bluuebunny/crossref_metadata_2025 huggingface dataset:
Apparent mineralocorticoid excess caused by novel compound heterozygous mutations in HSD11B2
Authors: Fan P , Zhang D , Yang K.Q , Zhang Y , Lu Y.T , Luo F , Tian T , Liu Y.X , Zhou X.L
Published: November 2020

Background

Apparent mineralocorticoid excess (AME) is a rare autosomal recessive genetic disorder caused by a mutation in the 11β-hydroxysteroid dehydrogenase type 2 gene (HSD11B2). AME is characterized by early-onset and severe hypertension, hypokalemia, and metabolic alkalosis.

Purpose

This study aimed to study the molecular genetics, clinical presentation, biochemical parameters, and treatment in the proband with AME from a non-consanguineous Chinese family.

Methods

Genomic DNA was recovered from peripheral blood leukocytes from nine subjects in this family. Next-generation sequencing and Sanger sequencing were performed to identify the HSD11B2 variants. In silico and genotype-phenotype correlations analyses were used to predict pathogenicity of candidate variants. A tailored therapy was performed for identified mutations carriers.

Results

Genetic analysis identified novel compound heterozygous HSD11B2 mutations (c.343-348del/c.1099-1101del) in the proband. In silico analysis predicted these HSD11B2 mutations were deleterious. The structural change and predicted consequences owing to the compound mutations have been modeled. The same compound mutations were not found in any other family members, 100 hypertensives, or 100 healthy controls. The proband had typical manifestations of AME, including early-onset and severe hypertension, hypokalemia, low plasma aldosterone concentration, hypokalemic alkalosis and nephrolithiasis. The probands' blood pressure and serum potassium level had returned to normal after treatmennt with dexamethasone (1.5 mg/day) and spirolactone (40 mg/day) for three months.

Conclusions

We conclude that this novel compound mutations are responsible for AME in the proband. These genetic and clinical data expand the genetic spectrum of HSD11B2 and demonstrate the pathogenic effects of identified mutations and genotype-phenotype correlations. It is emphasized that genetic diagnosis and specific treatment play an important role in patients with AME.

Figure 1

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Key Research and Development Program of China; PUMC Youth Fund and the Fundamental Research Funds for the Central Universities
Clinical response scores to predict blood pressure and renal function improvement following renal artery stenting for atherosclerotic renal artery stenosis
Authors: Kablak-Ziembicka A , Roslawiecka A , Badacz R , Sokolowski A , Musialek P , Rzeznik D , Legutko J , Zmudka K , Przewlocki T
Published: November 2020

Background

It is little known about predictors of systolic (SBP) and diastolic (DBP) blood pressure or renal function (eGFR) improvement in patients with atherosclerotic renal artery stenosis (ARAS) undergoing stent-assisted angioplasty (PTA). Therefore, we aimed to build a prediction scores that would indicate characteristics of patient subsets with ARAS most likely to have clinical improvement following PTA.

Methods

201 patients who underwent PTA for ARAS (2003–2018) were categorized as eGFR or SBP/DBP responders based on eGFR increase of ≥11 ml/min/1.73m2, decrease of SBP ≥20mmHg and DBP ≥5mmHg at 12-months following PTA. The remaining patients were classified as non-responders. The performance of logistic regression models were evaluated by basic decision characteristics. Continuous data have been transformed into binary coding with help of operating characteristic (ROC) curve. Predictive models have been constructed for each followed by construction of predictive models in each of 3 categories.

Results

Logistic regression analysis showed that: baseline SBP>145 mmHg, DBP >82 mmHg, previous myocardial infarction and Renal-Aotric-Ratio >5.1 were independent influencing factors of SBP response, with relative risk percentage shares of 69.8%; 12.1%; 10.9%; and 7.2%, respectively (sensitivity: 82%, specificity: 86.3%, positive (PPV):82% and negative (NPV) predictive values: 86.3%). The DBP decrease prediction model included baseline SBP >145 mmHg and DBP >82 mmHg, the ARAS progression, index kidney length >106 mm, and bilateral PTA with respective shares of 35.0%; 21.8%; 18.2%; 13.3% and 11.8%. (sensitivity: 76%, specificity: 77.8%, PPV: 80.7% and NPV: 72.6%). The eGFR increase was associated with baseline serum creatinine >122 μmol/L but eGFR greater than 30 ml/min/1.73m2, index kidney length >98 mm, end-diastolic velocity in index renal artery, renal resistive index <0.74, and requirement for >3 BP medications, with respective shares of 24.4%; 24.4%; 21.2%; 15% and 15% (sensitivity: 33.3%, specificity: 93.5%, PPV: 65.6% and NPV: 78.9%).

Conclusions

Current study identified clinical characteristics of patients who most likely to respond to PTA for ARAS. The sutability of the score should be verified in a prospective cohort of patients referred to PTA of ARAS

Funding Acknowledgement

Type of funding source: None
Blood pressure levels and risk of haemorrhagic stroke in patients with atrial fibrillation and anticoagulants: results from a primary care cohort with hypertension
Authors: Bager J.-E , Schioler L , Manhem K , Hjerpe P , Odesjo H , Mourtzinis G
Published: November 2020

Background

Haemorrhagic stroke (HS) is a serious condition that kills and debilitates many of those afflicted by it. Hypertension and oral anticoagulation (OAC) are independent risk factors for HS. Many patients with atrial fibrillation (AF) have hypertension and OAC. The concomitance of hypertension and OAC confers an even higher risk of haemorrhagic stroke, but less is known about the association between specific blood pressure levels and the risk of HS in patients with AF and OAC.

