ASCVD Risk Research Articles

The Association between Vitamin D Hypovitaminosis and Cardiovascular Disease Risk in Saudi Diabetic Patients Type II.

We evaluated the prevalence and association of Vitamin D deficiency with glycemic control and CVD risk in T2DM patients. Serum 25 (OH)D3, lipid profile, glucose panel, HbA1c, serum insulin, and HOMA-IR were assessed in 93 T2DM patients and 69 controls. 10 years and lifetime ASCVD risk scores were calculated. The levels of 25(OH)D3 were significantly low in T2DM patients compared to the control. T2DM patients with hypovitaminosis D displayed significantly increased FBG, insulin, and HOMA-IR compared to normovitaminosis. Their lifetime and 10-year ASCVD risk scores were significantly higher regardless of vitamin D deficiency levels (P=0.006; P=0.023) in comparison to patients with sufficient levels of vitamin D. Among patients, the lifetime and 10 years of ASCVD risk showed a significant negative correlation with serum 25(OH)D3 and HDLc (P=0.037; 0.018) (P=0.0001), respectively, and significant positive correlation with T2DM duration, serum insulin, and HOMA-IR (P=0.018; 0.0001) (P=0.002; 0.001) (P=0.005; 0.001), respectively. The 10-year ASCVD risk exhibited a significant positive correlation with FBG (P=0.003) and HbA1c (P=0.009). T2DM duration was a predictor of vitamin D deficiency among T2DM patients (β = 0.22; CI = 0.002–0.04). There is a considerable association between lifetime and 10 years of ASCVD risk with hypovitaminosis D in T2DM, regardless of the deficiency levels which could be predicted by the diabetes duration.

Epidemiological Characteristics and Risk Factors Associated with Acute Myocardial Infarction in Somalia: A Single-Center Experience.

IntroductionAcute myocardial infarction (AMI) is a clinical emergency condition that encompasses STEMI and NSTEMI that leads to significant morbidity and mortality rate.MethodsThis prospectively cohort study was obtained from adult (≥18 years) patients with definitive diagnosis of AMI based on the International Classification of Diseases (ICD; codes I21, I22) those visiting to our hospital from December 2020 to November 2021. Patients with no definite diagnosis of MI and those having with stable or unstable angina were excluded from the study. Descriptive methods including frequency of tables and bar charts for different categories were used for data analysis.ResultsOf 23,147 patients, 3526 were presented with chest pain in our emergency unit over the study period. A total of 97 patients met the inclusion criteria of AMI for this analysis. Of them, 73 (75.3%) had STEMI, and 24 (24.7%) had NSTEMI. Those with STEMI, anterior MI was common occlusion site (n=24, 32.9%) followed by inferior MI (n=15, 20.5%). The mean age of patients was 54.2±12.1 years. Of the total study subjects, 67 (69.1%) were males with no significant difference in subgroups. Most of the participants were married (n=41, 42.3%). More than half of the patients were employed (n=51, 52.6%), while most of the participants were no formal education (n-39, 44.2%). Regarding the ASCVD risk factors, history of hypertension, diabetes mellitus, previous history of coronary artery disease (CAD), and dyslipidemia were the most common comorbidities in STEMI and NSTEMI cases, 31 (41.2%), 36 (49.3%), 24 (32.9%) and 15 (20.5%) vs 14 (66.7%), 11 (45.8%), 11 (45.8%), and 6 (25%), respectively. On the initial clinical presentations, typical chest pain and palpitation were the most frequent clinical presenting symptoms in both STEMI and NSTEMI patients of our study (STEMI=80.4% vs NSTEMI=68% in each), followed by dyspnea (STEMI=72.6% vs NSTEMI=41.7%) and epigastric pain (STEMI=32.9% vs NSTEMI=29.2%). The use of aspirin, clopidogrel, and LMWH therapy within the first hours after the emergency were high and comparable in both subgroups (91.8%, vs 89.7% vs 89.7%). The majority of the patients developed heart failure (36.1%), arrhythmia (23.7%), and cardiogenic shock (18%).ConclusionAs registered, the present study has a higher proportion of STEMI cases among the AMI participants when compared to the NSTEMI. Hypertension, diabetes, hyperlipidemia, and family history of CAD respectively were the highest prevalence risk factors of AMI.

Integrating Advanced Lipid Testing and Biomarkers in Assessment and Treatment.

