Elevated Cardiovascular Disease Risk Research Articles

Cardiovascular Disease Management With Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Type 2 Diabetes: A Cardiology Primer.

Patients with type 2 diabetes face an elevated risk of cardiovascular disease. This review centers on sodium-glucose cotransporter-2 (SGLT2) inhibitors, a class of drugs that, according to a growing body of evidence, may have major potential for managing cardiovascular disease in patients with type 2 diabetes. This review presents findings from multiple clinical trials suggesting that SGLT2 inhibitors can not only serve as preventive therapeutic agents but also play a role in the active management of heart failure. The discussion includes the mechanism of action of SGLT2 inhibitors, emphasizing that they enhance urinary glucose excretion, which could lead to improved glycemic control and contribute to metabolic shifts beneficial to cardiac function. Alongside these cardiometabolic effects, safety concerns and practical considerations for prescribing these agents are addressed, taking into account potential adverse effects such as genitourinary infections and diabetic ketoacidosis as well as the financial implications for patients. Despite these drawbacks, therapeutic indications for SGLT2 inhibitors continue to expand, including for kidney protection, although further research is necessary to fully understand the mechanisms driving the cardioprotective and kidney-protective effects of SGLT2 inhibitors. By synthesizing current knowledge, this review intends to inform and guide clinical decision-making, thereby enhancing cardiovascular disease outcomes in patients with type 2 diabetes.

Cardiovascular disease in patients with systemic autoimmune diseases: The relationship between self-perceived risk and actual risk

IntroductionAutoimmune diseases are known to be associated with an elevated risk of cardiovascular diseases; however, there exists a lack of awareness regarding this increased risk among patients. ObjectiveThis study aimed to assess the prevalence of cardiovascular risk factors and events in various systemic autoimmune diseases, including Systemic Sclerosis (SSc), Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), and Sjögren's syndrome (SS), matched by age, sex, and disease duration. Additionally, the study aimed to evaluate the perceived and actual risks of cardiovascular disease among patients. MethodsA cross-sectional self-reported survey on the patient's perspective of cardiovascular risk was conducted between January and June 2023. Sociodemographic and clinical data, including disease activity, were collected through medical records and questionnaires. Traditional cardiovascular risk factors and events were assessed, alongside the perceived cardiovascular risk. The SCORE calculation and Charlson Comorbidity Index (CCI) were employed for cardiovascular risk assessment. ResultsSurvey responses from 180 patients (45 patients each with SSc, SLE, RA, and SS) with systemic autoimmune diseases revealed that 20% perceived a low risk, 23% perceived neither lower nor higher, and 56% perceived a higher risk of developing cardiovascular diseases in the next ten years. Only 45% agreed that their autoimmune disease could increase the risk of a heart attack, even in the absence of other risk factors, and 46.7% were unaware that NSAIDs pose a cardiovascular risk. An association between cardiovascular risk measured by SCORE, comorbidities, and risk perception was observed in RA, SSc, and SS patients, with no association found in SLE patients (p=0.27). Except for SS patients (p=0.02), no association between CCI and disease activity level was found. Regarding the influence of age, working status, and education in CVD risk perception, an association between CVD risk perception and age was observed (p=0.01), with patients over 40 years exhibiting a higher perception of CVD risk. No differences were found regarding working status (p=0.19) nor education level (p=0.06). ConclusionsPatients with SS, RA, and SSc displayed a heightened perception of cardiovascular risk, correlating with their actual risk and preexisting comorbidities. However, patients exhibited unawareness of certain cardiovascular risk behaviors. This underscores the need for tailored education programs on cardiovascular risk for autoimmune disease patients, to be implemented at the time of diagnosis and during follow-up in outpatient clinics.

A combination nutritional supplement reduces DNA methylation age only in older adults with a raised epigenetic age.

An increase in systemic inflammation (inflammaging) is one of the hallmarks of aging. Epigenetic (DNA methylation) clocks can quantify the degree of biological aging and this can be reversed by lifestyle and pharmacological intervention. We aimed to investigate whether a multi-component nutritional supplement could reduce systemic inflammation and epigenetic age in healthy older adults.We recruited 80 healthy older participants (mean age ± SD: 71.85 ± 6.23; males = 31, females = 49). Blood and saliva were obtained pre and post a 12-week course of a multi-component supplement, containing: Vitamin B3, Vitamin C, Vitamin D, Omega 3 fish oils, Resveratrol, Olive fruit phenols and Astaxanthin. Plasma GDF-15 and C-reactive protein (CRP) concentrations were quantified as markers of biological aging and inflammation respectively. DNA methylation was assessed in whole blood and saliva and used to derive epigenetic age using various clock algorithms.No difference between the epigenetic and chronological ages of participants was observed pre- and post-treatment by the blood-based Horvath or Hannum clocks, or the saliva-based InflammAge clock. However, in those with epigenetic age acceleration of ≥ 2 years at baseline, a significant reduction in epigenetic age (p = 0.015) and epigenetic age acceleration (p = 0.0058) was observed post-treatment using the saliva-based InflammAge clock. No differences were observed pre- and post-treatment in plasma GDF-15 and CRP, though participants with CRP indicative of an elevated cardiovascular disease risk (hsCRP ≥ 3µg/ml), had a reduction in CRP post-supplementation (p = 0.0195).Our data suggest a possible benefit of combined nutritional supplementation in individuals with an accelerated epigenetic age and inflammaging.

