Cardiovascular Risk Prediction Research Articles

Heart rate from intermittent home measurements within an atrial fibrillation screening program is associated with mortality

Abstract Introduction A high resting heart rate is a predictor of cardiovascular disease and cardiovascular mortality. Studies on the association between heart rate and outcomes often measure heart rate at a single time point, even though multiple measurements may be a stronger predictor of cardiovascular risk. Indeed, the association between short-term home heart rate measurements and outcomes has not been extensively studied. Purpose This sub study of the STROKESTOP trial explores the association of baseline and home resting heart rate measurements with all-cause and cardiovascular mortality. Methods The STROKESTOP randomised controlled trial consisted of an atrial fibrillation (AF) screening program among the 75- and 76-year-old inhabitants of two Swedish regions. Participants in the intervention group were invited to a two week intermittent screening program, consisting of twice daily measurements with an ECG-based handheld device. For this sub analysis, baseline heart rate, the median of 5 home morning heart rates and the median of 5 home evening heart rates were evaluated. Associations were evaluated by heart rate quintiles (41-63 bpm, 64-70 bpm, 71-76 bpm, 77-84 bpm and ≥85 bpm), with 64-70 bpm as the reference category. Hazard rations were obtained by Cox regression analysis. The full multivariable model included demograhic factors such as sex and educational level, medical history of several diseases and the use of cardiovascular medication. Both all-cause mortality and cardiovascular mortality were evaluated. Results In total, 5873 individuals were included in this analysis. Overall, 55.6% were women and the median baseline heart rate was 73 [65-81] bpm, whereas the median of morning heart rates was 71 [64-78] bpm and that of evening heart rates 71 [65-79] bpm. Having a baseline heart rate in the highest quintile compared to the reference quintile, showed a hazard ratio (HR) for all-cause mortality in unadjusted analysis of 1.39 (1.11-1.73) (p=0.004), and of 1.51 (1.20-1.90) in the fully adjusted analysis (p<.001). For cardiovascular mortality, HRs were 1.78 (1.21-2.63) (p=0.004) and 2.13 (1.42-3.20) (p=<.001), respectively. The association between the highest heart rate and all-cause mortality and cardiovascular mortality were substantially strengthened when median morning heart rates were considered (HR 2.03 (1.61-2.56) and 2.18 (1.72-2.76), p<.001 for all-cause mortality on univariable and multivariable analysis, HR 2.35 (1.57-3.51) and 2.59 (1.72-3.92), p<.001) for cardiovascular mortality). Associations between home evening heart rates and all-cause and cardiovascular mortality were not substantially stronger compared to the associations with baseline heart rate. Conclusion Our study shows that home-measured morning heart rate is more strongly associated with all-cause and cardiovascular mortality compared to a single time-point office heart rate.Hazard ratios for mortality

#521 Increasing levels of aortic peak wave velocity along with prolonged higher CaxP product is associated with mortality in peritoneal dialysis

Abstract Background and Aims Valvular calcification is concordant with vascular calcification and develops faster in end-stage renal disease patients than in the average population. There are contradictory reports about the pathophysiology and the predictive value of valvular calcification regarding mortality in this patient population. Aortic peak wave velocity (Vmax) measurement is a non-invasive and reliable marker for the diagnosis of valve calcification. Our study analyzes cardiovascular risk prediction effect of increasing levels of Vmax at different time points in peritoneal dialysis (PD) patients. Method We conducted a retrospective, single-center study of incident PD patients under follow-up between January 1992 and January 2023 in our clinic. Demographics, laboratory, and echocardiographic findings were obtained from medical records. Patients without a baseline echocardiography were excluded. ΔVmax is defined as the last Vmax minus baseline Vmax levels. The patients were divided into two subgroups: Vmax-stable and Vmax-increased. Results The baseline demographics, laboratory, and clinical characteristics, including daily elemental calcium and calcitriol usage, were similar between Vmax-stable and Vmax-increased groups. Baseline calcium (Ca), phosphate (P), and annual CaXP levels were significantly higher in Vmax-increased group [p = 0.01, p = 0.02, and (F(1,27) = 10.415, p = 0.003), respectively]. Cardiovascular mortality was 9.8% in Vmax-stable group and 26.8% in Vmax-increased group (p = 0.02). Conclusion During a follow-up of 20 years, increasing Vmax values were associated with higher CaxP levels in PD patients. Increased Vmax levels, along with higher CaxP levels, are associated with cardiovascular mortality. Even without clinical manifestations, Vmax follow-up is a non-invasive, easily accessible method and might identify the high-risk group regarding cardiovascular mortality in the PD population.

