High Cardiovascular Risk Score Research Articles

Outcomes of Patients with Normal LDL-Cholesterol at Admission for Acute Coronary Syndromes: Lower Is Not Always Better.

There are few prospective data on the prognostic value of normal admission low-density lipoprotein cholesterol (LDL-C) in statin-naïve patients with acute coronary syndromes (ACS) who are treated with a preemptive invasive strategy. We aimed to analyze the proportion of patients with normal LDL-C at admission for ACS in our practice, and their characteristics and clinical outcomes in comparison to patients with high admission LDL-C. Two institutions' prospective registries of patients with confirmed ACS from Jan 2017 to Jan 2023 were used to identify 1579 statin-naïve patients with no history of prior coronary artery disease (CAD), and with available LDL-C admission results, relevant clinical and procedural data, and short- and long-term follow-up data. Normal LDL-C at admission was defined as lower than 2.6 mmol/L. All demographic, clinical, procedural, and follow-up data were compared between patients with normal LDL-C and patients with a high LDL-C level (≥2.6 mmol/L) at admission. There were 242 (15%) patients with normal LDL-C at admission. In comparison to patients with high LDL-cholesterol at admission, they were significantly older (median 67 vs. 62 years) with worse renal function, had significantly more cases of diabetes mellitus (DM) (26% vs. 17%), peripheral artery disease (PAD) (14% vs. 9%), chronic obstructive pulmonary disease (COPD) (8% vs. 2%), and psychological disorders requiring medical attention (19% vs. 10%). There were no significant differences in clinical type of ACS. Complexity of CAD estimated by coronary angiography was similar between the two groups (median Syntax score 12 for both groups). There were no significant differences in rates of complete revascularization (67% vs. 72%). Patients with normal LDL-C had significantly lower left ventricular ejection fraction (LVEF) at discharge (median LVEF 52% vs. 55%). Patients with normal LDL-C at admission had both significantly higher in-hospital mortality (5% vs. 2%, RR 2.07, 95% CI 1.08-3.96) and overall mortality during a median follow-up of 43 months (27% vs. 14%, RR 1.86, 95% CI 1.45-2.37). After adjusting for age, renal function, presence of diabetes mellitus, PAD, COPD, psychological disorders, BMI, and LVEF at discharge in a multivariate Cox regression analysis, normal LDL-C at admission remained significantly and independently associated with higher long-term mortality during follow-up (RR 1.48, 95% CI 1.05-2.09). A spontaneously normal LDL-C level at admission for ACS in statin-naïve patients was not rare and it was an independent risk factor for both substantially higher in-hospital mortality and mortality during long-term follow-up. Patients with normal LDL-C and otherwise high total cardiovascular risk scores should be detected early and treated with optimal medical therapy. However, additional research is needed to reveal all the missing pieces in their survival puzzle after ACS-beyond coronary anatomy, PCI optimization, numerical LDL-C levels, and statin therapy.

Ibrutinib Dose Adjustment Does Not Impact Time to Next Treatment in First-Line Patients with Chronic Lymphocytic Leukemia: A Real-World Analysis of Electronic Medical Records from Academic and Non-Teaching Hospitals Using Target Trial Emulation

Introduction: Ibrutinib, a once-daily Bruton's tyrosine kinase inhibitor (BTKi), is recommended as first-line (1L) treatment for patients with chronic lymphocytic leukemia (CLL). Dosing flexibility with ibrutinib allows patients to adjust their daily dose to help prevent recurrence or worsening of adverse events, while maintaining efficacy by allowing patients to stay on treatment and benefit from long-term treatment outcomes. The current study aimed to compare time to next treatment (TTNT) in CLL patients initiating 1L single-agent ibrutinib at 420mg/day and staying on this dose versus those having a dose adjustment (DA) within 3-12 months. Methods: Specialty pharmacy electronic medical records from the Acentrus database, comprised primarily of academic and non-teaching hospital systems in the United States (1/1/2016-4/30/2022), were used to identify adults with CLL who initiated 1L single-agent ibrutinib at a starting dose of 420mg/day (index date) (N = 1,171). A washout period of ≥12 months pre-index (also used to evaluate baseline characteristics) was required to confirm use as 1L therapy. The following treatment strategies were compared: treatment for 3 months post-index at 420mg/day followed by DA to a dose below 420mg/day between 3-12 months post-index versus sustained treatment for ≥12 months post-index at 420mg/day. The first 3 months were required to be at 420mg/day for both strategies, as most DAs occur after this period. TTNT was defined as the time from the index date to the initiation of a next treatment. Administrative censoring included treatment discontinuation (based on treatment gap of ≥365 days), death, participation in a clinical trial, end of data availability, within-class BTKi switch (i.e., switching to another covalent BTKi), anti-CD20 antibody (i.e., obinutuzumab or rituximab), or venetoclax add-on within 180 days post-index. To account for immortal time bias (i.e., patients with DA are required to survive on 1L therapy until DA), as well as overlap between follow-up time and definition of treatment strategies, a target trial emulation approach was used, where all patients were cloned at index date and contributed follow-up to both treatment strategy arms. Hazard ratios (HRs) were approximated from odds ratios obtained from multivariate pooled logistic regression models comparing TTNT between the two treatment strategies. Sensitivity analyses using different time periods to capture DA (3-6, 3-9, and 3-18 months) were also conducted. Results were replicated in the subgroup of patients at high risk for a cardiovascular (CV) event (based on pre-existing CV conditions or a high CV risk score). Results: Among the 1,171 patients who initiated 1L single-agent ibrutinib at a starting dose of 420mg/day, the mean age was 70.4 years, with 34.6% being female. The mean Quan-Charlson Comorbidity Index score was 3.0, and 61.8% were classified as high risk for a CV event. The mean (median) follow-up was 29.8 (30.9) months. Overall, 229 (19.6%) patients had a DA at any time (178 [77.7%] adjusted their dose to 280mg/day), with a mean (median) time to DA of 9.0 (5.5) months. Of these patients, 111 (48.5%) had a DA between 3-12 months post-index date (3-6 months: 66 [28.8%] patients, 3-9 months: 87 [38.0%] patients, 3-18 months: 126 [55.0%] patients). A total of 90 (7.7%) patients initiated a next treatment, out of which 59 (65.6%) patients initiated a venetoclax-based regimen (beyond the first 180 days) as their subsequent therapy. After adjustment in a pooled logistic regression model, DA was not associated with an increased risk of having a next treatment (HR: 1.14, p-value: 0.469) ( Figure 1). In sensitivity analyses evaluating DA over periods of 3-6, 3-9, and 3-18 months, results remained non-significant, with HRs ranging from 1.13 to 1.30 (all p-values >0.05) ( Figure 2). Results were also consistent in the subgroup with high risk for a CV event. Conclusions: This large real-world analysis of CLL patients from academic and non-teaching hospital systems showed that undergoing DA of 1L ibrutinib yielded similar clinical outcomes compared to having no DA, with similar findings for the high CV risk subgroup. These findings, along with those from clinical trials and real-world community oncology practices, suggest that a flexible dosing approach with ibrutinib may be an effective approach in allowing patients to achieve optimal outcomes while remaining on long-term continuous 1L treatment.

