Atherosclerosis evaluation and cardiovascular risk estimation using coronary computed tomography angiography.

Clinical risk scores based on traditional risk factors of atherosclerosis correlate imprecisely to an individual's complex pathophysiological predisposition to atherosclerosis and provide limited accuracy for predicting major adverse cardiovascular events (MACE). Over the past two decades, computed tomography scanners and techniques for coronary computed tomography angiography (CCTA) analysis have substantially improved, enabling more precise atherosclerotic plaque quantification and characterization. The accuracy of CCTA for quantifying stenosis and atherosclerosis has been validated in numerous multicentre studies and has shown consistent incremental prognostic value for MACE over the clinical risk spectrum in different populations. Serial CCTA studies have advanced our understanding of vascular biology and atherosclerotic disease progression. The direct disease visualization of CCTA has the potential to be used synergistically with indirect markers of risk to significantly improve prevention of MACE, pending large-scale randomized evaluation.

Prevalence of diabetic cardiomyopathy in patients with type 2 diabetes in a large academic medical center.

BACKGROUND: Diabetic cardiomyopathy (DbCM) is characterized by asymptomatic stage B heart failure (SBHF) caused by diabetes-related metabolic alterations. DbCM is associated with an increased risk of progression to overt heart failure (HF). The prevalence of DbCM in patients with type 2 diabetes (T2D) is not well established. This study aims to determine prevalence of DbCM in adult T2D patients in real-world clinical practice. METHODS: Retrospective multi-step review of electronic medical records of patients with the diagnosis of T2D who had echocardiogram at UC San Diego Medical Center (UCSD) within 2010-2019 was conducted to identify T2D patients with SBHF. We defined "pure" DbCM when SBHF is associated solely with T2D and "mixed" SBHF when other medical conditions can contribute to SBHF. "Pure" DbCM was diagnosed in T2D patients with echocardiographic demonstration of SBHF defined as left atrial (LA) enlargement (LAE), as evidenced by LA volume index ≥ 34 mL/m2, in the presence of left ventricular ejection fraction (LVEF) ≥ 45%, while excluding overt HF and comorbidities that can contribute to SBHF. RESULTS: Of 778,314 UCSD patients in 2010-2019, 45,600 (5.9%) had T2D diagnosis. In this group, 15,182 T2D patients (33.3%) had echocardiogram and, among them, 13,680 (90.1%) had LVEF ≥ 45%. Out of 13,680 patients, 4,790 patients had LAE. Of them, 1,070 patients were excluded due to incomplete data and/or a lack of confirmed T2D according to the American Diabetes Association recommendations. Thus, 3,720 T2D patients with LVEF ≥ 45% and LAE were identified, regardless of HF symptoms. In this group, 1,604 patients (43.1%) had overt HF and were excluded. Thus, 2,116 T2D patients (56.9% of T2D patients with LVEF ≥ 45% and LAE) with asymptomatic SBHF were identified. Out of them, 1,773 patients (83.8%) were diagnosed with "mixed" SBHF due to comorbidities such as hypertension (58%), coronary artery disease (36%), and valvular heart disease (17%). Finally, 343 patients met the diagnostic criteria of "pure" DbCM, which represents 16.2% of T2D patients with SBHF, i.e., at least 2.9% of the entire T2D population in this study. CONCLUSIONS: Our findings provide insights into prevalence of DbCM in real-world clinical practice and indicate that DbCM affects a significant portion of T2D patients.

Deep Learning Automated Background Phase Error Correction for Abdominopelvic 4D Flow MRI.