Hypoxic indices for obstructive sleep apnoea severity and cardiovascular disease risk prediction: A comparison and application in a community population.

The apnoea-hypopnoea index (AHI) and oxygen desaturation index (ODI) encounter challenges in capturing the intricate relationship between obstructive sleep apnoea (OSA) and cardiovascular disease (CVD) risks. Although novel hypoxic indices have been proposed to tackle these limitations, there remains a gap in comprehensive validation and comparisons across a unified dataset. Samples were derived from the Sleep Heart Health Study (SHHS), involving 4485 participants aged over 40 years after data quality screening. The study compared several key indices, including AHI, ODI, the reconstructed hypoxic burden (rHB), the percentage of sleep time with the duration of respiratory events causing desaturation (pRED_3p) and the sleep breathing impairment index (SBII), in relation to CVD mortality and morbidity risks. Adjusted Cox proportional models were employed to calculate hazard ratios (HRs) for each index, and comparisons were performed. SBII and pRED_3p exhibited significant correlations with both CVD mortality and morbidity, with SBII showing the highest adjusted HR (95% confidence interval) for mortality (2.04 [1.25, 3.34]) and pRED_3p for morbidity (1.43 [1.09-1.88]). In contrast, rHB was only significant in predicting CVD mortality (1.63 [1.05-2.53]), while AHI and ODI did not show significant correlations with CVD outcomes. The adjusted models based on SBII and pRED_3p exhibited optimal performance in the CVD mortality and morbidity datasets, respectively. This study identified the optimal indices for OSA-related CVD risks prediction, SBII for mortality and pRED_3p for morbidity. The open-source online platform provides the computation of the indices.

Prediction of individual lifetime cardiovascular risk and potential treatment benefit: development and recalibration of the LIFE-CVD2 model to four European risk regions.

The 2021 European Society of Cardiology prevention guidelines recommend the use of (lifetime) risk prediction models to aid decisions regarding initiation of prevention. We aimed to update and systematically recalibrate the LIFEtime-perspective CardioVascular Disease (LIFE-CVD) model to four European risk regions for the estimation of lifetime CVD risk for apparently healthy individuals. The updated LIFE-CVD (i.e., LIFE-CVD2) models were derived using individual-participant data from 44 cohorts in 13 countries (687,135 individuals without established CVD, 30,939 CVD events in median 10.7 years of follow-up). LIFE-CVD2 uses sex-specific functions to estimate the lifetime risk of fatal and non-fatal CVD events with adjustment for the competing risk of non-CVD death, and is systematically recalibrated to four distinct European risk regions. The updated models showed good discrimination in external validation among 1,657,707 individuals (61,311 CVD events) from eight additional European cohorts in seven countries, with a pooled C-index of 0.795 (95%CI 0.767-0.822). Predicted and observed CVD event risks were well calibrated in population-wide electronic health records data in the UK (CPRD) and Netherlands (ELAN). When using LIFE-CVD2 to estimate potential gain in CVD-free life expectancy from preventive therapy, projections varied by risk region reflecting important regional differences in absolute lifetime risk. For example a 50-year-old smoking woman with a SBP of 140 mm Hg was estimated to gain 0.9 years in the low risk region versus 1.6 years in the very high risk region from lifelong 10 mm Hg SBP reduction. The benefit of smoking cessation for this individual ranged from 3.6 years in the low risk region to 4.8 years in the very high risk region. By taking into account geographical differences in CVD incidence using contemporary representative data sources, the recalibrated LIFE-CVD2 model provides a more accurate tool for the prediction of lifetime risk and CVD-free life expectancy for individuals without previous CVD, facilitating shared decision-making for cardiovascular prevention as recommended by 2021 European guidelines.

Enhancing cardiovascular risk prediction through AI-enabled calcium-omics

Whole-heart coronary calcium Agatston score is a well-established predictor of major adverse cardiovascular events (MACE), but it does not account for individual calcification features related to the pathophysiology of the disease (e.g., multiple-vessel disease, spread of the disease along the vessel, stable calcifications, numbers of lesions, and density). We used novel, hand-crafted calcification features (calcium-omics); Cox time-to-event modeling; elastic net; and up and down synthetic sampling methods for imbalanced data, to assess MACE risk. We used 2457 CT calcium score (CTCS) images enriched for MACE events from our large no-cost CLARIFY program (ClinicalTrials.gov Identifier: NCT04075162). Among calcium-omics features, numbers of calcifications, LAD mass, and diffusivity (a measure of spatial distribution) were especially important determinants of increased risk, with dense calcification (> 1000HU, stable calcifications) associated with reduced risk Our calcium-omics model with (training/testing, 80/20) gave C-index (80.5%/71.6%) and 2-year AUC (82.4%/74.8%). Although the C-index is notoriously impervious to model improvements, calcium-omics compared favorably to Agatston and gave a significant difference (P < 0.001). The calcium-omics model identified 73.5% of MACE cases in the high-risk group, a 13.2% improvement as compared to Agatston, suggesting that calcium-omics could be used to better identity candidates for intensive follow-up and therapies. The categorical net-reclassification index was NRI = 0.153. Our findings from this exploratory study suggest the utility of calcium-omics in improved risk prediction. These promising results will pave the way for more extensive, multi-institutional studies of calcium-omics.