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. 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.

A Review of Statin Intolerance: a Focus on Statin-Attributed Muscle Symptoms.

To provide a systematic approach to management of the patient with statin-attributed muscle symptoms. We examined the prevalence of statin intolerance, the role of the nocebo effect, key findings in the patient's history and laboratory studies, the potential value of coronary calcium scoring, and the importance of shared decision-making in considering statin re-initiation. Most patients with statin-attributed muscle symptoms can be successfully treated with statins or a combination of statins and non-statins to achieve successful ASCVD risk reduction.

Accuracy of the China-PAR and WHO risk models in predicting the ten-year risks of cardiovascular disease in the Chinese population

Objective: To externally validate and compare the accuracy of the China-PAR (Prediction for ASCVD Risk in China) model and the 2019 World Health Organization (WHO) cardiovascular disease risk charts for East Asian in predicting a 10-year cardiovascular disease in a general Chinese population. Methods: Participants aged 40-79 years without prior cardiovascular disease at baseline in the CHinese Electronic health Records Research in Yinzhou (CHERRY) were analyzed. The Kaplan-Meier analysis estimated the observed cardiovascular events (including non-fatal myocardial infarction, fatal coronary heart disease, and non-fatal or fatal stroke) rate within ten years. The expected risks were calculated using the WHO risk charts for East Asia (including the laboratory-based and non-laboratory-based models) and the China-PAR model. The expected-observed ratios were calculated to evaluate the overestimation or underestimation of the models in the cohort. Model accuracy was assessed by discrimination C-index, calibration χ2 value, and calibration plots. Results: During a median of 7.26 years of follow-up, 13 301 cardiovascular events were identified among 225 811 participants. The C-index for the China-PAR model, WHO laboratory-based model and WHO non-laboratory-based model were 0.741 (0.735-0.747), 0.747 (0.740-0.753), and 0.739 (0.733-0.746) for men, and 0.782 (0.776-0.788), 0.789 (0.783-0.795), and 0.782 (0.776-0.787) for women, respectively. The WHO laboratory-based model and non-laboratory-based model underestimated the 10-year ASCVD risk by around 15% in women and underestimated by 0.8% and 4.4% in men, respectively. The China-PAR model underestimated the risks by 19.5% and 42.3% for men and women. Conclusions: The China-PAR and WHO models all have pretty good discriminations for 10-year cardiovascular risk assessment in this general Chinese population. However, the accuracy should be improved in the highest-risk groups, suggesting further specific models are still needed for those with the highest risk, such as patients with diabetes or older persons.

Adherence to Clinical Guidelines on STATIN Prescribing Among Diabetic Patients Aged 40-75 Years Old in a Primary Care Setting: A Cross-Sectional Study.

BackgroundDiabetes mellitus (D.M.) is a chronic metabolic disease caused by decreased insulin secretion, which increases the risk of cardiovascular diseases. Evidence has shown that statins reduce cardiovascular risk in patients with diabetes; moreover, most clinical guidelines recommend statins.ObjectiveThis study aimed to assess the level and status of adherence to guidelines on statin prescription in patients with diabetes mellitus in a primary care setting in Palestine.MethodsA retrospective cross-sectional descriptive study was conducted at an ambulatory center in Palestine. Data were collected by auditing prescription records and reviewing medical charts of patients with diabetes who visited the clinic from February 15 to March 17, 2021. The collected data included patient characteristics, comorbidities, lipid profiles, and statin prescription. A chi-square test was used to evaluate the appropriateness of the prescribed statins with different demographic and clinical variables. Statistical significance was set at p < 0.05. Statistical Package for Social Sciences (SPSS) version 22 was used to analyze the data.ResultsOut Of 262 diabetic patients included in the analysis, 74% were prescribed appropriate statin therapy according to the American Diabetes Association (ADA) guidelines, and 24% of patients had inappropriate statin therapy or needed statins. Furthermore, 82.8% were on high-intensity statins, while 11% were not taking any statins. More than 60% of patients had uncontrolled diabetes and hypertension.ConclusionMost guidelines recommend statin therapy in diabetic patients owing to its benefits in preventing cardiovascular complications. In this study, most patients were on appropriate STATIN therapy; however, 50% of diabetic patients had LDL of more than 100 mg/dl, and 25% were not prescribed statins, increasing their risk of ASCVD. Therefore, we recommend strict adherence to the established guidelines on statins prescribed to patients with diabetes to prevent cardiovascular complications, save lives, and reduce healthcare costs.