Background Four-dimensional (4D) flow MRI has the potential to provide hemodynamic insights for a variety of abdominopelvic vascular diseases, but its clinical utility is currently impaired by background phase error, which can be challenging to correct. Purpose To assess the feasibility of using deep learning to automatically perform image-based background phase error correction in 4D flow MRI and to compare its effectiveness relative to manual image-based correction. Materials and Methods A convenience sample of 139 abdominopelvic 4D flow MRI acquisitions performed between January 2016 and July 2020 was retrospectively collected. Manual phase error correction was performed using dedicated imaging software and served as the reference standard. After reserving 40 examinations for testing, the remaining examinations were randomly divided into training (86% [85 of 99]) and validation (14% [14 of 99]) data sets to train a multichannel three-dimensional U-Net convolutional neural network. Flow measurements were obtained for the infrarenal aorta, common iliac arteries, common iliac veins, and inferior vena cava. Statistical analyses included Pearson correlation, Bland-Altman analysis, and F tests with Bonferroni correction. Results A total of 139 patients (mean age, 47 years ± 14 [standard deviation]; 108 women) were included. Inflow-outflow correlation improved after manual correction (ρ = 0.94, P < .001) compared with that before correction (ρ = 0.50, P < .001). Automated correction showed similar results (ρ = 0.91, P < .001) and demonstrated very strong correlation with manual correction (ρ = 0.98, P < .001). Both correction methods reduced inflow-outflow variance, improving mean difference from -0.14 L/min (95% limits of agreement: -1.61, 1.32) (uncorrected) to 0.05 L/min (95% limits of agreement: -0.32, 0.42) (manually corrected) and 0.05 L/min (95% limits of agreement: -0.38, 0.49) (automatically corrected). There was no significant difference in inflow-outflow variance between manual and automated correction methods (P = .10). Conclusion Deep learning automated phase error correction reduced inflow-outflow bias and variance of volumetric flow measurements in four-dimensional flow MRI, achieving results comparable with manual image-based phase error correction. © RSNA, 2021 See also the editorial by Roldán-Alzate and Grist in this issue.

Integrating Advanced Lipid Testing and Biomarkers in Assessment and Treatment.

PURPOSE OF REVIEW: Our ability to assess and stratify atherosclerotic disease risk in patients is evolving. Recent advances in advanced lipid testing have created opportunities for clinical application of novel biomarkers. RECENT FINDINGS: Until recently, LDL-C has served largely as the singular biomarker of ASCVD and guide for decisions in treatment for high-risk groups. There are important evolutions in the measurement of LDL-C but even still, the pathogenesis of atherosclerosis and ASCVD is not solely driven by LDL-C. As atherosclerosis is driven by multiple complex pathways including inflammation, it is important to expand our focus beyond LDL-C and utilize multiple biomarkers in the assessment of this disease process. Non-HDL, ApoB, LDL-P, Lp(a), and hsCRP are unique tools to aid in cardiac risk evaluation, especially in higher risk patients, though not limited to this population. A multifaceted approach to advanced lipid testing with novel biomarkers will enhance comprehensive ASCVD risk assessments.

Cardiac rehabilitation for coronary artery disease: latest updates.

PURPOSE OF REVIEW: To summarize recent innovations in cardiac rehabilitation and provide a view towards the future of cardiac rehabilitation as it adjusts to the pressures of a global pandemic. RECENT FINDINGS: Although cardiac rehabilitation has been shown to result in a mortality benefit, research continues to enumerate the benefits of cardiac rehabilitation to patient function and quality of life in a growing range of cardiovascular diseases. In addition, new methodologies and new models of cardiac rehabilitation have emerged with the goal of increasing patient referral and participation. SUMMARY: Cardiac rehabilitation continues to evolve and adapt to serve a growing and diversifying number of patients with cardiovascular disease with the goal of both decreasing mortality and improving patient function.

Cardiac Rehab in the COVID Era and Beyond: mHealth and Other Novel Opportunities.

PURPOSE OF REVIEW: The COVID-19 pandemic has forced many center-based cardiac rehabilitation (CBCR) programs to close or limit their usual offerings. In order for patients to continue to benefit from CR, programs need to rapidly adapt to the current environment. This review highlights ways CR has evolved, and reviews the history of CR and recent advancements in telemedicine including remote patient monitoring, and mobile health that can be applied to CR. RECENT FINDINGS: Despite that initial studies indicate that home-based CR (HBCR) is safe and effective, HBCR has faced several challenges that have prevented it from becoming more widely implemented. Many previous concerns can now be addressed through the use of new innovations in home-based healthcare delivery. Since its inception, CR has become increasingly recognized as an important tool to improve patient mortality and quality of life in a broad range of cardiac diseases. While there has been little need to modify the delivery of CR since the 1950s, COVID-19 now serves as the necessary impetus to make HBCR an equal alternative to CBCR.

