A genome-wide genomic score added to standard recommended stratification tools does not improve the identification of patients with very low bone mineral density.

The role of integrating genomic scores (GSs) needs to be assessed. Adding a GS to recommended stratification tools does not improve the prediction of very low bone mineral density. However, we noticed that the GS performed equally or above individual risk factors in discrimination. PURPOSE: We aimed to investigate whether adding a genomic score (GS) to recommended stratification tools improves the discrimination of participants with very low bone mineral density (BMD). METHODS: BMD was measured in three thoracic vertebrae using CT. All participants provided information on standard osteoporosis risk factors. GSs and FRAX scores were calculated. Participants were grouped according to mean BMD into very low (<80 mg/cm3), low (80-120 mg/cm3), and normal (>120 mg/cm3) and according to the Bone Health and Osteoporosis Foundation recommendations for BMD testing into an "indication for BMD testing" and "no indication for BMD testing" group. Different models were assessed using the area under the receiver operating characteristics curves (AUC) and reclassification analyses. RESULTS: In the total cohort (n=1421), the AUC for the GS was 0.57 (95% CI 0.52-0.61) corresponding to AUCs for osteoporosis risk factors. In participants without indication for BMD testing, the AUC was 0.60 (95% CI 0.52-0.69) above or equal to AUCs for osteoporosis risk factors. Adding the GS to a clinical risk factor (CRF) model resulted in AUCs not statistically significant from the CRF model. Using probability cutoff values of 6, 12, and 24%, we found no improved reclassification or risk discrimination using the CRF-GS model compared to the CRF model. CONCLUSION: Our results suggest adding a GS to a CRF model does not improve prediction. However, we noticed that the GS performed equally or above individual risk factors in discrimination. Clinical risk factors combined showed superior discrimination to individual risk factors and the GS, underlining the value of combined CRFs in routine clinics as a stratification tool.

Prevalence and severity of coronary artery disease linked to prognosis in psoriasis and psoriatic arthritis patients: a multi-centre cohort study.

OBJECTIVES: (i) To estimate the prevalence and severity of coronary artery disease and (ii) to assess the risk of cardiovascular events and mortality, in patients with psoriasis and psoriatic arthritis (PsA) in a large-scale cohort of patients referred to coronary computed tomography angiography (CTA). METHODS: This was a cross-sectional study with follow-up of 46,022 patients based on data from a Danish national CTA registry. Exposure was defined as psoriasis or PsA. A group of patients without psoriasis, PsA or any other inflammatory disease was used as reference. Cross-sectional primary outcomes were a coronary artery calcium score (CACS) >0 and CACS ≥400, and secondary outcome was obstructive CAD. At follow-up, the primary outcome was a composite endpoint of cardiovascular events and all-cause mortality. All outcomes were adjusted for traditional cardiovascular risk factors. RESULTS: We identified 1356 psoriasis and 370 PsA patients. The adjusted odds ratio (OR) for psoriasis patients for CACS >0, CACS ≥400 and obstructive CAD was 1.26 (1.10-1.46), 1.25 (1.04-1.50) and 1.14 (0.98-1.33), respectively. For PsA patients, OR for CACS >0 was 1.28 (1.00-1.64). We found a crude hazard ratio (HR) of 1.49 (1.21-1.85) and adjusted HR of 1.14 (0.92-1.41) for the primary outcome in psoriasis patients. CONCLUSIONS: In this population, both psoriasis and PsA were associated with an increased prevalence of coronary calcification. Psoriasis patients also showed an increased prevalence of severe calcification. Psoriasis patients were at increased risk for cardiovascular events and death, however not after adjusting for the effect of other predictors.

Hyperoxia improves autonomic function in individuals with long-duration type 1 diabetes and macroalbuminuria.