Management of significantly elevated lipoprotein(a) in patients without established ASCVD

Background and Aims : EAS/ESC and Canadian Cardiovascular Society (CCS) Guidelines recommend that everyone should have a determination of Lp(a) level once in a lifetime. 20% of the population will be found to have elevated Lp(a) above 50mg/dL (125nmoles/L) {high Lp(a)}. High Lp(a) produces significant risk of ASCVD particularly CAD. The majority of high Lp(a) patients will not have established ASCVD but need recommendations.

The Prediction of Cardiac Events Using Contemporary Risk Prediction Models after Radiation Therapy for Head and Neck Cancer.

Simple SummaryRadiation therapy is associated with an increased risk for atherosclerotic cardiovascular disease (ASCVD). Contemporary risk prediction models accurately predict ASCVD in general populations. Whether these models adequately capture ASCVD risk after radiation therapy (RT) is unknown. Our data show that these standard risk scores do not reliably differentiate between those who will and those who will not have an ASCVD event after RT and underestimate the risk for ASCVD among patients receiving RT for HNCA.This study aims to evaluate the efficacy of the Pooled Cohort Equation (PCE), U.S. Preventative Services Task Force (USPSTF), and Framingham Risk Score (FRS) models in predicting ASCVD events among patients receiving radiation therapy (RT) for head and neck cancer (HNCA). From a large cohort of HNCA patients treated with RT, ASCVD events were adjudicated. Observed vs. predicted ASCVD events were compared. We compared rates by statin eligibility status. Regression models and survival analysis were used to identify the relationship between predicted risk and post-RT outcomes. Among the 723 identified patients, 274 (38%) were statin-eligible based on USPSTF criteria, 359 (49%) based on PCE, and 234 (32%) based on FRS. During follow-up, 17% developed an ASCVD, with an event rate of 27 per 1000 person-years, 68% higher than predicted (RR 1.68 (95% CI: 1.02, 2.12), p < 0.001). In multivariable regression, there was no difference in event rates by statin eligibility status (p > 0.05). Post-RT, the observed event rate was higher than the predicted ASCVD risk across all grades of predicted risk (p < 0.05) and the observed risk of an ASCVD event was high even among patients predicted to have a low risk of ASCVD. In conclusion, current ASCVD risk calculators significantly underestimate the risk for ASCVD among patients receiving RT for HNCA.

Identification of protective biologic factors in patients with high cardiovascular risk, but normal coronary arteries (NormCorn).

Endothelial progenitor cells (EPCs) have an important role in repair following vascular injury. Telomere length has been shown to be correlated with genome stability and overall cell health. We hypothesized that both EPCs and telomere size are related to protective mechanisms against coronary artery disease. Our aim was to evaluate the level and function of circulating EPCs and telomere length in patients with multiple cardiovascular risk factors and anatomically normal coronary arteries vs. matched controls. We included 24 patients, with coronary CTA demonstrating normal coronaries and a high risk of CAD of >10% by ASCVD risk estimator. Control groups included 17 patients with similar cardiovascular profiles but with established CAD and a group of 20 healthy volunteers. Circulating EPCs levels were assessed by flow cytometry for expression of vascular endothelial growth factor receptor 2, CD34 and CD133. The capacity of the cells to form colony forming units (CFUs) was quantified after 1 week of culture. Telomere length was determined by the southern blotting technique. Patients with high risk for CVD and normal coronaries had augmented EPCs function, compared with the CAD group (1.1 vs. 0.22 CFU/f; P = 0.04) and longer telomeres compared with the CAD group (10.7 kb vs. 2.8 kb P = 0.015). These patients displayed a similar profile to the healthy group. Patients with a high risk for CAD, but normal coronary arteries have EPCs function and telomere length which resemble healthy volunteers, and augmented compared with patients with established CAD, which could serve as a protective mechanism against atherosclerosis development in these high-risk patients.

