An outcome-driven threshold for pulse pressure amplification.

Pulse pressure amplification (PPA) is the brachial-to-aortic pulse pressure ratio and decreases with age and cardiovascular risk factors. This individual-participant meta-analysis of population studies aimed to define an outcome-driven threshold for PPA. Incidence rates and standardized multivariable-adjusted hazard ratios (HRs) of cardiovascular and coronary endpoints associated with PPA, as assessed by the SphygmoCor software, were evaluated in the International Database of Central Arterial Properties for Risk Stratification (n = 5608). Model refinement was assessed by the integrated discrimination (IDI) and net reclassification (NRI) improvement. Age ranged from 30 to 96 years (median 53.6). Over 4.1 years (median), 255 and 109 participants experienced a cardiovascular or coronary endpoint. In a randomly defined discovery subset of 3945 individuals, the rounded risk-carrying PPA thresholds converged at 1.3. The HRs for cardiovascular and coronary endpoints contrasting PPA < 1.3 vs ≥1.3 were 1.54 (95% confidence interval [CI]: 1.00-2.36) and 2.45 (CI: 1.20-5.01), respectively. Models were well calibrated, findings were replicated in the remaining 1663 individuals analyzed as test dataset, and NRI was significant for both endpoints. The HRs associating cardiovascular and coronary endpoints per PPA threshold in individuals <60 vs ≥60 years were 3.86 vs 1.19 and 6.21 vs 1.77, respectively. The proportion of high-risk women (PPA < 1.3) was higher at younger age (<60 vs ≥60 years: 67.7% vs 61.5%; P < 0.001). In conclusion, over and beyond common risk factors, a brachial-to-central PP ratio of <1.3 is a forerunner of cardiovascular coronary complications and is an underestimated risk factor in women aged 30-60 years. Our study supports pulse wave analysis for risk stratification.

Prognostic Value of Cardiovascular Biomarkers in the Population.

Importance: Identification of individuals at high risk for atherosclerotic cardiovascular disease within the population is important to inform primary prevention strategies. Objective: To evaluate the prognostic value of routinely available cardiovascular biomarkers when added to established risk factors. Design, Setting, and Participants: Individual-level analysis including data on cardiovascular biomarkers from 28 general population-based cohorts from 12 countries and 4 continents with assessments by participant age. The median follow-up was 11.8 years. Exposure: Measurement of high-sensitivity cardiac troponin I, high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, B-type natriuretic peptide, or high-sensitivity C-reactive protein. Main Outcomes and Measures: The primary outcome was incident atherosclerotic cardiovascular disease, which included all fatal and nonfatal events. The secondary outcomes were all-cause mortality, heart failure, ischemic stroke, and myocardial infarction. Subdistribution hazard ratios (HRs) for the association of biomarkers and outcomes were calculated after adjustment for established risk factors. The additional predictive value of the biomarkers was assessed using the C statistic and reclassification analyses. Results: The analyses included 164 054 individuals (median age, 53.1 years [IQR, 42.7-62.9 years] and 52.4% were women). There were 17 211 incident atherosclerotic cardiovascular disease events. All biomarkers were significantly associated with incident atherosclerotic cardiovascular disease (subdistribution HR per 1-SD change, 1.13 [95% CI, 1.11-1.16] for high-sensitivity cardiac troponin I; 1.18 [95% CI, 1.12-1.23] for high-sensitivity cardiac troponin T; 1.21 [95% CI, 1.18-1.24] for N-terminal pro-B-type natriuretic peptide; 1.14 [95% CI, 1.08-1.22] for B-type natriuretic peptide; and 1.14 [95% CI, 1.12-1.16] for high-sensitivity C-reactive protein) and all secondary outcomes. The addition of each single biomarker to a model that included established risk factors improved the C statistic. For 10-year incident atherosclerotic cardiovascular disease in younger people (aged <65 years), the combination of high-sensitivity cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein resulted in a C statistic improvement from 0.812 (95% CI, 0.8021-0.8208) to 0.8194 (95% CI, 0.8089-0.8277). The combination of these biomarkers also improved reclassification compared with the conventional model. Improvements in risk prediction were most pronounced for the secondary outcomes of heart failure and all-cause mortality. The incremental value of biomarkers was greater in people aged 65 years or older vs younger people. Conclusions and Relevance: Cardiovascular biomarkers were strongly associated with fatal and nonfatal cardiovascular events and mortality. The addition of biomarkers to established risk factors led to only a small improvement in risk prediction metrics for atherosclerotic cardiovascular disease, but was more favorable for heart failure and mortality.

