Impact of sex and gender on post-COVID-19 syndrome, Switzerland, 2020.

BackgroundWomen are overrepresented among individuals with post-acute sequelae of SARS-CoV-2 infection (PASC). Biological (sex) as well as sociocultural (gender) differences between women and men might account for this imbalance, yet their impact on PASC is unknown.AimWe assessed the impact of sex and gender on PASC in a Swiss population.MethodOur multicentre prospective cohort study included 2,856 (46% women, mean age 44.2 ± 16.8 years) outpatients and hospitalised patients with PCR-confirmed SARS-CoV-2 infection.ResultsAmong those who remained outpatients during their first infection, women reported persisting symptoms more often than men (40.5% vs 25.5% of men; p < 0.001). This sex difference was absent in hospitalised patients. In a crude analysis, both female biological sex (RR = 1.59; 95% CI: 1.41-1.79; p < 0.001) and a score summarising gendered sociocultural variables (RR = 1.05; 95% CI: 1.03-1.07; p < 0.001) were significantly associated with PASC. Following multivariable adjustment, biological female sex (RR = 0.96; 95% CI: 0.74-1.25; p = 0.763) was outperformed by feminine gender-related factors such as a higher stress level (RR = 1.04; 95% CI: 1.01-1.06; p = 0.003), lower education (RR = 1.16; 95% CI: 1.03-1.30; p = 0.011), being female and living alone (RR = 1.91; 95% CI: 1.29-2.83; p = 0.001) or being male and earning the highest income in the household (RR = 0.76; 95% CI: 0.60-0.97; p = 0.030).ConclusionSpecific sociocultural parameters that differ in prevalence between women and men, or imply a unique risk for women, are predictors of PASC and may explain, at least in part, the higher incidence of PASC in women. Once patients are hospitalised during acute infection, sex differences in PASC are no longer evident.

Long-term impact of myocardial inflammation on quantitative myocardial perfusion-a descriptive PET/MR myocarditis study.

PURPOSE: Whether myocardial inflammation causes long-term sequelae potentially affecting myocardial blood flow (MBF) is unknown. We aimed to assess the effect of myocardial inflammation on quantitative MBF parameters, as assessed by 13N-ammonia positron emission tomography myocardial perfusion imaging (PET-MPI) late after myocarditis. METHODS: Fifty patients with a history of myocarditis underwent cardiac magnetic resonance (CMR) imaging at diagnosis and PET/MR imaging at follow-up at least 6 months later. Segmental MBF, myocardial flow reserve (MFR), and 13N-ammonia washout were obtained from PET, and segments with reduced 13N-ammonia retention, resembling scar, were recorded. Based on CMR, segments were classified as remote (n = 469), healed (inflammation at baseline but no late gadolinium enhancement [LGE] at follow-up, n = 118), and scarred (LGE at follow-up, n = 72). Additionally, apparently healed segments but with scar at PET were classified as PET discordant (n = 18). RESULTS: Compared to remote segments, healed segments showed higher stress MBF (2.71 mL*min-1*g-1 [IQR 2.18-3.08] vs. 2.20 mL*min-1*g-1 [1.75-2.68], p < 0.0001), MFR (3.78 [2.83-4.79] vs. 3.36 [2.60-4.03], p < 0.0001), and washout (rest 0.24/min [0.18-0.31] and stress 0.53/min [0.40-0.67] vs. 0.22/min [0.16-0.27] and 0.46/min [0.32-0.63], p = 0.010 and p = 0.021, respectively). While PET discordant segments did not differ from healed segments regarding MBF and MFR, washout was higher by ~ 30% (p < 0.014). Finally, 10 (20%) patients were diagnosed by PET-MPI as presenting with a myocardial scar but without a corresponding LGE. CONCLUSION: In patients with a history of myocarditis, quantitative measurements of myocardial perfusion as obtained from PET-MPI remain altered in areas initially affected by inflammation. CMR = cardiac magnetic resonance; PET = positron emission tomography; LGE = late gadolinium enhancement.

Left ventricular function and volumes from gated [13N]-ammonia positron emission tomography myocardial perfusion imaging: A prospective head-to-head comparison against CMR using a hybrid PET/MR device.

