Protein intake and type 2 diabetes mellitus: an umbrella review of systematic reviews for the evidence-based guideline for protein intake of the German Nutrition Society.

PURPOSE: Protein-rich foods show heterogeneous associations with the risk of type 2 diabetes (T2D) and it remains unclear whether habitual protein intake is related to T2D risk. We carried out an umbrella review of systematic reviews (SR) of randomised trials and/or cohort studies on protein intake in relation to risks of T2D. METHODS: Following a pre-specified protocol (PROSPERO: CRD42018082395), we retrieved SRs on protein intake and T2D risk published between July 1st 2009 and May 22nd 2022, and assessed the methodological quality and outcome-specific certainty of the evidence using a modified version of AMSTAR 2 and NutriGrade, respectively. The overall certainty of evidence was rated according to predefined criteria. RESULTS: Eight SRs were identified of which six contained meta-analyses. The majority of SRs on total protein intake had moderate or high methodological quality and moderate outcome-specific certainty of evidence according to NutriGrade, however, the latter was low for the majority of SRs on animal and plant protein. Six of the eight SRs reported risk increases with both total and animal protein. According to one SR, total protein intake in studies was ~ 21 energy percentage (%E) in the highest intake category and 15%E in the lowest intake category. Relative Risks comparing high versus low intake in most recent SRs ranged from 1.09 (two SRs, 95% CIs 1.02-1.15 and 1.06-1.13) to 1.11 (1.05-1.16) for total protein (between 8 and 12 cohort studies included) and from 1.13 (1.08-1.19) to 1.19 (two SRs, 1.11-1.28 and 1.11-1.28) (8-9 cohort studies) for animal protein. However, SRs on RCTs examining major glycaemic traits (HbA1c, fasting glucose, fasting insulin) do not support a clear biological link with T2D risk. For plant protein, some recent SRs pointed towards risk decreases and non-linear associations, however, the majority did not support an association with T2D risk. CONCLUSION: Higher total protein intake was possibly associated with higher T2D risk, while there is insufficient evidence for a risk increase with higher intakes of animal protein and a risk decrease with plant protein intake. Given that most SRs on plant protein did not indicate an association, there is possibly a lack of an effect.

Protein intake and body weight, fat mass and waist circumference: an umbrella review of systematic reviews for the evidence-based guideline on protein intake of the German Nutrition Society.

PURPOSE: This umbrella review aimed to assess whether dietary protein intake with regard to quantitative (higher vs. lower dietary protein intake) and qualitative considerations (total, plant-based or animal-based protein intake) affects body weight (BW), fat mass (FM) and waist circumference (WC). METHODS: A systematic literature search was conducted in PubMed, Embase and Cochrane Database of Systematic Reviews for systematic reviews (SRs) with and without meta-analyses of prospective studies published between 04 October 2007 and 04 January 2022. Methodological quality and outcome-specific certainty of evidence of the retrieved SRs were assessed by using AMSTAR 2 and NutriGrade, respectively, in order to rate the overall certainty of evidence using predefined criteria. RESULTS: Thirty-three SRs were included in this umbrella review; 29 were based on randomised controlled trials, a few included cohort studies. In studies without energy restriction, a high-protein diet did not modulate BW, FM and WC in adults in general (all "possible" evidence); for older adults, overall certainty of evidence was "insufficient" for all parameters. Under hypoenergetic diets, a high-protein diet mostly decreased BW and FM, but evidence was "insufficient" due to low methodological quality. Evidence regarding an influence of the protein type on BW, FM and WC was "insufficient". CONCLUSION: "Possible" evidence exists that the amount of protein does not affect BW, FM and WC in adults under isoenergetic conditions. Its impact on the reduction in BW and FM under hypoenergetic conditions remains unclear; evidence for an influence of protein type on BW, FM and WC is "insufficient".

Dietary protein and blood pressure: an umbrella review of systematic reviews and evaluation of the evidence.