Predictors of cardiovascular risk in familial hypercholesterolemia.

Familial Hypercholesterolemia is associated with an increased risk of cardiovascular disease. The current international guidelines of the main scientific societies consider that all people with familial hypercholesterolemia have a high or very high cardiovascular risk. However, the occurrence of atherosclerotic cardiovascular disease is very heterogeneous in this population. Stratifying risk within people with familial hypercholesterolemia is essential to identify individuals who require intensive cholesterol-lowering therapies. In the last year, several studies have been published focusing on the contribution of diabetes to familial hypercholesterolemia, the role of stroke, as a manifestation of atherosclerotic disease, and the external validation of the SAFEHEART risk equation in the English population diagnosed with Familial Hypercholesterolemia. It is necessary the development of a tool that allows us to identify, in a simple, reproducible, and universal way, patients who may have a high risk of suffering a cardiovascular event and who are susceptible to more intensive treatments to reduce cholesterol levels.

Association of Triglyceride Glucose-Derived Indexes with Recurrent Events Following Atherosclerotic Cardiovascular Disease.

Triglyceride glucose (TyG) and TyG-body mass index (TyG-BMI) are reliable surrogate indexes of insulin resistance and used for risk stratification and outcome prediction in patients with atherosclerotic cardiovascular disease (ASCVD). Here, we inserted estimated average glucose (eAG) into the TyG (TyAG) and TyG-BMI (TyAG-BMI) as derived parameters and explored their clinical significance in cardiovascular risk prediction. This was a population-based cohort study of 9,944 Chinese patients with ASCVD. The baseline admission fasting glucose and A1C-derived eAG values were recorded. Cardiovascular events (CVEs) that occurred during an average of 38.5 months of follow-up were recorded. We stratified the patients into four groups by quartiles of the parameters. Baseline data and outcomes were analyzed. Distribution of the TyAG and TyAG-BMI indexes shifted slightly toward higher values (the right side) compared with TyG and TyG-BMI, respectively. The baseline levels of cardiovascular risk factors and coronary severity increased with quartile of TyG, TyAG, TyG-BMI, and TyAG-BMI (all P<0.001). The multivariate-adjusted hazard ratios for CVEs when the highest and lowest quartiles were compared from low to high were 1.02 (95% confidence interval [CI], 0.77 to 1.36; TyG), 1.29 (95% CI, 0.97 to 1.73; TyAG), 1.59 (95% CI, 1.01 to 2.58; TyG-BMI), and 1.91 (95% CI, 1.16 to 3.15; TyAG-BMI). The latter two showed statistical significance. This study suggests that TyAG and TyAG-BMI exhibit more information than TyG and TyG-BMI in disease progression among patients with ASCVD. The TyAG-BMI index provided better predictive performance for CVEs than other parameters.