Tofacitinib Treatment Is Associated With Modest and Reversible Increases in Serum Lipids in Patients With Ulcerative Colitis.

BACKGROUND & AIMS: Tofacitinib is an oral, small-molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We analyzed inflammation, lipid concentrations, and incidence rates of major adverse cardiovascular (CV) events (MACEs) in patients who received tofacitinib in worldwide studies. METHODS: We collected data from 1157 patients who participated in 3 8-week induction studies (1 phase-2 study and 2 phase-3 studies; patients received tofacitinib 10 mg twice daily or placebo), a 52-week phase-3 maintenance study of responders (patients received tofacitinib 5 or 10 mg twice daily or placebo), and an ongoing long-term extension study of patients who did and did not respond to induction or maintenance therapy (patients received tofacitinib 5 or 10 mg twice daily). Lipid concentrations were assessed from induction baseline to week 61 (week 52 of maintenance therapy). We calculated MACE incidence rates (patients with ≥1 event per 100 patient-years of exposure) and Reynolds risk score (RRS; a composite score used to determine CV risk) for patients given tofacitinib vs placebo. RESULTS: The mean RRS was <5% at baseline and week 8 of treatment with tofacitinib. At week 8, there were greater increases from baseline in total cholesterol, high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol in patients given tofacitinib compared with placebo. There were correlations between reduced levels of high-sensitivity C-reactive protein and increased serum concentrations of lipid in patients given tofacitinib or placebo (P < .001). Lipid concentrations were increased in patients given tofacitinib vs patients given placebo through week 61. Overall, ratios of low-density lipoprotein cholesterol to HDL-c and total cholesterol to HDL-c did not change significantly over the 61-week period. Four MACEs were reported; the incidence rate was 0.24 (95% CI, 0.07-0.62) and 3 of these patients had 4 or more CV risk factors. CONCLUSIONS: In an analysis of data from 5 trials of patients with UC who received tofacitinib, we found reversible increases in lipids with treatment and inverse correlations with reduced levels of high-sensitivity C-reactive protein. We did not find clinically meaningful changes in lipid ratios or RRS. MACEs were infrequent and not dose-related. Clinicaltrials.gov: A3921063 (NCT00787202); OCTAVE Induction 1 (NCT01465763); OCTAVE Induction 2 (NCT01458951); OCTAVE Sustain (NCT01458574); OCTAVE Open (NCT01470612).

Enhanced Inflammation is a Marker for Risk of Post-Infarct Ventricular Dysfunction and Heart Failure.

Acute ST-segment elevation myocardial infarction (STEMI) activates inflammation that can contribute to left ventricular systolic dysfunction (LVSD) and heart failure (HF). The objective of this study was to examine whether high-sensitivity C-reactive protein (CRP) concentration is predictive of long-term post-infarct LVSD and HF. In 204 patients with a first STEMI, CRP was measured at hospital admission, 24 h (CRP24), discharge (CRPDC), and 1 month after discharge (CRP1M). LVSD at 6 months after discharge (LVSD6M) and hospitalization for HF in long-term multi-year follow-up were prospectively evaluated. LVSD6M occurred in 17.6% of patients. HF hospitalization within a median follow-up of 5.6 years occurred in 45.7% of patients with LVSD6M vs. 4.9% without LVSD6M (p < 0.0001). Compared to patients without LVSD6M, the patients with LVSD6M had higher CRP24 and CRPDC and persistent CRP1M ≥ 2 mg/L. CRP levels were also higher in patients in whom LVSD persisted at 6 months (51% of all patients who had LVSD at discharge upon index STEMI) vs. patients in whom LVSD resolved. In multivariable analysis, CRP24 ≥ 19.67 mg/L improved the prediction of LVSD6M with an increased odds ratio of 1.47 (p < 0.01). Patients with LVSD6M who developed HF had the highest CRP during index STEMI. Elevated CRP concentration during STEMI can serve as a synergistic marker for risk of long-term LVSD and HF.