INTRODUCTION: This umbrella review aimed to investigate the evidence of an effect of dietary intake of total protein, animal and plant protein on blood pressure (BP), and hypertension (PROSPERO: CRD42018082395). METHODS: PubMed, Embase and Cochrane Database were systematically searched for systematic reviews (SRs) of prospective studies with or without meta-analysis published between 05/2007 and 10/2022. The methodological quality and outcome-specific certainty of evidence were assessed by the AMSTAR 2 and NutriGrade tools, followed by an assessment of the overall certainty of evidence. SRs investigating specific protein sources are described in this review, but not included in the assessment of the overall certainty of evidence. RESULTS: Sixteen SRs were considered eligible for the umbrella review. Ten of the SRs investigated total protein intake, six animal protein, six plant protein and four animal vs. plant protein. The majority of the SRs reported no associations or effects of total, animal and plant protein on BP (all "possible" evidence), whereby the uncertainty regarding the effects on BP was particularly high for plant protein. Two SRs addressing milk-derived protein showed a reduction in BP; in contrast, SRs investigating soy protein found no effect on BP. The outcome-specific certainty of evidence of the SRs was mostly rated as low. DISCUSSION/CONCLUSION: This umbrella review showed uncertainties whether there are any effects on BP from the intake of total protein, or animal or plant proteins, specifically. Based on data from two SRs with milk protein, it cannot be excluded that certain types of protein could favourably influence BP.

Protein intake and cancer: an umbrella review of systematic reviews for the evidence-based guideline of the German Nutrition Society.

PURPOSE: It has been proposed that a higher habitual protein intake may increase cancer risk, possibly via upregulated insulin-like growth factor signalling. Since a systematic evaluation of human studies on protein intake and cancer risk based on a standardised assessment of systematic reviews (SRs) is lacking, we carried out an umbrella review of SRs on protein intake in relation to risks of different types of cancer. METHODS: Following a pre-specified protocol (PROSPERO: CRD42018082395), we retrieved SRs on protein intake and cancer risk published before January 22th 2024, and assessed the methodological quality and outcome-specific certainty of the evidence using a modified version of AMSTAR 2 and NutriGrade, respectively. The overall certainty of evidence was rated according to predefined criteria. RESULTS: Ten SRs were identified, of which eight included meta-analyses. Higher total protein intake was not associated with risks of breast, prostate, colorectal, ovarian, or pancreatic cancer incidence. The methodological quality of the included SRs ranged from critically low (kidney cancer), low (pancreatic, ovarian and prostate cancer) and moderate (breast and prostate cancer) to high (colorectal cancer). The outcome-specific certainty of the evidence underlying the reported findings on protein intake and cancer risk ranged from very low (pancreatic, ovarian and prostate cancer) to low (colorectal, ovarian, prostate, and breast cancer). Animal and plant protein intakes were not associated with cancer risks either at a low (breast and prostate cancer) or very low (pancreatic and prostate cancer) outcome-specific certainty of the evidence. Overall, the evidence for the lack of an association between protein intake and (i) colorectal cancer risk and (ii) breast cancer risk was rated as possible. By contrast, the evidence underlying the other reported results was rated as insufficient. CONCLUSION: The present findings suggest that higher total protein intake may not be associated with the risk of colorectal and breast cancer, while conclusions on protein intake in relation to risks of other types of cancer are restricted due to insufficient evidence.

The Efficacy and Safety of a Low-Dose Tranexamic Acid Bolus-Only Protocol Compared with the Moderate-Dose Protocol in Valvular Heart Surgery.

In 873 propensity score-matched pairs of patients undergoing valvular heart surgery, we compared a "moderate dose" of tranexamic acid (TXA) protocol (group 1; median TXA dose: 24 mg/kg body weight) with a 1.5-g "bolus-only" protocol (group 2; median TXA dose: 19 mg/kg body weight). The number of transfused patients was higher in group 2 than in group 1 (74.5 vs 66.0%, p < 0.001), as was the number of transfused red blood cell concentrates (p = 0.001). The risks of re-exploration and convulsive seizures were similar between groups (p > 0.50). Data indicate an impaired efficacy following the "bolus-only" protocol, without a significant safety improvement.

Early and Late Results after Surgical Mitral Valve Repair: A High-Volume Center Experience.

