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Functional versus morphological assessment of vascular age in patients with coronary heart disease
(2021)
Communicating cardiovascular risk based on individual vascular age (VA) is a well acknowledged concept in patient education and disease prevention. VA may be derived functionally, e.g. by measurement of pulse wave velocity (PWV), or morphologically, e.g. by assessment of carotid intima-media thickness (cIMT). The purpose of this study was to investigate whether both approaches produce similar results. Within the context of the German subset of the EUROASPIRE IV survey, 501 patients with coronary heart disease underwent (a) oscillometric PWV measurement at the aortic, carotid-femoral and brachial-ankle site (PWVao, PWVcf, PWVba) and derivation of the aortic augmentation index (AIao); (b) bilateral cIMT assessment by high-resolution ultrasound at three sites (common, bulb, internal). Respective VA was calculated using published equations. According to VA derived from PWV, most patients exhibited values below chronological age indicating a counterintuitive healthier-than-anticipated vascular status: for VA(PWVao) in 68% of patients; for VA\(_{AIao}\) in 52% of patients. By contrast, VA derived from cIMT delivered opposite results: e.g. according to VA\(_{total-cIMT}\) accelerated vascular aging in 75% of patients. To strengthen the concept of VA, further efforts are needed to better standardise the current approaches to estimate VA and, thereby, to improve comparability and clinical utility.
Aims
Cognitive dysfunction occurs frequently in patients with heart failure (HF), but early detection remains challenging. Serum glial fibrillary acidic protein (GFAP) is an emerging biomarker of cognitive decline in disorders of primary neurodegeneration such as Alzheimer's disease. We evaluated the utility of serum GFAP as a biomarker for cognitive dysfunction and structural brain damage in patients with stable chronic HF.
Methods and results
Using bead-based single molecule immunoassays, we quantified serum levels of GFAP in patients with HF participating in the prospective Cognition.Matters-HF study. Participants were extensively phenotyped, including cognitive testing of five separate domains and magnetic resonance imaging (MRI) of the brain. Univariable and multivariable models, also accounting for multiple testing, were run. One hundred and forty-six chronic HF patients with a mean age of 63.8 ± 10.8 years were included (15.1% women). Serum GFAP levels (median 246 pg/mL, quartiles 165, 384 pg/mL; range 66 to 1512 pg/mL) did not differ between sexes. In the multivariable adjusted model, independent predictors of GFAP levels were age (T = 5.5; P < 0.001), smoking (T = 3.2; P = 0.002), estimated glomerular filtration rate (T = −4.7; P < 0.001), alanine aminotransferase (T = −2.1; P = 0.036), and the left atrial end-systolic volume index (T = 3.4; P = 0.004). NT-proBNP but not serum GFAP explained global cerebral atrophy beyond ageing. However, serum GFAP levels were associated with the cognitive domain visual/verbal memory (T = −3.0; P = 0.003) along with focal hippocampal atrophy (T = 2.3; P = 0.025).
Conclusions
Serum GFAP levels are affected by age, smoking, and surrogates of the severity of HF. The association of GFAP with memory dysfunction suggests that astroglial pathologies, which evade detection by conventional MRI, may contribute to memory loss beyond ageing in patients with chronic HF.
Background
Chronic heart failure (HF) is known to increase the risk of developing Alzheimer’s dementia significantly. Thus, detecting and preventing mild cognitive impairment, which is common in patients with HF, is of great importance. Serum biomarkers are increasingly used in neurological disorders for diagnostics, monitoring, and prognostication of disease course. It remains unclear if neuronal biomarkers may help detect cognitive impairment in this high-risk population. Also, the influence of chronic HF and concomitant renal dysfunction on these biomarkers is not well understood.
Methods
Within the monocentric Cognition.Matters-HF study, we quantified the serum levels of phosphorylated tau protein 181 (pTau) and neurofilament light chain (NfL) of 146 extensively phenotyped chronic heart failure patients (aged 32 to 85 years; 15.1% women) using ultrasensitive bead-based single-molecule immunoassays. The clinical work-up included advanced cognitive testing and cerebral magnetic resonance imaging (MRI).