Frank's Sign and Cardiovascular Risk: An Observational Descriptive Study

PurposeThis study was undertaken to analyze the relationship between the diagonal earlobe crease and the main indices of cardiovascular risk, considering the crease's anatomical variations. MethodsThe study group consisted of 1050 adults residing in Spain. Participants underwent the following determinations: age, sex, body mass index, smoking habit, blood pressure, glycemia, glycated hemoglobin, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and cardiovascular events. Cardiovascular risk was calculated applying the Framingham-Anderson equation, the Systematic Coronary Risk Evaluation equation, and the Atherosclerotic Cardiovascular Disease Risk Score calculator. Both earlobes were examined, recording diagonal earlobe crease presence, length and depth, and presence of accessory creases. Results were analyzed by using chi-square test, Student's t test, analysis of variance, and Mann-Whitney or Kruskal-Wallis tests. To extract the functions of cardiovascular risk, a script in R was created (https://cran.r-project.org/). ResultsThe estimated cardiovascular mortality risk was significantly higher in individuals who presented diagonal earlobe crease (P < .001). The number of individuals with moderate, high, or very high cardiovascular risk increased significantly as the presence of the crease increased (23.8% had no crease, 35.6% had unilateral creases, and 58% had bilateral creases; P < .001). The mean cardiovascular risk estimated was significantly higher for individuals with longest and deepest diagonal earlobe crease (P < .001 and P < .001, respectively), and with accessory creases (P < .001). ConclusionsThe diagonal earlobe crease is independently associated with higher cardiovascular risk scores, especially when the crease is complete, bilateral, deep, and has accessory creases.

Flash'O real-world evidence programme - Attitude and practices toward the use of omega-3 FA by physicians from Middle East Countries.

The Flash'O project was designed to provide insights into the current use of prescription omega-3 and their perceived benefits by physicians in real-world clinical practice, in Russia, Saudi Arabia, Thailand, and Gulf countries, and to determine the adherence of physicians to dyslipidemia management guidelines. The present study focuses on Flash'O's process and results in Middle East countries. A total of 338 physicians and specialists completed the online questionnaire. Most responding physicians were male (91.7%), general practitioners (42.6%) with more than 5 years of seniority (80.4%) and saw more than 50 patients a week (71.5%). Most surveyed physicians (64.2%) reported using guidelines in their daily practice for the management of their patients with dyslipidemia. They mostly followed national guidelines (68.6%). American or European ones were less commonly used. Responding physicians thought that omega-3 supplementation could be more beneficial in all types of dyslipidemia, except high non- hight density lipoproteins, and for patients suffering from obesity, type 2 diabetes mellitus, acute coronary syndrome with ST-segment elevation myocardial infarction and high cardiovascular diseases risk (score ≥ 5% and < 10%), but less beneficial in chronic kidney disease. Respondents recommended omega-3 to their patients mainly after statin treatment in patients with dyslipidemia and for the treatment of dyslipidemia. This survey confirmed that omega-3 fatty acids are at the heart of the cardiovascular medical strategy.

Cardiocerebrovascular risk in sensorineural hearing loss: results from the National Health and Nutrition Examination Survey 2015 to 2018.