AIM: Acute oxygen inhalation and slow deep breathing improve measures of autonomic function transiently in individuals with short-duration type 1 diabetes. Our aims were to examine these interventions and changes in autonomic function in individuals with long-duration type 1 diabetes and to explore interactions with the presence of macroalbuminuria or existing cardiovascular autonomic neuropathy. METHODS: Individuals with type 1 diabetes (n = 54) were exposed to acute oxygen inhalation, slow deep breathing and a combination of both (hereafter 'the combination'). Primary outcomes were change in baroreflex sensitivity and heart rate variability. Associations between changes in outcomes were evaluated using mixed effects models. RESULTS: Mean age ± sd was 60 ± 10 years and diabetes duration was 38 ± 14 years. Changes are presented as per cent difference from baseline with 95% confidence intervals. Acute oxygen inhalation, slow deep breathing and the combination increased baroreflex sensitivity by 21 (10, 34)%, 32 (13, 53)% and 30 (10, 54)%, respectively. Acute oxygen inhalation trended towards increasing heart rate variability 8 (-1, 17)% (P = 0.056), and slow deep breathing and the combination increased heart rate variability by 33 (18, 49)% and 44 (27, 64)% respectively. Macroalbuminuria or cardiovascular autonomic neuropathy did not modify results. CONCLUSION: Autonomic function is improved transiently in individuals with long-duration type 1 diabetes and normoalbuminuria or macroalbuminuria by acute oxygen inhalation and slow deep breathing. There is a risk of survival bias. Autonomic dysfunction might be a reversible condition, and hypoxia might represent a target of intervention.

Repeated Contrast Administration Is Associated With Low Risk of Postcontrast Acute Kidney Injury and Long-Term Complications in Patients With Severe Chronic Kidney Disease.

Patients with chronic kidney disease (CKD) frequently require radiographic examinations. We investigated the impact of repeated contrast administrations on short- and long-term kidney function and mortality in kidney transplantation candidates. In a prospective study, 81 predialysis transplantation candidates underwent computed tomography angiography (CTA) and invasive coronary angiography (ICA) as part of a pretransplant cardiovascular evaluation. Postcontrast plasma creatinine (P-creatinine) changes were compared with a precontrast control period. We identified postcontrast acute kidney injury (AKI) in 10 patients (13%) after CTA and in two patients (3%) after ICA. Compared with the control period, relative changes in P-creatinine were significantly higher after CTA (p < 0.001) and ICA (p < 0.01). Diabetic kidney failure (p < 0.05) and contrast dose >0.8 mL/kg (p < 0.001) were associated with increases in P-creatinine. All cases of postcontrast AKI were reversible, and we found no differences between the progression rates of the kidney failure during 12 months before and after contrast exposure (p = 0.56). In a Cox regression analysis, creatinine changes after CTA or ICA were not associated with increased need for dialysis treatment or mortality. Contrast exposure and transient postcontrast AKI did not increase the risk of accelerated CKD progression or the time to initiation of dialysis or death.

Association of anemia with the risk of cardiovascular adverse events in overweight/obese patients.

OBJECTIVE: Anemia is associated with increased cardiovascular risks. Obesity may cause anemia in several ways, for example, by low-grade inflammation and relative iron deficit. The outcomes associated with anemia in overweight/obese patients at high cardiovascular risk are however not known. Therefore, we investigated the cardiovascular prognosis in overweight/obese subjects with anemia. METHODS: A total of 9,687 overweight/obese cardiovascular high-risk patients from the Sibutramine Cardiovascular OUTcomes trial were studied. Patients were stratified after baseline hemoglobin level and followed for the risks of primary event (comprising nonfatal myocardial infarction, nonfatal stroke, resuscitated cardiac arrest or cardiovascular death) and all-cause mortality. Risk estimates (hazard ratios (HR) with 95% confidence intervals (CI)) were calculated using Cox regression models. RESULTS: Anemia was unadjusted associated with increased risk for the primary event, HR 1.73 (CI 1.37-2.18) and HR 2.02 (CI 1.34-3.06) for patients with mild or moderate-to-severe anemia, respectively, compared with patients without anemia. Adjusted for several confounders, anemia remained of prognostic importance. Increased risk of the primary events appeared to be driven by risk of cardiovascular death, adjusted HR 1.82 (CI 1.33-2.51) for mild anemia and adjusted HR 1.65 (CI 0.90-3.04) for moderate-to-severe anemia, and all-cause mortality, adjusted HR 1.50 (CI 1.17-1.93) for mild and adjusted HR 1.61 (CI 1.04-2.51) for moderate-to-severe anemia. While adding serum creatinine to the models, the increased risk of mild anemia was still a significant predictor for mortality (cardiovascular and all-cause), whereas moderate-to-severe anemia was not. For the primary events, anemia was no longer of independent prognostic importance when including serum creatinine. CONCLUSION: Anemia is associated with an increased risk of long-term adverse cardiovascular events and deaths among overweight/obese cardiovascular high-risk patients. The increased risk appeared to be driven by the risk of cardiovascular death and all-cause mortality, and renal impairments seemed to have a role in the increased risk.