Endogenous Acetylcholine Contributes to Flow-Mediated Dilation in Humans

Background &amp; Objective. Flow-mediated dilation (FMD) is a crucial function of the vascular endothelium wherein intraluminal shear stress stimulates endothelium-dependent vasodilation mediated primarily by nitric oxide. Brachial artery FMD (baFMD) is widely evaluated in clinical research as an index of endothelial function, and impaired baFMD is an independent predictor of cardiovascular risk. Despite the physiological and clinical relevance of FMD, the mechanisms by which shear stress is transduced to endothelium-dependent vasodilation (i.e., upstream of nitric oxide production) remain unclear. baFMD corresponds closely with sensitivity to the endothelium-dependent vasodilator acetylcholine (ACh), and preclinical models suggest ACh is released from endothelial cells in response to shear stress. Therefore, the present study tested the hypothesis that activation of muscarinic ACh receptors facilitates baFMD in humans. Methods. baFMD was evaluated using Doppler ultrasound in healthy participants (n=11; 5F/6M; 23±2 y; means ± SE) under control conditions and following local inhibition of muscarinic ACh receptors via intra-arterial atropine infused proximal to the measurement site. baFMD was assessed in response to transient and sustained shear stimuli in separate trials: 1) reactive hyperemia following 5 min of arterial cuff occlusion (RH-FMD) and 2) steady-state rhythmic handgrip exercise at graded intensities (10, 15, 20, &amp; 25% maximal voluntary contraction, MVC) to produce step increases in shear rate (EX-FMD). Blockade effcacy was confirmed via a dose-response to intra-arterial ACh infusion pre and post atropine. Results. Baseline brachial artery diameter and forearm blood flow were similar in all trials (all P&gt;0.05). Atropine reduced peak brachial artery dilation following cuff release (RH-FMD, Δ diameter, atropine: 4.6±0.8 vs. control: 6.5±0.8%, P=0.04) and increased the shear stimulus (shear rate area under the curve, SRAUC: atropine, 29±3 vs. control: 21±3 s−1×103, P=0.01) such that the percent change in brachial diameter was diminished by 35±16% when normalized to SRAUC (baFMD:SRAUC ratio, atropine: 1.7±0.3 vs. control: 3.9±1.0, P=0.02). Similarly, in the EX-FMD trial, atropine reduced brachial artery diameter at all exercise intensities (25% MVC, percent change in diameter: atropine, 10.8±1.4 vs. control, 15.5±1.7%, P=0.04) despite a greater shear stimulus (shear rate: atropine, 10.9±1.1 vs. control, 9.3±0.9 s−1×102, P=0.01). Thus, atropine reduced the slope describing the relationship between brachial artery vasodilation (percent change) and the change in shear rate by 38±8% across all exercise intensities (slope, atropine: 1.3±0.1 vs. control: 2.4±0.4% Δ×s×10−2, P=0.007). As expected, atropine reduced brachial artery vasodilation in response to upstream infusion of ACh (1.5 μg ACh/dl forearm volume/min, Δ diameter, atropine: 2±1 vs. control: 23±4%, P=0.001). Conclusions. The results suggest endogenous ACh facilitates baFMD in response to both transient and sustained shear stimuli, which highlights a novel physiological role of endogenous ACh in vascular regulation in humans and provides insight regarding the basic mechanisms of flow-mediated vasodilation. NIH R01 HL119337 and F31 HL142240. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Cardiovascular risk prediction - now and the future

Current cardiovascular risk estimation systems that estimate 10-year risk based on cohort studies starting at around age 40 have probably reached their limits based on current methods. The challenges are to develop new systems that will permit personalised risk estimation earlier in life with better estimates of true lifetime risk and likely treatment benefits. We outline approaches to address these issues.

Effect of lipid-lowering therapy on carotid plaque burden in older adults

BackgroundLittle is known about the benefits of lipid-lowering medications in those age ≥ 75 years. We assessed the effect of lipid-lowering medications on progression to severe atherosclerosis in patients age > 75. MethodsData was retrospectively obtained from the Stroke Prevention & Atherosclerosis Research Centre, Canada. Atherosclerosis burden was measured as carotid total plaque area (TPA), a powerful predictor of cardiovascular risk. Survival time free of severe atherosclerosis (SFSA) was defined as the period when TPA remained <1.19 cm2. Kaplan–Meier, multiple Cox proportional hazard and hierarchical mixed-effect models were used to determine the effects of lipid-lowering medications on progression to severe atherosclerosis. ResultsIn total 1404 cases (mean age 81 ± 4 years; women 52%) were included. Those taking lipid-lowering medications were more likely to have a history of diabetes and a higher burden of atherosclerosis at baseline. In Kaplan–Meier analysis, the SFSA was significantly longer in those receiving lipid-lowering therapy. In multivariable-adjusted analyses, those not receiving lipid lowering therapy (irrespective of their vascular disease at baseline) were more likely to have TPA > 1.19 cm2 (hazard ratio (HR) = 1.37, 95% confidence interval (CI): 1.09,0.71). Similar findings were observed in mixed effects models when plaque progression was defined as any change >0.05 cm2 per year (odds ratio (OR):2.17, 95% CI:1.38,3.57). ConclusionLipid-lowering therapy is effective in controlling the burden of atherosclerosis among older adults with and without vascular disease. The measurement of plaque burden can guide selection and follow-up of those who may benefit from treatment.