BACKGROUND: Positron emission tomography (PET) myocardial perfusion imaging (MPI) can be used to evaluate left ventricular (LV) volumes and function. We performed a head-to-head comparison of LV function and volumes obtained simultaneously using [13N]-ammonia-PET and cardiac magnetic resonance (CMR), with the latter serving as the reference standard. METHODS AND RESULTS: In this prospective study, 51 patients underwent [13N]-ammonia-PET MPI and CMR using a hybrid PET/MR device. Left ventricular end-systolic volumes (LVESV), end-diastolic volumes (LVEDV), stroke volumes (LVSV), ejection fractions (LVEF), and segmental wall motion were analyzed for both methods and were compared using correlational and Bland-Altman (BA) analysis; segmental wall motion was compared using ANOVA. The agreement between [13N]-ammonia-PET and CMR for LVEF was good, with minimal bias (- .6%) and narrow BA limits of agreement (- 7.9% to 6.8%), but [13N]-ammonia-PET systematically underestimated LV volumes, with high bias in LVESV (- 11.2 ml), LVEDV (- 28.9 ml), and LVSV (- 17.5 ml). Mean segmental wall motion in [13N]-ammonia-PET differed significantly among the corresponding normokinetic (6.6 ± 2 mm), hypokinetic (5.1 ± 2 mm), and akinetic (3.3 ± 2 mm) segments in CMR (P < .01). CONCLUSION: LVEF and LV wall motion can be accurately assessed using [13N]-ammonia-PET MPI, although LV volumes are significantly underestimated compared to CMR.

Splenic switch-off as a novel marker for adenosine response in nitrogen-13 ammonia PET myocardial perfusion imaging: Cross-validation against CMR using a hybrid PET/MR device.

BACKGROUND: No methodology is available to distinguish truly reduced myocardial flow reserve (MFR) in positron emission tomography myocardial perfusion imaging (PET MPI) from seemingly impaired MFR due to inadequate adenosine response. The adenosine-induced splenic switch-off (SSO) sign has been proposed as a potential marker for adequate adenosine response in cardiac magnetic resonance (CMR). We assessed the feasibility of detecting SSO in nitrogen-13 ammonia PET MPI using SSO in CMR as the standard of reference. METHODS AND RESULTS: Fifty patients underwent simultaneous CMR and PET MPI on a hybrid PET/MR device with co-injection of a gadolinium-based contrast agent and nitrogen-13 ammonia during rest and adenosine-induced stress. In CMR, SSO was assessed visually (positive vs negative SSO) and quantitatively by calculating the ratio of the peak signal intensity of the spleen during stress over rest (SIR). In PET MPI, the splenic signal activity ratio (SAR) was calculated as the maximal standard uptake value of the spleen during stress over rest. The median SIR was significantly lower in patients with positive versus negative SSO in CMR (0.57 [IQR 0.49 to 0.62] vs 0.89 [IQR 0.76 to 0.98]; P < .001). Similarly, median SAR in PET MPI was significantly lower in patients with positive versus negative SSO (0.40 [IQR 0.32 to 0.45] vs 0.80 [IQR 0.47 to 0.98]; P < .001). CONCLUSION: Similarly to CMR, SSO can be detected in nitrogen-13 ammonia PET MPI. This might help distinguish adenosine non-responders from patients with truly impaired MFR due to microvascular dysfunction or multivessel coronary artery disease.

Myocardial creep-induced misalignment artifacts in PET/MR myocardial perfusion imaging.