Results
Serum concentrations of NfL ranged from 5.4 to 215.0 pg/ml (median 26.4 pg/ml) and of pTau from 0.51 to 9.22 pg/ml (median 1.57 pg/ml). We detected mild cognitive impairment (i.e., T-score < 40 in at least one cognitive domain) in 60% of heart failure patients. pTau (p = 0.014), but not NfL, was elevated in this group. Both NfL (ρ = − 0.21; p = 0.013) and pTau (ρ = − 0.25; p = 0.002) related to the cognitive domain visual/verbal memory, as well as white matter hyperintensity volume and cerebral and hippocampal atrophy. In multivariable analysis, both biomarkers were independently influenced by age (T = 4.6 for pTau; T = 5.9 for NfL) and glomerular filtration rate (T = − 2.4 for pTau; T = − 3.4 for NfL). Markers of chronic heart failure, left atrial volume index (T = 4.6) and NT-proBNP (T = 2.8), were further cardiological determinants of pTau and NfL, respectively. In addition, pTau was also strongly affected by serum creatine kinase levels (T = 6.5) and ferritin (T = − 3.1).
Conclusions
pTau and NfL serum levels are strongly influenced by age-dependent renal and cardiac dysfunction. These findings point towards the need for longitudinal examinations and consideration of frequent comorbidities when using neuronal serum biomarkers.
Background:
While data from primary care suggest an insufficient control of vascular risk factors, little is known about vascular risk factor control in the general population. We therefore aimed to investigate the adoption of adequate risk factor control and its determinants in the general population free of cardiovascular disease (CVD).
Methods:
Data from the Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) Cohort Study, a population-based study of inhabitants aged 30 to 79 years from the general population of Würzburg (Germany), were used. Proportions of participants without established CVD meeting targets for risk factor control recommended by 2016 ESC guideline were identified. Determinants of the accumulation of insufficiently controlled vascular risk factors (three or more) were assessed.
Results:
Between December 2013 and April 2015, 1379 participants without CVD were included; mean age was 53.1 ± 11.9 years and 52.9% were female; 30.8% were physically inactive, 55.2% overweight, 19.3% current smokers. Hypertension, dyslipidemia, and diabetes mellitus were prevalent in 31.8%, 57.6%, and 3.9%, respectively. Treatment goals were not reached despite medication in 52.7% of hypertensive, in 37.3% of hyperlipidemic and in 44.0% of diabetic subjects. Insufficiently controlled risk was associated with male sex (OR 1.94, 95%CI 1.44–2.61), higher age (OR for 30–39 years vs. 70–79 years 4.01, 95%CI 1.94–8.31) and lower level of education (OR for primary vs. tertiary 2.15, 95%CI 1.48–3.11).
Conclusions:
In the general population, prevalence of vascular risk factors was high. We found insufficient identification and control of vascular risk factors and a considerable potential to improve adherence to cardiovascular guidelines for primary prevention. Further studies are needed to identify and overcome patient- and physician-related barriers impeding successful control of vascular risk factors in the general population.
Background.
Effective antihypertensive treatment depends on patient compliance regarding prescribed medications. We assessed the impact of beliefs related towards antihypertensive medication on blood pressure control in a population-based sample treated for hypertension.
Methods.
We used data from the Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) study investigating 5000 inhabitants aged 30 to 79 years from the general population of Würzburg, Germany. The Beliefs about Medicines Questionnaire German Version (BMQ-D) was provided in a subsample without established cardiovascular diseases (CVD) treated for hypertension. We evaluated the association between inadequately controlled hypertension (systolic RR >140/90 mmHg; >140/85 mmHg in diabetics) and reported concerns about and necessity of antihypertensive medication.
Results.
Data from 293 participants (49.5% women, median age 64 years [quartiles 56.0; 69.0]) entered the analysis. Despite medication, half of the participants (49.8%) were above the recommended blood pressure target. Stratified for sex, inadequately controlled hypertension was less frequent in women reporting higher levels of concerns (OR 0.36; 95%CI 0.17-0.74), whereas no such association was apparent in men. We found no association for specific-necessity in any model.