Purpose

To assess the risk of haemorrhagic stroke at different systolic blood pressure (SBP) levels in a primary care population with hypertension, AF and OAC.

Methods

We identified 3972 patients with hypertension, AF and OAC in a primary care database in southern Sweden. We followed patients from Jan 1, 2006 until a first event of HS, death, cessation of OAC or Dec 31, 2016. HS was defined as ICD-10 diagnosis codes: I60, I61, and I62. We analysed the association between SBP levels and HS by dividing SBP into five categories: <130, 130–139, 140–159, 160–179 and ≥180 mmHg. We also fitted a spline curve to visualise the relationship between SBP and HS. Hazard ratios (HR) were calculated for the SBP categories with a Cox proportional hazards model. The 130–139 group was used as a reference in the model. We identified age, sex, previous stroke, platelet inhibitor treatment, alcohol abuse and smoking as possible confounders with a directed acyclic graph and included them as co-variates in the model.

Results

We identified 51 cases of HS during follow-up. In the categorical analysis of SBP, point estimates of HRs for HS increased gradually from the lowest SBP category to the 160–179 category. Only the 160–179 category had a significantly different HR (3.76, CI 1.56–9.04) than the reference 130–139 category, however. See Table 1. No other co-variates were significantly associated with HS. The spline curve, Figure 1, illustrates a significantly increased HR for HS in the 140–175 SBP range.

Conclusions

In this real-world primary care cohort with hypertension, AF and OAC, we found that SBP in the 160–179 mmHg range was significantly associated with an increased risk of haemorrhagic stroke. Our findings emphasise the importance of blood pressure control in this patient category.

Figure 1. Continuous and categorical SBP & HS risk

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): The study was financed by grants from the Swedish state under the agreement between the Swedish government and the country councils, the ALF-agreement.
Single pill regimen improves persistence and leads lo better clinical outcome compared to identical multi pill combination. Results of START, a German claims data analysis
Authors: Predel H.G , Weisser B , Schmieder R.E , Wassmann S , Blettenberg J , Gillessen A , Fournier V , Noetel A , Randerath O , Boehm M
Published: November 2020

Background/Introduction

The current ESC/ESH-Guidelines for the treatment of arterial hypertension (AH) recommend initiation and escalation of medical treatment using renin–angiotensin–aldosterone system (RAAS) blocker, diuretics (D) and/or calcium channel blockers (CCB). They also recommend a single pill (SP) regimen to improve persistence, to increase blood pressure control and to reduce cardiovascular events.

Purpose

Data showing an advantage for a SP regimen compared to the identical loose combination (LC) regarding all these parameters in a single study are missing. We report now the results comparing SP with identical LC regarding persistence and cardiovascular outcomes in daily practice.

Methods

This was a retrospective, non-interventional analysis of an anonymized claims dataset covering patients suffering from cardiovascular diseases insured by the German AOK PLUS public health insurance in the years 2012–2017. Patients at age ≥18 years with an indication for the use of a combination of RAAS-blockers, D and/or CCB as SP or identical LC were followed up for 1 year. After 1:1-Propensity Score Matching (PSM) persistence (defined as redemption of prescription with a lack >60 days) and clinical outcomes were compared using non-parametric tests.

Results

After PSM, baseline characteristics were comparable between SP and LC groups. Each group included 10,801 patients with valsartan/amlodipine, 1,026 with candesartan/amlodipine, 1,823 with amlodipine/valsartan/hydrochlorothiazide (HCT), and 15,349 with ramipril/amlodipine as SP or identical LC. 8 clinical outcomes were compared for each combination. Persistence to treatment was significant higher in the SP group. In 27 of 32 comparisons a significantly lower Incidence Rate Ratio (IRR) was identified for SP. This was confirmed by time-to-event-analysis. The largest patient group (ramipril/amlodipine) showed a significant lower risk for SP observed for stroke (IRR=0.746; 95% CI 0.627–0.886; p<0.001), transitory ischemic attack (IRR=0.693; 95% CI 0.496–0.963; p=0.023), myocardial infarction (IRR=0.623; 95% CI 0.493–0.784; p<0.001), coronary artery disease (IRR=0.579; 95% CI 0.462–0.723; p<0.001), heart failure (IRR=0.468; 95% CI 0.409–0.534; p<0.001), all cause hospitalization (IRR=0.670; 95% CI 0.652–0.687; p<0.001), cardiovascular hospitalization (IRR=0.596; 95% CI 0.519–0.685; p<0.001), and all cause mortality (IRR=0.526; 95% CI 0.463–0.596; p<0.001) compared to LC.

Conclusion

A SP regimen improves persistence to medication, reduces cardiovascular events and total mortality compared to identical LC. The results of the START study strongly support the use of a SP concept in the AH medication treatment as recommended by the current ESH/ESC-Guidelines for the treatment of AH.

Funding Acknowledgement

Type of funding source: None
Beta-blockers are associated with incident heart failure: a secondary analysis of the systolic blood pressure intervention (SPRINT) trial
Authors: Silverman D.N , De Lavallaz J.D.F , Plante T.B , Goyal P , Infeld M.M , Meyer M
Published: November 2020

Background

The Systolic Blood Pressure Intervention Trial (SPRINT) evaluated whether a blood pressure (BP) goal of less than 120mmHg versus less than 140mmHg would reduce cardiovascular outcomes in subjects with at least one cardiovascular risk factor and without heart failure. Participating investigators were encouraged to use any antihypertensive medication class with a strong evidence base. The SPRINT trial was halted early due to a lower rate of the composite primary outcome in the 120mmHg group, which was mainly driven by a reduction in heart failure (HF).