Pulmonary primary oxysterol and bile acid synthesis as a predictor of outcomes in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a rare and fatal vascular disease with heterogeneous clinical manifestations. To date, molecular determinants underlying the development of PAH and related outcomes remain poorly understood. Herein, we identify pulmonary primary oxysterol and bile acid synthesis (PPOBAS) as a previously unrecognized pathway central to PAH pathophysiology. Mass spectrometry analysis of 2,756 individuals across five independent studies revealed 51 distinct circulating metabolites that predicted PAH-related mortality and were enriched within the PPOBAS pathway. Across independent single-center PAH studies, PPOBAS pathway metabolites were also associated with multiple cardiopulmonary measures of PAH-specific pathophysiology. Furthermore, PPOBAS metabolites were found to be increased in human and rodent PAH lung tissue and specifically produced by pulmonary endothelial cells, consistent with pulmonary origin. Finally, a poly-metabolite risk score comprising 13 PPOBAS molecules was found to not only predict PAH-related mortality but also outperform current clinical risk scores. This work identifies PPOBAS as specifically altered within PAH and establishes needed prognostic biomarkers for guiding therapy in PAH.

Mortality and Cardiovascular End Points In Relation to the Aortic Pulse Wave Components: An Individual-Participant Meta-Analysis.

BACKGROUND: Wave separation analysis enables individualized evaluation of the aortic pulse wave components. Previous studies focused on the pressure height with overall positive but differing results. In the present analysis, we assessed the associations of the pressure of forward and backward (Pfor and Pref) pulse waves with prospective cardiovascular end points, with extended analysis for time to pressure peak (Tfor and Tref). METHODS: Participants in 3 IDCARS (International Database of Central Arterial Properties for Risk Stratification) cohorts (Argentina, Belgium, and Finland) aged ≥20 years with valid pulse wave analysis and follow-up data were included. Pulse wave analysis was done using the SphygmoCor device, and pulse wave separation was done using the triangular method. The primary end points consisted of cardiovascular mortality and nonfatal cardiovascular and cerebrovascular events. Multivariable-adjusted Cox regression was used to calculate hazard ratios. RESULTS: A total of 2206 participants (mean age, 57.0 years; 55.0% women) were analyzed. Mean±SDs for Pfor, Pref, Tfor, and Tfor/Tref were 31.0±9.1 mm Hg, 20.8±8.4 mm Hg, 130.8±35.5, and 0.51±0.11, respectively. Over a median follow-up of 4.4 years, 146 (6.6%) participants experienced a primary end point. Every 1 SD increment in Pfor, Tfor, and Tfor/Tref was associated with 27% (95% CI, 1.07-1.49), 25% (95% CI, 1.07-1.45), and 32% (95% CI, 1.12-1.56) higher risk, respectively. Adding Tfor and Tfor/Tref to existing risk models improved model prediction (∆Uno's C, 0.020; P<0.01). CONCLUSIONS: Pulse wave components were predictive of composite cardiovascular end points, with Tfor/Tref showing significant improvement in risk prediction. Pending further confirmation, the ratio of time to forward and backward pressure peak may be useful to evaluate increased afterload and signify increased cardiovascular risk.

Association of work-related psychosocial factors and day-to-day home blood pressure variation: the Finn-Home study.