Elevated Resting and Postprandial Digestive Proteolytic Activity in Peripheral Blood of Individuals With Type-2 Diabetes Mellitus, With Uncontrolled Cleavage of Insulin Receptors.

Objective: To examine resting and postprandial peripheral protease activity in healthy controls and individuals with type 2 diabetes mellitus (T2DM) and pre-T2DM. Methods: Individuals with T2DM or pre-T2DM and healthy controls (mean age 55.8 years) were studied before and for a span of 300 minutes following a single high-calorie McDonald's breakfast. Metalloproteases-2/-9 (MMP-2/-9), elastase, and trypsin activities were assessed in whole blood before and following the meal using a novel high-precision electrophoretic platform. Also assessed were circulating levels of inflammatory biomarkers and insulin receptor density on peripheral blood mononuclear cells (PBMCs) in relationship to protease activity. Results: Premeal MMP-2/-9 and elastase activity levels in T2DM and in pre-T2DM participants were significantly elevated as compared to controls. The T2DM group showed a significant increase in elastase activity 15 minutes after the meal; elastase activity continued to increase to the 30-minute time point (p < 0.01). In control participants, MMP-2/-9, elastase, and trypsin were significantly increased at 15 minutes after the meal (p < 0.05) and returned to premeal values within a period of approximately 30 to 60 minutes post meal. PBMCs incubated for 1 hour with plasma from T2DM and pre-T2DM participants had significantly lower levels of insulin receptor density compared to those incubated with plasma from control participants (p < 0.001). Conclusions: The results of this study suggest that individuals with T2DM and pre-T2DM have higher resting systemic protease activity than nonsymptomatic controls. A single high-calorie/high-carbohydrate meal results in further elevations of protease activity in the systemic circulation of T2DM and pre-T2DM, as well as in healthy controls. The protease activity in turn can lead to a downregulation of insulin receptor density, potentially supporting a state of insulin resistance.

Intensive Cardiac Rehabilitation: an Underutilized Resource.

PURPOSE OF REVIEW: To review evidence-based lifestyle modification strategies for secondary prevention and explore how they are incorporated in traditional cardiac rehabilitation (CR) and intensive cardiac rehabilitation (ICR) programs. RECENT FINDINGS: While physical activity is an important element of cardiac rehabilitation, more recent studies support a variety of methods, including stress management and plant-based diets, to reduce cardiovascular risk factors. Patients who participate in traditional CR programs demonstrate clinical improvement, which are significantly greater in intensive CR (ICR). Yet, there is still a disparity in numbers between those who are eligible and those who ultimately enroll. Research into non-surgical and non-pharmacological health management approaches continues to validate the effectiveness of multidisciplinary intensive CR programs, but there is an increasing need to connect patients with these opportunities.

Effect of alirocumab on lipids and lipoproteins in individuals with metabolic syndrome without diabetes: Pooled data from 10 phase 3 trials.

AIMS: This analysis assessed the efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in patients with or without metabolic syndrome (MetS) using pooled data from 10 phase 3 ODYSSEY trials. MATERIALS AND METHODS: Data from 4983 randomized patients (1940 with MetS; 1642 with diabetes excluded) were assessed in subgroups by MetS status. Efficacy data were analysed in 4 pools per study design: 2 placebo-controlled pools (1 using alirocumab 150 mg every 2 weeks [Q2W], 1 using 75/150 mg Q2W) with background statin, and 2 ezetimibe-controlled pools (both alirocumab 75/150 mg Q2W), 1 with and 1 without background statin. Alirocumab 75/150 mg indicates possible dose increase from 75 to 150 mg at Week 12 based on Week 8 LDL-C. RESULTS: LDL-C percentage reduction from baseline at Week 24 with alirocumab was 63.9% (MetS) and 56.8% (non-MetS) in the pool of alirocumab 150 mg Q2W, and 42.2% to 52.2% (MetS) and 45.0% to 52.6% (non-MetS) in 3 pools using 75/150 mg Q2W. Levels of other lipid and lipoprotein parameters were also improved with alirocumab treatment, including apolipoprotein B, non-high-density lipoprotein cholesterol (non-HDL-C), lipoprotein(a) and HDL-C. Overall, the percentage change at Week 24 in LDL-C and other lipids and lipoproteins did not vary by MetS status. Adverse event rates were generally similar between treatment groups, regardless of MetS status; injection-site reactions occurred more frequently in alirocumab vs control groups. CONCLUSIONS: Across study pools, alirocumab-associated reductions in LDL-C, apolipoprotein B, and non-HDL-C were significant vs control, and did not vary by MetS status.