BACKGROUND: Surgical mitral valve repair is the gold standard treatment of severe primary mitral regurgitation (MR). In the light of rapidly evolving percutaneous technologies, current surgical outcome data are essential to support heart-team-based decision-making. METHODS: This retrospective, high-volume, single-center study analyzed in 1779 patients with primary MR early morbidity and mortality, postoperative valve function, and long-term survival after mitral valve (MV) repair. Surgeries were performed between 2009 and 2022. Surgical approaches included full sternotomy (FS) and right-sided minithoracotomy (minimally invasive cardiac [MIC] surgery). RESULTS: Of the surgeries (mean age: 59.9 [standard deviation:11.4] years; 71.5% males), 85.6% (n = 1,527) were minithoracotomies. Concomitant procedures were performed in 849 patients (47.7%), including tricuspid valve and/or atrial septal defect repair, cryoablation, and atrial appendage closure. The majority of patients did not need erythrocyte concentrates. Mediastinitis and rethoracotomy for bleeding rates were 0.1 and 4.3%, respectively. Reoperation before discharge for failed repair was necessary in 12 patients (0.7%). Freedom from more than moderate MR was > 99%. Thirty-day mortality was 0.2% and did not differ significantly between groups (p = 0.37). Median follow-up was 48.2 months with a completeness of 95.9%. Long-term survival was similar between groups (p = 0.21). In the FS and MIC groups, 1-, 5-, and 10-year survival rates were 98.8 and 98.8%, 92.9 and 94.4%, and 87.4 and 83.1%, respectively. CONCLUSION: MV surgery, both minimally invasive and via sternotomy, is associated with high repair rates, excellent perioperative outcomes, and long-term survival. Data underscore the effectiveness of surgical repair in managing MR, even in the era of advancing interventional techniques.

Protein intake and bone health: an umbrella review of systematic reviews for the evidence-based guideline of the German Nutrition Society.

This umbrella review aimed at assessing whether a protein intake exceeding the current recommendation for younger (0.8 g/kg body weight [BW]/day) and older (1.0 g/kg BW/day) adults affects bone mineral density and fracture risk. Moreover, the effect of animal or plant protein was evaluated. A systematic literature search was conducted in PubMed, Embase, and Cochrane Database of Systematic Reviews for systematic reviews (SRs) with or without meta-analysis of prospective studies published between 11/2008 and 08/2021. Methodological quality, outcome-specific certainty of evidence, and overall certainty of evidence of the retrieved SRs were assessed using established tools and predefined criteria. Eleven SRs of randomized controlled trials (RCTs) and/or cohort studies were included. In SRs of cohort studies and RCTs, protein intake/kg BW/day ranged between 0.21-0.95 g (low intake) and > 1.24 g (high intake), respectively, and between 0.67-1.1 g (control groups) and 1.01-1.69 g (intervention groups), respectively. The vast majority of outcome-specific certainty of evidence was rated "low" or "very low." The overall certainty of evidence for an association (cohort studies) or effect (RCTs) of total, animal or plant protein intake on each of the investigated outcomes was rated "insufficient," with the exception of possible evidence for a reduced hip fracture risk by high vs. low protein intake. Since protein intakes in low/control and high/intervention groups were very heterogeneous and with low certainty of evidence, it remains unclear whether a dose above the current recommendation or type of protein intake (animal or plant protein) affects bone health overall. However, there is possible evidence for reduced hip fracture risk with high versus low protein intake.