OBJECTIVES: Stress, and particularly job strain, has been found to associate with ambulatory blood pressure (BP). Moreover, BP is known to vary between days. One potential over-looked factor underlying this day-to-day BP variation could be work-related psychosocial factors. Thus, we aimed to study the association between job strain, job demands, job control and day-to-day BP variation. METHODS: The home BP of 754 regularly working participants (mean age 50.9 ±â€Š4.8, women 51%) of the Finn-Home Study was measured twice in the morning and twice in the evening over seven days. Average SBP and DBP were calculated for each day. Work-related psychosocial factors were measured with survey. Multivariable-adjusted generalized linear models were used for statistical analysis. RESULTS: We found a greater SBP/DBP decrease between weekdays and weekend among participants with high job strain (-1.8 [95% confidence interval, 95% CI, -2.7 to -0.8]/-1.7 [95% CI, -2.3 to -1.1] mmHg) compared to participants with low job strain (-0.7 [95% CI, -1.1 to -0.2]/-0.7 [95% CI, -1.0 to -0.4] mmHg). The participants with high job demands showed a higher BP decrease between weekdays and weekend (-1.4 [95% CI, -2.0 to -0.8]/-1.3 [95% CI, -1.6 to -0.9] mmHg) than the participants with low job demands (-0.5 [95% CI, -1.1 to 0.0]/-0.6 [95% CI, -1.0 to -0.3] mmHg). We did not find BP differences regarding job control. CONCLUSION: High job strain and high job demands were associated with a greater BP reduction from weekdays to the weekend. Work-related psychosocial factors should be considered when assessing day-to-day BP variation.

Use of electronic health record data mining for heart failure subtyping.

OBJECTIVE: To assess whether electronic health record (EHR) data text mining can be used to improve register-based heart failure (HF) subtyping. EHR data of 43,405 individuals from two Finnish hospital biobanks were mined for unstructured text mentions of ejection fraction (EF) and validated against clinical assessment in two sets of 100 randomly selected individuals. Structured laboratory data was then incorporated for a categorization by HF subtype (HF with mildly reduced EF, HFmrEF; HF with preserved EF, HFpEF; HF with reduced EF, HFrEF; and no HF). RESULTS: In 86% of the cases, the algorithm-identified EF belonged to the correct HF subtype range. Sensitivity, specificity, PPV and NPV of the algorithm were 94-100% for HFrEF, 85-100% for HFmrEF, and 96%, 67%, 53% and 98% for HFpEF. Survival analyses using the traditional diagnosis of HF were in concordance with the algorithm-based ones. Compared to healthy individuals, mortality increased from HFmrEF (hazard ratio [HR], 1.91; 95% confidence interval [CI], 1.24-2.95) to HFpEF (2.28; 1.80-2.88) to HFrEF group (2.63; 1.97-3.50) over a follow-up of 1.5 years. We conclude that quantitative EF data can be efficiently extracted from EHRs and used with laboratory data to subtype HF with reasonable accuracy, especially for HFrEF.

Derivation of an Outcome-Driven Threshold for Aortic Pulse Wave Velocity: An Individual-Participant Meta-Analysis.

BACKGROUND: Aortic pulse wave velocity (PWV) predicts cardiovascular events (CVEs) and total mortality (TM), but previous studies proposing actionable PWV thresholds have limited generalizability. This individual-participant meta-analysis is aimed at defining, testing calibration, and validating an outcome-driven threshold for PWV, using 2 populations studies, respectively, for derivation IDCARS (International Database of Central Arterial Properties for Risk Stratification) and replication MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease Health Survey - Copenhagen). METHODS: A risk-carrying PWV threshold for CVE and TM was defined by multivariable Cox regression, using stepwise increasing PWV thresholds and by determining the threshold yielding a 5-year risk equivalent with systolic blood pressure of 140 mm Hg. The predictive performance of the PWV threshold was assessed by computing the integrated discrimination improvement and the net reclassification improvement. RESULTS: In well-calibrated models in IDCARS, the risk-carrying PWV thresholds converged at 9 m/s (10 m/s considering the anatomic pulse wave travel distance). With full adjustments applied, the threshold predicted CVE (hazard ratio [CI]: 1.68 [1.15-2.45]) and TM (1.61 [1.01-2.55]) in IDCARS and in MONICA (1.40 [1.09-1.79] and 1.55 [1.23-1.95]). In IDCARS and MONICA, the predictive accuracy of the threshold for both end points was ≈0.75. Integrated discrimination improvement was significant for TM in IDCARS and for both TM and CVE in MONICA, whereas net reclassification improvement was not for any outcome. CONCLUSIONS: PWV integrates multiple risk factors into a single variable and might replace a large panel of traditional risk factors. Exceeding the outcome-driven PWV threshold should motivate clinicians to stringent management of risk factors, in particular hypertension, which over a person's lifetime causes stiffening of the elastic arteries as waypoint to CVE and death.