This study aims to determine whether the risks of cardiocerebrovascular disease are relevant to sensorineural hearing loss (SNHL) based on a national database. A total of 1,321 participants aged from 18 to 69 with complete data including medical history and audiometry from the NHANES database (2015-2018) were analyzed. All included participants had available hearing data and the average thresholds of the hearing data were measured and calculated as low-frequency pure-tone average (LFPTA; 500, 1,000, and 2,000 Hz) and high-frequency pure-tone average (HFPTA; 3,000, 4,000, 6,000, and 8,000 kHz). SNHL was defined as an average pure tone of more than or equal to 20 dB in at least one better ear. Multivariable models to assess the association between cardiocerebrovascular risks and SNHL were used in this study. The prevalence of stroke was 1.6% in individuals with SNHL and 0.4% in individuals without SNHL (p = 0.023). A higher cardiovascular risk score was observed in SNHL patients compared to participants without SNHL (1.58 vs. 0.90, p < 0.001). Stroke was associated with a 3.67-fold increase in the risk of SNHL (95% CI: 1.12-12.00, p = 0.032) in univariable logistic regression, and the association (OR = 4.22, 95%CI = 1.28-13.93, p = 0.020) remained significant after adjusting for several covariates. Multivariable logistic regression models indicated a positive correlation between cardiovascular risk and SNHL (OR = 1.66, 95% CI = 1.40-1.96, p < 0.001), but no significant relationship was shown with all covariates adjusted. However, significant associations were found between SNHL and both age and sex in both univariable and multivariable logistic regression models. Our findings suggested that a higher cardiocerebrovascular risk burden was associated with an increased risk of SNHL, and the relationship may be influenced by age and sex. Future longitudinal studies are needed to investigate the mechanistic and pathologic vascular hypothesis of SNHL.

#3934 SAFETY AND EFFICACY OF EVOLOCUMAB AMONG KIDNEY TRANSPLANT PATIENTS AT HIGH CARDIOVASCULAR RISK

Abstract Background and Aims Proprotein convertase subtilisin/Kexin type A(PCSK-9) inhibitors have not been evaluated among kidney transplant recipients (KTR) despite its favorable cardiovascular profile. We aimed to evaluate the safety and efficacy of evolocumab in reducing lipids and cardiovascular events among risky KTR. Method One hundred ninety-five KTR - who were followed up in Hamed Al-Essa organ transplant center with high cardiovascular risk score (&amp;gt;20)-were enrolled in this prospective randomized controlled study between June 2017 and June 2018. Patients who received statin and evolocumab (140 mg/ 2 weeks, group1, n = 97) while those maintained on statin alone comprised group 2(n = 98). After 24 months, they were followed up clinically and by laboratory investigations. Results The two groups had comparable demographics. Before enrollment in the study, we observed a higher prevalence of NODAT in group 2 and more smokers in group 1(p &amp;lt; 0.05). Basal graft function was significantly higher in group 1, while the type of immunosuppression was equivalent in both groups(p &amp;gt; 0.05). We found no significant differences between the two groups concerning cardiovascular events, and both graft and patient outcomes (p &amp;gt; 0.05). Despite the comparable triglycerides levels, we found significantly higher basal cholesterol in group 1(5.5 vs. 4.7, p &amp;lt; 0.001), which came down significantly in the same group after three months and thereafter (p = 0.031) compared to group 2 and basal values (p &amp;lt; 0.001). We reported 2 cases of acute MI and one atrial fibrillation in group2. Conclusion Evolocumab is a promising lipid-lowering agent among risky KTR. Earlier cholesterol reduction was observed in group 1 without significant positive cardiovascular impact.

Real-world (RW) dosing patterns and outcomes among chronic lymphocytic leukemia (CLL) patients (pts) with or without an ibrutinib (IBR) dose adjustment (DA) in first-line (1L).

7537 Background: Pts treated for CLL with IBR, a once-daily Bruton’s tyrosine kinase inhibitor with dosing flexibility options, may adjust their daily dose to help prevent recurrence or worsening of adverse events, while preserving efficacy. This RW study describes outcomes for CLL pts treated with 1L IBR who did or did not have a DA. Methods: Electronic medical records from the Acentrus database (1/1/2016-4/30/2022) were used to identify CLL pts initiated on 1L IBR (index date). The first 6 months post-index were used to identify pts who remained on a starting dose of 420mg/day or with a DA (reducing to a dose lower than 420mg/day; reasons for DA not available). Treatment adherence (measured by proportion of days covered [PDC] and medication possession ratio [MPR]) and time to next treatment (TTNT) were described for patients with and without a DA. Descriptive analyses are reported for all pts and among a subgroup of pts with high cardiovascular (CV) risk, defined as having a pre-existing CV comorbidity or a high CV risk score (CV subgroup). Results: 1,171 CLL patients were initiated on 1L IBR at the recommended dose of 420mg/day (Table). Of those, 1,038 (88.6%) remained on 420 mg for ≥6 months (mean age=70.2 years, 33.6% female, median follow-up: 30.5 months); 229 (19.6%) had a DA at any time post-index (median time to DA: 5.5 months) and 126 had the DA during the first 6 months (mean age=72.2 years, 42.9% female, median follow-up: 35.1 months). Mean PDC and MPR were descriptively higher in pts with a DA (overall: PDC=0.81, MPR=0.84; CV subgroup: PDC=0.78, MPR=0.81) relative to pts with no DA (overall: PDC=0.70, MPR=0.73; CV subgroup: PDC=0.69, MPR=0.72). Median TTNT was not reached for pts with or without a DA; 12-month Kaplan-Meier (KM) rates were similar for pts with a DA (overall: 89.1%; CV subgroup: 92.7%) and with no DA (overall: 92.5%; CV subgroup: 92.0%). Conclusions: Among CLL pts initiating 1L with standard-of-care IBR, 19.6% had a DA. Those with a DA had descriptively higher treatment adherence with no detriment to TTNT, relative to those who maintained 420mg/day starting dose, regardless of baseline CV risk. These findings are consistent with other RW studies and suggest that IBR DA can be an effective treatment strategy that does not negatively affect efficacy while being well-tolerated outside of clinical trials. [Table: see text]

HDL Function and Size in Patients with On-Target LDL Plasma Levels and a First-Onset ACS.