PURPOSE: Misalignment between positron emission tomography (PET) datasets and attenuation correction (AC) maps is a potential source of artifacts in myocardial perfusion imaging (MPI). We assessed the impact of adenosine on the alignment of AC maps derived from magnetic resonance (MR) and PET datasets during MPI on a hybrid PET/MR scanner. METHODS: Twenty-eight volunteers underwent adenosine stress and rest 13N-ammonia MPI on a PET/MR. We acquired Dixon sequences for the creation of MRAC maps. After reconstruction of the original non-shifted PET images, we examined MRAC and PET datasets for cardiac spatial misalignment and, if necessary, reconstructed a second set of shifted PET images after manually adjusting co-registration. Summed rest, stress, and difference scores (SRS, SSS, and SDS) were compared between shifted and non-shifted PET images. Additionally, we measured the amount of cranial movement of the heart (i.e., myocardial creep) after termination of adenosine infusion. RESULTS: Realignment was necessary for 25 (89.3%) stress and 12 (42.9%) rest PET datasets. Median SRS, SSS, and SDS of the non-shifted images were 6 (IQR = 4-7), 12 (IQR = 7-18), and 8 (IQR = 2-11), respectively, and of the shifted images 2 (IQR = 1-6), 4 (IQR = 7-18), and 1 (IQR = 0-2), respectively. All three scores were significantly higher in non-shifted versus shifted images (all p < 0.05). The difference in SDS correlated moderately but significantly with the amount of myocardial creep (r = 0.541, p = 0.005). CONCLUSION: Misalignment of MRAC and PET datasets commonly occurs during adenosine stress MPI on a hybrid PET/MR device, potentially leading to an increase in false-positive findings. Our results suggest that myocardial creep may substantially account for this and prompt for a careful review and correction of PET/MRAC data.

Prognostic value of regional myocardial flow reserve derived from 13N-ammonia positron emission tomography in patients with suspected coronary artery disease.

PURPOSE: To assess the prognostic value of regional quantitative myocardial flow measures as assessed by 13N-ammonia positron emission tomography (PET) myocardial perfusion imaging (MPI) in patients with suspected coronary artery disease (CAD). METHODS: We retrospectively included 150 consecutive patients with suspected CAD who underwent clinically indicated 13 N-ammonia PET-MPI and who did not undergo revascularization within 90 days of PET-MPI. The presence or absence of a decreased global myocardial flow reserve (i.e., MFR < 2) as well as decreased regional MFR (i.e., ≥ 2 adjacent segments with MFR < 2) was recorded, and patients were classified as having preserved global and regional MFR (MFR group 1), preserved global but decreased regional MFR (MFR group 2), or decreased global and regional MFR (MFR group 3). We obtained follow-up regarding major adverse cardiac events (MACE, i.e., a combined endpoint including all-cause death, non-fatal myocardial infarction, and late revascularization) and all-cause death. RESULTS: Over a median follow-up of 50 months (IQR 38-103), 30 events occurred in 29 patients. Kaplan-Meier analysis showed significantly reduced event-free and overall survival in MFR groups 2 and 3 compared to MFR group 1 (log-rank: p = 0.015 and p = 0.013). In a multivariable Cox regression analysis, decreased regional MFR was an independent predictor for MACE (adjusted HR 3.44, 95% CI 1.17-10.11, p = 0.024) and all-cause death (adjusted HR 4.72, 95% CI 1.07-20.7, p = 0.04). CONCLUSIONS: A decreased regional MFR as assessed by 13 N-ammonia PET-MPI confers prognostic value by identifying patients at increased risk for future adverse cardiac outcomes and all-cause death.

Splenic switch-off as a predictor for coronary adenosine response: validation against 13N-ammonia during co-injection myocardial perfusion imaging on a hybrid PET/CMR scanner.