Diabetes and heart failure associations in women and men: Results from the MORGAM consortium.

Background: Diabetes and its cardiovascular complications are a growing concern worldwide. Recently, some studies have demonstrated that relative risk of heart failure (HF) is higher in women with type 1 diabetes (T1DM) than in men. This study aims to validate these findings in cohorts representing five countries across Europe. Methods: This study includes 88,559 (51.8% women) participants, 3,281 (46.3% women) of whom had diabetes at baseline. Survival analysis was performed with the outcomes of interest being death and HF with a follow-up time of 12 years. Sub-group analysis according to sex and type of diabetes was also performed for the HF outcome. Results: 6,460 deaths were recorded, of which 567 were amongst those with diabetes. Additionally, HF was diagnosed in 2,772 individuals (446 with diabetes). A multivariable Cox proportional hazard analysis showed that there was an increased risk of death and HF (hazard ratio (HR) of 1.73 [1.58-1.89] and 2.12 [1.91-2.36], respectively) when comparing those with diabetes and those without. The HR for HF was 6.72 [2.75-16.41] for women with T1DM vs. 5.80 [2.72-12.37] for men with T1DM, but the interaction term for sex differences was insignificant (p for interaction 0.45). There was no significant difference in the relative risk of HF between men and women when both types of diabetes were combined (HR 2.22 [1.93-2.54] vs. 1.99 [1.67-2.38] respectively, p for interaction 0.80). Conclusion: Diabetes is associated with increased risks of death and heart failure, and there was no difference in relative risk according to sex.

Biomarker-based prediction of fatal and non-fatal cardiovascular outcomes in individuals with diabetes mellitus.

AIMS: The role of biomarkers in predicting cardiovascular outcomes in high-risk individuals is not well established. We aimed to investigate benefits of adding biomarkers to cardiovascular risk assessment in individuals with and without diabetes. METHODS AND RESULTS: We used individual-level data of 95 292 individuals of the European population harmonized in the Biomarker for Cardiovascular Risk Assessment across Europe consortium and investigated the prognostic ability of high-sensitivity cardiac troponin I (hs-cTnI), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hs-CRP). Cox-regression models were used to determine adjusted hazard ratios of diabetes and log-transformed biomarkers for fatal and non-fatal cardiovascular events. Models were compared using the likelihood ratio test. Stratification by specific biomarker cut-offs was performed for crude time-to-event analysis using Kaplan-Meier plots. Overall, 6090 (6.4%) individuals had diabetes at baseline, median follow-up was 9.9 years. Adjusting for classical risk factors and biomarkers, diabetes [HR 2.11 (95% CI 1.92, 2.32)], and all biomarkers (HR per interquartile range hs-cTnI 1.08 [95% CI 1.04, 1.12]; NT-proBNP 1.44 [95% CI 1.37, 1.53]; hs-CRP 1.27 [95% CI 1.21, 1.33]) were independently associated with cardiovascular events. Specific cut-offs for each biomarker identified a high-risk group of individuals with diabetes losing a median of 15.5 years of life compared to diabetics without elevated biomarkers. Addition of biomarkers to the Cox-model significantly improved the prediction of outcomes (likelihood ratio test for nested models P < 0.001), accompanied by an increase in the c-index (increase to 0.81). CONCLUSION: Biomarkers improve cardiovascular risk prediction in individuals with and without diabetes and facilitate the identification of individuals with diabetes at highest risk for cardiovascular events.