Patients admitted for acute coronary syndrome (ACS) usually have high cardiovascular risk scores with low levels of high-density lipoprotein cholesterol (HDL-C) and high low-density lipoprotein cholesterol (LDL-C) levels. Here, we investigated the role of lipoprotein functionality as well as particle number and size in patients with a first-onset ACS with on-target LDL-C levels. Ninety-seven patients with chest pain and first-onset ACS with LDL-C levels of 100 ± 4 mg/dL and non-HDL-C levels of 128 ± 4.0 mg/dL were included in the study. Patients were categorized as ACS and non-ACS after all diagnostic tests were performed (electrocardiogram, echocardiogram, troponin levels and angiography) on admission. HDL-C and LDL-C functionality and particle number/size by nuclear magnetic resonance (NMR) were blindly investigated. A group of matched healthy volunteers (n = 31) was included as a reference for these novel laboratory variables. LDL susceptibility to oxidation was higher and HDL-antioxidant capacity lower in the ACS patients than in the non-ACS individuals. ACS patients had lower HDL-C and Apolipoprotein A-I levels than non-ACS patients despite the same prevalence of classical cardiovascular risk factors. Cholesterol efflux potential was impaired only in the ACS patients. ACS-STEMI (Acute Coronary Syndrome-ST-segment-elevation myocardial infarction) patients, had a larger HDL particle diameter than non-ACS individuals (8.4 ± 0.02 vs. 8.3 ± 0.02 and, ANOVA test, p = 0.004). In conclusion, patients admitted for chest pain with a first-onset ACS and on-target lipid levels had impaired lipoprotein functionality and NMR measured larger HDL particles. This study shows the relevance of HDL functionality rather than HDL-C concentration in ACS patients.

A diagnostic proposal for sarcopenic obesity in adults based on body composition phenotypes.

Sarcopenic obesity (SO) associates a decrease in lean body mass (LBM) with an excessive increase in fat mass (FM). A number of diagnostic methods, definitions criteria, and thresholds have been proposed for SO resulting in markedly discordant prevalence estimates in populations with obesity. In this study, we first assessed several previously described SO diagnostic criteria and their limitations, and then we propose an innovative approach for identifying SO. Data were from a cross-sectional study of a cohort of overweight/obese patients who underwent clinical, laboratory, and body composition assessments by dual-energy X-ray absorptiometry (DXA). We performed unsupervised machine learning through clustering analysis to discriminate lean and fat compartments, and multivariate logistic regressions which provided prognostic variables applied on sex-specific models for SO diagnosis evaluation based on a training dataset (80% of total sample, n=1165). The predicted models were validated by random forest (RF) machine learning algorithm in the validation dataset (20% of total sample, n=262). Data from 1427 subjects were analyzed, 79.8% women, mean (±s.d.) age 45.0 (±12.9) years, grade III obesity (BMI over 40kg/m2) in 42.7%, diabetes in 20.7%, dyslipidemia in 86.3%, and arterial hypertension in 30.3%. Patients with grade III obesity had higher amounts of LBM, FM, and bone mass than subjects with overweight (BMI between 25.0 and 29.9kg/m2) (p-values < 0.001). When published definitions of SO were applied to this cohort, the prevalence ranged from 0.6% to 96.6%. We built a model that identified 62 (4.3%) individuals as SO, 1125 (78.9%) as non-SO, and 240 (16.8%) as borderline-SO. SO patients showed higher body weight, FM, bone mass, leptin levels, and hepatic steatosis index, but lower LBM and all muscle indexes than non-SO subjects (p-values ≤ 0.001). Patients in the SO and borderline-SO categories were more often females than males (4.5% vs. 3.8% and 16.9% vs. 16.7% respectively, p-value < 0.001) and had significantly higher prevalence of metabolic syndrome and hypertension than non-SO subjects. Males with SO also had higher cardiovascular risk score, while females had higher prevalence of respiratory disorders (p-values < 0.05 for all). Current diagnostic criteria for SO result in widely discrepant prevalence values leading to diagnosis uncertainty. We developed and validated diagnostic criteria based on body composition phenotypes, specifically for overweight/obese subjects, which identified patients at risk of cardio-metabolic complications. This approach may improve the identification of sarcopenia in subjects with obesity.

Associations between cardiovascular disease risk factors and spinal pain may be moderated by sex and health-related physical activity (CHAMPS Study-DK).