Abstract 6294: Subclinical atherosclerosis in newly diagnosed colorectal cancer patients

Abstract Introduction: Recent advances in early detection and treatment have improved survival rates for patients with colorectal cancer (CRC), and emerging data suggests patients may be at elevated risk of cardiovascular disease (CVD). However, there are no standard recommendations for assessing CVD risk in patients with CRC. Coronary artery calcium (CAC) is a measure of the quantity of coronary artery calcification using noninvasive scanning and has been shown to be predictive of CVD risk. This prospective cohort study utilizes CAC to evaluate the occurrence of subclinical atherosclerosis at the time of CRC diagnosis and the risk of major adverse cardiovascular events (MACE). Methods: The ColoCare Study is a prospective cohort study across six U.S. and European sites. Data from one of the ColoCare consortium sites in Los Angeles, California was analyzed. Adults with newly diagnosed stage I- IV colorectal cancer and available non-contrast CT scans were included. Electronic medical records were reviewed for assessment of baseline cardiovascular risk factors and adverse events. Subclinical atherosclerosis was defined as the presence of CAC (CAC>0). CAC was manually measured from routine oncologic diagnostic CT and PET-CT scans at the time of cancer diagnosis using the Agatston method. MACE was defined as hospitalization due to heart failure, cardiomyopathy, ischemic heart disease, or ischemic stroke after the diagnosis of CRC cancer. Multivariable-adjusted Cox regression was used to evaluate the association between CAC at diagnosis and the risk of MACE. Results: Among 109 individuals with CAC measured at the time of CRC diagnosis, 41 (37.6%) had subclinical atherosclerosis (CAC=1-399 [n=29], CAC>400 [n=12]). Individuals with CAC>0 were older (67.0 vs. 51.9 years, p<0.01), more likely to be former or current smokers (48.0 vs. 29.0 years, p=0.04), and to have hypertension (61% vs. 23%, p<0.01) compared to those without CAC (CAC=0). Among individuals with CAC (n=41), 51.2% had scores >100, and 29.2% had scores >400, indicating moderate and severe atherosclerosis respectively. Among patients with moderate or greater CAC burden (>100; statin therapy indicated), 28.6% were not on statin therapy. CAC>0 was associated with an increased incidence of MACE (13% vs. 53%, p<0.01). Discussion: Subclinical atherosclerosis was observed in nearly 40% of patients with CRC at diagnosis and MACE occurred in 38.2% of patients. Most patients were under-optimized for CVD risk, with nearly 30% of statin-eligible patients with at least moderate CAC burden not prescribed statin therapy. These findings highlight an opportunity for improved CVD risk mitigation in patients with CRC, including guidelines-based CVD risk factor modification. Citation Format: Julia A. Levy, Maimoona Nadri, Elham Kazemian, Katelyn M. Atkins, Jordan O. Gasho, Katrina D. Silos, Cody Ramin, Andriana P. Nikolova, Erin M. Siegel, Biljana Gigic, Adetunji T. Toriola, Jennifer Ose, Christopher I. Li, David Shibata, Cornelia M. Ulrich, Jane C. Figueiredo. Subclinical atherosclerosis in newly diagnosed colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6294.

Use of activity trackers to improve blood pressure in young people at risk for cardiovascular disease: a pilot randomized controlled trial.

Promoting physical activity among young individuals with cardiovascular disease (CVD) risk factors such as hypertension, diabetes, or chronic kidney disease can lower systolic blood pressure (BP). We sought to determine whether a 6-month intervention using a physical activity tracker was feasible and effective, compared with usual care. Participants were recruited at a single academic medical center. Those aged 8-30years were randomized in a 2:1 ratio to either the intervention (use of a Fitbit physical activity tracker coupled with feedback regarding the participant's step count) or usual care. The primary feasibility outcomes were screening-to-enrollment ratio and 6-month retention rates; the primary clinical outcome was a change in systolic BP from 0-6months. Sixty-three participants were enrolled (57% male; mean age: 18 ± 4years). The screening-to-enrollment ratio was 1.8:1. Six-month retention was 62% in the intervention group and 86% in the control group (p = 0.08). Mean change in systolic BP in the intervention group was not significantly different from the control group at 6months (- 2.3mmHg; 95% CI - 6.5, 1.8 vs. 3.0mmHg; 95% CI - 2.5, 8.4, respectively, p = 0.12). Among children and young adults at elevated CVD risk, the use of a physical activity tracker coupled with tailored feedback regarding their step count progress was feasible but not sustained over time. Physical activity tracker use did not have a statistically significant effect on BP after 6months. Augmented strategies to mitigate risk in young patients at high risk for early-onset CVD should be explored. This trial is registered at ClinicalTrials.gov (NCT03325426).