In this work, the role of cardiac biomarkers measured from blood to predict cardiovascular events and death is tested in individuals of the general population and particularly in those with known diabetes. The work is based on a cooperation of different population studies across Europe and includes more than 90 000 individuals, with more than 6000 having diabetes. We could demonstrate that the determination of three cardiac biomarkers helps to identify individuals at highest risk for cardiovascular events (e.g. myocardial infarction or stroke) and death, despite accounting for known cardiovascular risk factors in these individuals. Therefore, these biomarkers should be considered for routine risk assessment for cardiovascular diseases and could improve the early identification of high-risk individuals, consequently leading to an earlier initiation of preventive therapies.

Changes in ambulatory blood pressure during the transition to retirement.

OBJECTIVES: Retirement is a major life event characterized by removal of work-related stressors and changes in health behaviours. The association between retirement and changes in blood pressure (BP), and particularly in ambulatory BP, has been scarcely studied. We aimed to examine changes in ambulatory BP during retirement transition. METHODS: Two hundred and fifty ageing workers (mean age 63.2 years, 84% women) from the Finnish Retirement and Aging study participated in annual office BP measurements and 114 (mean age 63.1, 90% women) of them underwent annual ambulatory BP measurements before and after retirement. On average, the participants provided data on ambulatory BP at 2.7 (range 2-4) measurements. We used generalized linear models to examine BP changes at retirement. RESULTS: Most marked changes in BP during the follow-up were observed for asleep SBP, which decreased before retirement, increased during retirement transition and plateaued after retirement (before retirement vs. retirement transition P  = 0.07 and after retirement vs. retirement transition P  = 0.02). Awake SBP and 24-h SBP declined with most apparent decrease before retirement (before retirement vs. retirement transition P  = 0.07 and P  = 0.07). Awake DBP and 24-h DBP showed relatively consistent decline throughout the follow-up with no differences between the time periods. SBP and DBP dipping reduced before and during retirement transition, but not after retirement. Among shift workers, asleep BP increased and BP dipping decreased more than in regular day workers. CONCLUSION: Retirement was found to associate with beneficial changes in awake BP but unfavourable changes in asleep BP, especially in shift workers.

Home blood pressure monitoring schedule: optimal and minimum based on 2122 individual participants' data.

OBJECTIVES: Home blood pressure (HBP) monitoring has become a primary method for hypertension diagnosis and management. This analysis aimed to investigate the optimal and minimum schedule for HBP monitoring. METHODS: A retrospective analysis of cross-sectional data was performed, which involved HBP and 24-h ambulatory blood pressure (ABP) monitoring in adults performed within the context of clinical studies in Finland, Greece and UK. Participants with six to seven HBP monitoring days and at least 12 HBP readings were included. The stability of HBP was assessed by evaluating the average value of an increasing number of readings and its variability (SD). Its association with awake ABP was also assessed. RESULTS: Data from 2122 participants were analysed (mean age 53.9 ±â€Š11.3 years, males 53%, treated 34%). A progressive HBP decline was observed in succeeding days, reaching a plateau after day 3. Day 1 HBP was higher than in the next days by about 2.8/1.4 mmHg (systolic/diastolic, P < 0.001). In a 3-day HBP monitoring schedule, the exclusion of day 1 reduced average HBP and SD, with a clinically important HBP decline in 115 participants (5%) and different hypertension diagnosis in 120 participants (6%). For schedules including more than three HBP monitoring days, the exclusion of day 1 had negligible impact. The 3-day average HBP was strongly correlated with awake ABP, with a little improvement thereafter. CONCLUSION: These data support the recommendation for 7 days of HBP monitoring with a minimum of 3 days. Readings of the first day should be discarded, particularly when the minimum 3-day monitoring schedule is obtained (average readings of second and third day).

Variability independent of mean blood pressure as a real-world measure of cardiovascular risk.