Spinal pain has been previously linked with cardiovascular disease risk factors in children. This study investigated the prospective associations between cardiovascular disease risk factors and non-traumatic spinal pain occurrences in children, and examined the moderating role of sex and health-related physical activity in these relationships. We used prospective data from the Childhood Health, Activity, and Motor Performance School Study Denmark (CHAMPS Study-DK). The exposure variables were a clustered cardiovascular risk score and homeostasis assessment model-estimated insulin resistance (HOMA-IR) score collected in 2008 and 2010. The spinal pain outcome comprised the number of weeks of non-traumatic spinal pain from 2008-2010 and 2010-2012. Potential confounders included age, sex, and time spent in moderate-to-vigorous intensity physical activity. We constructed age-adjusted mixed negative binominal regression models to investigate the prospective associations of cardiovascular disease risk factors and non-traumatic spinal pain, while considering the potential moderating roles of sex and physical activity in these relationships. Girls with low HOMA-IR scores and boys with low clustered cardiovascular disease risk scores, who engaged in higher levels of moderate-to-vigorous physical activity, reported more weeks of spinal pain, compared to girls with high HOMA-IR scores (p = 0.001) and boys with high clustered cardiovascular disease risk scores (p = 0.024). whereas boys with higher clustered cardiovascular disease risk who had less time in moderate-to-vigorous physical activity reported more weeks of spinal pain than boys with low clustered cardiovascular disease risk score (p = 0.024). Our results show that cardiovascular disease risk factors are related to future occurrences of non-traumatic spinal pain. However, these relationships appear complex and dependent on the nature of the interactions with sex and physical activity.

Atherogenic lipoprotein profile associated with anthropometric indices of obesity and their association with cardiometabolic risk markers: a cross-sectional study in community

Abstract Background Obesity, especially abdominal fat accumulation, is strongly associated with various metabolic comorbidities. Whether simple anthropometric measures are independently associated with atherogenic lipoproteins is not completely clear. Methods We randomly recruited 505 participants (51.5% women; mean age: 48.8 years) from the Flemish community, who had undergone lipoprotein particle measurements by nuclear magnetic resonance spectroscopy and conventional lipid measurements. Each lipoprotein fraction was subgrouped into large, medium, and small subclass. Anthropometric measures included body mass index (BMI) and waist-to-hip ratio (WHR), and defined BMI obesity as BMI ≥30 kg/m2, and WHR obesity as WHR ≥0.85 (women) or 0.9 (men). Results In the multivariable logistic regression analysis, total very-low-density lipoprotein (VLDL) particle and its subclasses were positively associated with BMI obesity (adjusted odds ratio [OR] for total VLDL: 2.37; 95% confidence interval [CI]: 1.70–3.31) and WHR obesity (OR for total VLDL: 2.06 [95% CI: 1.55–2.73]). The level of total high-density lipoprotein (HDL) particle and its subclass was negatively associated with BMI (OR for total HDL: 0.63 [95% CI: 0.45–0.90), but not with WHR (P≥0.11). None of the low-density lipoprotein (LDL) particles was associated with the two types of obesity (P≥0.092). BMI was inversely associated with the size of LDL and HDL particles, whereas high WHR was significantly associated with smaller VLDL and HDL sizes. For conventional lipid measures, both BMI and WHR were independently associated with high triglyceride and remnant cholesterol, both mainly driven from VLDL particles, and low HDL cholesterol (P≤0.008). These associations were confirmed in multivariable linear regression analysis, except the association of BMI with HDL number and the association of WHR with HDL size. With partial least squares analysis, the lipoprotein profiles of BMI and WHR were significantly associated with a high 10-year cardiovascular disease risk score, the homeostasis model assessment-estimated insulin resistance (HOMA-IR), and C-reactive protein. Conclusion BMI and WHR were independently associated with high triglyceride-rich lipoproteins, decreased HDL cholesterol. The size of LDL and HDL was more consistently associated with BMI than WHR. The lipoprotein alterations may link obesity with high cardiometabolic risk. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): The European Research Council; the European Research Area Net for Cardiovascular Diseases

Higher cardiovascular risk scores and liver fibrosis risk estimated by biomarkers in patients with metabolic-dysfunction-associated fatty liver disease.

BACKGROUNDThe definition of metabolic-dysfunction-associated fatty liver disease (MAFLD) allows identification of metabolically complicated patients. Fibrosis risk scores are related to cardiovascular risk (CVR) scores and could be useful for the identification of patients at risk of systemic complications.AIMTo evaluate the relationship between MAFLD and CVR using the Framingham risk score in a group of Mexican patients.METHODSCross-sectional, observational and descriptive study carried out in a cohort of 585 volunteers in the state of Veracruz with MAFLD criteria. The risk of liver fibrosis was calculated with aspartate aminotransferase-to-platelet ratio index, nonalcoholic fatty liver disease score and fibrosis-4, as well as with transient hepatic elastography with Fibroscan®. The CVR was determined by the Framingham system.RESULTSOne hundred and twenty-five participants (21.4%) with MAFLD criteria were evaluated, average age 54.4 years, 63.2% were women, body mass index 32.3 kg/m2. The Framingham CVR was high in 43 patients (33.9%). Transient elastography was performed in 55.2% of volunteers; 39.1% with high CVR and predominance in advanced fibrosis (F3–F4). The logistic regression analysis showed that liver fibrosis, diabetes and hypertension independently increased CVR. CONCLUSIONOne of every three patients with MAFLD had a high CVR, and in those with high fibrosis risk, the CVR risk was even greater.