How B-Type Natriuretic Peptide (BNP) and Body Weight Changes Vary in Heart Failure With Preserved Ejection Fraction Compared With Reduced Ejection Fraction: Secondary Results of the HABIT (HF Assessment With BNP in the Home) Trial.

BACKGROUND: Heart failure is a common cause of hospitalization and can be divided into types with preserved and reduced ejection fraction (HFpEF and HFrEF, respectively). In this subanalysis of the HABIT (Heart Failure Assessment With BNP in the Home) trial, we examined the differences between home B-type natriuretic peptide (BNP) testing and weight monitoring in patients with HFpEF and with HFrEF before decompensation. METHODS AND RESULTS: This was a retrospective review of patients with HFpEF and HFrEF from the HABIT trial. The HFpEF patients compared with HFrEF patients were older and more obese and had lower baseline BNP values. Intra-individual BNP dispersion (spread of distribution over time) was greater in HFpEF than in HFrEF owing to rapid fluctuations (within 3 days). Slowly varying changes in BNP (estimated by a moving average) were equally predictive of ADHF risk in both HFpEF and HFrEF. However, in HFpEF, a rapid rise in BNP >200 pg/mL within 3 days was associated with an increased risk of acute decompensated heart failure (ADHF; hazard ratio 4.0), whereas a similar association was not observed in HFrEF. Weight gain ≥5 lb in 3 days had a high specificity but low sensitivity for ADHF in both HFpEF and HFrEF, whereas a lower threshold of ≥2 lb weight gain over 3 days in patients with HFpEF (but not HFrEF) was a moderately sensitive cutoff associated with decompensation (60% sensitivity). CONCLUSIONS: Patients with HFpEF and HFrEF have variations in their BNP and weight before decompensation. The rapid time scale behaves differently between the groups. In those with HFpEF, a 3-day period characterized by ≥2 lb weight gain and/or >200 pg/mL BNP rise was significantly associated with decompensation. Future prospective studies investigating different weight and BNP cutoffs for home monitoring of HFpEF and HFrEF patients should be performed to fully learn the value of BNP changes before clinical deompensation.

Procalcitonin predicts mortality in HIV-infected Ugandan adults with lower respiratory tract infections.

BACKGROUND AND OBJECTIVE: In low and middle-income countries where HIV infection is prevalent, identifying patients at high risk of dying from lower respiratory tract infections is challenging and validated prognostic models are lacking. Serum procalcitonin may be a useful prognostic tool in these settings. We sought to determine if elevated serum procalcitonin is associated with increased in-hospital mortality and to combine serum procalcitonin with available clinical characteristics to create a clinically useful prognostic model. METHODS: We conducted a prospective, nested case-control study of 241 HIV-infected adults admitted to Mulago Hospital in Kampala, Uganda with cough ≥2 weeks in duration. We collected demographic and clinical information, baseline serum for procalcitonin analysis, and followed patients to determine in-hospital mortality. RESULTS: Serum procalcitonin was a strong and independent predictor of inpatient mortality (aOR = 7.69, p = 0.01, sensitivity = 93%, negative predictive value = 97%). Best subset multivariate analysis identified 3 variables that were combined into a prognostic model to risk stratify patients; these variables included respiratory rate ≥30 breaths/minute (aOR = 2.07, p = 0.11), oxygen saturation <90% (aOR = 3.07, p = 0.02), and serum procalcitonin >0.5 ng/ml (aOR = 7.69, p = 0.01). The predicted probability of inpatient mortality ranged from 1% when no variables were present, to 42% when all variables were present. CONCLUSIONS: Elevated serum procalcitonin >0.5 ng/ml is an independent predictor of in-hospital mortality. Elevated serum procalcitonin, tachypnea, and hypoxemia may be combined into a prognostic model to identify patients at high risk of dying in the hospital. This model may be used to estimate the probability of death and to guide triage and treatment decisions.