P081 Out-patient management of gout in secondary care: Results from the North West regional audit

Abstract Background/Aims Recommendations for gout management have significantly evolved as outlined by the latest National Institute for Health and Care Excellence (NICE), European League Against Rheumatism (EULAR), British Society for Rheumatology (BSR) and the Medicines and Healthcare products Regulatory Agency (MHRA) guidelines, with increased emphasis being placed on optimising cardiovascular risk. This regional audit aimed to assess concordance with these guidelines within rheumatology outpatient settings in the North West region of England. Methods New or follow-up patients with gout, presenting to a rheumatology outpatient setting within the Greater Manchester and Lancashire area over a five-week period between 1/3/23 and 7/4/23 were included. We collated data on demographics, co-morbidity assessment including cardiovascular risk, prescribing of febuxostat in major cardiovascular disease, diuretic use and advice, setting of treat-to-target levels, use of cardiovascular risk prediction tools and subsequent follow up arrangements. For new patients, collected data also included referral reason, and prescription recommendations for first-line urate-lowering therapy (ULT) and co-prescriptions for flare prophylaxis. Results Ninety-two patients (mean age 60 years, 80% male) were included from 13 rheumatology departments. Twenty-three patients were new referrals. Sixty-seven patients (73%) had ≥ 1 relevant comorbidity; hypertension being the most common (55%). Twenty (22%) patients were on diuretics. Twelve (55%) of these patients had a diagnosis of hypertension without heart failure; none received recommendations to reduce or stop diuretics. In line with current guidelines, no patient with major cardiovascular disease was treated with febuxostat. Treat-to-target levels were agreed in 49 (57%) applicable patients. Cardiovascular prediction tools were only calculated or known in three (3%) patients. However, clinic data collected would have allowed a risk assessment calculation in 13 (14%) patients. Sixteen (17%) patients audited had no planned follow-up. Compared to NICE guidelines, 18 (78%) new patients reviewed in clinic were referred appropriately to rheumatology services. Twenty-two (96%) new patients referred were eligible to start ULT, of which 15 (75%) were started on a NICE/ EULAR recommended first-line ULT treatment (14 patients on allopurinol including 11 patients with no major cardiovascular disease, one patient on febuxostat). Eleven (79%) patients started on allopurinol were initiated on a low dose (50-100mg), as recommended by NICE and the BSR. Ten (67%) patients of those initiated on ULT were also prescribed prophylactic colchicine. Two additional patients were prescribed NSAIDs with PPI cover and one patient was prescribed oral steroids without PPI cover. Conclusion Most new patients were referred and prescribed first-line ULT treatment appropriately, often with colchicine prophylaxis. Uptake of febuxostat as first-line therapy was limited. Cardiovascular risk assessment was rarely done; further work exploring barriers to undertaking these assessments in rheumatology clinics is likely to improve both patient care and guideline compliance. Disclosure L. Gould: Other; L.G. has received conference fees from Eli Lilly. A. Richards: None. L. Gray: Other; L.G. has received travel and conference fees from Eli Lilly. M. Badarulla: Other; M.B. has received conference fees from Eli Lilly. L. Mercer: Other; L.M. has received conference fees from Nordic Pharma and UCB. R. Farid: None. R. Heaton: Consultancies; R.H. has received consultancy fees from Galapagos. Honoraria; R.H. has received speaker honorarium from Abbvie and Nordic. Other; R.H. has received conference fees from UCB. M. Al-Attar: None. M. Whitehead: None. S. Kamath: None. L. Teh: None. A. Odekunle: None. C.A. Sharp: None. A. Babiker: None. S. Hopping: None. A. Oldroyd: None. K. Lazarewicz: None. C. Saleh: None. S. Horton: None. D. Roy: Honoraria; D.R. has an honorary University of Manchester research assistant contract. A. Opeseyitan: None. D. Das: None. S. Varughese: None. D. Yidana: None. S. Wig: None. J. Bluett: Grants/research support; J.B. has received a research grant award from Pfizer. Other; J.B. has received travel/conference fees from UCB, Fresenius Kabi, Pfizer and Eli Lilly.

Machine-learning-based models to predict cardiovascular risk using oculomics and clinic variables in KNHANES