Associations between levels of oxidative nucleoside damage and cardiovascular risk in patients newly diagnosed with bipolar disorder and their unaffected relatives

Enhanced oxidative stress-generated nucleoside damage may contribute to the increased cardiovascular disease mortality in patients with bipolar disorder (BD) but the association has never been investigated. We investigated the associations between oxidative stress-generated damage to DNA (8-oxodG) and RNA (8-oxoGuo), respectively, and three measures reflecting cardiovascular risk; namely, the Framingham 30-year risk score of cardiovascular diseases, the metabolic syndrome, and the insulin resistance index in 360 patients newly diagnosed with BD, 102 of their unaffected relatives (UR) and 197 healthy control individuals (HC). In sex- and age-adjusted models, the 30-year cardiovascular risk score increased by 20.8% (CI = 7.4–35.9%, p = 0.002) for every one nM/mM creatinine increase in 8-oxoGuo and by 15.6% (95% CI = 5.8–26.4%, p = 0.001) for every one nM/mM creatinine increase in 8-oxodG, respectively. Further, insulin resistance index increased by 24.1% (95% CI = 6.7–43%, p = 0.005) when 8-oxoGuo increased one nM/mM creatinine. The associations between cardiovascular measures and oxidative nucleoside damage were more pronounced in patients with BD compared with UR, and HC. Metabolic syndrome was not associated with nucleoside damage. Overall, higher oxidative stress-generated nucleoside damage was associated with a higher cardiovascular risk score and a higher degree of insulin resistance index, and having BD impacted the associations. Further, within patients, treatment with psychotropics seemed to enhance the associations between 30-year CVD risk score and insulin resistance index, respectively, and oxidatively stress-generated nucleoside damage. Our findings support enhanced oxidative stress-generated nucleoside damage as a putative pathophysiological mechanism that may mediate the higher cardiovascular risk observed in patients with BD already at the time of diagnosis.

Integration of a multicomponent intervention for hypertension into primary healthcare services in Singapore-A cluster randomized controlled trial.

Despite availability of clinical practice guidelines for hypertension management, blood pressure (BP) control remains sub-optimal (<30%) even in high-income countries. This study aims to assess the effectiveness of a potentially scalable multicomponent intervention integrated into primary care system compared to usual care on BP control. A cluster-randomized controlled trial was conducted in 8 government clinics in Singapore. The trial enrolled 916 patients aged ≥40 years with uncontrolled hypertension (systolic BP (SBP) ≥140 mmHg or diastolic BP (DBP) ≥90 mmHg). Multicomponent intervention consisted of physician training in risk-based treatment of hypertension, subsidized losartan-HCTZ single-pill combination (SPC) medications, nurse training in motivational conversations (MCs), and telephone follow-ups. Usual care (controls) comprised of routine care in the clinics, no MC or telephone follow-ups, and no subsidy on SPCs. The primary outcome was mean SBP at 24 months' post-baseline. Four clinics (447 patients) were randomized to intervention and 4 (469) to usual care. Patient enrolment commenced in January 2017, and follow-up was during December 2018 to September 2020. Analysis used intention-to-treat principles. The primary outcome was SBP at 24 months. BP at baseline, 12 and 24 months was modeled at the patient level in a likelihood-based, linear mixed model repeated measures analysis with treatment group, follow-up, treatment group × follow-up interaction as fixed effects, and random cluster (clinic) effects. A total of 766 (83.6%) patients completed 2-year follow-up. A total of 63 (14.1%) and 87 (18.6%) patients in intervention and in usual care, respectively, were lost to follow-up. At 24 months, the adjusted mean SBP was significantly lower in the intervention group compared to usual care (-3.3 mmHg; 95% CI: -6.34, -0.32; p = 0.03). The intervention led to higher BP control (odds ratio 1.51; 95% CI: 1.10, 2.09; p = 0.01), lower odds of high (>20%) 10-year cardiovascular risk score (OR 0.67; 95% CI: 0.47, 0.97; p = 0.03), and lower mean log albuminuria (-0.22; 95% CI: -0.41, -0.02; p = 0.03). Mean DBP, mortality rates, and serious adverse events including hospitalizations were not different between groups. The main limitation was no masking in the trial. A multicomponent intervention consisting of physicians trained in risk-based treatment, subsidized SPC medications, nurse-delivered motivational conversation, and telephone follow-ups improved BP control and lowered cardiovascular risk. Wide-scale implementation of a multicomponent intervention such as the one in our trial is likely to reduce hypertension-related morbidity and mortality globally. Trial Registration: Clinicaltrials.gov NCT02972619.

Exercise-Induced Pulmonary Hypertension Is Associated with High Cardiovascular Risk in Patients with HIV.

Background and Aim: Pulmonary hypertension (PH) at rest can be preceded by the onset of exercise-induced PH (ExPH). We investigated its association with the cardiovascular (CV) risk score in patients with human immunodeficiency virus (HIV). Methods: In 46 consecutive patients with HIV with low (n = 43) or intermediate (n = 3) probability of resting PH, we evaluated the CV risk score based on prognostic determinants of CV risk. Diagnosis of ExPH was made by cardiopulmonary exercise test (CPET) and exercise stress echocardiogram (ESE). Results: Twenty-eight % (n = 13) of the enrolled patients had ExPH at both CPET and ESE, with good agreement between the two methods (Cohen’s kappa = 0.678). ExPH correlated directly with a higher CV score (p < 0.001). Patients with a higher CV score also had lower CD4+ T-cell counts (p = 0.001), a faster progression to acquired immunodeficiency syndrome (p < 0.001), a poor immunological response to antiretroviral therapy (p = 0.035), higher pulmonary vascular resistance (p = 0.003) and a higher right atrial area (p = 0.006). Conclusions: Isolated ExPH is associated with a high CV risk score in patients with HIV. Assessment of ExPH may better stratify CV risk in patients with HIV.