Objective

As there is a concern that beta-blocker use may be associated with an excess risk for incident HF in subjects with a normal left ventricular systolic function, we evaluated the association between beta-blocker use and HF. Beta-blockers were compared with other major classes of antihypertensive medications. We also studied the association of antihypertensive class with loop-diuretic initiation.

Methods and results

In the 9,012 subjects, without HF at baseline, the association of beta-blocker exposure and incident HF was examined using time-variant competing risk analysis. Beta-blocker exposure was associated with an increased HF risk (HR 1.18; CI 1.07–1.30; p<0.001) and more frequent and earlier loop diuretic-use compared to other antihypertensive agents (both p<0.01). Sensitivity analyses of propensity-score matched cohorts confirmed a strong association of beta-blocker use and HF. Other major antihypertensive medication classes did not show this association.

Conclusions

Beta-blocker exposure was associated with a higher incidence of HF in hypertensive subjects without HF at baseline.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institutes of Health
External applicability of blood pressure-lowering drug trials to real-world patients with manifest cardiovascular disease
Authors: Bonekamp N.E , Spiering W , Nathoe H.M , Kappelle L.J , De Borst G.J , Visseren F.L.J , Westerink J
Published: November 2020

Background

Randomised controlled trials (RCTs) are the main source of evidence for clinical treatment guidelines. However, there are concerns that strict eligibility criteria for participant selection may limit applicability of trial results to real-world patients.

Purpose

To assess the applicability of blood pressure-lowering drug trials in real-world secondary preventive care in stable coronary artery disease, peripheral artery disease and cerebrovascular disease.

Methods

Eligibility criteria from the largest guideline-informing RCTs on blood pressure-lowering drugs, the EUROPA, PEACE, HOPE-PAD, PRoFESS and PROGRESS trials, were applied to three subcohorts within the UCC-SMART study with coronary artery disease (n=5155), peripheral artery disease (n=1487) and cerebrovascular disease (n=2515). Baseline differences between would-be trial eligible and ineligible patients were estimated. Differences in all-cause mortality and a composite major adverse cardiovascular event (MACE) outcome of cardiovascular death, myocardial infarction and stroke were calculated and adjusted for age, sex and cardiovascular risk factors using Cox proportional hazard models.

Results

Seventy-five percent of UCC-SMART patients with the appropriate cardiovascular disease were eligible for EUROPA, 84% for PEACE, 59% for HOPE-PAD, 17% for PRoFESS and 100% for PROGRESS. Across trials, the main reasons for UCC-SMART patients' ineligibility were age younger than 50 or 55 years and cardiovascular history. On average, eligible patients were older (range 1.4–14.6 years across trials). Incidence rates for all-cause mortality and MACE were higher for trial eligible patients (Figure 1). After adjustment for age and sex, EUROPA and PEACE eligible patients had a lower risk of mortality (EUROPA: hazard ratio (HR) 0.68 95% confidence interval (CI) 0.59–0.77, PEACE: HR 0.52 95% CI 0.43–0.64) and MACE (EUROPA: HR 0.88 95% CI 0.76–1.01, PEACE: 0.56 95% CI 0.46–0.69), while differences between HOPE-PAD and PRoFESS eligible and ineligible patients were not statistically significant.

Conclusion

The results from the landmark trials on blood pressure-lowering drugs, specifically RAASi, in patients with peripheral artery and cerebrovascular disease are widely applicable to real-world patient populations. Although the majority of coronary artery disease patients is eligible for the EUROPA and PEACE trial, the results of these trials should be applied to trial ineligible patients with caution.

Funding Acknowledgement

Type of funding source: Public hospital(s). Main funding source(s): UMC Utrecht
HFpEF score discriminates severity of cardiovascular profile in asymptomatic treated hypertensive patients: the campania salute network
Authors: Losi M.A , Grieco F , Canciello G , Mancusi C , Izzo R , Manzi M.V , De Luca N , Trimarco B , De Simone G , Barbato E
Published: November 2020

Background

The heart failure with preserved ejection fraction (HFpEF) score is easy to use and potentially useful to discriminate HFpEF from noncardiac causes of dyspnea. HFpEF score may be expressed also as probability to have HFpEF.

Purpose

We investigated whether a high HFpEF score can identify specific cardiovascular (CV) profile in treated hypertensive patients even without dyspnea.

Methods

From September to December 2019, we consecutively enrolled treated hypertensive patients without dyspnea, with normal left ventricular (LV) ejection fraction (>50%), and chronic kidney disease of no more than stage III. In addition to standard echocardiographic parameters we evaluated: 1) inappropriate LV mass, identified as a percent of predicted LV mass >128%, 2) myocardial energetic efficiency as the ratio of stroke volume to heart rate normalized by LV mass (MEEi), and 3) an estimate of arterial stiffness, i.e. the ratio of pulse pressure and stroke index (by allometric normalization by height), as previously reported. The probability of HFpEF was calculated from the HFpEF score, using body mass index, pulmonary systolic pressure, mitral E/E' ratio, age, and history or evidence of atrial fibrillation.