Multi-dimensional characterization of prediabetes in the Project Baseline Health Study

BackgroundWe examined multi-dimensional clinical and laboratory data in participants with normoglycemia, prediabetes, and diabetes to identify characteristics of prediabetes and predictors of progression from prediabetes to diabetes or reversion to no diabetes.MethodsThe Project Baseline Health Study (PBHS) is a multi-site prospective cohort study of 2502 adults that conducted deep clinical phenotyping through imaging, laboratory tests, clinical assessments, medical history, personal devices, and surveys. Participants were classified by diabetes status (diabetes [DM], prediabetes [preDM], or no diabetes [noDM]) at each visit based on glucose, HbA1c, medications, and self-report. Principal component analysis (PCA) was performed to create factors that were compared across groups cross-sectionally using linear models. Logistic regression was used to identify factors associated with progression from preDM to DM and for reversion from preDM to noDM.ResultsAt enrollment, 1605 participants had noDM; 544 had preDM; and 352 had DM. Over 4 years of follow-up, 52 participants with preDM developed DM and 153 participants reverted to noDM. PCA identified 33 factors composed of clusters of clinical variables; these were tested along with eight individual variables identified a priori as being of interest. Six PCA factors and six a priori variables significantly differed between noDM and both preDM and DM after false discovery rate adjustment for multiple comparisons (q < 0.05). Of these, two factors (one comprising glucose measures and one of anthropometry and physical function) demonstrated monotonic/graded relationships across the groups, as did three a priori variables: ASCVD risk, coronary artery calcium, and triglycerides (q < 10–21 for all). Four factors were significantly different between preDM and noDM, but concordant or similar between DM and preDM: red blood cell indices (q = 8 × 10-10), lung function (q = 2 × 10-6), risks of chronic diseases (q = 7 × 10-4), and cardiac function (q = 0.001), along with a priori variables of diastolic function (q = 1 × 10-10), sleep efficiency (q = 9 × 10-6) and sleep time (q = 6 × 10-5). Two factors were associated with progression from prediabetes to DM: anthropometry and physical function (OR [95% CI]: 0.6 [0.5, 0.9], q = 0.04), and heart failure and c-reactive protein (OR [95% CI]: 1.4 [1.1, 1.7], q = 0.02). The anthropometry and physical function factor was also associated with reversion from prediabetes to noDM: (OR [95% CI]: 1.9 [1.4, 2.7], q = 0.02) along with a factor of white blood cell indices (OR [95% CI]: 0.6 [0.4, 0.8], q = 0.02), and the a priori variables ASCVD risk score (OR [95% CI]: 0.7 [0.6, 0.9] for each 0.1 increase in ASCVD score, q = 0.02) and triglycerides (OR [95% CI]: 0.9 [0.8, 1.0] for each 25 mg/dl increase, q = 0.05).ConclusionsPBHS participants with preDM demonstrated pathophysiologic changes in cardiac, pulmonary, and hematology measures and declines in physical function and sleep measures that precede DM; some changes predicted an increased risk of progression to DM. A factor with measures of anthropometry and physical function was the most important factor associated with progression to DM and reversion to noDM. Future studies may determine whether these changes elucidate pathways of progression to DM and related complications and whether they can be used to identify individuals at higher risk of progression to DM for targeted preventive interventions.Trial registration ClinicalTrials.gov NCT03154346

Association of Coronary Events with Burden and Distribution of Coronary Artery Calcification: Results from the Multi-Ethnic Study of Atherosclerosis