BACKGROUND: Inadequate coronary adenosine response is a potential cause for false negative ischemia testing. Recently, the splenic switch-off (SSO) sign has been identified as a promising tool to ascertain the efficacy of adenosine during vasodilator stress cardiovascular magnetic resonance imaging (CMR). We assessed the value of SSO to predict adenosine response, defined as an increase in myocardial blood flow (MBF) during quantitative stress myocardial perfusion 13 N-ammonia positron emission tomography (PET). METHODS: We prospectively enrolled 64 patients who underwent simultaneous CMR and PET myocardial perfusion imaging on a hybrid PET/CMR scanner with co-injection of gadolinium based contrast agent (GBCA) and 13N-ammonia during rest and adenosine-induced stress. A myocardial flow reserve (MFR) of  > 1.5 or ischemia as assessed by PET were defined as markers for adequate coronary adenosine response. The presence or absence of SSO was visually assessed. The stress-to-rest intensity ratio (SIR) was calculated as the ratio of stress over rest peak signal intensity for splenic tissue. Additionally, the spleen-to-myocardium ratio, defined as the relative change of spleen to myocardial signal, was calculated for stress (SMRstress) and rest. RESULTS: Sixty-one (95%) patients were coronary adenosine responders, but SSO was absent in 18 (28%) patients. SIR and SMRstress were significantly lower in patients with SSO (SIR: 0.56 ± 0.13 vs. 0.93 ± 0.23; p < 0.001 and SMRstress: 1.09 ± 0.47 vs. 1.68 ± 0.62; p < 0.001). Mean hyperemic and rest MBF were 2.12 ± 0.68 ml/min/g and 0.78 ± 0.26 ml/min/g, respectively. MFR was significantly higher in patients with vs. patients without presence of SSO (3.07 ± 1.03 vs. 2.48 ± 0.96; p = 0.038), but there was only a weak inverse correlation between SMRstress and MFR (R = -0.378; p = 0.02) as well as between SIR and MFR (R = -0.356; p = 0.004). CONCLUSIONS: The presence of SSO implies adequate coronary adenosine-induced MBF response. Its absence, however, is not a reliable indicator for failed adenosine-induced coronary vasodilatation.

Value of 12-lead electrocardiogram to predict myocardial scar on FDG PET in heart failure patients.

PURPOSE: A surface 12-lead electrocardiogram (ECG) is widely available, fast, inexpensive, and safe. However, its value to predict a true myocardial scar in patients with ischemic cardiomyopathy (ICM) has not been studied extensively yet. This study was conducted to assess whether Q waves on resting surface 12-lead ECG are predictive of non-viable myocardium in patients with ICM. METHODS: We analyzed resting ECGs of 149 patients with ICM undergoing cardiac positron emission tomography (PET) with 13N-ammonia (NH3) and 18F-fluorodeoxyglucose (FDG) at our institution. Pathological Q waves and QS complexes were assigned to one of three coronary artery territories and compared to the PET findings. Myocardial scar was defined as 2 or more contiguous myocardial segments with an average (matched) reduction of NH3 and FDG uptake <50% of the maximum value. RESULTS: Pathological Q waves had a sensitivity and specificity of 70% and 40%, respectively, and a PPV and NPV of 37% and 73%, respectively, to detect myocardial scar on FDG PET. For QS complexes, sensitivity and specificity were 46% and 59%, respectively, and PPV and NPV were 36% and 68%, respectively. Sensitivity was lower, but specificity was significantly higher in both the LCX and RCA compared to the LAD territory (p<0.001), particularly for QS complexes. CONCLUSION: Pathological Q waves on resting 12-lead ECG have poor or at best moderate sensitivity and specificity to detect myocardial scar on FDG PET. These findings support the use of more advanced imaging techniques to assess myocardial viability in ICM.

Role of quantitative myocardial blood flow and 13N-ammonia washout for viability assessment in ischemic cardiomyopathy.

OBJECTIVE: Positron emission tomography (PET) integrating assessment of perfusion with 13N-ammonia (NH3) and viability with 18F-fluorodeoxyglucose (FDG) has high accuracy to identify viable, hibernating myocardium. We tested whether quantification of myocardial blood flow (MBF) and washout (k2) can predict myocardial viability using FDG as standard of reference. METHODS: In 180 consecutive patients with ischemic cardiomyopathy, myocardium was categorized on a segment-level into normal, ischemic, hibernating, and scar. From dynamic images, stress MBF, rest MBF, and k2 were derived and myocardial flow reserve (MFR) and volume of distribution (VD) were calculated. RESULTS: Across myocardial tissues, all parameters differed significantly. The area under the curve (AUC) was 0.564 (95% CI 0.527-0.601), 0.635 (0.599-0.671), 0.553 (0.516-0.591), 0.520 (0.482-0.559), and 0.560 (0.522-0.597) for stress MBF, rest MBF, MFR, k2, and VD. The generalized linear mixed model correctly classified 81% of scar as viable, hibernating myocardium. If the threshold of rest MBF to predict viability was set to 0.45 mL·min-1·g-1, sensitivity and specificity were 96% and 12%, respectively. CONCLUSION: Quantitative NH3 PET parameters have low to moderate diagnostic performance to predict viability in ischemic cardiomyopathy. However, if rest MBF falls below 0.45 mL·min-1·g-1, viability testing by FDG-PET may be safely deferred.