Dietary patterns to promote cardiometabolic health.

Multiple professional societies recommend the Mediterranean and/or Dietary Approaches to Stop Hypertension dietary patterns in their cardiovascular disease prevention guidelines because these diets can improve cardiometabolic health and reduce the risk of cardiovascular events. Furthermore, low sodium intake can be particularly beneficial for patients with hypertension. Carbohydrate restriction, with an emphasis on including high-quality carbohydrates and limiting refined starches and foods and beverages with added sugars, can promote weight loss and cardiometabolic benefits in the short term, compared with higher carbohydrate intake. Evidence is lacking for sustained, long-term effects of low carbohydrate and very low carbohydrate intake on cardiometabolic risk and cardiovascular outcomes. Time-restricted eating, in the context of an overall healthy dietary pattern, can promote cardiometabolic health by aligning food intake with the circadian rhythm, although its effect on hard clinical outcomes remains to be proven. Although there is no one dietary pattern that is appropriate for all patients, engaging in shared decision-making with patients, utilizing behaviour-change principles and engaging members of the health-care team, such as registered dietitian nutritionists, can lead to substantial improvement in the lifestyle and overall health trajectory of a patient. Emphasizing the similarities, rather than differences, of recommended dietary patterns, which include an emphasis on vegetables, fruits, legumes, nuts, whole grains and minimally processed protein foods, such as fatty fish or plant-based proteins, can simplify the process for both patients and clinicians alike.

Harnessing RNA Interference for Cholesterol Lowering: The Bench-to-Bedside Story of Inclisiran.

Lowering low-density lipoprotein cholesterol (LDL-C) is a cornerstone of reducing risk for atherosclerotic cardiovascular disease. Despite the approval of nonstatin therapies for LDL-C lowering over the past 2 decades, these medications are underused, and most patients are still not at guideline-recommended LDL-C goals. Barriers include poor adherence, clinical inertia, concern for side effects, cost, and complex prior authorization processes. With atherosclerotic cardiovascular disease-related mortality increasing globally, there remains a need for additional therapeutic options for lowering LDL-C as part of an atherosclerotic cardiovascular disease prevention strategy. Following the identification of PCSK9 (proprotein convertase subtilisin/kexin type 9) as a promising therapeutic target, inclisiran was developed using the natural process of RNA interference for robust, sustained prevention of hepatic PCSK9 synthesis. Twice-yearly maintenance subcutaneous inclisiran (following initial loading doses at Day 1 and Day 90) reduces circulating LDL-C levels by ≈50% versus placebo when added to maximally tolerated statins. Long-term safety and tolerability of inclisiran have been assessed, with studies underway to evaluate the effects of inclisiran on cardiovascular outcomes and to provide additional safety and effectiveness data. In 2021, <20 years after the discovery of PCSK9, inclisiran became the first RNA interference therapeutic approved in the United States for LDL-C lowering in patients with established atherosclerotic cardiovascular disease or familial hypercholesterolemia and has since been approved for use in patients with primary hyperlipidemia. This article reviews the journey of inclisiran from bench to bedside, including early development, the clinical trial program, key characteristics of inclisiran, and practical points for its use in the clinic.

Unique features of dyslipidemia in women across a lifetime and a tailored approach to management.