Background: Individual-level blood pressure (BP) variability, independent of mean BP levels, has been associated with increased risk for cardiovascular events in cohort studies and clinical trials using standardized BP measurements. The extent to which BP variability relates to cardiovascular risk in the real-world clinical practice setting is unclear. We sought to determine if BP variability in clinical practice is associated with adverse cardiovascular outcomes using clinically generated data from the electronic health record (EHR). Methods: We identified 42,482 patients followed continuously at a single academic medical center in Southern California between 2013 and 2019 and calculated their systolic and diastolic BP variability independent of the mean (VIM) over the first 3 years of the study period. We then performed multivariable Cox proportional hazards regression to examine the association between VIM and both composite and individual outcomes of interest (incident myocardial infarction, heart failure, stroke, and death). Findings: Both systolic (HR, 95% CI 1.22, 1.17-1.28) and diastolic VIM (1.24, 1.19-1.30) were positively associated with the composite outcome, as well as all individual outcome measures. These findings were robust to stratification by age, sex and clinical comorbidities. In sensitivity analyses using a time-shifted follow-up period, VIM remained significantly associated with the composite outcome for both systolic (1.15, 1.11-1.20) and diastolic (1.18, 1.13-1.22) values. Interpretation: VIM derived from clinically generated data remains associated with adverse cardiovascular outcomes and represents a risk marker beyond mean BP, including in important demographic and clinical subgroups. The demonstrated prognostic ability of VIM derived from non-standardized BP readings indicates the utility of this measure for risk stratification in a real-world practice setting, although residual confounding from unmeasured variables cannot be excluded. Funding: This study was funded in part by National Institutes of Health grants R01-HL134168, R01-HL131532, R01-HL143227, R01-HL142983, U54-AG065141; R01-HL153382, K23-HL136853, K23-HL153888, and K99-HL157421; China Scholarship Council grant 201806260086; Academy of Finland (Grant no: 321351); Emil Aaltonen Foundation; Finnish Foundation for Cardiovascular Research.

A plasma metabolite score of three eicosanoids predicts incident type 2 diabetes: a prospective study in three independent cohorts.

INTRODUCTION: Peptide markers of inflammation have been associated with the development of type 2 diabetes. The role of upstream, lipid-derived mediators of inflammation such as eicosanoids, remains less clear. The aim of this study was to examine whether eicosanoids are associated with incident type 2 diabetes. RESEARCH DESIGN & METHODS: In the FINRISK (Finnish Cardiovascular Risk Study) 2002 study, a population-based sample of Finnish men and women aged 25-74 years, we used directed, non-targeted liquid chromatography-mass spectrometry to identify 545 eicosanoids and related oxylipins in the participants' plasma samples (n=8292). We used multivariable-adjusted Cox regression to examine associations between eicosanoids and incident type 2 diabetes. The significant independent findings were replicated in the Framingham Heart Study (FHS, n=2886) and DIetary, Lifestyle and Genetic determinants of Obesity and Metabolic syndrome (DILGOM) 2007 (n=3905). Together, these three cohorts had 1070 cases of incident type 2 diabetes. RESULTS: In the FINRISK 2002 cohort, 76 eicosanoids were associated individually with incident type 2 diabetes. We identified three eicosanoids independently associated with incident type 2 diabetes using stepwise Cox regression with forward selection and a Bonferroni-corrected inclusion threshold. A three-eicosanoid risk score produced an HR of 1.56 (95% CI 1.41 to 1.72) per 1 SD increment for risk of incident diabetes. The HR for comparing the top quartile with the lowest was 2.80 (95% CI 2.53 to 3.07). In the replication analyses, the three-eicosanoid risk score was significant in FHS (HR 1.24 (95% CI 1.10 to 1.39, p<0.001)) and directionally consistent in DILGOM (HR 1.12 (95% CI 0.99 to 1.27, p=0.07)). Meta-analysis of the three cohorts yielded a pooled HR of 1.31 (95% CI 1.05 to 1.56). CONCLUSIONS: Plasma eicosanoid profiles predict incident type 2 diabetes and the clearest signals replicate in three independent cohorts. Our findings give new information on the biology underlying type 2 diabetes and suggest opportunities for early identification of people at risk.

Risk Stratification by Cross-Classification of Central and Brachial Systolic Blood Pressure.

