Composite Cardiovascular Risk Research Articles

Association of blood pressure and heart rate with carotid markers of vascular remodeling in the young: a case for early prevention.

The association of childhood blood pressure (BP) and heart rate (HR) with intermediate markers of cardiovascular disease several decades later has been shown, but studies on more short-term outcomes are scarce. Using population-based data, this study investigates the association of four BP parameters and HR in childhood with three carotid markers for vascular remodeling one decade later. At the 11-year follow-up, 4607 participants of the nationwide KiGGS cohort aged 14 to 28 years had semi-automated sonographic carotid intima media thickness (CIMT) measurements. We investigated associations of baseline (age 3-17 years) and follow-up SBP, DBP, mean arterial pressure (MAP), pulse pressure (PP) and resting heart rate (RHR), with CIMT and lumen diameter at or above the 90th percentile and distensibility coefficient at or below the tenth percentile in logistic regressions. Analyses were further adjusted using a composite cardiovascular risk (CVR) score of BMI, triglycerides, total/HDL-cholesterol-ratio and HbA1c. SBP, DBP, MAP and RHR were significantly and similarly associated with all carotid measures 11 years later, for example an odds ratio (OR) of 1.17 [confidence interval (CI) 1.06-1.29] for one standard deviation SBP increase with elevated CIMT when adjusting for sex, age and CVR score. Cross-sectionally, the strongest association was found for MAP with reduced distensibility coefficient (OR 1.76; CI 1.59-1.94). This population-based cohort study shows robust and consistent associations between childhood BP and RHR and three carotid measures of vascular remodeling only one decade later, clearly underscoring the potential importance of preventing high BP already early in the life course.

Antithrombotics prescription pattern and clinical outcomes in atrial fibrillation patients with type 2 diabetes mellitus

Abstract Funding Acknowledgements Type of funding sources: None. Background Atrial fibrillation (AF) and Diabetes mellitus (DM) often coexist. As DM is considered while calculating the thromboembolic risk for AF patients, little is known about the prescription pattern of antithrombotic therapies in patients with AF and DM and their clinical outcomes. Purpose In this subsidiary study, we examined the prescription patterns of antithrombotic therapies and clinical outcomes of AF patients with type 2 DM. Methods We analyzed data from a single-center cohort of patients with a primary diagnosis of AF in a tertiary cardiac referral hospital in Malaysia from 1st January 2018 to 31st December 2020. Patients' clinical data and information related to antithrombotic therapy were traced through electronic Hospital Information system. A data collection form was used for data collection. The primary endpoint of the study was a composite cardiovascular (CV) event which consists of all-cause mortality, acute coronary syndrome (ACS), ischemic stroke and transient ischemic attack (TIA). The safety endpoint of the study was a bleeding event, defined as hemoglobin drop more than 2 g/dl, blood transfusion and bleeding at critical area. Results Of the 1006 AF patients (59.2% male; mean age 64.2 (12.1) years), 400 (39.8%) had a history of DM. Of these, 45.8% (n=183) were using warfarin; 46.5% (n=159) used direct oral anticoagulant (DOAC), 54.0% (n=216) used a single antiplatelet, 11.5% (n=46) used a double antiplatelet, 8.0% (n=32) used triple therapy which consists of two antiplatelet agents with one anticoagulant. The use of single antiplatelet agent (54.0% vs 46.4%, p=0.018) and double antiplatelet agents (11.5% vs 7.1%, p=0.016) was significantly associated with AF with DM patients, whereas there was no association between anticoagulant use and AF patients with or without DM (85.5% vs 82.5%, p=0.209). There was no association in composite CV events between AF patients with or without DM (12.0% vs 10.4%, p=0.427). The proportion of subjects who reported having bleeding events were also did not differ by the presence of AF patients with or without DM. (4.5% vs 2.8%, p=0.151). Conclusion Diabetes was associated with increased use of antiplatelet agents; however, DM was not associated with increased risk of composite CV events and bleeding events in patients with concurrent AF. The lack of an association between diabetes and CV risk contrasts with previous research, which could be due to improved diabetes treatment in this cohort of patients with relatively low fasting sugar readings. Further study on the degree of blood glucose as measured by glycosylated hemoglobin (HbA1c) is needed to confirm the finding.