Purpose of Review: Cardiovascular disease is a leading cause of death worldwide. Dyslipidemia is a critical modifiable risk factor for the prevention of cardiovascular disease. Dyslipidemia affects a large population of women and is especially pervasive within racial/ethnic minorities. Recent Findings: Dyslipidemia in pregnancy leads to worse outcomes for patients and creates increased cardiovascular risk for women at an older age. However, women remain underscreened and undertreated compared to men. Females also comprise a small portion of clinical trial participants for lipid lowering agents with increased disease prevalence compared to trial representation. However, recent lipid trials have shown different efficacies of therapies such as ezetimibe, inclisiran, and bempedoic acid with a greater relative benefit for women. Summary: Pathophysiology of dyslipidemia varies between men and women and across a woman's lifetime. While increased lipid levels or lipid imbalances are more common in postmenopausal women over age 50, conditions such as PCOS and FH produce higher cardiovascular risk for young women.Best practices for management of women with dyslipidemia include early screening with lifestyle intervention and pharmacotherapy with statin and non-statin agents to achieve guideline directed LDL-C thresholds.

Feasibility and Cardiometabolic Effects of Time-Restricted Eating in Patients with Metabolic Syndrome.

Metabolic syndrome (MetS) and a prolonged daily eating window (EW) are associated with circadian rhythm disruption and increased cardiometabolic risk. Misalignment between circadian timing system and daily rhythms of food intake adversely impacts metabolic regulatory mechanisms and cardiovascular function. Restricting the daily EW by imposing an eating-fasting cycle through time-restricted eating (TRE) can restore robust circadian rhythms, support cellular metabolism, and improve cardiometabolic health. The aim of this study was to assess a feasibility of 12-week TRE intervention with self-selected 10 h EW and effects of TRE on EW duration, cardiometabolic outcomes, daily rhythms of behavior, and wellbeing in Polish patients with MetS and EW ≥ 14 h/day. Dietary intake was monitored with a validated myCircadianClock application (mCC app). Adherence to TRE defined as the proportion of days recorded with mCC app in which participants satisfied 10-h TRE was the primary outcome. A total of 26 patients (aged 45 ± 13 years, 62% women, 3.3 ± 0.5 MetS criteria, EW 14 ± 1.5 h/day) were enrolled. Coexistence of increased waist circumference (WC) (96% of patients), elevated fasting plasma glucose (FPG) (77%), and elevated blood pressure (BP) (69%) was the most common MetS pattern (50%). TRE intervention (mean duration of 81.6 ± 12.6 days) led to reducing daily EW by 28% (p < 0.0001). Adherence to TRE was 87 ± 13%. Adherence to logging food intake on mCC app during TRE was 70 ± 27%. Post TRE, a decrease in body weight (2%, 1.7 ± 3.6 kg, p = 0.026), body mass index (BMI) (1%, 0.5 ± 1.2 kg/m2, p = 0.027), WC (2%, 2.5 ± 3.9 cm, p = 0.003), systolic BP (4%, 4.8 ± 9.0 mmHg, p = 0.012), FPG (4%, 3.8 ± 6.9 mg/dL, p = 0.037), glycated hemoglobin (4%, 0.2 ± 0.4%, p = 0.011), mean fasting glucose level from continuous glucose monitor (CGM) (4%, 4.0 ± 6.1 mg/dL, p = 0.002), and sleepiness score (25%, 1.9 ± 3.2 points, p = 0043) were observed. A significant decrease in body weight (2%), BMI (2%), WC (3%), mean CGM fasting glucose (6%), sleepiness score (27%), and depression score (60%) was found in patients with mean post-TRE EW ≤ 10 h/day (58% of total), and not in patients with EW > 10 h/day. Adherence to TRE was higher in patients with post-TRE EW ≤ 10 h/day vs. patients with EW > 10 h/day (94 ± 6% vs. 77 ± 14%, p = 0.003). Our findings indicate that 10-h TRE was feasible in the European MetS population. TRE resulted in reducing daily EW and improved cardiometabolic outcomes and wellbeing in patients with MetS and prolonged EW. Use of the mCC app can aid in implementing TRE. This pilot clinical trial provides exploratory data that are a basis for a large-scale randomized controlled trial to determine the efficacy and sustainability of TRE for reducing cardiometabolic risks in MetS populations. Further research is needed to investigate the mechanisms of TRE effects, including its impact on circadian rhythm disruption.

A focused update to the 2019 NLA scientific statement on use of lipoprotein(a) in clinical practice.