Long-term supplementation with 3200 to 4000 IU of vitamin D daily and adverse events: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: The upper tolerable intake level for vitamin D in the general population has been set at 4000 international units (IU) daily, but considerable uncertainty remains. We summarized reported harmful effects of a daily vitamin D supplement of 3200-4000 IU in trials lasting ≥ 6 months. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials in several databases and identified 22 trials reporting safety data. Parameters of calcium metabolism, falls, hospitalization, and mortality were assessed. RESULTS: The selected trials comprised a total number of 12,952 participants. All trials used supplemental vitamin D3. The relative risk (RR) of hypercalcemia in the vitamin D vs. control arm was 2.21 (95%CI: 1.26-3.87; 10 studies), with a vitamin D-induced frequency of hypercalcemia of 4 cases per 1000 individuals. Subgroup analysis in trials with > 100 and ≤ 100 study participants revealed an RR of 2.63 (95%CI: 1.30-5.30; 7 studies) and 0.80 (95%CI: 0.24-2.62; 3 studies), respectively (Pinteraction = 0.06). Risks of falls and hospitalization were also significantly increased in the vitamin D arm with an RR of 1.25 (95%CI: 1.01-1.55; 4 studies) and 1.16 (95%CI: 1.01-1.33; 7 studies), respectively. Risks of hypercalciuria, kidney stones, and mortality did not differ significantly between study arms. Quality assessment revealed high risk of incomplete reporting of safety-related outcome data. CONCLUSION: Supplemental vitamin D doses of 3200-4000 IU/d appear to increase the risk of hypercalcemia and some other adverse events in a small proportion of individuals, indicating that this dose is not completely safe. In future studies, rigorous reporting of safety-related outcomes is needed when using moderately high doses of vitamin D.

Protein intake and risk of urolithiasis and kidney diseases: an umbrella review of systematic reviews for the evidence-based guideline of the German Nutrition Society.

PURPOSE: Changes in dietary protein intake metabolically affect kidney functions. However, knowledge on potential adverse consequences of long-term higher protein intake (HPI) for kidney health is lacking. To summarise and evaluate the available evidence for a relation between HPI and kidney diseases, an umbrella review of systematic reviews (SR) was conducted. METHODS: PubMed, Embase and Cochrane Database of SRs published until 12/2022 were searched for the respective SRs with and without meta-analyses (MA) of randomised controlled trials or cohort studies. For assessments of methodological quality and of outcome-specific certainty of evidence, a modified version of AMSTAR 2 and the NutriGrade scoring tool were used, respectively. The overall certainty of evidence was assessed according to predefined criteria. RESULTS: Six SRs with MA and three SRs without MA on various kidney-related outcomes were identified. Outcomes were chronic kidney disease, kidney stones and kidney function-related parameters: albuminuria, glomerular filtration rate, serum urea, urinary pH and urinary calcium excretion. Overall certainty of evidence was graded as 'possible' for stone risk not to be associated with HPI and albuminuria not to be elevated through HPI (above recommendations (> 0.8 g/kg body weight/day)) and graded as 'probable' or 'possible' for most other kidney function-related parameters to be physiologically increased with HPI. CONCLUSION: Changes of the assessed outcomes may have reflected mostly physiological (regulatory), but not pathometabolic responses to higher protein loads. For none of the outcomes, evidence was found that HPI does specifically trigger kidney stones or diseases. However, for potential recommendations long-term data, also over decades, are required.

Moderate Dose of Tranexamic Acid and Complications after Valvular Heart Surgery.

BACKGROUND: In valvular open-heart surgery, data regarding the effect of a moderate dose of tranexamic acid (TXA) on clinical outcomes are limited. METHODS: Out of a cohort of 13,293 patients, we performed a propensity-score-matched analysis in 6,106 patients and assessed the risk of convulsive seizures (CS, primary endpoint), stroke, renal replacement therapy, and mortality (secondary endpoints). In the entire study cohort of 13,293 patients, we also assessed the multivariable-adjusted association of CS with postoperative outcomes. RESULTS: The risk of CS was significantly higher in the TXA group (2.4%; n = 72) than in the non-TXA group (1.0%; n = 32), with a relative risk ratio (RR) of 2.28 (95% confidence interval [CI]: 1.50-3.47; p < 0.001). The risk of CS was also higher in patients receiving TXA doses ≥25 mg/kg body weight (3.7%; n = 40) than in patients receiving <25 mg/kg body weight (1.6%; n = 32; p < 0.001). Perioperative secondary clinical endpoints and 1-year mortality did not differ significantly between study groups (p-value > 0.05). Compared with non-CS patients (n = 13,000), patients with nonhemorrhagic, nonembolic CS (n = 253) revealed higher multivariable-adjusted in-hospital risks of stroke (RR: 3.82 [95% CI: 2.44-5.60; p < 0.001]) and mortality (RR: 2.07 [95% CI: 1.23-3.48; p = 0.006]), and a higher 1-year mortality risk (RR: 1.85 [95% CI: 1.42-2.41; p < 0.001]). CONCLUSION: A moderate TXA dose was associated with a significantly higher risk of seizure, but not with other clinical complications such as stroke, renal replacement therapy, and mortality. However, in the small group of patients experiencing a seizure, the risks of stroke and short- and mid-term mortality were substantially higher than in patients not experiencing a seizure, indicating that the use of a low-dose TXA protocol (<25 mg/kg body weight) should be considered.