The effectiveness of Fuzi in combination with routine heart failure treatment on chronic heart failure patients

Ethnopharmacological relevanceFuzi, Aconiti Lateralis Radix Praeparata, is widely used in Traditional Chinese Medicine (TCM) for the treatment of acute heart failure (HF) for 2000 years. However, the clinical evidence of Fuzi in the treatment of chronic HF is limited, especially when used in combination with Western medications. Materials and methodsThis population-based propensity score (PS)-matched cohort study aimed to evaluate the effectiveness of Fuzi on the chronic HF. From 4753 chronic HF patients who had used TCM herbal medicine, we performed 1:1 PS matching and selected target patients with (n = 921) and without (n = 921) Fuzi use for further analysis. The primary outcomes were all-cause mortality and composite cardiovascular (CV) outcomes. Hazard ratio (HR) was calculated by Cox proportional hazard regression and the competing risk analysis. The dose-response relationship and the association between the initiation of TCM herbal medicine and the primary outcomes were evaluated by restricted cubic spline (RCS) functions. ResultsThere was no difference in all-cause mortality (HR, 0.99; 95% confidence interval [CI], 0.76–1.27) and composite CV outcomes (HR, 0.96; 95% CI, 0.84–1.11) between the Fuzi user and non-user groups. For CV safety issue, the result showed that Fuzi use was not associated with a higher risk of cardiac arrhythmias (HR, 1.03; 95% CI, 0.83–1.29). The dose-response relationship showed that Fuzi cumulative dose (≥150g) was associated with lower composite CV risk (HR, 0.76; 95% CI, 0.59–0.99). In addition, the RCS model showed that late initiation (≥2.5 years) of TCM herbal drugs in chronic HF patients had a higher risk of all-cause mortality (HR, 1.81; 95%CI, 1.07–3.08). ConclusionsThis study is the first real-world evidence to demonstrate the effect of Fuzi combined with routine HF treatment. Importantly, the result indicated that long-term Fuzi use had a significant benefit in preventing cardiovascular events. The late initiation of TCM herbal drugs was associated with a higher risk of all-cause mortality. Further clinical trials are needed to support or undermine the assumption of using Fuzi and current Western medications to treat chronic HF.

PREDICTIVE POWER OF 24-HOUR AMBULATORY PULSE PRESSURE AND ITS COMPONENTS FOR MORTALITY AND CARDIOVASCULAR OUTCOMES IN 11,848 PARTICIPANTS RECRUITED FROM 13 POPULATIONS

Objective: The role of pulse pressure ’widening’ at older age, as a cardiovascular risk factor is still controversial. 24-hour ambulatory pulse pressure (PP) was previously expressed as a sum of two components: ’elastic’ PP (elPP) and 'stiffening’ PP (stPP) associated, respectively, with arterial stiffness at diastole and the change in stiffness during systole. We investigated the association of PP, elPP and stPP (’PP variables’) with mortality and composite cardiovascular (CV) events in different age classes. Design and method: Longitudinal population-based cohort study of adults from Europe, Asia, and South America with baseline observations, including 24-hour ambulatory BP. Age classes were age < 50, 50–60, 60–70, and > 70 year. Co-primary endpoints were total mortality and composite CV events. Hazard ratios (HRs) per 1-SD increase in the PP variables were calculated from multivariable adjusted Cox regression models. Results: The 11,848 participants from 13 cohorts (age 53 ± 16, 50% males) were followed up for 13.4 ± 6.9 years. A total of 2946 participants died (18.1 per 1000 person-years) and 2093 experienced a fatal or non-fatal cardiovascular event (12.9 per 1000 person-years). PP components were uncorrelated (r = -0.07), and the ratio stPP/elPP was 0.143. PP and elPP showed a curvilinear relationship with age reaching a nadir around middle-age, whereas stPP steadily increased from age 30 years onwards. In persons ?50 years of age, but not in those < 50 years, both PP and elPP were associated with increased risk for the primary endpoints. For total mortality and cardiovascular events hazard ratios for PP decreased from 50–60 years old participants to those aged > 70 years (P < 0.02); from 1.29[95%CI: 1.13–1.46] to 1.11[1.05–1.15], and from 1.40[1.24–1.58] to 1.16[1.10–1.23], respectively, and for elPP for cardiovascular events; from 1.29[1.14–1.45] to 1.16[1.09–1.23]. On the other hand, stPP was associated with increased risk for the primary endpoints in subjects 50 to 60 years of age but not in the older age groups. Conclusions: The age-related increase in PP variables is not reflected in a corresponding PP-associated increase in cardiovascular risk. Results support the view that normal ageing weakens the association of PP variables with CV risk.

Acute coronary syndromes in chronic kidney disease patients: the good, the bad or the ugly?