Results

188 patients with complete data were analyzed (42% women, age 61±14 years, 9% diabetic). Patients were then divided into 3 groups according to HFpEF probability tertiles and compared by ANOVA and trend analysis (Table 1).

Conclusions

Probability of HFpEF using HFpEF score and non-standard echocardiographic parameters identify worse CV profile in treated hypertensive patients without dyspnea.

Funding Acknowledgement

Type of funding source: None
Clinical and psychological aspects of true arterial hypertension and white coat hypertension
Authors: Legkonogov A , Sokolovskaya E
Published: November 2020

Purpose

To compare the clinical and psychological features, as well as echocardiographic and ambulatory blood pressure monitoring (ABPM) data in patients with true arterial hypertension (AH) and white coat hypertension (WCH).

Methods

Were studied 154 subjects (58 men and 96 women, average age 52.9±0.7 years) with increased office blood pressure. The control group consisted of 31 healthy individuals (12 men and 19 women, average age 51.5±2.4 years). All individuals underwent ABPM, Doppler echocardiography, and psychological status studies using the MMPI and Spielberger tests.

Results

ABPM confirmed the presence of AH in 127 (47 men and 80 women, average age 53.3±0.8 years) of 154 examined patients. 27 patients (17.5%) were diagnosed with WCH - 11 men and 16 women, the average age of 50.8±1.4 years. Among healthy individuals, dippers prevailed, while among AH patients the proportion of dippers was significantly lower (p<0.001) compared with the control group, and a larger number of non-dippers, over-dippers and night-peakers was noted (p<0.01). The distribution of patients with WCH by the type of the daily profile of blood pressure (BP) did not significantly differ from that in healthy individuals (p>0.05). Patients with AH compared with healthy patients had higher average values of the left ventricular (LV) posterior wall as well as interventricular septum thickness, left atrium diameter, and LV myocardial mass index. We found no signs of LV hypertrophy in WCH patients and healthy individuals. The correlation analysis confirmed a reliable relationship between most echocardiographic parameters and ABPM in AH patients (p<0.05). The results of the MMPI and Spielberger tests revealed higher levels of reactive and personal anxiety in patients with AH compared with healthy individuals. Patients with WCH were characterized by disharmonious personality profiles and, in comparison with the control group, more pronounced hypochondriac, hysteroid, and psychasthenic features. Compared with AH patients, subjects with WCH were characterized by less pronounced depression, isolation, rigidity of anxious affect, as well as a more pronounced demonstrative behavior.

Conclusions

In people with AH patients the structural and functional characteristics of the heart there correlate with the ABPM results. In contrast, echocardiographic findings in individuals with WCH do not significantly differ from those in healthy subjects. Individuals with WCH have more pronounced hypochondriacs, anxious-suspicious and hysteroid personality traits, while for patients with AH depression, isolation, and rigidity of anxious affect are more common.

Funding Acknowledgement

Type of funding source: None
Cerebral hemodynamics in patients with arterial hypertension of the older age groups with orthostatic hypotensive reactions
Authors: Atyunina I , Oschepkova E , Rogoza A , Lazareva N
Published: November 2020

Objective

To study cerebrovascular autoregulation in pts with arterial hypertension (AH) with orthostatic hypotensive reactions (OHR) during an active orthostatic test (AOT).

50 pts with AH (40 g, 10 m), 68.5±5.3 years, I-III gr. were examined. Blood pressure monitoring (BPM) by “BP Lab”, Russia. AOT was performed with continuous measurement of systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the digital artery (“Task Force Monitor”, “CNSystems” Austria). The criteria for the OHR were evaluated according to guidelines ESC, 2018. Cerebral hemodynamics in the middle cerebral artery (MCA) was monitored during the AOT (Angiodin-2K (BIOSS company, Russia), using a transcranial sensor with a freq. of 2 MHz. In the MCA, systolic (Vs), diastolic (Vd), average cerebral blood flow velocity (Vm), pulsation index (Pi), and vascular resistance index (Ri), the difference ΔVm30s,% and ΔVm30s, were recorded. Statistical analysis was performed using the non-parametric Mann-Whitney method using Statistica 6.0

Results

In 17 (34%) pts with AH, OHR was detected. BP in pts with OHR compared with pts without OHR (mmHg), SBP: 131.7±12.2 vs 131.3±13.8, p>0.05; DBP 74.3±11.8 vs 75.3±8.9, p>0.05). In AOT in pts with OHR, the Vm in the orthostasis significantly decreased compared to pts without OHR, both in the first 30 s. and at 3 min. (Tabl.1).

Conclusions

In pts with AH of older age groups with OHR, in comparison with the same category of pts without OHR, there is a change in cerebral autoregulation in the form of a more pronounced decrease in cerebral blood flow velocity in MCA in the orthostatic position.

Funding Acknowledgement

Type of funding source: None
Combined effect of fasting glucose and body mass index on mortality by age and sex in over 15 million adults: a cohort study
Authors: Jung M , Yi S.W , An S.J , Ihm S.H
Published: November 2020

Background

We aimed to elucidate whether synergic combined association of body mass index (BMI) and fasting blood glucose (FBG) on mortality exist and to identify FBS-BMI subgroups with higher mortality according to sex and age.

Methods

A total of 15,149,275 Korean adults participated in health examinations during 2003–2006 and were followed up until December 2018. Hazard ratios (HRs) of 40 BMI-FBG combined groups for mortality were assessed by Cox proportional hazards models.