BACKGROUND: Whether cardiovascular risk is more tightly associated with central (cSBP) than brachial (bSBP) systolic pressure remains debated, because of their close correlation and uncertain thresholds to differentiate cSBP into normotension versus hypertension. METHODS: In a person-level meta-analysis of the International Database of Central Arterial Properties for Risk Stratification (n=5576; 54.1% women; mean age 54.2 years), outcome-driven thresholds for cSBP were determined and whether the cross-classification of cSBP and bSBP improved risk stratification was explored. cSBP was tonometrically estimated from the radial pulse wave using SphygmoCor software. RESULTS: Over 4.1 years (median), 255 composite cardiovascular end points occurred. In multivariable bootstrapped analyses, cSBP thresholds (in mm Hg) of 110.5 (95% CI, 109.1-111.8), 120.2 (119.4-121.0), 130.0 (129.6-130.3), and 149.5 (148.4-150.5) generated 5-year cardiovascular risks equivalent to the American College of Cardiology/American Heart Association bSBP thresholds of 120, 130, 140, and 160. Applying 120/130 mm Hg as cSBP/bSBP thresholds delineated concordant central and brachial normotension (43.1%) and hypertension (48.2%) versus isolated brachial hypertension (5.0%) and isolated central hypertension (3.7%). With concordant normotension as reference, the multivariable hazard ratios for the cardiovascular end point were 1.30 (95% CI, 0.58-2.94) for isolated brachial hypertension, 2.28 (1.21-4.30) for isolated central hypertension, and 2.02 (1.41-2.91) for concordant hypertension. The increased cardiovascular risk associated with isolated central and concordant hypertension was paralleled by cerebrovascular end points with hazard ratios of 3.71 (1.37-10.06) and 2.60 (1.35-5.00), respectively. CONCLUSIONS: Irrespective of the brachial blood pressure status, central hypertension increased cardiovascular and cerebrovascular risk indicating the importance of controlling central hypertension.

Sex Differences in Myocardial and Vascular Aging.

It is well known that cardiovascular disease manifests differently in women and men. The underlying causes of these differences during the aging lifespan are less well understood. Sex differences in cardiac and vascular phenotypes are seen in childhood and tend to track along distinct trajectories related to dimorphism in genetic factors as well as response to risk exposures and hormonal changes during the life course. These differences underlie sex-specific variation in cardiovascular events later in life, including myocardial infarction, heart failure, ischemic stroke, and peripheral vascular disease. With respect to cardiac phenotypes, females have intrinsically smaller body size-adjusted cardiac volumes and they tend to experience greater age-related wall thickening and myocardial stiffening with aging. With respect to vascular phenotypes, sexual dimorphism in both physiology and pathophysiology are also seen, including overt differences in blood pressure trajectories. The majority of sex differences in myocardial and vascular alterations that manifest with aging seem to follow relatively consistent trajectories from the very early to the very later stages of life. This review aims to synthesize recent cardiovascular aging-related research to highlight clinically relevant studies in diverse female and male populations that can inform approaches to improving the diagnosis, management, and prognosis of cardiovascular disease risks in the aging population at large.

Gut Microbiome Composition Is Predictive of Incident Type 2 Diabetes in a Population Cohort of 5,572 Finnish Adults.

OBJECTIVE: To examine the previously unknown long-term association between gut microbiome composition and incident type 2 diabetes in a representative population cohort. RESEARCH DESIGN AND METHODS: We collected fecal samples from 5,572 Finns (mean age 48.7 years; 54.1% women) in 2002 who were followed up for incident type 2 diabetes until 31 December 2017. The samples were sequenced using shotgun metagenomics. We examined associations between gut microbiome composition and incident diabetes using multivariable-adjusted Cox regression models. We first used the eastern Finland subpopulation to obtain initial findings and validated these in the western Finland subpopulation. RESULTS: Altogether, 432 cases of incident diabetes occurred over the median follow-up of 15.8 years. We detected four species and two clusters consistently associated with incident diabetes in the validation models. These four species were Clostridium citroniae (hazard ratio [HR] 1.21; 95% CI 1.04-1.42), C. bolteae (HR 1.20; 95% CI 1.04-1.39), Tyzzerella nexilis (HR 1.17; 95% CI 1.01-1.36), and Ruminococcus gnavus (HR 1.17; 95% CI 1.01-1.36). The positively associated clusters, cluster 1 (HR 1.18; 95% CI 1.02-1.38) and cluster 5 (HR 1.18; 95% CI 1.02-1.36), mostly consisted of these same species. CONCLUSIONS: We observed robust species-level taxonomic features predictive of incident type 2 diabetes over long-term follow-up. These findings build on and extend previous mainly cross-sectional evidence and further support links between dietary habits, metabolic diseases, and type 2 diabetes that are modulated by the gut microbiome. The gut microbiome can potentially be used to improve disease prediction and uncover novel therapeutic targets for diabetes.