<h3>Lead Author's Financial Disclosures</h3> Nothing to disclose. <h3>Study Funding</h3> None. <h3>Background/Synopsis</h3> Coronary artery calcium (CAC), even when mild, is associated with increased risk for coronary heart disease (CHD) events. <h3>Objective/Purpose</h3> We sought to characterize the association between number of vessels with CAC and specific artery involvement with incident CHD. <h3>Methods</h3> We evaluated participants with baseline CAC >0, free of cardiovascular disease (CVD), and follow-up from the Multi-Ethnic Study of Atherosclerosis (MESA) Exam 1 visit until adjudicated CHD, death, or censoring date of December 31st, 2018. We used Cox proportional hazard regression analyses to characterize incident CHD by number of vessels with CAC and specific artery involvement with sequential multivariable models adjusting for ASCVD risk score, body mass index, and log-transformed total calcification volume. <h3>Results</h3> There were 3,290 participants (mean age, 66 years; 42% female) with baseline CAC >0. Among these, 33% had CAC >0 in only 1 artery, 25% in 2 arteries, 30% in 3 arteries, and 12% in all 4 coronary arteries. Of those with single-vessel involvement, CAC was most frequently in the left anterior descending artery (LAD) (75%), followed by the right coronary artery (RCA) (12%), left circumflex (LCx) (10%), and left main (LM) (3%). Over follow-up of 18.5 years, 589 participants (18%) developed CHD with a mean time to event of 12.6 years. In the multivariable- adjusted Cox model, CHD risk was 1.7x higher for 3- vs 1- (95% CI 1.2-2.3, p=0.002) and 1.6x higher for 3- vs 2-vessel involvement (95% CI 1.2-2.0, p=0.0004), though similar for 1- vs 2- (p=0.7) and 3- vs 4 (p=0.8) [Figure]. Single-vessel CAC in the LAD conferred a similar risk for CHD when compared to single-vessel CAC in the LM (p=0.66), LCx (p=0.83), and RCA (p=0.31). <h3>Conclusions</h3> Subclinical coronary artery disease was most commonly in 1, 2, and 3 number of arteries, and most frequently included the LAD. Compared with having CAC in only 1 to 2 arteries, those with CAC in 3 to 4 arteries had a 60-70% higher risk of incident CHD. In the context of the multivariable-adjusted model accounting for total CAC volume, no specific artery conferred a higher CHD risk than others. Number of vessels with CAC but not specific artery distribution were important characteristics for individualized risk stratification.

507 Visual Aortic Calcium Scoring On Chest Ct Predicts Mortality In Patients With Ldl-c≥190 Mg/dl

Introduction: Current guidelines recommend Coronary Artery Calcium scoring (CAC) only in borderline to intermediate ASCVD risk score with LDL-C (70-190 mg/dL) and do not comment on Thoracic Aortic Calcification (TAC). It remains unknown if TAC, detected on routine chest CT, can provide further risk stratification in patients with LDL-C≥190 mg/dL.

Four recommendations for aspirin use to reduce ASCVD risk: An evidence-based review

Four recommendations for aspirin use to reduce ASCVD risk: An evidence-based review

NLA scientific statement on statin intolerance: a new definition and key considerations for ASCVD risk reduction in the statin intolerant patient

Although statins are generally well tolerated, statin intolerance is reported in 5-30% of patients and contributes to reduced statin adherence and persistence, as well as higher risk for adverse cardiovascular outcomes. This Scientific Statement from the National Lipid Association was developed to provide an updated definition of statin intolerance and to inform clinicians and researchers about its identification and management. Statin intolerance is defined as one or more adverse effects associated with statin therapy which resolves or improves with dose reduction or discontinuation and can be classified as a complete inability to tolerate any dose of a statin or partial intolerance with inability to tolerate the dose necessary to achieve the patient-specific therapeutic objective. To classify a patient as having statin intolerance, a minimum of two statins should have been attempted, including at least one at the lowest approved daily dosage. This Statement acknowledges the importance of identifying modifiable risk factors for statin intolerance and recognizes the possibility of a “nocebo” effect (patient expectation of harm resulting in perceived side effects). To identify a tolerable statin regimen it is recommended that clinicians consider using several different strategies (e.g., different statin, dose, and/or dosing frequency). Non-statin therapy may be required for patients who cannot reach therapeutic objectives with lifestyle and maximal tolerated statin therapy. If so, therapies with outcomes data from randomized trials showing reduced cardiovascular events are favored. In high and very high risk patients who are statin intolerant, clinicians should consider initiating non-statin therapy while additional attempts are made to identify a tolerable statin in order to limit the time of exposure to elevated levels of atherogenic lipoproteins.

Sex-specific performance of the ASCVD pooled cohort equation risk calculator as a correlate of coronary artery calcium in Kampala, Uganda