BackgroundRecent researches have found a strong correlation between the triglyceride-glucose (TyG) index or the atherogenic index of plasma (AIP) and cardiovascular disease (CVD) risk. However, there is a lack of research on non-invasive and rapid prediction of cardiovascular risk. We aimed to develop and validate a machine-learning model for predicting cardiovascular risk based on variables encompassing clinical questionnaires and oculomics.MethodsWe collected data from the Korean National Health and Nutrition Examination Survey (KNHANES). The training dataset (80% from the year 2008 to 2011 KNHANES) was used for machine learning model development, with internal validation using the remaining 20%. An external validation dataset from the year 2012 assessed the model’s predictive capacity for TyG-index or AIP in new cases. We included 32122 participants in the final dataset. Machine learning models used 25 algorithms were trained on oculomics measurements and clinical questionnaires to predict the range of TyG-index and AIP. The area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, and F1 score were used to evaluate the performance of our machine learning models.ResultsBased on large-scale cohort studies, we determined TyG-index cut-off points at 8.0, 8.75 (upper one-third values), 8.93 (upper one-fourth values), and AIP cut-offs at 0.318, 0.34. Values surpassing these thresholds indicated elevated cardiovascular risk. The best-performing algorithm revealed TyG-index cut-offs at 8.0, 8.75, and 8.93 with internal validation AUCs of 0.812, 0.873, and 0.911, respectively. External validation AUCs were 0.809, 0.863, and 0.901. For AIP at 0.34, internal and external validation achieved similar AUCs of 0.849 and 0.842. Slightly lower performance was seen for the 0.318 cut-off, with AUCs of 0.844 and 0.836. Significant gender-based variations were noted for TyG-index at 8 (male AUC=0.832, female AUC=0.790) and 8.75 (male AUC=0.874, female AUC=0.862) and AIP at 0.318 (male AUC=0.853, female AUC=0.825) and 0.34 (male AUC=0.858, female AUC=0.831). Gender similarity in AUC (male AUC=0.907 versus female AUC=0.906) was observed only when the TyG-index cut-off point equals 8.93.ConclusionWe have established a simple and effective non-invasive machine learning model that has good clinical value for predicting cardiovascular risk in the general population.

Worldwide Increasing Use of Nonfasting Rather Than Fasting Lipid Profiles.

Historically, lipids and lipoproteins were measured in the fasting state for cardiovascular risk prediction; however, since 2009 use of nonfasting lipid profiles has increased substantially worldwide. For patients, nonfasting lipid profiles are convenient and avoid any risk of hypoglycemia. For laboratories, blood sampling in the morning and extra visits for patients who have not fasted are avoided. For patients, clinicians, hospitals, and society, nonfasting sampling allows same-day visits with first blood sampling followed by a short wait for test results before clinical consultation. Therefore, nonfasting compared to fasting lipid profiles will save money and time and may improve patient compliance with cardiovascular prevention programs. We report on the progression of endorsement and implementation of nonfasting lipid profiles for cardiovascular risk prediction worldwide and summarize the recommendations from major medical societies and health authorities in different countries. We also describe practical advantages and disadvantages for using nonfasting lipid profiles. Further, we include a description of why fasting has been the standard historically, the barriers against implementation of nonfasting lipid profiles, and finally we suggest the optimal content of a nonfasting lipid profile. Lipid, lipoprotein, and apolipoprotein concentrations vary minimally in response to normal food intake and nonfasting lipid profiles are equal or superior to fasting profiles for cardiovascular risk prediction. Major guidelines and consensus statements in Europe, the United States, Canada, Brazil, Japan, India, and Australia now endorse use of nonfasting lipid profiles in some or all patients; however, there are still gaps in endorsement and implementation of nonfasting lipid profiles worldwide.

Do Hepatic Fibrosis and Steatosis Measured by Hepatic Transient Elastography (FibroScan) Predict Cardiovascular Risk in Patients with Non-alcoholic Fatty Liver Disease: An Observational Cross-sectional Study

Objectives: Non-alcoholic fatty liver disease (NAFLD) has been associated with increased cardiovascular risk (CVR) in the previous studies. In the majority, ultrasonography has been used to diagnose and stage NAFLD, which lacks sensitivity and is non-quantitative. Other more sensitive, comprehensive, and quantitative diagnostic tools such as vibration-controlled transient elastography (TE) have largely been underused in research work. TE-driven liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) provide an accurate and simplified estimation of liver fibrosis and steatosis, respectively. Therefore, we aimed to analyze the association between these two objective, robust parameters and CVR. Materials and Methods: In this observational cross-sectional study, NAFLD participants were divided into two distinct categories of steatosis (CAP &lt;290 and ≥290 dB) and fibrosis (LSM &lt;10 and ≥10 kPa). Their CVR assessment was done by calculating Framingham risk score (FRS), American College of Cardiology/American Heart Association Pooled Cohort Equation Score (ACC/AHA PCES), and carotid intimal medial thickness (CIMT). Results: A greater number of participants presented with mild-moderate fibrosis (n = 41, 62.1%) as compared to severe fibrosis (n = 25, 37.8%) whereas severe steatosis participants predominated (n = 52, 78%) as compared to mild-moderate steatosis. The presence of significant fibrosis (LSM ≥10 kPa) was independently and significantly associated with FRS, ACC/AHA PCES, and CIMT. On the other hand, the presence of significant steatosis (CAP ≥290 dB/m) was not significantly associated with any CVR marker (FRS, ACC/AHA PCES, or CIMT), though a greater number of participants with CIMT &gt;0.7 belonged to severe steatosis group. Conclusion: Subjects with severe fibrosis (LSM ≥10) had a significantly higher CVR, whereas severe steatosis (CAP ≥290) alone failed to predict CVR. Therefore, CVR reduction strategies can be targeted primarily in NAFLD subjects with fibrosis, particularly in resource-limited healthcare settings.