Hepatosteatosis and Atherosclerotic Plaque at Coronary CT Angiography.

To assess the association between nonalcoholic fatty liver disease (NAFLD) and quantitative atherosclerotic plaque at CT. In this post hoc analysis of the prospective Scottish Computed Tomography of the HEART trial (November 2010 to September 2014), hepatosteatosis and coronary artery calcium score were measured at noncontrast CT. Presence of stenoses, visually assessed high-risk plaque, and quantitative plaque burden were assessed at coronary CT angiography. Multivariable models were constructed to assess the impact of hepatosteatosis and cardiovascular risk factors on coronary artery disease. Images from 1726 participants (mean age, 58 years ± 9 [SD]; 974 men) were included. Participants with hepatosteatosis (155 of 1726, 9%) had a higher body mass index, more hypertension and diabetes mellitus, and higher cardiovascular risk scores (P < .001 for all) compared with those without hepatosteatosis. They had increased coronary artery calcium scores (median, 43 Agatston units [AU] [interquartile range, 0-273] vs 19 AU [0-225], P = .046), more nonobstructive disease (48% vs 37%, P = .02), and higher low-attenuation plaque burden (5.11% [0-7.16] vs 4.07% [0-6.84], P = .04). However, these associations were not independent of cardiovascular risk factors. Over a median of 4.7 years, there was no evidence of a difference in myocardial infarction between those with and without hepatosteatosis (1.9% vs 2.4%, P = .92). Hepatosteatosis at CT was associated with an increased prevalence of coronary artery disease at CT, but this was not independent of the presence of cardiovascular risk factors.Keywords: CT, Cardiac, Nonalcoholic Fatty Liver Disease, Coronary Artery Disease, Hepatosteatosis, Plaque QuantificationClinical trial registration no. NCT01149590 Supplemental material is available for this article. © RSNA, 2022See also commentary by Abohashem and Blankstein in this issue.

Utilization of Risk Scores for Coronary Heart Disease Diagnosis in Rural China.

ObjectiveThe current study was to design a cardiovascular risk score for the diagnosis of coronary heart disease (CHD) in the rural area of China and the sensitivity and specificity of this score would be assessed.MethodsA total of 520 patients were enrolled and based on the results from coronary artery angiography, patients were divided into three groups: CHD group (coronary artery ≥50% stenosis), atherosclerosis group (coronary artery <50% stenosis) and normal groups (without stenosis). Between-group differences were evaluated and the sensitivity and specificity of cardiovascular risk score were evaluated.ResultsCompared to the normal and atherosclerosis groups, patients in the CHD group were older, had higher body mass index, and more likely to be smoking and obese, and had dyslipidemia, hypertension and diabetes, and had higher cardiovascular risk score (4.05 ± 2.15 vs 2.94 ± 1.90 vs 2.54 ± 1.59). Patients in the CHD group were more likely to have cardiovascular risk scores ≥2 (90.2% CHD group vs 74.2% atherosclerosis group vs 76.1% normal group, P < 0.05). The area under the ROC was 0.673, with 95% confidence interval was 0.623–0.722 (P < 0.001), and the sensitivity and specificity were highest when the cardiovascular risk score was 4, indicating that the value of cardiovascular risk score of 4 was a good cutoff point for CHD diagnosis.ConclusionUsing cardiovascular risk score can improve CHD diagnosis which may help to reduce health disparities between rural and urban area.

Change of cardiovascular risk associated serologic biomarkers after gastric bypass: A comparison of diabetic and non-diabetic Asian patients

BackgroundWhile clinical findings demonstrate a superior benefit of cardiovascular (CV) risk reduction in obese patients with type 2 diabetes mellitus (T2D) receiving bariatric surgery over non-T2D patients, the mechanism is unclear. This study aimed to investigate the changes in the CV risk score and five CV-associated biomarkers after gastric bypass surgery. MethodWe enrolled 80 obese subjects who underwent gastric bypass (40 T2D and 40 non-T2D). CV risks were assessed using the United Kingdom Prospective Diabetes Study (UKPDS) engine before and after surgery. Levels of five biomarkers —fasting serum fibroblast growth factor (FGF)-19, FGF-21, corin, oxidized low-density lipoprotein (ox-LDL), and soluble receptor for advanced glycation end-products (sRAGE)—were measured before surgery and one year after surgery. ResultsThe T2D group was significantly older and had a higher CV risk score than the non-T2D group, but body mass index (BMI) was similar between the groups. Preoperative biomarker levels were similar in both the T2D and the non-T2D groups. One year after surgery, the percentage of total weight loss (%TWL) was similar between the two groups (32.2 ± 19.5% versus 34.1% ± 8.8%, p = 0.611). Complete T2D remission (hemoglobin A1c (HbA1c) < 6.0%) was achieved in 29 patients (72.5%). The 10-year CV risk scores by the UKPDS risk engine reduced significantly in both the T2D and the non-T2D groups, but more in the T2D group. Three of five biomarkers changed significantly after surgery: the FGF-19 increased from 195.6 ± 249.1 pg/mL to 283.2 ± 211.8 pg/mL, corin increased from 3.3 ± 2.3 ng/mL to 4.6 ± 3.7 ng/mL, and ox-LDL decreased from 148.5 ± 71.7–107.9 U/L; the P values were 0.002, 0.002 and < 0.001, respectively. The T2D group showed a significantly different change in FGF-19 increase and FGF-21 decrease compared to the non-T2D group. The changes in corin and ox-LDL levels were not different between the T2D and non-T2D groups. ConclusionGastric bypass surgery resulted in a higher UKPDS CV risk score reduction in obese T2D Asians than in those without. FGF-19 and FGF-21 may be associated with the underlying mechanism of this difference.