Conclusion.
Beliefs regarding the necessity of prescribed medication did not affect hypertension control. An inverse association between concerns about medication and inappropriately controlled hypertension was found for women only. Our findings highlight that medication-related beliefs constitute a serious barrier of successful implementation of treatment guidelines and underline the role of educational interventions taking into account sex-related differences.
This expert opinion paper on cardiac imaging after acute ischemic stroke or transient ischemic attack (TIA) includes a statement of the "Heart and Brain" consortium of the German Cardiac Society and the German Stroke Society. The Stroke Unit-Commission of the German Stroke Society and the German Atrial Fibrillation NETwork (AFNET) endorsed this paper. Cardiac imaging is a key component of etiological work-up after stroke. Enhanced echocardiographic tools, constantly improving cardiac computer tomography (CT) as well as cardiac magnetic resonance imaging (MRI) offer comprehensive non- or less-invasive cardiac evaluation at the expense of increased costs and/or radiation exposure. Certain imaging findings usually lead to a change in medical secondary stroke prevention or may influence medical treatment. However, there is no proof from a randomized controlled trial (RCT) that the choice of the imaging method influences the prognosis of stroke patients. Summarizing present knowledge, the German Heart and Brain consortium proposes an interdisciplinary, staged standard diagnostic scheme for the detection of risk factors of cardio-embolic stroke. This expert opinion paper aims to give practical advice to physicians who are involved in stroke care. In line with the nature of an expert opinion paper, labeling of classes of recommendations is not provided, since many statements are based on expert opinion, reported case series, and clinical experience.
Impact of cardiovascular risk factors on myocardial work-insights from the STAAB cohort study
(2022)
Myocardial work is a new echocardiography-based diagnostic tool, which allows to quantify left ventricular performance based on pressure-strain loops, and has been validated against invasively derived pressure-volume measurements. Myocardial work is described by its components (global constructive work [GCW], global wasted work [GWW]) and indices (global work index [GWI], global work efficiency [GWE]). Applying this innovative concept, we characterized the prevalence and severity of subclinical left ventricular compromise in the general population and estimated its association with cardiovascular (CV) risk factors. Within the Characteristics and Course of Heart Failure STAges A/B and Determinants of Progression (STAAB) cohort study we comprehensively phenotyped a representative sample of the population of Würzburg, Germany, aged 30-79 years. Indices of myocardial work were determined in 1929 individuals (49.3% female, mean age 54 ± 12 years). In multivariable analysis, hypertension was associated with a mild increase in GCW, but a profound increase in GWW, resulting in higher GWI and lower GWE. All other CV risk factors were associated with lower GCW and GWI, but not with GWW. The association of hypertension and obesity with GWI was stronger in women. We conclude that traditional CV risk factors impact selectively and gender-specifically on left ventricular myocardial performance, independent of systolic blood pressure. Quantifying active systolic and diastolic compromise by derivation of myocardial work advances our understanding of pathophysiological processes in health and cardiac disease.
Introduction: Left ventricular (LV) dilatation and LV hypertrophy are acknowledged precursors of myocardial dysfunction and ultimately of heart failure, but the implications of abnormal LV geometry on myocardial function are not well-understood. Non-invasive LV myocardial work (MyW) assessment based on echocardiography-derived pressure-strain loops offers the opportunity to study detailed myocardial function in larger cohorts. We aimed to assess the relationship of LV geometry with MyW indices in general population free from heart failure.
Methods and Results: We report cross-sectional baseline data from the Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) cohort study investigating a representative sample of the general population of Würzburg, Germany, aged 30–79 years. MyW analysis was performed in 1,926 individuals who were in sinus rhythm and free from valvular disease (49.3% female, 54 ± 12 years). In multivariable regression, higher LV volume was associated with higher global wasted work (GWW) (+0.5 mmHg% per mL/m\(^2\), p < 0.001) and lower global work efficiency (GWE) (−0.02% per mL/m\(^2\), p < 0.01), while higher LV mass was associated with higher GWW (+0.45 mmHg% per g/m\(^2\), p < 0.001) and global constructive work (GCW) (+2.05 mmHg% per g/m\(^2\), p < 0.01) and lower GWE (−0.015% per g/m\(^2\), p < 0.001). This was dominated by the blood pressure level and also observed in participants with normal LV geometry and concomitant hypertension.