Introduction: The prevalence of cardiovascular disease (CVD) is rising in Sub-Saharan Africa, but it is not known whether current risk assessment tools predict coronary atherosclerosis in the region. Furthermore, sex-specific performance and interaction with HIV serostatus has not been well studied. Methods: This cross-sectional study compared ASCVD risk scores and detectable coronary artery calcium (CAC>0) by sex in Kampala, Uganda (n = 200). The cohort was enriched for persons living with HIV, and all participants had at least one CVD risk factor. We fit log binomial regression models and constructed ROC curves to assess the correlation between ASCVD scores and CAC>0. Results: The mean age was 56. 62% were female and 50% of both men and women were living with HIV. The median 10-year ASCVD risk score was significantly higher in men (11.0%, IQR 7.6–19.4%) than in women (5.1%, IQR 3.2–8.7%), although the prevalence of CAC>0 was similar (8.1 vs 10.5%, p = 0.63). Each 10% increase in ASCVD risk was associated with increased risk of CAC>0 in men (PR 1.59, 95% CI 1.00–2.55, p = 0.05) but not women (PR 1.15, 95% CI 0.44–3.00, p = 0.77). ROC curves demonstrated an AUC of 0.57 for women vs 0.70 for men. Adjustment for HIV serostatus improved the predictive value of ASCVD in women only (AUC 0.78, p = 0.02). Conclusions: ASCVD risk score did not correlate with the presence of CAC in women. When HIV status was added to the ASCVD risk score, correlation with CAC was improved in women but not in men.

CARDIOVASCULAR AND GLUCO-METABOLIC COMPLICATIONS IN PATIENTS WITH PRIMARY HYPERALDOSTERONISM

Objective: Primary hyperaldosteronism (PA) is an under-diagnosed cause of hypertension. The presentation is classically known to occur in a patient with hypertension and hypokalemia. However, in reality, most patients will present without hyperkalemia. PA is characterized by the development of cardiovascular, renal and metabolic complications, including left ventricular hypertrophy, myocardial infarction, atrial fibrillation and stroke, microalbuminuria, as well as metabolic syndrome. The aim of our study was to assess the metabolic, renal, and cardiovascular alterations, in patients with primary hyperaldosteronism. Design and method: It’s a retrospective study with 50 patients with a primary hyperaldosteronism (aldosterone-producing adenoma: n = 34; adrenal hyperplasia: n = 16). In all patients were collected clinical and biological data, as well as electrocardiogram and cardiac ultrasound. Cardiovascular risk was assessed using the ASCVD risk score. Results: There were 34 (68 %) women and 16 (32%) men, with a mean age at the diagnosis of hypertension of 41.7 ± 10.9 years. Overweight, obesity, diabetes mellitus, dyslipidemia, and metabolic syndrome were diagnosed in 34, 48, 31, 44, and 71% of cases, respectively. Hypokalemia was present in 30 patients (60 %). Kalaemia was negatively correlated with plasma aldosterone level (P = 0.013). Albuminuria and chronic renal failure were found in 57 and 18% of cases, respectively. The average 10-year ASCVD risk was 18.6 ± 12.4%. It was significantly correlated with age, fasting glucose (P = 0.013), glycated hemoglobin (P = 0.008), triglycerides level (P = 0.005), and creatinine level (P = 0.001). 26% of patients had a low risk, 21% had a moderate risk and 53 % had a high risk. 31% had subepicardial ischemia, 59% had left ventricular hypertrophy and 10% had a low left ventricular ejection fraction. A history of stroke was found in 18% of patients. Conclusions: Aldosterone is a key mediator of the cardiometabolic syndrome in primary aldosteronism. PA is associated with a high prevalence of metabolic disorders and renal disease. These complications are significantly associated with cardiovascular risk.

DIABETIC STATUS AND NIGHT-TIME SYSTOLIC BLOOD PRESSURE PREDICT EARLY MYOCARDIAL DAMAGE IN NEWLY DIAGNOSED DIABETES MELLITUS TYPE 2 PATIENTS AS THIS IS DEPICTED BY GALECTIN-3 LEVELS