High Efficacy and Low Early Mortality in High-Volume Center Tricuspid Valve Surgery.

BACKGROUND: Isolated tricuspid valve surgery has been associated with early mortality rates of up to 10%. With rapidly emerging interventional catheter-based options, the question arises whether current technical and perioperative protocols in cardiac surgery translate into lower than previously expected mortality rates, especially when looking at data from high-volume centers. METHODS: We performed a retrospective single-center analysis in 369 patients undergoing isolated tricuspid valve repair (n = 256) or replacement (n = 113) between 2009 and 2021. Surgical approaches included full sternotomy, as well as right-sided minithoracotomy. According to a recently introduced clinical risk score, patients were divided into scoring groups, and observed (O) versus expected (E) early mortality were compared. Pre- and postoperative tricuspid valve function was also analyzed. RESULTS: Overall, 30-day mortality was 4.1%, ranging from 0% (scoring group 0-1 points) to 8.7% (scoring group ≥ 10 points), which was substantially lower than the expected early mortality (2% in the lowest to 34% in the highest scoring group). Preoperative tricuspid regurgitation was severe in 71.3% (n = 263), moderate to severe in 14.9% (n = 55), and mild or less in 6.5% (n = 24). The corresponding postoperative values were 0% (n = 0), 1.4% (n = 5), and 81.6% (n = 301). CONCLUSION: Our high-volume center data indicate substantially lower than predicted 30-day mortality in different cardiac surgical risk scoring groups. The majority of patients had zero to minimal residual tricuspid valve insufficiency postoperatively. Randomized controlled trials are needed to compare tricuspid valve functional results and long-term outcomes of surgical versus interventional procedures in patients undergoing isolated tricuspid valve procedures.

High-sensitivity cardiac troponin I after coronary artery bypass grafting for post-operative decision-making.

AIMS: Current troponin cut-offs suggested for the post-operative workup of patients following coronary artery bypass graft (CABG) surgery are based on studies using non-high-sensitive troponin assays or are arbitrarily chosen. We aimed to identify an optimal cut-off and timing for a proprietary high-sensitivity cardiac troponin I (hs-cTnI) assay to facilitate post-operative clinical decision-making. METHODS AND RESULTS: We performed a retrospective analysis of all patients undergoing elective isolated CABG at our centre between January 2013 and May 2019. Of 4684 consecutive patients, 161 patients (3.48%) underwent invasive coronary angiography after surgery, of whom 86 patients (53.4%) underwent repeat revascularization. We found an optimal cut-off value for peak hs-cTnI of >13 000 ng/L [>500× the upper reference limit (URL)] to be significantly associated with repeat revascularization within 48 h after surgery, which was internally validated through random repeated sampling with 1000 iterations. The same cut-off also predicted 30-day major adverse cardiovascular events and all-cause mortality after a median follow-up of 3.1 years, which was validated in an external cohort. A decision tree analysis of serial hs-cTnI measurements showed no added benefit of hs-cTnI measurements in patients with electrocardiographic or echocardiographic abnormalities or haemodynamic instability. Likewise, early post-operative hs-cTnI elevations had a low yield for clinical decision-making and only later elevations (at 12-16 h post-operatively) using a threshold of 8000 ng/L (307× URL) were significantly associated with repeat revascularization with an area under the curve of 0.92 (95% confidence interval 0.88-0.95). CONCLUSION: Our data suggest that for hs-cTnI, higher cut-offs than currently recommended should be used in the post-operative management of patients following CABG.