Results

During mean 13.7 years of follow-up, 1,213,401 individuals died. The association between hyperglycemia and mortality was stronger in leaner than more obese individuals and these effects were more prominent in younger than older adults. Compared with overweight (BMI 25–27.4kg/m2) normoglycemic (FBG 80–94mg/dL), age, sex-adjusted HRs of leanest (BMI <20kg/m2) normoglycemic, overweight diabetes (FBG ≥180mg/dL), and leanest diabetes were 1.66, 2.17, and 4.77, respectively. Corresponding HRs in those aged 18–44 years were 1.29, 2.59, and 11.18, respectively, while corresponding HRs in those aged 75–99 years were 1.56, 1.72, and 2.87, respectively (Figure 1). The interpretation of BMI-FBG subgroups associated with higher mortality was not straightforward. For example, prediabetes (FBG 110–125 mg/dL) with BMI 20–22.4 kg/m2 had similar or higher mortality than low diabetes (FBG 126–179 mg/dL) with BMI ≥22.5 kg/m2. In non-diabetic women aged <45 years, BMI ≥27.5 kg/m2 was associated with the highest mortality, whereas the leanest had the worst mortality in each given FBG level in other age-sex groups.

Conclusions

Leanness and hyperglycemia interact together to increase mortality supra-multiplicatively, especially in younger adults, while complex interaction of BMI, FBG, sex and age on mortality exist.

Figure 1

Funding Acknowledgement

Type of funding source: None
Subclinical measures of peripheral atherosclerosis and risk of new-onset atrial fibrillation in men and women from general population
Authors: Geurts S , Brunborg C , Ikram M.A , Kavousi M
Published: November 2020

Background

Limited data on the link between peripheral vascular atherosclerosis measures and the risk of new-onset atrial fibrillation (AF) in the general population exists. Moreover, comprehensive assessment of the association between the two conditions among men and women is sparse.

Purpose

To determine the association between baseline and longitudinal measures of carotid intima-media thickness (cIMT), carotid plaque, and ankle-brachial index (ABI) with new-onset AF.

Methods

12840 participants free of AF at baseline were included in this large prospective population-based cohort study. Among the 12840 included participants, 11998 had at least one available measure for cIMT and 8532 for ABI. Presence of carotid plaque was only measured at baseline (n=11766). Three repeated measurements for cIMT and two repeated measurements for ABI were available during follow-up. The association between baseline cIMT, carotid plaque, and ABI as well as longitudinal changes in cIMT and ABI with incident AF were assessed using Cox regression and joint models respectively. Models were adjusted for age and traditional cardiovascular risk factors.

Results

During a median follow-up of 9.1 years, 1362 incident AF occurred. Baseline cIMT (adjusted hazard ratio–HR; 95% confidence interval–CI: 3.46; 1.97–6.05) and longitudinal changes in cIMT (adjusted HR; 95% CI: 3.35; 1.89–5.95) showed strong independent associations with incident AF among women (Figure 1). Baseline ABI showed a significant association with incident AF among men (adjusted HR; 95% CI: 0.61; 0.38–0.97) and a borderline significant association among women (adjusted HR; 95% CI: 0.65; 0.41–1.02). Longitudinal changes in ABI were not associated with the risk of incident AF independent of traditional risk factors.

Conclusions

Carotid atherosclerosis at baseline and progression of carotid atherosclerosis during follow-up were strongly associated with new-onset AF among women. Lower extremity peripheral atherosclerosis at baseline, but not its longitudinal changes during follow-up, was significantly associated with incident AF, in particular among men. Our findings imply that screening and monitoring for carotid atherosclerosis carry a potential for prevention of AF among women.

Figure 1. HR of baseline cIMT and AF

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): Netherlands Organization for the Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE)
Sex-specific reference values and determinants of infra-renal abdominal aortic diameter among women and men from general population
Authors: Zhu F , Arshi B , Ikram M , De Knegt R , Kavousi M
Published: November 2020

Introduction

Abdominal aortic diameter has shown to be a marker of adverse cardiovascular outcomes. Among the non-aneurysmal populations, studies regarding abdominal aortic diameter normal reference values are sparse. Moreover, data regarding the associations between cardiovascular risk factors and aortic diameter among men and women are limited.

Purpose

To establish age- and sex-specific distribution of the infra-renal abdominal aortic diameters among non-aneurysmal older adults from the general population and to investigate the associations between cardiovascular risk factors and aortic diameters in men and women.

Methods

From a population-based cohort, 4032 participants (mean age, 67.2 years; 60.4% women) with infra-renal diameter assessment and without history of cardiovascular disease were included. Mean and quantile values of diameters were calculated in different age groups. Multiple linear regression analysis was used to detect the association of cardiovascular risk factors with diameters in men and women.

Results

The mean crude diameter was larger in men [mean (SD): 19.5 (2.6) mm] compared to women [17.0 (2.4)mm] but after adjustment for body surface area (BSA), the differences were small. There was a non-linear relationship between age and diameter (p<0.001). After 66 years of age, the increase in diameter with increasing age was attenuated. After age 74 years in women and 71 years in men, the relationship between age and infra-renal aortic diameter was no longer statistically significant (Figure). Waist [standardized β (95% CI): 0.02 (0.0–0.04) in women and 0.03 (0.01–0.06) in men] and diastolic blood pressure [0.04 (0.02–0.05) in women and 0.02 (0.0–0.04) in men] were the risk factors for diameters in both sexes. Body mass index [0.02 (0.01–0.09)], systolic blood pressure [−0.01 (−0.02 to −0.01)], smoking status [0.21 (0.02–0.39)], cholesterol [−0.19 (−0.29 to −0.09)], and lipid-lowering medication [−0.47 (−0.71 to −0.23)] were significantly associated with aortic diameter only in women.