Conclusion: Abnormal LV geometric profiles were associated with a higher amount of wasted work, which translated into reduced work efficiency. The pattern of a disproportionate increase in GWW with higher LV mass might be an early sign of hypertensive heart disease.
Background
The guideline recommendation to not measure carotid intima-media thickness (CIMT) for cardiovascular risk prediction is based on the assessment of just one single carotid segment. We evaluated whether there is a segment-specific association between different measurement locations of CIMT and cardiovascular risk factors.
Methods
Subjects from the population-based STAAB cohort study comprising subjects aged 30 to 79 years of the general population from Würzburg, Germany, were investigated. CIMT was measured on the far wall of both sides in three different predefined locations: common carotid artery (CCA), bulb, and internal carotid artery (ICA). Diabetes, dyslipidemia, hypertension, smoking, and obesity were considered as risk factors. In multivariable logistic regression analysis, odds ratios of risk factors per location were estimated for the endpoint of individual age- and sex-adjusted 75th percentile of CIMT.
Results
2492 subjects were included in the analysis. Segment-specific CIMT was highest in the bulb, followed by CCA, and lowest in the ICA. Dyslipidemia, hypertension, and smoking were associated with CIMT, but not diabetes and obesity. We observed no relevant segment-specific association between the three different locations and risk factors, except for a possible interaction between smoking and ICA.
Conclusions
As no segment-specific association between cardiovascular risk factors and CIMT became evident, one simple measurement of one location may suffice to assess the cardiovascular risk of an individual.
Background:
Adherence to pharmacotherapeutic treatment guidelines in patients with heart failure (HF) is of major prognostic importance, but thorough implementation of guidelines in routine care remains insufficient. Our aim was to investigate prevalence and characteristics of HF in patients with coronary heart disease (CHD), and to assess the adherence to current HF guidelines in patients with HF stage C, thus identifying potential targets for the optimization of guideline implementation.
Methods:
Patients from the German sample of the European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EuroAspire) IV survey with a hospitalization for CHD within the previous six to 36 months providing valid data on echocardiography as well as on signs and symptoms of HF were categorized into stages of HF: A, prevalence of risk factors for developing HF; B, asymptomatic but with structural heart disease; C, symptomatic HF. A Guideline Adherence Indicator (GAI-3) was calculated for patients with reduced (≤40%) left ventricular ejection fraction (HFrEF) as number of drugs taken per number of drugs indicated; beta-blockers, angiotensin converting enzyme inhibitors/angiotensin receptor blockers, and mineralocorticoid receptor antagonists (MRA) were considered.
Results:
509/536 patients entered analysis. HF stage A was prevalent in n = 20 (3.9%), stage B in n = 264 (51.9%), and stage C in n = 225 (44.2%) patients; 94/225 patients were diagnosed with HFrEF (42%). Stage C patients were older, had a longer duration of CHD, and a higher prevalence of arterial hypertension. Awareness of pre-diagnosed HF was low (19%). Overall GAI-3 of HFrEF patients was 96.4% with a trend towards lower GAI-3 in patients with lower LVEF due to less thorough MRA prescription.
Conclusions:
In our sample of CHD patients, prevalence of HF stage C was high and a sizable subgroup suffered from HFrEF. Overall, pharmacotherapy was fairly well implemented in HFrEF patients, although somewhat worse in patients with more reduced ejection fraction. Two major targets were identified possibly suited to further improve the implementation of HF guidelines: 1) increase patients´ awareness of diagnosis and importance of HF; and 2) disseminate knowledge about the importance of appropriately implementing the use of mineralocorticoid receptor antagonists.
Trial registration:
This is a cross-sectional analysis of a non-interventional study. Therefore, it was not registered as an interventional trial.