Association between vertebral bone mineral density, myocardial perfusion, and long-term cardiovascular outcomes: A sex-specific analysis.

BACKGROUND: Sexual dimorphism in the manifestation of coronary artery disease (CAD) has unleashed a call to reconsider cardiovascular risk assessment. Alterations of bone mineral density (BMD) have been associated with congestive heart failure and appear to be modified by sex. However, the sex-specific association between BMD, myocardial perfusion, and cardiovascular outcomes is currently unknown. METHODS: A total number of 491 patients (65.9 ± 10.7 years, 32.4% women) underwent 13N-ammonia positron emission tomography/computed tomography for evaluation of CAD, and were tracked for major adverse cardiac events (MACEs). RESULTS: Event-free survival (median follow-up time of 4.3 ± 2.0 years) was significantly reduced in patients with low (≤ 100 Hounsfield units) compared to those with higher BMD (log-rank P = .037). Accordingly, reduced BMD was chosen as significant predictor of MACE in a fully adjusted proportional hazards regression model (P = .015). Further, a first-order interaction term consisting of sex and BMD was statistically significant (P = .007). BMD was significantly lower in patients with abnormal myocardial perfusion or impaired left ventricular ejection fraction (P < .05). This difference, however, was noticed in men, but not in women. CONCLUSIONS: The association between low BMD and cardiovascular disease is sex dependent. Our data suggest that quantification of BMD during myocardial perfusion imaging for evaluation of CAD may be particularly useful in men.

Potential of Radiation Dose Reduction by Optimizing Z-Axis Coverage in Coronary Computed Tomography Angiography on a Latest-Generation 256-Slice Scanner.

OBJECTIVE: The purpose of this study was to quantify the reduction in radiation dose achievable by using the optimal z-axis coverage in coronary computed tomography (CT) angiography (CCTA) on a latest-generation 256-slice scanner. METHODS: A total of 408 scans were reviewed that were performed on a wide-range detector scanner allowing up to 16-cm z-axis coverage (adjustable in 2-cm increments). For each CCTA study, we assessed the radiation dose (ie, dose-length product and volume CT dose index) and measured the minimum z-axis coverage necessary to cover the complete cardiac anatomy. We calculated the potential radiation dose savings achievable through reduction of the z-axis coverage to the minimum necessary. RESULTS: The majority of the CCTA scans were performed with a z-axis coverage of 16 cm (n = 285, 69.9%), followed by 14 cm (n = 121, 29.7%) and 12 cm (n = 2, 0.5%). In the group that was scanned with a collimation of 16 cm, radiation dose could have been reduced by 12.5% in 55 patients, 25% in 195 patients, and 37.5% in 33 patients when using optimal z-axis coverage for CCTA. In the group that was scanned with a collimation of 14 cm, radiation dose could have been reduced by 14.3% in 90 patients, and 28.6% in 30 patients, whereas in the group that was scanned with a collimation of 12 cm, dose could have been reduced by 16.7% in 2 patients. CONCLUSIONS: Using correct z-axis coverage in CCTA on a latest-generation 256-slice scanner yields average dose reductions of 22.0% but may be as high as 37.5%.

Heart rate reserve during pharmacological stress is a significant negative predictor of impaired coronary flow reserve in women.