Evaluation of the relation between subclinical systolic dysfunction defined by four-dimensional speckle-tracking echocardiography and growth differentiation factor-15 levels in patients with acromegaly.

In patients with acromegaly, the long-term presence of elevated GH and IGF-1 levels is associated with an unfavorable cardiovascular risk profile. We aimed to assess the relationship of four-dimensional speckle tracking echocardiographic (4DSTE) measurements with growth differentiation factor-15 (GDF-15) levels and the Framingham Cardiovascular Risk Score (FRS) in patients with acromegaly. A single-center, cross-sectional study was conducted. The study included 40 acromegaly and 32 age- and gender-matched controls. Anthropometric, biochemical, and echocardiographic assessments were performed. GDF-15 levels were measured using ELISA. In the controlled acromegaly group, global longitudinal (GLS), circumferential (GCS), area (GAS), and radial (GRS) strain measurements identified by 4DSTE were lower than those of the controls (p < 0.05). Moreover, strain parameters were lower in active acromegaly patients than in controls, but the difference was not statistically significant. The GLS was negatively correlated with age, the estimated disease duration, and FRS. Serum GDF-15 levels showed no significant difference between the acromegaly and control groups. In patients with acromegaly, serum GDF-15 levels were positively correlated with age, waist-to-hip ratio, systolic and diastolic blood pressure, FRS, fasting plasma glucose, and HbA1c, but not with strain parameters. The multiple regression analysis revealed that FRS was an independent factor associated with serum GDF-15 levels in patients with acromegaly and the overall cohort (p < 0.001). Our study demonstrates that while LVEF was within normal limits, global strain parameters (GLS, GCS, GAS, and GRS) measured by using a novel imaging technique, 4DSTE, were lower in patients with acromegaly, suggesting the presence of subclinical systolic dysfunction in patients with acromegaly. GDF-15 can be a potential predictor of cardiovascular risk in patients with acromegaly.

Development and validation of a new algorithm for improved cardiovascular risk prediction

QRISK algorithms use data from millions of people to help clinicians identify individuals at high risk of cardiovascular disease (CVD). Here, we derive and externally validate a new algorithm, which we have named QR4, that incorporates novel risk factors to estimate 10-year CVD risk separately for men and women. Health data from 9.98 million and 6.79 million adults from the United Kingdom were used for derivation and validation of the algorithm, respectively. Cause-specific Cox models were used to develop models to predict CVD risk, and the performance of QR4 was compared with version 3 of QRISK, Systematic Coronary Risk Evaluation 2 (SCORE2) and atherosclerotic cardiovascular disease (ASCVD) risk scores. We identified seven novel risk factors in models for both men and women (brain cancer, lung cancer, Down syndrome, blood cancer, chronic obstructive pulmonary disease, oral cancer and learning disability) and two additional novel risk factors in women (pre-eclampsia and postnatal depression). On external validation, QR4 had a higher C statistic than QRISK3 in both women (0.835 (95% confidence interval (CI), 0.833–0.837) and 0.831 (95% CI, 0.829–0.832) for QR4 and QRISK3, respectively) and men (0.814 (95% CI, 0.812–0.816) and 0.812 (95% CI, 0.810–0.814) for QR4 and QRISK3, respectively). QR4 was also more accurate than the ASCVD and SCORE2 risk scores in both men and women. The QR4 risk score identifies new risk groups and provides superior CVD risk prediction in the United Kingdom compared with other international scoring systems for CVD risk.

Polygenic risk scores for cardiovascular risk prediction: moving towards implementation into clinical practice?

Polygenic risk scores for cardiovascular risk prediction: moving towards implementation into clinical practice?

A Cross-Sectional Evaluation of Cardiovascular Risk Assessment in Type 2 Diabetes Mellitus Patients Using the Framingham Risk Score.