Since the 2019 National Lipid Association (NLA) Scientific Statement on Use of Lipoprotein(a) in Clinical Practice was issued, accumulating epidemiological data have clarified the relationship between lipoprotein(a) [Lp(a)] level and cardiovascular disease risk and risk reduction. Therefore, the NLA developed this focused update to guide clinicians in applying this emerging evidence in clinical practice. We now have sufficient evidence to support the recommendation to measure Lp(a) levels at least once in every adult for risk stratification. Individuals with Lp(a) levels <75 nmol/L (30 mg/dL) are considered low risk, individuals with Lp(a) levels ≥125 nmol/L (50 mg/dL) are considered high risk, and individuals with Lp(a) levels between 75 and 125 nmol/L (30-50 mg/dL) are at intermediate risk. Cascade screening of first-degree relatives of patients with elevated Lp(a) can identify additional individuals at risk who require intervention. Patients with elevated Lp(a) should receive early, more-intensive risk factor management, including lifestyle modification and lipid-lowering drug therapy in high-risk individuals, primarily to reduce low-density lipoprotein cholesterol (LDL-C) levels. The U.S. Food and Drug Administration approved an indication for lipoprotein apheresis (which reduces both Lp(a) and LDL-C) in high-risk patients with familial hypercholesterolemia and documented coronary or peripheral artery disease whose Lp(a) level remains ≥60 mg/dL [∼150 nmol/L)] and LDL-C ≥ 100 mg/dL on maximally tolerated lipid-lowering therapy. Although Lp(a) is an established independent causal risk factor for cardiovascular disease, and despite the high prevalence of Lp(a) elevation (∼1 of 5 individuals), measurement rates are low, warranting improved screening strategies for cardiovascular disease prevention.

Perturbations in skeletal muscle sarcomere structure in patients with heart failure and type 2 diabetes: restorative effects of (-)-epicatechin-rich cocoa.

HF (heart failure) and T2D (Type 2 diabetes) associate with detrimental alterations in SkM (skeletal muscle) structure/function. We have demonstrated recently that (-)-ERC (epicatechin-rich cocoa) improves SkM mitochondrial structure [Taub, Ramirez-Sanchez, Ciaraldi, Perkins, Murphy, Naviaux, Hogan, Ceballos, Maisel, Henry et al. (2012) Clin. Trans. Sci. 5, 43-47]. We hypothesized that an improved mitochondrial structure may facilitate the reversal of detrimental alterations in sarcomeric microstructure. In a pilot study, five patients with HF and T2D consumed ERC for 3 months; treadmill testing [VO2max (maximum oxygen consumption)] and SkM biopsies were performed. Western blot analysis, immunohistochemistry and electron microscopy were used. We report severe perturbations in components of the DAPC (dystrophin-associated protein complex) as well as sarcomeric microstructure at baseline. ERC induced recovery/enhancement of DAPC protein levels, sarcomeric microstructure and, in a co-ordinated fashion, alterations in markers of SkM growth/differentiation consistent with myofibre regeneration. VO2max increased (~24%) but did not reach statistical significance. These initial results warrant further rigorous investigation, since the use of ERC (or pure epicatechin) may represent a safe and novel means of improving muscle function.

Beneficial and detrimental effects of glycemic control on cardiovascular disease in type 2 diabetes.

Epidemiological data demonstrates that improved regulation of blood glucose correlates with better cardiovascular (CV) outcomes. Conversely, some interventional studies have demonstrated that tight glycemic control has no benefit or can even result in worse CV outcomes. These conclusions parallel the paradox that glycemic control has proven beneficial for microvascular outcomes, while few studies have demonstrated significant macrovascular benefits. This imprecise understanding conveys the need to better comprehend the mechanisms of glycemic control and its impact on CV disease. Such variations in data also require a more comprehensive approach to diabetes and CV disease in which multiple biomarkers such as low density lipoprotein (LDL), low adiponectin, elevated C-reactive protein (CRP) and well established clinical parameters such as high blood pressure, weight, and functional status are incorporated into clinical decision making. Reliance on one parameter in isolation such as glycemic control and one biomarker such as HbA1C does not provide an accurate assessment of CV outcomes.