PURPOSE: Evidence to date has failed to adequately explore determinants of cardiovascular risk in women with coronary microvascular dysfunction (CMVD). Heart rate responses to adenosine mirror autonomic activity and may carry important prognostic information for the diagnosis of CMVD. METHODS: Hemodynamic changes during adenosine stress were analyzed in a propensity-matched cohort of 404 patients (202 women, mean age 65.9 ± 11.0) who underwent clinically indicated myocardial perfusion 13N-ammonia Positron-Emission-Tomography (PET) at our institution between September 2013 and May 2017. RESULTS: Baseline heart rate (HR) was significantly higher in patients with abnormal coronary flow reserve (CFR, p < 0.001 vs normal CFR). Accordingly, a blunted HR response to adenosine (=reduced heart rate reserve, %HRR) was seen in patients with abnormal CFR, with a most pronounced effect being observed in female patients free of myocardial ischemia (45.9 ± 34.9 vs 26.5 ± 18.0, p < 0.001 in women and 29.1 ± 16.9 vs 24.3 ± 21.7, p = 0.15 in men). Hence, a fully-adjusted multivariate logistic regression model identified HRR as the strongest negative predictor of reduced CFR in women free of myocardial ischemia, but not in men. Accordingly, receiver operating characteristics (ROC) curves for the presence of reduced CFR revealed that a %HRR <35 was a powerful predictor for abnormal CFR with a sensitivity of 81% and a specificity of 60% in women. CONCLUSION: A blunted HRR <35% is associated with abnormal CFR in women. Taking into account HR responses during stress test in women may help to risk stratify the heterogeneous female population of patients with non-obstructive coronary artery disease (CAD).

Non-Invasive Assessment of Endothelial Shear Stress in Myocardial Bridges Using Coronary Computed Tomography Angiography.

Myocardial bridging (MB) is a segment of coronary arteries with an intramural course, typically spared from atherosclerosis, while the adjacent proximal segment is reported to be atherosclerosis-prone, a phenomenon contributed to local endothelial shear stress (ESS). We aimed to describe the ESS milieu in coronaries with MBs combining coronary computed tomography angiography with computational fluid dynamics and to investigate the association of atherosclerosis presence proximal to MBs with hemorheological characteristics. Patients (n = 36) were identified and 36 arteries with MBs (11 deep and 25 superficial) were analyzed. ESS did not fluctuate 5 mm proximally to MBs vs 5 mm within MBs (0.94 vs 1.06 Pa, p = .56). There was no difference when comparing ESS in the proximal versus mid versus distal MB segments (1.48 vs 1.37 vs 1.9 Pa, p = ns). In arteries with plaques (n = 12), no significant ESS variances were observed around the MB entrance, when analyzing all arteries (p = .81) and irrespective of morphological features of the bridged segment (deep MBs; p = .65, superficial MBs; p = .84). MBs are characterized by homogeneous, atheroprotective ESS, possibly explaining the absence of atherosclerosis within bridged segments. The interplay between ESS and atherosclerosis is potentially not different in arteries with MB compared with arteries without bridges.

FIMICS: A panel of long noncoding RNAs for cardiovascular conditions.

Cardiovascular disorders such as heart failure are leading causes of mortality. Patient stratification via identification of novel biomarkers could improve management of cardiovascular diseases of complex etiologies. Long-noncoding RNAs (lncRNAs) are highly tissue-specific in nature and have emerged as important biomarkers in human diseases. In this study, we aimed to identify cardiac-enriched lncRNAs as potential biomarkers for cardiovascular conditions. Deep RNA sequencing and quantitative PCR identified differentially expressed lncRNAs between failing and non-failing hearts. An independent dataset was used to evaluate the enrichment of lncRNAs in normal hearts. We identified a panel of 2906 lncRNAs, named FIMICS, that were either cardiac-enriched or differentially expressed between failing and non-failing hearts. Expression of lncRNAs in blood samples differentiated patients with myocarditis and acute myocardial infarction. We hereby present the FIMICS panel, a readily available tool to provide insights into cardiovascular pathologies and which could be helpful for diagnosis, monitoring and prognosis purposes.

Long-Term Mortality after New-Onset Atrial Fibrillation in COVID-19.

