Methods We analyzed LA structure (LA maximal [LAViMax] and minimal volume indexed by body surface area) and function (LA emptying fraction, LA reservoir, conduit, and contraction strain) in 4,901 participants from the ARIC (Atherosclerosis Risk In Communities) study (mean age 75 ± 5 years, 40% male, and 19% Black) without prevalent HF. We assessed sex-specific 10th and 90th percentile ARIC-based reference limits in 301 participants free of prevalent cardiovascular disease, and related LA measures to NT-proBNP and incident HF or death (median follow-up of 5 …

ImportanceAt a given estimated glomerular filtration rate (eGFR), individuals who are Black have higher rates of mortality and kidney failure with replacement therapy (KFRT) compared with those who are non-Black. Whether the recently adopted eGFR equations without race preserve racial differences in risk of mortality and KFRT at a given eGFR is unknown.ObjectiveTo assess whether eGFR equations with and without race and cystatin C document racial differences in risk of KFRT and mortality in populations including Black and non-Black participants.Design, Setting, and ParticipantsRetrospective individual-level data analysis of 62 011 participants from 5 general population and 3 chronic kidney disease (CKD) US-based cohorts with serum creatinine, cystatin C, and follow-up for KFRT and mortality from 1988 to 2018.ExposuresChronic Kidney Disease Epidemiology Collaboration equation with serum …

Background Whether coronary artery disease (CAD) is a significant risk factor for heart failure (HF) with preserved ejection fraction (HFpEF) is unclear. Methods and Results Among 9902 participants in the ARIC (Atherosclerosis Risk in Communities) study, we assessed the association of incident CAD with subsequent incident HFpEF (left ventricular ejection fraction [≥50%]) and HF with reduced ejection fraction (HFrEF; left ventricular ejection fraction <50%) using survival models with time‐updated variables. We also assessed the extent to which echocardiographic correlates of prevalent CAD account for the relationship between CAD and incident HFpEF. Over 13‐year follow‐up, incident CAD developed in 892 participants and 178 subsequently developed HF (86 HFrEF, 71 HFpEF). Incident HFrEF and HFpEF risk were both greatest early after the CAD event. At >1 year post‐CAD event, adjusted incidence of …

Background & aimsAtherosclerosis and arteriosclerosis contribute to vascular aging and cardiovascular disease (CVD) risk. Both processes can be assessed simply in the lower-limbs and reflect systemic pathology. However, only atherosclerosis is routinely assessed, typically via ankle-brachial index (ABI). Arteriosclerosis can be assessed using femoral-ankle pulse wave velocity (faPWV), but no studies have identified whether ABI and faPWV similarly associate with overt CVD and risk factors, nor whether faPWV confers additional information. The aims of this study were to (i) compare associations of ABI and faPWV with traditional CVD risk factors, including age, sex, systolic blood pressure (SBP), high-density lipoprotein (HDL), total cholesterol (TC), smoking, and diabetes; and (ii) determine the independent and additive associations of ABI and faPWV with a composite measure of prevalent CVD.MethodsWe …

A reliable, individualized, and dynamic surrogate of cardiovascular risk, synoptic for key biologic mechanisms, could shorten the path for drug development, enhance drug cost-effectiveness and improve patient outcomes. We used highly multiplexed proteomics to address these objectives, measuring about 5000 proteins in each of 32,130 archived plasma samples from 22,849 participants in nine clinical studies. We used machine learning to derive a 27-protein model predicting 4-year likelihood of myocardial infarction, stroke, heart failure, or death. The 27 proteins encompassed 10 biologic systems, and 12 were associated with relevant causal genetic traits. We independently validated results in 11,609 participants. Compared to a clinical model, the ratio of observed events in quintile 5 to quintile 1 was 6.7 for proteins versus 2.9 for the clinical model, AUCs (95% CI) were 0.73 (0.72 to 0.74) versus 0.64 (0.62 to 0 …