Dietary protein intake and health-related outcomes: a methodological protocol for the evidence evaluation and the outline of an evidence to decision framework underlying the evidence-based guideline of the German Nutrition Society.

PURPOSE: The present work aimed to delineate (i) a revised protocol according to recent methodological developments in evidence generation, to (ii) describe its interpretation, the assessment of the overall certainty of evidence and to (iii) outline an Evidence to Decision framework for deriving an evidence-based guideline on quantitative and qualitative aspects of dietary protein intake. METHODS: A methodological protocol to systematically investigate the association between dietary protein intake and several health outcomes and for deriving dietary protein intake recommendations for the primary prevention of various non-communicable diseases in the general adult population was developed. RESULTS: The developed methodological protocol relies on umbrella reviews including systematic reviews with or without meta-analyses. Systematic literature searches in three databases will be performed for each health-related outcome. The methodological quality of all selected systematic reviews will be evaluated using a modified version of AMSTAR 2, and the outcome-specific certainty of evidence for systematic reviews with or without meta-analysis will be assessed with NutriGrade. The general outline of the Evidence to Decision framework foresees that recommendations in the derived guideline will be given based on the overall certainty of evidence as well as on additional criteria such as sustainability. CONCLUSION: The methodological protocol permits a systematic evaluation of published systematic reviews on dietary protein intake and its association with selected health-related outcomes. An Evidence to Decision framework will be the basis for the overall conclusions and the resulting recommendations for dietary protein intake.

Tranexamic Acid and the Risk of Delirium after Off-Pump Surgery.

We investigated whether in patients undergoing off-pump coronary artery bypass grafting surgery a single bolus of 1 g tranexamic acid (TXA) impacts the risk of postoperative delirium using the propensity score matching approach. In 2,757 pairs, the risk of delirium was 4.2% (TXA group) and 5.0% (non-TXA group), with a relative risk in the TXA versus the non-TXA group of 0.83 (95% confidence interval: 0.65-1.07; p = 0.16). There was no significant interaction between TXA administration and renal function on the risk of delirium (p = 0.12). Data indicate that a single bolus of 1 g TXA does not increase the risk of delirium in patients undergoing off-pump surgery.

Preoperative Risk Factors and Early Outcomes of Delirium in Valvular Open-Heart Surgery.

BACKGROUND: Compared with coronary artery bypass grafting surgery, data regarding postoperative delirium are scant in valvular open-heart surgery. Therefore, the goal of this retrospective study was to investigate the incidence, preoperative risk factors, and early outcomes of delirium in a large group of patients undergoing valvular open-heart surgery. METHODS: In 13,229 patients with isolated valvular or combined valvular and bypass surgery, the incidence of postoperative delirium was assessed until discharge. Independent risk factors of delirium were evaluated by multivariable logistic regression analysis. Moreover, we assessed the multivariable-adjusted risk of prolonged intensive care unit (ICU) stay (>48 hours) and in-hospital mortality in patients with delirium. RESULTS: Overall, the incidence of postoperative delirium was 8.4%. The incidence in patients experiencing a postoperative stroke or seizure was 23.1 and 29.7%, respectively. Twelve preoperative risk factors, mostly nonmodifiable, were independently associated with the risk of delirium, including advanced age, renal impairment, stroke, the need for emergency surgery, and severe preoperative anemia (hemoglobin < 9 g/dL). Postoperative delirium was associated with an adjusted odds ratio (OR) of prolonged ICU stay of 9.48 (95% confidence interval [CI]: 7.96-11.30). Adjusted in-hospital mortality was, however, significantly lower in patients with delirium versus patients without delirium (OR, 0.56; 95% CI: 0.38-0.83). CONCLUSION: In valvular open-heart surgery, postoperative delirium is a frequent neurological complication that is associated with other postoperative neurological complications and several, mostly nonmodifiable, preoperative risk factors. Although postoperative delirium was associated with a significantly increased risk of prolonged ICU stay, this did not translate into an increased short-term mortality.

Long-Term Clinical Outcome in Elderly Patients Undergoing Mitral Valve Repair.