The global burden of type 2 diabetesmellitus (T2DM) is continuously increasing, particularly in India. The risk of cardiovascular disease (CVD) is higher in T2DM individuals when compared to non-diabetics, which imposes significant morbidity and mortality. The main aim of the present study was to assess the risk factorsfor CVD in T2DM patients. The secondary aim was to assess the association between cardiovascular risk profile and10-year cardiovascular risk using theFramingham risk score. This was a cross-sectional study conducted on 110 T2DM patients, and the anthropometric and biochemical parameters were analyzed. The Framingham cardiovascular risk prediction model was used to calculate the 10-year risk for CVD. The CVD risk factor was compared among the genders. Further, the association between the Framingham cardiovascular risk and the various categories of risk factors was also analyzed. Based on the Framingham cardiovascular risk score, 23 (20.9%) were at low risk, 39 (35.5%) were at moderate risk, and 48 (43.6%) were at low risk. A higher proportion of males had hypertension (55.2 vs. 17.3%; p=0.007), elevated cholesterol levels (48.3% vs. 23.1%; p=0.008), and smoking or tobacco use (31% vs. 7.7%; p=0.006) as compared to females. The significant risk factors for high 10-year CVD risk were hypertension (p=0.001), elevated total cholesterol (p=0.03), smoking or tobacco use (p=0.007), and glycemic control (p=0.04). The Framingham cardiovascular risk score estimates reveal that male gender, hypertension, smoking, and uncontrolled diabetes are the important risk factors for CVD progression among diabetic patients. Therefore, it is imperative to generate awareness regarding the potential risks and then implement suitable interventions during the early phases at the primary healthcare level.

Is Waist to Height Ratio Better than Other Indices of Obesity in Determining Cardiovascular Risk?

Background: The indices of obesity (measured by Body Mass Index, waist circumference, and weight-to-height ratio) have been observed to be strongly associated with cardiovascular risk. Body mass index (BMI) is a measure of general obesity while waist circumference (WC) and waist-to-height ratio (WHtR) are used to measure central obesity, with the latter suggested to be the indicator for the prediction of cardiovascular risks. This study aimed to determine the advantage of WHtR for cardiovascular risk over the use of other indices of obesity. Methods: The study was a cross-sectional descriptive design carried out among 441 participants at the Metabolic Research Laboratory LTH Ogbomoso excluding pregnant or breastfeeding mothers, thyroid disease, those diagnosed with hypertension, diabetes, or hyperlipidemia, those on blood-pressure, blood-glucose or lipid-lowering medications; those on weight-control medications or supplements. A structured self-administer questionnaire was distributed to obtain socio-demographic data of participants. Physical examination was done with anthropometry measurements. Fasting blood samples were obtained for blood glucose and lipid profiles. Data analysis was done using SPSS version 21. Results: The study included 441 subjects with male to female ratio of 1:1.47 mean age of 37.92±11.80 and 34.72±12.16 respectively. Blood pressure, pulse rate, height and other obesity indices except waist circumference were all statistically significantly higher in the males than in the females p &lt;0.05. There was a statistically significant difference in the BMI between the sexes for all categories with the majority of female subjects having abnormal BMI and waist circumference. There was a statistically significant relationship between all the obesity indices (BMI, WHtR &amp; WC) and the cardiovascular risk factors excluding TG and HDLC P &lt;0.05. Conclusion: It was observed that all indices of obesity measured in this study were sensitive and significant in determining cardiovascular risk. It could be concluded that WHtR does not have a special or greater advantage over BMI and WC as all indices showed a significant association with cardiovascular risks. Also, the level of statistical significance suggested that either of these obesity indices could be used independently as a predictor of cardiovascular risk.

Bariatric Surgery Improves Serum CD40L Levels as a Predictor of Cardiovascular Risk: Systematic Review and Meta-analysis.

CD40 and its ligand have been recently implicated in the pathogenesis of cardiovascular disease (CVD). This meta-analysis examined the effect of bariatric surgery in reducing circulating CD40L levels. A systematic review was performed using Embase, Google Scholar, PubMed, Scopus, and Web of Science. The meta-analysis was provided by Comprehensive Meta-Analysis (CMA) V4 software. The overall effect size was detected by a random-effects meta-analysis and the leave-one-out approach. Random-effects meta-analysis of 7 studies including 191 subjects showed a significant reduction in CD40L after bariatric surgery (standardized mean difference (SMD), - 0.531; 95% CI, - 0.981, - 0.082; p = 0.021; I2, 87.00). Circulating levels of CD40L are decreased after bariatric surgery which may represent a mechanism for improvement of metabolic profile.