Objective: Long standing Diabetes Mellitus Type 2 (T2DM) shows a high frequency of cardiovascular events. However, it is not known if newly diagnosed patients with T2DM present early signs of cardiovascular dysfunction. On the other hand, galectin has been introduced as a novel biomarker of myocardial fibrosis. The aim of the study was to evaluate levels of galectin-3 in patients with a very recent diagnosis of T2DM without established cardiovascular disease. In addition, hemodynamic parameters as well as their possible correlation with galactin-3 levels were studied. Design and method: Patients with a recent diagnosis of T2DM (&lt;6 months) and non-T2DM volunteers were studied. A thorough medical history with emphasis on hypertension and relevant comorbidities, somatometric measurements and blood tests was obtained from all participants. Serum levels of galectin-3 were determined by ELISA. Myocardial function and hemodynamic profile were noninvasively assessed with impedance cardiography. Furthermore, Atherosclerotic Cardiovascular Disease Risk (ASCVD) was calculated. Results: We studied 135 subjects, 79 T2DM patients with a median disease duration of 1 month (IR: 5) and 56 controls matched by age, sex and hypertension. T2DM patients had significantly higher values of galectin-3 (90 ± 88ng/dl vs 32.92 ± 6.32ng/dl, p &lt; 0.001), Cardiac Output (CO), ASCVD Risk compared to controls. Galectin-3 was associated with T2DM (p &lt; 0.001), fasting glucose (p &lt; 0.001), glycosylated hemoglobin (p &lt; 0.001). Furthermore, galectin-3 was associated with CO (p = 0.023), nighttime systolic blood pressure (SBP) (p = 0.03) and ASCVD Risk (p = 0.001). In multiple linear regression analysis, T2DM (Beta: 0.406, p &lt; 0.001) and nighttime SBP (Beta: 0.196, p = 0.028), were identified as independent predictors of galectin-3, after adjustment for age, sex, Body Mass Index and CO. Conclusions: Galectin-3 is elevated in patients with early stage T2DM even in the absence of established cardiovascular disease, and is independently correlated with T2DM and nighttime SBP. In this group of patients galectin may be used as a biomarker of early myocardial damage. Nighttime SBP emerge as an important mediator in early target organ damage in cardiovascular diseases.

221-LB: Normalisation of Glycemic and Extraglycemic Parameters with T2DM Remission—Insights from RCT Enabled by Whole-Body Digital Twin Technology

We analyzed the efficacy of Twin Precision Treatment (TPT) : a novel whole-body digital twin enabled precision nutrition that measures weight, physical activity, sleep, and sensor glucose values, for achieving remission, at six months among 199 people with T2D enrolled in RCT. The mean age was 43 years (±8.7) ; diabetes duration was 3.7 years (±2.7) . 83.9% (167/199) achieved diabetes remission (HbA1c &amp;lt; 6.5, with the absence of glucose-lowering pharmacotherapy, for at least 3 months) . We looked at the change in the number and percentage of patients who were within the normal range for the biochemical, glycemic metrics, metabolic markers, and BMI, waist circumference, and ASCVD risk score (Figure) . There was a significant increase in the number of people having normal ranges at 90 and 180 days compared to baseline. The parameters for which ≥ 90% in the normal range at 180 days were A1C, FPG, GMI, CV, NAFLD FS, MICR, ASCVD risk score, and hsCRP. The proportion of normalisation rates were 60-90% for HOMA2B, HOMA2IR, BMI, waist circumference, TG/HDL, sdLDL, NAFLD LFS, TIR. Our study demonstrates the diverse metabolic benefits which can be obtained by whole-body digital twin enabled precision nutrition in addition to diabetes remission. Disclosure P. Shamanna: None. A. Keshavamurthy: None. M. Thajudeen: None. S. Bhonsley: None. S. R. Joshi: Advisory Panel; AstraZeneca, Consultant; Biocon, Franco India, Glenmark Pharmaceuticals, Marico, Sanofi, Twinhealth, Zydus Cadila, Speaker's Bureau; Abbott, Serdia Pharmaceuticals (India) Pvt. Ltd. L. Shah: None. M. Mohamed: None. J. Mohammed: None. T. Poon: None. M. Dharmalingam: None. A. Vadavi: None. B. Saboo: None. S. Damodharan: None.

Optimised Glucose “Time in Range” Using Continuous Glucose Monitors in 4,805 Non-Diabetic Individuals Is Associated With Favourable Diet and Health: The ZOE PREDICT Studies