Conclusion

The differences in the crude abdominal aortic diameter between women and men diminished after taking into account the BSA. The abdominal aortic diameter increased steeply with advancing age and up to 66 years of age. However, after 74 years in women and 71 years in men, the diameter values reached a plateau. We also observed sex differences in the associations of cardiovascular risk factors with abdominal aortic diameter.

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): Netherlands Organization for the Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE)
Longitudinal changes of left ventricular systolic function and risk of heart failure and mortality among men and women from a general population
Authors: Arshi B , Papageorgiou G , Rueda-Ochoa O.L , Ikram M.A , Rizopoulos D , Kavousi M
Published: November 2020

Background

The incidence and characteristics of heart failure (HF) differ between men and women. However, evidence regarding sex differences in determinants and changes of cardiac function in association with incidence of HF remains scarce.

Purpose

To study the evolution and determinants of left ventricular ejection fraction (LVEF) over time and its association with incident mortality and HF among men and women.

Methods

From a population-based cohort, we included 7923 participants, 3319 men and 4604 women, free of heart failure (HF) and atrial fibrillation with up to 3 repeated echocardiographic measurements. Using joint models, we analyzed the evolution of LVEF and its associated traditional cardiovascular risk factors among men and women. Second, we studied the association of LVEF changes with incident HF and mortality as a composite outcome adjusted for age (time-varying covariate) and traditional cardiovascular risk factors. We then performed the analyses with HF and mortality as competing events.

Results

Mean (SD) age was 65.7 (9.6) in men and 66.5 (10) in women. During a median follow-up of 9 years, 988 events in men and 840 events in women occurred. LVEF had a one-directional nonlinear declining with increasing age among men and women (Figure). Up to age of 70, LVEF showed a sharper decline per year among men compared to women. Every unit increase in systolic blood pressure (SBP) was associated with 0.03% (0.05% to 0.02%) decrease in LVEF per year in men. Among women, SBP had an inverse J-shaped association with LVEF changes (P<0.001). Diastolic blood pressure (DBP) also showed a non-linear association with LVEF in both sexes. Prevalent diabetes was not associated with LVEF change. In the survival analysis, every 5% decrease in LVEF was associated with 35% and 30% increase in the risk of the composite outcome among men [HR (95% CI): 1.35 (1.26 to 1.43)] and women [HR (95% CI): 1.30 (1.22 to 1.40)].

Conclusion(s)

Despite a similar risk of LVEF decline for the composite outcome, the evolution of LVEF, especially before 70 years of age, differ between men and women. Cardiovascular risk factors, especially blood pressure, play diverse roles in the evolution of left ventricular systolic function among men and women.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam.
Gender-related nutritional risk differences in hospitalized patients after primary angioplasty for ST-segment myocardial infarction. Prognostic implications
Authors: Silva-Obregon A , Arroyo-Espliguero R , Viana-Llamas M.C , Estrella-Alonso A , Marian-Crespo C , Saboya-Sanchez S , Uribe-Heredia G , Tirado-Fernandez M.A , Eguileor-Marin Z , Ruiz De Santaquiteria-Torres V , Arriero-Fernandez N , Toran-Martinez C , Castillo-Sandoval A , Perez-Sanchez A , Garcia-Magallon B
Published: November 2020

Background

The prevalence of undernutrition among hospitalized patients is common and it has been associated to worse clinical outcomes, especially in heart failure and coronary artery disease patients. Female gender has been associated with major adverse events after a ST-segment myocardial infarction (STEMI).

Purpose

Assess the relationship between gender-based differences in nutritional status and one-year all-cause mortality among hospitalized patients after a primary angioplasty (PA) for STEMI.

Methods

Cohort of 321 consecutive patients (64.4 years [54.3–75.2]; 22.4% women) admitted to our general ICU after a PA for STEMI between November-2013 and February-2017. NRI was calculated as 1.519 × serum albumin (g/L) + 41.7 × (actual body weight [kg] / ideal weight [kg]). Patients were dichotomized in no to mild (NRI ≥97.5) and moderate to severe nutritional risk (NRI <97.5). The Clinical Frailty Scale (CFS) was used to assess biological frailty. Analyses were made using crosstab tables with Pearson's chi-squared and likelihood-ratio goodness-of-fit tests. Cramér's V test or Kendall rank correlation coefficient were used to measure the degree of association between variables.

Results

Gender distribution among nutritional risk categories showed a significant degree of association (value 0.251; P=0.017) between female gender and moderate to severe NRI (55.7% women vs. 34.9% men, P=0.002) (Figure 1), independently of frailty (P=0.172). Women had significantly greater one-year mortality rate than men (20.8% vs. 5.2%: OR 4.78, 95% confidence interval [CI], 2.15–10.60, P<0.001). Combination of moderate to high nutritional risk (NRI <97.5) and biological vulnerability (CFS ≥4) significantly increased one-year mortality rate in women (53.3% in women vs. 26.7% in men; P<0.001).

Conclusion

Among STEMI patients undergoing PA, women had a greater nutritional risk than men, regardless of biological frailty, and a greater one-year mortality rate. Undernutrition may be a risk factor implicated in the worse clinical outcome of female gender after STEMI.