BACKGROUND: Long-term data on patients over 75 years undergoing mitral valve (MV) repair are scarce. At our high-volume institution, we, therefore, aimed to evaluate mortality, stroke risk, and reoperation rates in these patients. METHODS: We investigated clinical outcomes in 372 patients undergoing MV repair with (n = 115) or without (n = 257) tricuspid valve repair. The primary endpoint was the probability of survival up to a maximum follow-up of 9 years. Secondary clinical endpoints were stroke and reoperation of the MV during follow-up. Univariate and multivariable Cox regression analysis was performed to assess independent predictors of mortality. Mortality was also compared with the age- and sex-adjusted general population. RESULTS: During a median follow-up period of 37 months (range: 0.1-108 months), 90 patients died. The following parameters were independently associated with mortality: double valve repair (hazard ratio, confidence interval [HR, 95% CI]: 2.15, 1.37-3.36), advanced age (HR: 1.07, CI: 1.01-1.14 per year), diabetes (HR: 1.97, CI: 1.13-3.43), preoperative New York Heart Association (NYHA) functional class (HR: 1.41, CI: 1.01-1.97 per class), and operative creatininemax levels (HR: 1.32, CI: 1.13-1.55 per mg/dL). The risk of stroke in the isolated MV and double valve repair groups at postoperative year 5 was 5.0 and 4.1%, respectively (p = 0.65). The corresponding values for the risk of reoperation were 4.0 and 7.0%, respectively (p = 0.36). Nine-year survival was comparable with the general population (53.2 vs. 53.1%). CONCLUSION: Various independent risk factors for mortality in elderly MV repair patients could be identified, but overall survival rates were similar to those of the general population. Consequently, our data indicates that repairing the MV in elderly patients represents a suitable and safe surgical approach.

Randomized trial of vitamin D versus placebo supplementation on markers of systemic inflammation in hypertensive patients.

BACKGROUND AND AIMS: Animal and cell models indicated that vitamin D modulates inflammatory activity, which is considered relevant in the pathogenesis of arterial hypertension and cardiovascular diseases. We therefore aimed to investigate the effect of vitamin D supplementation on systemic markers of inflammation in a cohort of hypertensive patients. METHODS AND RESULTS: The Styrian Vitamin D Hypertension Trial is a single-centre, double-blind, placebo-controlled study conducted from 2011 to 2014 in Austria. We enrolled 200 study participants with arterial hypertension and 25-hydroxy-vitamin-D (25(OH)D) concentration below 30 ng/mL. Study participants were randomized to receive either 2800 IU of vitamin D3 per day or placebo for 8 weeks. The present investigation is a post-hoc analysis using analysis of co-variance (ANCOVA). Outcome measures were biomarkers of inflammation including CRP, leukocytes including subtypes and leukocyte-to-lymphocyte ratio, leucine and kynurenic acid. A total of 187 participants (mean age 60.1 ± 11.3years; 47% women; mean baseline 25(OH)D 21.1 ± 5.6 ng/mL) completed the trial. ANCOVA revealed a mean treatment effect for none of the respective outcomes and no significant results were detected in various subgroup analyses. CONCLUSION: Vitamin D3 supplementation in hypertensive patients with insufficient 25(OH)D concentrations has no significant effect on lowering markers of systemic inflammation. Further studies investigating the effect of vitamin D on other inflammatory pathways and in populations with severe vitamin D deficiency and a significant inflammatory burden are required. REGISTRATION: ClinicalTrials.gov Identifier: NCT02136771; EudraCT No. 2009-018,125-70. Start Date: 2011-04-06.

Long-term outcomes after transcatheter aortic valve implantation in failed bioprosthetic valves.