Coronary artery disease risk reclassification using an acoustic-based score in view of the new European Society of Cardiology 2019 guidelines on Chronic Coronary Syndromes.

In August 2019, ESC published new guidelines on Chronic Coronary Syndromes including a new risk assessment paradigm for estimation of pre-test-probability. The CAD-score is an acoustic-based score for ruling-out of coronary artery disease (CAD). In the current letter to the editor we re-evaluate the re-classification potential the CAD-score in the view of the new guidelines.

Coronary artery disease risk reclassification by a new acoustic-based score.

To determine the potential of a non-invasive acoustic device (CADScor®System) to reclassify patients with intermediate pre-test probability (PTP) and clinically suspected stable coronary artery disease (CAD) into a low probability group thereby ruling out significant CAD. Audio recordings and clinical data from three studies were collected in a single database. In all studies, patients with a coronary CT angiography indicating CAD were referred to coronary angiography. Audio recordings of heart sounds were processed to construct a CAD-score. PTP was calculated using the updated Diamond-Forrester score and patients were classified according to the current ESC guidelines for stable CAD: low < 15%, intermediate 15-85% and high > 85% PTP. Intermediate PTP patients were re-classified to low probability if the CAD-score was ≤ 20. Of 2245 patients, 212 (9.4%) had significant CAD confirmed by coronary angiography ( ≥ 50% diameter stenosis). The average CAD-score was higher in patients with significant CAD (38.4 ± 13.9) compared to the remaining patients (25.1 ± 13.8; p < 0.001). The reclassification increased the proportion of low PTP patients from 13.6% to 41.8%, reducing the proportion of intermediate PTP patients from 83.4% to 55.2%. Before reclassification 7 (3.1%) low PTP patients had CAD, whereas post-reclassification this number increased to 28 (4.0%) (p = 0.52). The net reclassification index was 0.209. Utilization of a low-cost acoustic device in patients with intermediate PTP could potentially reduce the number of patients referred for further testing, without a significant increase in the false negative rate, and thus improve the cost-effectiveness for patients with suspected stable CAD.

Influence of Cardiac CT based disease severity and clinical symptoms on the diagnostic performance of myocardial perfusion.

We aimed to identify factors influencing the sensitivity of perfusion imaging after an initial positive coronary computed tomography angiography (CCTA) using invasive coronary angiography (ICA) with conditional fractional flow reserve (FFR) as reference. Secondly we aimed to identify factors associated with revascularisation and to evaluate treatment outcome after ICA. We analysed 292 consecutive patients with suspected significant coronary artery disease (CAD) at CCTA, who underwent perfusion imaging with either cardiac magnetic resonance (CMR) or myocardial perfusion scintigraphy (MPS) followed by ICA with conditional FFR. Stratified analysis and uni- and multiple logistic regression analyses were performed to identify predictors of diagnostic agreement between perfusion scans and ICA and predictors of revascularisation. Myocardial ischemia evaluated with perfusion scans was present in 65/292 (22%) while 117/292 (40%) had obstructive CAD evaluated by ICA. Revascularisation rate was 90/292 (31%). The overall sensitivity for perfusion scans was 39% (30-48), specificity 89% (83-93), PPV 69% (57-80) and NPV 68% (62-74). Stratified analysis showed higher sensitivities in patients with multi-vessel disease at CCTA 49% (37-60) and typical chest pain 50% (37-60). Predictors of revascularisation were multi-vessel disease by CCTA (OR 3.51 [1.91-6.48]) and a positive perfusion scan (OR 4.69 [2.49-8.83]). The sensitivity for perfusion scans after CCTA was highest in patients with typical angina and multiple lesions at CCTA and predicted diagnostic agreement between perfusion scans and ICA. Abnormal perfusion and multi vessel disease at CCTA predicted revascularisation.