Figure 1. Gender distribution among NRI categories

Funding Acknowledgement

Type of funding source: None
Cardiac remodeling in ambitious endurance-trained amateur athletes older than 50 years
Authors: Dalos D , Dachs T , Gatterer C , Schneider M , Binder T , Bonderman D , Hengstenberg C , Panzer S , Aschauer S
Published: November 2020

Background

Data on cardiac remodeling in athletes are conflicting and rarely available in veteran athletes.

Purpose

Therefore, in this study we aimed to define echocardiographic features of healthy endurance athletes older than 50 years.

Methods

We included probands aged >50 years, who have performed endurance sports at 70% of their maximum heart rate for at least 1 hour 3 times per week over the previous 5 years.

Results

Between November 2018 and May 2019, 69 probands were recruited. Median age was 57 years (IQR 52–64) and 26% were female. Groups were formed according to the median training time of 6 hours per week: (A) 45 probands with ≥6 hours (IQR 6–10) and (B) 24 probands with <6 hours (IQR 3.5–5). Age, sex and body mass index were similar. Group A demonstrated slightly smaller right atrial and left atrial (LA) diameters when compared to probands in B (53mm (IQR 49–55) vs. 53mm (IQR 51–58), p=0.045, and 52mm (IQR 49–55) vs. 53mm (IQR 52–58), p=0.039, respectively) and showed preserved diastolic function (p=0.026) with lower E/E' ratio (7 (IQR 6–9) vs. 9 (IQR 7–10), p=0.039). Interventricular septal thickness and relative wall thickness ratio were similar.

Global right and left ventricular (LV) strain were similar, but LA reservoir strain was higher in group A than in B (27% (IQR 22–34) vs. 20% (IQR 15–29), p=0.016).

Conclusion

Endurance training in healthy athletes older than 50 years does not result in relevant chamber dilatation or LV hypertrophy and a weekly training duration of ≥6 hours seems beneficial to preserve diastolic function associated with an increased LA reservoir function.

Funding Acknowledgement

Type of funding source: None
Obstructive sleep apnoe and cardiovascular, heart failure and mortality outcomes with empagliflozin versus placebo in the EMPA-REG OUTCOME trial
Authors: Yaggi H.K , Eliasson B , Kasai T , Marx N , Zinman B , Inzucchi S.E , Wanner C , Zwiener I , Wojeck B , Neeland I , Johansen O
Published: November 2020

Background/Introduction

Obstructive sleep apnoe (OSA) and type 2 diabetes (T2D) occurs more frequently in persons with obesity, and both OSA and T2D are associated with metabolic disturbances that increases the risk for cardiovascular disease (CVD). In EMPA-REG OUTCOME, a randomized placebo-controlled outcome trial involving 7020 patients with T2D and CVD, the sodium glucose co-transporter (SGLT)-2 inhibitor empagliflozin reduced HbA1c, systolic blood pressure, waist circumference, and weight, and also reduced the risk of 3-point major adverse CV events (3P- MACE) by 14%, CV death by 38% and hospitalization for heart failure (HHF) by 35%.

Purpose

We investigated incidence rates of CV, HHF, and mortality outcomes in patients with or without OSA at baseline, and the treatment effect of empagliflozin, in EMPA-REG OUTCOME.

Methods

The trial included patients from 42 countries with T2D (with HbA1c 7.0–9.0% for drug-naïve patients and 7.0–10.0% for those on stable glucose-lowering therapy), established CVD, and estimated glomerular filtration rate >30 mL/min/1.73 m2. Patients were randomised (1:1:1) to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo once daily in addition to standard of care. All CV outcomes were independently adjudicated and events were pooled for the 10 and 25mg doses. In this post-hoc analysis, OSA were assessed based on investigator reports using MedDRA 18.0 and incidence rates for outcomes were reported by adjusted event-rates per 100 patient-years. Analysis of effects on outcomes were performed using Cox regression models with multivariable adjustments.

Results

Of 7020 patients with T2D and CVD, OSA was reported in 391 (5.6% [placebo 5.4%; pooled empagliflozin doses 5.7%]. Compared with patients without OSA at baseline, those with OSA were more frequent males (82.9% vs 70.8%), living in region North-America (63.2% vs 17.3%), and had more obesity (BMI ≥35 kg/m2: 55.2% vs 18.2%) and more coronary artery disease (88.0 vs 74.9%). Over a median 3.1 years, individuals with OSA at baseline relative to those without OSA in the placebo group, experienced 1.3–2.0 fold higher event rates for 3P-MACE (OSA vs no OSA: 6.49 vs 4.27/100-patient-year), CV death (2.57 vs 1.99), HHF (2.71 vs 1.38) and all-cause mortality (4.29 vs 2.78). Empagliflozin improved CV, HHF, and mortality outcomes regardless of presence of OSA at baseline (p-for interactions >0.05 [Figure 1]).

Conclusions

In this post-hoc exploratory analysis, patients with OSA had higher frequency of events for 3P-MACE, HHF and mortality. The cardio-protective effects of empagliflozin was consistent in those with and without OSA at baseline.

Figure 1. Sleep apnea and empagliflozin

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Boehringer Ingelheim and Eli Lilly Diabetes Alliance
An absolute risk-guided approach to cardiovascular risk management within a chest pain clinic: the ARCPAC randomized trial
Authors: Black J.A , Campbell J , Sharman J , Nelson M , Parker S , Hamilton G , Marwick T
Published: November 2020

Background

The majority of patients attending chest pain clinics are found not to have a cardiac cause of their symptoms, but have a high burden of cardiovascular risk factors that may be opportunistically addressed. Absolute risk calculators are recommended to guide risk factor management, although it is uncertain to what extent these calculations may assist with patient engagement in risk factor modification.