Outcomes after coronary artery bypass grafting and percutaneous coronary intervention in diabetic and non-diabetic patients.

AIMS: To assess the prognosis of patients with coronary heart disease (CHD) after first myocardial revascularisation procedure in real-world practice and to compare the differences in outcomes of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) among diabetic and non-diabetic patients. METHODS AND RESULTS: A database was compiled from the national hospital discharge register to collect data on all cardiac revascularisations performed in Finland in 2000-2015. The outcomes (all-cause deaths, cardiovascular (CV) deaths, major CV events and need for repeat revascularisation) after the first revascularisation were identified from the national registers at 28 day, 1 year, and 3 year time points.A total of 139 242 first-time revascularisations (89 493 PCI and 49 749 CABG) were performed during the study period. Of all the revascularised patients, 24% had diabetes, and 76% were non-diabetic patients. At day 28, the risk of fatal outcomes was lower after PCI than after CABG among non-diabetic patients, whereas no difference was seen among diabetic patients. In long-term follow-up the situation was reversed with PCI showing higher risk compared with CABG for most of the outcomes. In particular, at 3 year follow-up the risk of all-cause deaths was elevated among diabetic patients [HR 1.30 (95% CI 1.22-1.38) comparing PCI with CABG] more than among non-diabetic patients [HR 1.09 (1.04-1.15)]. The same was true for CV deaths [HR 1.29 (1.20-1.38) among diabetic patients, and HR 1.03 (0.98-1.08) among non-diabetic patients]. CONCLUSION: Although PCI was associated with better 28 day prognosis, CABG seemed to produce better long-term prognosis especially among diabetic patients.

The International Database of Central Arterial Properties for Risk Stratification: Research Objectives and Baseline Characteristics of Participants.

OBJECTIVE: To address to what extent central hemodynamic measurements, improve risk stratification, and determine outcome-based diagnostic thresholds, we constructed the International Database of Central Arterial Properties for Risk Stratification (IDCARS), allowing a participant-level meta-analysis. The purpose of this article was to describe the characteristics of IDCARS participants and to highlight research perspectives. METHODS: Longitudinal or cross-sectional cohort studies with central blood pressure measured with the SphygmoCor devices and software were included. RESULTS: The database included 10,930 subjects (54.8% women; median age 46.0 years) from 13 studies in Europe, Africa, Asia, and South America. The prevalence of office hypertension was 4,446 (40.1%), of which 2,713 (61.0%) were treated, and of diabetes mellitus was 629 (5.8%). The peripheral and central systolic/diastolic blood pressure averaged 129.5/78.7 mm Hg and 118.2/79.7 mm Hg, respectively. Mean aortic pulse wave velocity was 7.3 m per seconds. Among 6,871 participants enrolled in 9 longitudinal studies, the median follow-up was 4.2 years (5th-95th percentile interval, 1.3-12.2 years). During 38,957 person-years of follow-up, 339 participants experienced a composite cardiovascular event and 212 died, 67 of cardiovascular disease. CONCLUSIONS: IDCARS will provide a unique opportunity to investigate hypotheses on central hemodynamic measurements that could not reliably be studied in individual studies. The results of these analyses might inform guidelines and be of help to clinicians involved in the management of patients with suspected or established hypertension.