Diagnosing coronary artery disease after a positive coronary computed tomography angiography: the Dan-NICAD open label, parallel, head to head, randomized controlled diagnostic accuracy trial of cardiovascular magnetic resonance and myocardial perfusion scintigraphy.

Aims: Perfusion scans after coronary computed tomography angiography (CCTA) in patients with suspected coronary artery disease (CAD) may reduce unnecessary invasive coronary angiographies (ICAs). However, the diagnostic accuracy of perfusion scans after primary CCTA is unknown. The aim of this study was to determine the diagnostic accuracy of cardiac magnetic resonance (CMR) and myocardial perfusion scintigraphy (MPS) against ICA with fractional flow reserve (FFR) in patients suspected of CAD by CCTA. Methods and results: Included were consecutive patients (1675) referred to CCTA with symptoms of CAD and low/intermediate risk profile. Patients with suspected CAD based on CCTA were randomized 1:1 to CMR or MPS followed by ICA with FFR. Obstructive CAD was defined as FFR ≤ 0.80 or > 90% diameter stenosis by visual assessment. After initial CCTA, 392 patients (23%) were randomized; 197 to CMR and 195 to MPS. Perfusion scans and ICA were completed in 292 patients (CMR 148, MPS 144). Based on the ICA, 117/292 (40%) patients were classified with CAD. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) for CMR were 41%, 95% CI [28-54], 84% [75-91], 62% [45-78], and 68% [58-76], respectively. For the MPS group 36% [24-50], 94% [87-98], 81% [61-93], and 68% [59-76], respectively. Conclusion: Patients with low/intermediate CAD risk and a positive CCTA scan represent a challenge to perfusion techniques indicated by the low sensitivity of both CMR and MPS with FFR as a reference. The mechanisms underlying this discrepancy need further investigation.

Multistep determination of enzyme activity by flow injection and sequential injection analysis. Assay of amyloglucosidase.

A multi-point assay for determination of the activity of amyloglucosidase (AMG) by FIA and SIA is described. The assay is based on two consecutive reactions that are mutually incompatible. Both the FIA and SIA procedures allow these two reactions to be completely separated, whereby each of the processes can be individually optimized with respect to operational parameters. Special emphasis is placed on comparing the performance and applicability of the two procedures for this type of assay.

Submergence of roots for alveolar ridge preservation. A failure (4-year follow-up study).

A 4-year clinical and radiographic follow-up study of 20 cases of crown-resected root-filled roots, covered by mucosal flaps, distributed among 15 patients, has been carried out. Only cases of uneventful submergence of the root with intact healthy mucosa were regarded as successful. This study shows that: (1) The number of failures increases with the years; from 3 cases at the 1-year to 11 cases at the 4-year follow-up, corresponding to 53% (8/15) of the patients. In the failures, an exposure of the root-surface was seen, but without inflammation in the surrounding tissue. These roots could be extracted without bone loss. (2) Alveolar ridge atrophy is not prevented by retained roots, and is probably the primary reason for failure of coverage. The 11 failures showed alveolar ridge atrophy, which was observed before failure in 6 cases. None of the successful cases showed alveolar ridge atrophy. The present method cannot be recommended as a routine procedure.

Extraction of teeth with root preservation.

A method for covering single root-filled roots by mucosal flaps has been developed. The method has been used for patients attending the Royal Dental College, Copenhagen, for total extractions of teeth and full denture treatment. The operative method consists in covering a crown-resected, root-filled root by a combined buccal trapezoid flap and a bridge-shaped lingual flap. Twenty-seven operations were carried out on 17 patients, nine men and eight women 26-60 years old (mean 43 years). Results after a 2-month follow-up are presented. In the first 11 operations only a single buccal flap was used for covering the root. As only five of these operations healed uneventfully the method was modified into a combined buccallingual flap. This method was used in 16 cases with primary, uneventful healing in 15 cases.