AIMS: Due to bioprosthetic valve degeneration, aortic valve-in-valve (ViV) procedures are increasingly performed. There are no data on long-term outcomes after aortic ViV. Our aim was to perform a large-scale assessment of long-term survival and reintervention after aortic ViV. METHODS AND RESULTS: A total of 1006 aortic ViV procedures performed more than 5 years ago [mean age 77.7 ± 9.7 years; 58.8% male; median STS-PROM score 7.3% (4.2-12.0)] were included in the analysis. Patients were treated with Medtronic self-expandable valves (CoreValve/Evolut, Medtronic Inc., Minneapolis, MN, USA) (n = 523, 52.0%), Edwards balloon-expandable valves (EBEV, SAPIEN/SAPIEN XT/SAPIEN 3, Edwards Lifesciences, Irvine, CA, USA) (n = 435, 43.2%), and other devices (n = 48, 4.8%). Survival was lower at 8 years in patients with small-failed bioprostheses [internal diameter (ID) ≤ 20 mm] compared with those with large-failed bioprostheses (ID > 20 mm) (33.2% vs. 40.5%, P = 0.01). Independent correlates for mortality included smaller-failed bioprosthetic valves [hazard ratio (HR) 1.07 (95% confidence interval (CI) 1.02-1.13)], age [HR 1.21 (95% CI 1.01-1.45)], and non-transfemoral access [HR 1.43 (95% CI 1.11-1.84)]. There were 40 reinterventions after ViV. Independent correlates for all-cause reintervention included pre-existing severe prosthesis-patient mismatch [subhazard ratio (SHR) 4.34 (95% CI 1.31-14.39)], device malposition [SHR 3.75 (95% CI 1.36-10.35)], EBEV [SHR 3.34 (95% CI 1.26-8.85)], and age [SHR 0.59 (95% CI 0.44-0.78)]. CONCLUSIONS: The size of the original failed valve may influence long-term mortality, and the type of the transcatheter valve may influence the need for reintervention after aortic ViV.

Vitamin D and Cardiovascular Disease: An Updated Narrative Review.

During the last two decades, the potential impact of vitamin D on the risk of cardiovascular disease (CVD) has been rigorously studied. Data regarding the effect of vitamin D on CVD risk are puzzling: observational data indicate an inverse nonlinear association between vitamin D status and CVD events, with the highest CVD risk at severe vitamin D deficiency; however, preclinical data and randomized controlled trials (RCTs) show several beneficial effects of vitamin D on the surrogate parameters of vascular and cardiac function. By contrast, Mendelian randomization studies and large RCTs in the general population and in patients with chronic kidney disease, a high-risk group for CVD events, largely report no significant beneficial effect of vitamin D treatment on CVD events. In patients with rickets and osteomalacia, cardiovascular complications are infrequently reported, except for an increased risk of heart failure. In conclusion, there is no strong evidence for beneficial vitamin D effects on CVD risk, either in the general population or in high-risk groups. Whether some subgroups such as individuals with severe vitamin D deficiency or a combination of low vitamin D status with specific gene variants and/or certain nutrition/lifestyle factors would benefit from vitamin D (metabolite) administration, remains to be studied.

Associations of preoperative stroke and tranexamic acid administration with convulsive seizures in valvular open-heart surgery.

In cardiac surgery, use of the antifibrinolytic agent tranexamic acid (TXA) and acute perioperative stroke are both associated with convulsive seizures. We hypothesized that an older (preoperative) stroke increases the risk of TXA-associated seizures as well. To test this hypothesis, we retrospectively analyzed data from 16,110 patients who had undergone open-heart valvular surgery at our institution between 2009 and 2020. The dosing of TXA was moderate. Use of TXA and a history of stroke were both independently associated with convulsive seizure with an adjusted odds ratio (OR) of 2.40 (95%CI: 1.71-3.37) and 1.79 (95%CI: 1.27-2.54), respectively. Compared to patients without TXA administration, the adjusted OR of experiencing a seizure in TXA patients without a history of stroke was 2.44 (95%CI: 1.71-3.46) and in patients receiving TXA with a history of stroke 4.30 (95%CI: 2.65-6.99). However, there was no significant interaction between TXA use and preoperative stroke on convulsive seizures (P = 0.77). Compared to patients without seizure, for patients with seizure, the inverse probability-weighted ORs of in-hospital mortality and 30-day mortality were 3.58 (95%CI: 2.20-5.83) and 4.04 (95%CI: 2.34-6.98), respectively. We conclude that, in patients undergoing open-heart surgery, a history of stroke is independently associated with convulsive seizures but is not a contraindication for TXA use.