Abstract Background Patients with chronic kidney disease (CKD) are at increased risk of composite cardiovascular (CV) events and all-cause mortality. However, current aggressiveness of therapeutic strategies may minimize the course of the disease. Aim To assess the prognostic impact of optimized medical treatment in a CKD population with acute coronary syndrome (ACS). Methods 355 ACS patients admitted to a single coronary care with CKD who were discharged from hospital were included. Those with end-stage renal disease were excluded. Three groups were created based on the KDIGO classification: Group A (Stage 3A, eGFR [estimated glomerular filtration rate] 45–59mL/min/1.73 m2) N=190; Group B (Stage 3B, eGFR 30–44mL/min/1.73 m2) N=113; and Group C (Stage 3B, eGFR 15–29mL/min/1.73 m2) N=52. The primary endpoint was long-term all-cause mortality. Kaplan-Meyer survival curves and Cox regression were done. The median of follow-up was 32 (IQ 15–70) months. Results Groups were similar regarding demographics, CV risk factors, ACS type, heart failure diagnosis, left ventricular (LV) systolic function, peak troponin, multivessel disease, treatment option (PCI, CABG or OMT) and medical therapy at discharge. More advance renal failure patients had a higher prevalence of diabetes mellitus (DM), a lower haemoglobin, a higher NT-proBNP and were less likely to receive ACE inhibitors/angiotensin II antagonist at discharge. 170 patients met the primary outcome. Kaplan-Meyer curves showed decreased survival with worse renal function (Group A 68% vs Group B 57% vs Group C 37%, Log Rank P=0.006 – Figure 1). After adjustment for age, DM, haemoglobin, NT-proBNP, LV systolic function and ACE inhibitors/angiotensin II antagonist at discharge, eGFR was not associated with increased death (HR 1.00, 95% CI 0.98–1.01). In this model, only age (HR 1.04, 95% CI 1.01–1.07), haemoglobin (HR 0.86, 95% CI 0.979–0.94), Nt-proBNP (HR 1.00, 95% CI 1.00–1.00) and impaired LV function (LV ejection fraction 40–49%: HR 2.95, 95% CI 1.89–4.81; LV ejection fraction <40%: HR 2.15, 95% CI 1.44–3.21) remained associated with the outcome. Conclusion The worse outcome attributed to CKD after an ACS seems to be related not the eGFR itself but to associated comorbidities such as age, anaemia, fluid overload and impaired LV function. The fact that some of these comorbidities may be altered by intensive therapy indicates that CKD patients should also be candidates to optimized medical treatment. Funding Acknowledgement Type of funding source: None

Disease Activity Influences Cardiovascular Risk Reclassification Based on Carotid Ultrasound in Patients with Psoriatic Arthritis.

Because the addition of carotid ultrasound (US) into composite cardiovascular (CV) risk scores has been found effective for identifying patients with inflammatory arthritis and high CV risk, we aimed to determine whether its use would facilitate the reclassification of patients with psoriatic arthritis (PsA) into the very high Systematic Coronary Risk Evaluation (SCORE) risk category and whether this might be related to disease features. This was a cross-sectional study involving 206 patients who fulfilled ClASsification for Psoriatic ARthritis criteria for PsA, and 179 controls. We assessed lipid profile, SCORE, disease activity measurements, and the presence of carotid plaques and carotid intima-media thickness by ultrasonography. A multivariable regression analysis, adjusted for classic CV risk factors, was performed to evaluate whether the risk of reclassification could be explained by disease-related features and to assess the most parsimonious combination of risk reclassification predictors. Forty-seven percent of patients were reclassified into a very high SCORE risk category after carotid US compared to 26% of controls (p < 0.001). Patients included in the low SCORE risk category were those who were more commonly reclassified (30% vs 14%, p = 0.002). The Disease Activity Index for PsA (DAPSA) score was associated with reclassification (β 1.10, 95% CI 1.02-1.19; p = 0.019) after adjusting for age and traditional CV risk factors. A model containing SCORE plus age, statin use, and DAPSA score yielded the highest discriminatory accuracy compared to the SCORE-alone model (area under the receiver-operating characteristic curve 0.863, 95% CI 0.789-0.936 vs 0.716, 95% CI 0.668-0.764; p < 0.001). Patients with PsA are more frequently reclassified into the very high SCORE risk category following carotid US assessment than controls. This was independently explained by the disease activity.