Purpose

We sought to determine the usefulness of a proactive, absolute risk-based approach, to guide opportunistic cardiovascular risk factor management within a chest pain clinic.

Methods

This was a prospective, open-label, blinded-endpoint study in 192 enhanced risk (estimated 5-year risk ≥8%, based on Australian Absolute Risk Calculator) patients presenting to a tertiary hospital chest pain clinic. Patients were randomized to best practice usual care, or intervention with development of a proactive cardiovascular risk management strategy framed around a discussion of the individual's absolute risk. Patients found to have a cardiac cause of symptoms were excluded as they constitute a secondary prevention population. Primary outcome was 5-year absolute cardiovascular risk score at minimum 12 months follow up. Secondary outcomes were individual modifiable risk factors (lipid profile, blood pressure, smoking status).

Results

192 people entered the study; 100 in the intervention arm and 92 in usual care. There was no statistical difference between the two groups' baseline sociodemographic and clinical variables. The intervention group showed greater reduction in 5-year absolute risk scores (difference −2.77; p<0.001), and more favourable individual risk factors, although only smoking status and LDL cholesterol reached statistical significance (table).

Conclusion

An absolute risk-guided proactive risk factor management strategy employed opportunistically in a chest pain clinic significantly improves 5-year cardiovascular risk scores.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Tasmanian Community Fund
Comparison of two recent ceramide-based coronary risk prediction scores: CERT and CERT-2
Authors: Leiherer A , Muendlein A , Saely C.H , Laaksonen R , Laaperi M , Vonbank A , Fraunberger P , Drexel H
Published: November 2020

The Coronary Event Risk Test (CERT) is a validated cardiovascular risk predictor that uses circulating ceramide concentrations to allocate patients into one of four risk categories. This test has recently been updated (CERT-2), now additionally including phosphatidylcholine concentrations.

The purpose of this study was to investigate the power of CERT and CERT-2 to predict cardiovascular mortality in patients with cardiovascular disease (CVD).

We investigated a cohort of 999 patients with established CVD.

Overall, comparing survival curves (figure) for over 12 years of follow up and the predictive power of survival models using net reclassification improvement (NRI), CERT-2 was the best predictor of cardiovascular mortality, surpassing CERT (NRI=0.456; p=0.01) and also the 2019 ESC-SCORE (NRI=0.163; p=0.04). Patients in the highest risk category of CERT as compared to the lowest category had a HR of 3.63 [2.09–6.30] for cardiovascular death; for CERT-2 the corresponding HR was 6.02 [2.47–14.64]. Among patients with T2DM (n=322), the HR for cardiovascular death was 3.00 [1.44–6.23] using CERT and 7.06 [1.64–30.50] using CERT-2; the corresponding HRs among non-diabetic subjects were 2.99 [1.20–7.46] and 3.43 [1.03–11.43], respectively.

We conclude that both, CERT and CERT-2 scores are powerful predictors of cardiovascular mortality in CVD patients, especially in those patients with T2D. Performance is even higher with CERT-2.

Funding Acknowledgement

Type of funding source: None
Longitudinal obesity exposure over two decades is associated with subclinical myocardial injury: the Nord-Trondelag Health Study
Authors: Lyngbakken M.N , Rosjo H , Hveem K , Omland T
Published: November 2020

Background

Obesity is associated with subclinical myocardial injury as quantified by concentrations of cardiac troponin, but whether excess weight history is associated with increased cardiac troponin I (cTnI) remains unclear. We aimed to explore the association of obesity with cTnI using different indices of cumulative obesity exposure.

Methods

We analyzed cTnI with a high-sensitivity assay in 14,157 participants with follow-up over two decades in the prospective observational Nord-Trøndelag Health (HUNT) Study at study visit 4 (2017–2019). All subjects were free from known cardiovascular disease at baseline, and we excluded subjects with BMI <18.5 kg/m2. BMI was assessed at study visit 2 (1995–1997), 3 (2006–2008) and 4, and we categorized participants as normal weight (BMI <25), overweight (BMI ≥25 to <30) and obesity (BMI ≥30). At each study visit, BMI was designated a score of 0 (normal weight), 1 (overweight) or 2 (obesity), totaling a score from 0 to 6. Cumulative obesity exposure was calculated as average BMI above 25 kg/m2 between visits multiplied by the time between visits (excess BMI years, kg/m2 × years).

Results

Median age at visit 4 was 64.1 (range 40.9 to 101.5) years and 60% were women. Concentrations of cTnI were detectable in 77.2% of study participants, and were median 2.2 (1.3 to 3.9) ng/L. There was a linear increase in cTnI with increasing BMI score (p for trend <0.001) and increasing BMI score was associated with increased risk of high cTnI (p for trend <0.001; Table 1). For every 100 excess BMI years, there was a 15.6 (95% CI, 13.0 to 18.2) % increase in cTnI at study visit 4 (Figure 1).

Conclusion

Cumulative obesity exposure is associated with a linear increase in cTnI, a highly sensitive index of subclinical myocardial injury, reflecting the detrimental effect of long standing obesity on cardiovascular health.

Figure 1. BMI years and cTnI

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): South-Eastern Norway Regional Health Authority