Sex and APOE ɛ4 modify the effect of cardiovascular risk on tau in cognitively normal older adults.

The interaction between APOE ɛ4 and vascular risk factors on cognitive function is stronger in women than in men. These effects may be mediated by the amount of tau pathology in the brain. Therefore, we examined whether APOE ɛ4 and sex modify cross-sectional associations between cardiovascular risk and tau deposition in cognitively normal older adults from the Alzheimer’s Disease Neuroimaging Initiative. We calculated the Framingham Heart Study cardiovascular disease risk score for 141 participants (74 women, 47 APOE ɛ4 carriers) with complete medical history data, processed tau-PET data and a Clinical Dementia Rating global score of 0.0 at the time of the tau-PET scan, implying no significant cognitive or functional impairment. We used linear regression models to examine the effects of sex, APOE ɛ4, cardiovascular risk and their interactions on tau deposition in the entorhinal cortex, inferior temporal cortex and a composite meta-region of interest of temporal lobe areas. We found a significant three-way interaction among sex, APOE ɛ4 status and cardiovascular disease risk on tau deposition in the entorhinal cortex (β = 0.04; 95% CI, 0.01–0.07; P = 0.008), inferior temporal cortex (β = 0.02; 95% CI, 0.0–0.05; P = 0.029) and meta-region (β = 0.02; 95% CI, 0.0–0.04; P = 0.042). After stratifying by APOE ɛ4 status to examine interactions between sex and cardiovascular disease risk on tau in APOE ɛ4 carriers and non-carriers, we found a significant two-way interaction between sex and cardiovascular disease risk on tau in the entorhinal cortex (β = 0.05; 95% CI, 0.02–0.08; P = 0.001), inferior temporal cortex (β = 0.03; 95% CI, 0.01–0.05; P =0.009) and meta-region (β = 0.02; 95% CI, 0.01–0.04; P = 0.008) only among APOE ɛ4 carriers. In analyses stratified by sex, higher cardiovascular risk scores were associated with higher levels of tau in the entorhinal cortex (β = 0.05; 95% CI, 0.02–0.08; P = 0.002), inferior temporal cortex (β = 0.02; 95% CI, 0.0–0.05; P = 0.023) and meta-region (β = 0.02; 95% CI, 0.01–0.04; P = 0.013) in female APOE ɛ4 carriers but not in male carriers. Our findings suggest that cognitively normal older women carrying at least one APOE ɛ4 allele, may be particularly vulnerable to the effects of cardiovascular disease risk on early tau deposition.

Procalcitonin Correlates With Cardiovascular Risk Better Than Highly Sensitive C-Reactive Protein in Patients With Type 2 Diabetes in Sub-Saharan Africa: Results From a Cross-Sectional Study.

ObjectiveInflammatory markers such as C-reactive protein and procalcitonin have been shown to be independent markers of cardiovascular diseases. We aimed to assess the correlation between serum levels of procalcitonin, C-reactive protein and cardiovascular risk in type 2 diabetes.MethodsWe carried out a cross-sectional study at a tertiary level reference hospital in Yaounde, Cameroon. We assessed the cardiovascular risk using the Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation (ADVANCE) cardiovascular risk prediction model in 80 adults with type 2 diabetes. Serum procalcitonin and C-reactive protein were measured in 80 and 76 subjects respectively, using a highly sensitive quantitative enzyme-linked immunosorbent assay (ELISA) method. Correlations were examined using Spearman’s rank correlation test and the correlation coefficients were compared using the Z-test statistic.ResultsFemales represented the majority of the study population (62.5%). The median duration of diabetes was 5 (3-10) years and 62.5% of participants had a high cardiovascular risk score. Median serum procalcitonin levels was significantly higher in females compared to male participants: 2.48 (1.76-3.01 ng/mL) vs 1.42 (0.86-1.87 ng/mL); p<0.001. There was no difference in the serum C-reactive protein levels between females and males: 1.20 (0.33-3.33) mg/L vs 0.85 (0.36-2.77) mg/L; p=0.669. Procalcitonin was moderately correlated with cardiovascular risk (r=0.58, p<0.001). The correlation was slightly higher in females (R=0.56, p<0.001) versus males (R=0.49, p=0.005) although not significantly different (Z-statistic=0.734, p=0.463). Serum C-reactive protein did not show a meaningful correlation with cardiovascular risk (R=0.23, p=0.050). At a threshold of 2 ng/ml, serum procalcitonin identified participants with a high cardiovascular risk score, with a sensitivity and specificity of 64% and 80% respectively.ConclusionCompared to C-reactive protein, procalcitonin may be a better surrogate marker for cardiovascular risk prediction in this population with type 2 diabetes.