Background: Atrial fibrillation (AF) has been described as a common cardiovascular manifestation in patients suffering from coronavirus disease 2019 (COVID-19) and has been suggested to be a potential risk factor for a poor clinical outcome. Methods: In this observational study, all patients hospitalized due to COVID-19 in 2020 in the Cantonal Hospital of Baden were included. We assessed clinical characteristics, in-hospital outcomes as well as long-term outcomes with a mean follow-up time of 278 (±90) days. Results: Amongst 646 patients diagnosed with COVID-19 (59% male, median age: 70 (IQR: 59-80)) in 2020, a total of 177 (27.4%) patients were transferred to the intermediate/intensive care unit (IMC/ICU), and 76 (11.8%) were invasively ventilated during their hospitalization. Ninety patients (13.9%) died. A total of 116 patients (18%) showed AF on admission of which 34 (29%) had new-onset AF. Patients with COVID-19 and newly diagnosed AF were more likely to require invasive ventilation (OR: 3.5; p = 0.01) but did not encounter an increased in-hospital mortality. Moreover, AF neither increased long-term mortality nor the number of rehospitalizations during follow-up after adjusting for confounders. Conclusions: In patients suffering from COVID-19, the new-onset of AF on admission was associated with an increased risk of invasive ventilation and transfer to the IMC/ICU but did not affect in-hospital or long-term mortality.

PCSK 9: A Link Between Inflammation and Atherosclerosis.

Proprotein convertase subtilisin/Kexin 9 (PCSK 9) is revealed to be a key player in lipid metabolism and, therefore, in the development and progression of atherosclerosis. PCSK 9 binds to the low-density lipoprotein (LDL) receptor, induces its degradation, and increases circulating blood LDL. As a result, PCSK 9 inhibitors represent an essential pillar in cardiovascular risk reduction therapies due to their highly sufficient LDL decreasing properties. While the influence of PCSK 9 on lipid metabolism has been widely investigated, the full pathophysiological spectrum of PCSK 9 is yet to be determined. Statins have already been demonstrated to have beneficial anti-inflammatory effects. In this context, evidence suggests that PCSK 9 also interferes with inflammatory processes, thereby contributing to the development of atherosclerosis. As lipid metabolism on its own affects inflammatory processes, it is difficult to distinguish between lipid-dependent and -independent inflammatory properties of PCSK 9. A body of evidence has revealed that PCSK9 LDL-independently regulates the secretion of pro-inflammatory cytokines and inflammation-underlying pathways in vascular walls, whereas recent observations suggest that PCSK9 also interacts with lectin-like oxidized LDL receptor-1 (LOX-1) and dampens inflammatory responses through LDL reduction. In conclusion, this review provides mounting evidence indicating how PCSK9 promotes vascular inflammation and subsequent atherosclerosis to shed light on the anti-inflammatory effects of PCSK9 inhibitors in the prevention of atherosclerosis.

Impact of Adaptive Statistical Iterative Reconstruction-V on Coronary Artery Calcium Scores Obtained From Low-Tube-Voltage Computed Tomography - A Patient Study.

OBJECTIVE: To evaluate the impact of adaptive statistical iterative reconstruction-V (ASIR-V) on the accuracy of ultra-low-dose coronary artery calcium (CAC) scoring. MATERIALS AND METHOD: One-hundred-and-three patients who underwent computed tomography (CT) for CAC scoring were prospectively included. All underwent standard scanning with 120-kilovolt-peak (kVp) and with 80- and 70-kVp tube voltage. ASiR-V was applied to the 80- and 70-kVp scans at different levels. The 120-kVp scans reconstructed with filtered back projection served as the standard of reference. Recently published novel kVp-adapted thresholds were used for calculation of CAC scores from 80- and 70-kVp scans and the resulting CAC scores were compared against the standard of reference. Patients were stratified into six CAC score risk categories: 0, 1-10, 11-100, 101-400, 401-1000, and >1000. RESULTS: Increasing levels of ASIR-V led to an increasing underestimation of CAC scores with bias ranging from -128 to -118 and from -205 to -198 for the 80- and 70-kVp scans, respectively, when compared with the standard of reference. Reconstruction with 20% and 40% ASIR-V for the 80- and 70-kVp scans, respectively, yielded noise levels comparable to the standard of reference. Nevertheless, a change in risk-class was observed in 29 (28.6%) and 46 (44.7%) patients, exclusively to a lower risk-class, when CAC scores were derived from these reconstructions. CONCLUSION: ASIR-V leads to noise reduction in CT scans acquired with low tube-voltages. However, ASIR-V introduces substantial inaccuracies and marked underestimation of ultra-low-dose CAC scoring as compared with standard-dose CAC scoring despite normalization of noise.