P6447Prediabetes versus diabetes mellitus in acute coronary syndrome patients: two sides of the same coin

Abstract Background Prediabetic patients are at increased risk of composite cardiovascular (CV) events and all-cause mortality. The impact of prediabetes diagnosis in the context of an acute coronary syndrome (ACS) remains to be determined. Purpose To assess the differences on long-term mortality between well controlled diabetic and prediabetic patients admitted with non-ST elevation ACS. Methods 352 non-ST elevation ACS patients admitted to a single coronary care unit between 2009 and 2016 were included. Clinical, laboratorial and echocardiographic data were evaluated. Two groups were created based on the diabetic status and HBA1c level: Group A (prediabetic patients, HBA1c between 5.7–6.4%) N=229; Group B (diabetic patients, HBA1c ≤7%) N=123. The primary endpoint was long-term all-cause mortality. Kaplan-Meyer survival curves and Cox regression were done. The mean time of follow up was 48±30 months. Results The groups were similar regarding demographics, CV risk factors, ACS type, heart failure diagnosis, peak troponin I, left ventricular (LV) systolic function, multivessel disease and treatment option (PCI, CABG or OMT). On the contrary, well controlled diabetic patients had a higher prevalence of chronic kidney disease (CKD) (27.9% vs 39.0%, P&lt;0.05), hypertension (82.5% vs 91.9%, P&lt;0.05), higher body mass index (BMI) (23±4 vs 24±4 kg/m2, P&lt;0.05) and previous coronary artery disease (37.1% vs 51.2%, P&lt;0.05). 95 patients met the primary outcome. Kaplan-Meyer curves showed a tendency to decreased survival in the diabetic group (72.8% vs 66.4%, Log Rank P=0.09 – Figure 1). After adjustment for age, CKD, BMI (6 categories), heart failure diagnosis, peak troponin I and LV systolic function, controlled diabetes was not associated with increased death (HR 1.40, 95% CI 0.87–2.26). In this model, only age (HR 1.05, 95% CI 1.02–1.08), peak troponin (HR 1.01, 95% CI 1.00–1.01) and moderate to severely impaired LV function (HR 2.00, 95% CI 1.12–3.56) remained associated with the outcome. Conclusion In the context of an ACS, prediabetics should be regarded as a high-risk group. This study raises the provocative question that prediabetics and diabetics patients should be approached in similar ways in terms of risk stratification and therapeutic options after an ACS. In these patients, age, peak troponin and impaired LV function appear to be the main contributors to decreased survival.

DETAILED DESCRIPTION OF MYOCARDIAL INFARCTIONS AND THE VARIOUS SUBTYPES IN THE LEADER TRIAL

Type 2 diabetes (T2D) is associated with increased risk of myocardial infarction (MI). In the LEADER trial (NCT01179048), liraglutide reduced the risk of a composite cardiovascular (CV) outcome (time to the first occurrence of CV death, non-fatal MI, or non-fatal stroke) versus placebo, both in addition to standard care. This result was driven by all components, but detailed characterization of the MIs has not been performed. The aim of this post hoc analysis was to characterize MIs in the trial, and within each treatment arm. A total of 9340 subjects, with T2D and established CV disease or high CV risk, were randomized 1:1 to receive liraglutide or placebo (both in addition to standard care) and followed for 3.5–5 years. Subjects experiencing MI were included in this analysis. A total of 780 MIs (first and recurrent) were observed: 359 with liraglutide and 421 with placebo (p=0.02). Of the MIs observed, 17.8% were silent. Numerically fewer fatal MIs were observed in the liraglutide arm compared with the placebo arm (Table). More liraglutide-versus placebo-treated subjects with MI had a history of coronary artery bypass graft (30.8% vs. 21.5%; p=0.008) and percutaneous coronary intervention (47.6% vs. 40.4%; p=0.070), while fewer had a history of left ventricular diastolic dysfunction (13.4% vs. 18.9%; p=0.061), peripheral arterial disease in the lower extremities (9.9% vs. 17.7%; p=0.005) and >50% stenosis of coronary, carotid or other arteries (33.2% vs. 41.0%; p=0.044) at baseline. Overall, 641 symptomatic MIs (555 non-ST-segment elevation MI [non-STEMI; 86.6%]) were observed: 297 with liraglutide and 344 with placebo. Among subjects who had a symptomatic MI and troponin information, a numerically lower proportion had troponin levels >5 times the upper reference limit (URL) in the liraglutide arm than in the placebo arm (Table). Fewer MIs and fatal MIs were observed in liraglutide-treated subjects than placebo-treated subjects. Symptomatic MIs in both arms were mainly non-STEMI. In subjects who had a symptomatic MI, there was a trend toward a lower proportion of subjects with troponin levels >5 times the URL with liraglutide versus placebo. Our results are suggestive of reduced infarct severity with liraglutide, which could impact the clinical prognosis of subjects experiencing MI.