ObjectivesContinuous glucose monitoring (CGM) enables the dynamic measurement of glycemic control. In diabetic cohorts, time in range (TIR), measured by CGM, is discriminatory of future disease development. However, the value of CGM metrics in non-diabetic populations and their relationship with health outcomes is unclear. This research developed ‘optimised’ TIR targets specific to healthy populations and explored their relationship with diet and health.MethodsThe ZOE PREDICT studies, one (n = 1002, UK), two (n = 987, US) and three (n = 4,500, US) collected demographic information, habitual and free-living diet data, cardiometabolic blood biomarkers and postprandial responses to standardized meals in clinic and free-living settings. TIR was calculated from CGMs (2–4 days free-living) using 1) the American Diabetes Association (ADA); 70–140 mg/dL (TIRADA) and 2) a novel optimised; 70–100 mg/dL (TIRoptimised) target. Habitual diet quality (plant-based diet indices; PDI, healthy-PDI and unhealthy-PDI), and free-living nutrient intakes (% energy) were calculated. Associations (spearman's, adjusted for age, sex and BMI) between TIR and diet were examined, and differences in diet and health outcomes between quintile 1 (Q1) and 5 (Q5) of TIR targets were assessed.ResultsMean fasting glucose was 91 ± 10 mg/dL, HbA1c 5.3 ± 0.4%, TIRoptimised 70 ± 17% and TIRADA 91 ± 13% (n = 4805 after exclusions, 78% females, mean age 46 ± 12y). Individuals with better glycemic control (TIRoptimised Q5 vs Q1) were younger (mean ± SD) (45 ± 11 vs 49 ± 12y), had lower HbA1c (5.2 ± 0.4 vs 5.5 ± 0.5) and fasting glucose (91 ± 14 vs 97 ± 23 mg/dL) and higher HDL-cholesterol (1.7 ± 0.4 vs 1.6 ± 0.5mmol/L) (P< 0.001 for all). TIRoptimised (PREDICT 1 n = 868) was associated with a favourable diet (lower unhealthy-PDI and carbohydrate intakes and higher protein intakes) and cardiometabolic risk profile (lower HbA1c and ASCVD) (P < 0.05 for all). However, TIRADA was not associated with diet or health outcomes.ConclusionsWe demonstrate that an optimised TIR target (70–100 mg/dL) is discriminatory of ASCVD risk despite normal fasting HbA1c. These findings demonstrate the utility of CGM's in non-diabetic populations and highlight the potential application of dietary strategies to improve TIR and subsequent metabolic complications.Funding SourcesZOE Ltd.

CLINICAL EVENT REDUCTIONS IN HIGH-RISK HYPERTENSION PATIENTS TREATED WITH RENAL DENERVATION: 10-YEAR PROJECTIONS BASED ON 3-YEAR FOLLOW-UP FROM THE GLOBAL SYMPLICITY REGISTRY

Objective: Clinical event rates over 3 years have been published for patients with uncontrolled hypertension treated with radiofrequency renal denervation (RDN) in the Global SYMPLICITY Registry (GSR). We estimated 10-year clinical event reductions following RDN vs. a simulated control group without RDN, for two high-risk subgroups and the full GSR cohort. Design and method: A Markov model was used to compare projected 10-year clinical events [stroke, myocardial infarction (MI), cardiovascular death (CVD), heart failure (HF), all-cause death (ACD), and a composite of major adverse cardiac events (MACE, calculated as sum of stroke, MI, and CVD)] for RDN patients vs. a hypothetical control for the high atherosclerotic vascular disease risk (ASCVD) subgroup (n = 737; 69 ± 8 years), the type-2 diabetes mellitus (T2DM) subgroup (n = 1,007; 64 ± 10 years), and for all GSR patients (n = 2,651; 61 ± 12 years). The simulated control assumed maintenance of baseline office systolic blood pressure (oSBP) over time. The model was calibrated to 3-year stroke and MI events reported in the GSR and used published meta-regression data to calculate risk reduction based on cohort-specific changes in oSBP from baseline. Relative risks (RRs), events avoided, and numbers needed to treat (NNTs) were calculated at 3 and 10 years, along with the ratio of 10- vs. 3-year projected events avoided. Results: 10-year MACE events were 35.8% vs. 48.5% (-12.7%, RR = 0.74) for RDN vs. control for all GSR patients, 37.8% vs. 52.4% (-14.6%, RR = 0.72) for the high ASCVD risk cohort, and 40.5% vs. 54.0% (-13.5%, RR = 0.75) for the T2DM cohort. Across all three cohorts, events avoided were highest for stroke and lowest for MI. 10-year NNTs for MACE were comparable between the three cohorts, estimated between 7 to 8. The ratio of model-projected MACE at 10- vs. 3-years was 5.20, 5.46, and 5.03 for the full GSR, high ASCVD risk, and T2DM cohorts, respectively. Conclusions: Model-based projections based on 3- year events observed in the GSR suggest meaningful event reductions after treatment with radiofrequency RDN at 10 years that might be up to 5-times higher than the projected events avoided at 3 years under the assumption of maintained treatment effect versus baseline.