Association Between Cancer and Cardiovascular Toxicity: A Nationwide Cross-Sectional Study on NHANES 1999-2018.

There is a dearth of evidence pertaining to the relationship of cardiovascular disease (CVD) and its subtype with adjudicated cancer, thereby limiting our understanding of the heightened risk of CVD resulting from long-term complications of cancer and its therapies. The aim of this study was to quantify the risks of CVD and its subtypes in adult cancer survivors compared with cancer-free controls in a nationwide cross-sectional study on Continuous National Health and Nutrition Examination Survey (NHANES). We included 44,442 participants ranging in age from 20 to 85 years. Cancer and CVD diagnoses were ascertained via the household questionnaires. The association of cancer status with the risk of CVD and CVD subtype was examined using weighted logistic regression. Stratification analyses were also performed byage, sex, race, marital status, income status, educational level, and hyperlipidemia. The Wald test was used to calculate P-value for interaction. A total of 4178 participants have cancer, while 4829 participants had CVD, respectively. In the multivariable-adjusted model, the cancer was consistently linked to an elevated risk of CVD. Stratification analyses showed that stronger association between cancer status and CVD risk was found in younger adults, non-white, and participants living without a spouse or partner, and without hyperlipidemia. Our study confirmed that cancer participants were strongly linked to living with CVD, independent of traditional cardiovascular risk factors, especially in younger adults, non-white, and participants living without a spouse or partner, and without hyperlipidemia. There exists a pressing requirement to establish effective strategies for the prevention of CVD within this population characterized by a heightened risk.

Pemafibrate and other triglyceride-lowering therapies to reduce risk of cardiovascular and metabolic disease.

Although high triglycerides are consistently associated with elevated risk of cardiovascular disease (CVD), therapies that reduce triglyceride levels have inconsistently translated into reduced CVD risk. To date, three clinical trials have tested triglyceride-lowering therapies in patients with hypertriglyceridemia (HTG) and elevated risk of incident/recurrent CVD. In REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), assignment to IPE, a highly purified eicosapentanoic acid (EPA), resulted in a 25% reduction in nonfatal myocardial infarction), nonfatal stroke, cardiovascular death, coronary revascularization and hospitalization for unstable angina. By contrast, the combination of EPA and docosahexanoic acid (DHA) carboxylic fatty acids used in the STRENGTH trial (Statin Residual Risk With Epanova in High Cardiovascular Risk Patients With Hypertriglyceridemia) failed to reduce CVD risk. Most recently, PROMINENT (Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes) also failed to demonstrate reduction in CVD events despite use of a potent triglyceride-lowering, fibric-acid derivative. However, improvement in HTG-associated metabolic complications (e.g. nonalcoholic fatty liver disease) was observed with pemafibrate as well as with another potent triglyceride-lowering therapy (i.e. pegozafermin). Moreover, trials are underway evaluating whether the most fatal metabolic complication of HTG, pancreatitis, may be reduced with highly potent triglyceride-lowering therapies (e.g. apolipoprotein C3 inhibitors). Taken together, HTG is associated with increased risk of CVD and attendant adverse metabolic sequalae. To this end, a potentially promising and evidence-based landscape is emerging for treating a clinical phenotype that in the past has been insufficiently addressed.

Cathelicidin Antimicrobial Peptide Levels in Atherosclerosis and Myocardial Infarction in Mice and Human.

Obesity represents a worldwide health challenge, and the condition is accompanied by elevated risk of cardiovascular diseases caused by metabolic dysfunction and proinflammatory adipokines. Among those, the immune-modulatory cathelicidin antimicrobial peptide (human: CAMP; murine: CRAMP) might contribute to the interaction of the innate immune system and metabolism in these settings. We investigated systemic CAMP/CRAMP levels in experimental murine models of atherosclerosis, myocardial infarction and cardiovascular patients. Atherosclerosis was induced in low-density lipoprotein receptor-deficient (Ldlr-/-) mice by high-fat diet (HFD). C57BL/6J wild-type mice were subjected to myocardial infarction by permanent or transient left anterior descending (LAD)-ligation. Cramp gene expression in murine organs and tissues was investigated via real-time PCR. Blood samples of 234 adult individuals with or without coronary artery disease (CAD) were collected. Human and murine CAMP/CRAMP serum levels were quantified by ELISA. Atherosclerotic mice exhibited significantly increased CRAMP serum levels and induced Cramp gene expression in the spleen and liver, whereas experimental myocardial infarction substantially decreased CRAMP serum levels. Human CAMP serum quantities were not significantly affected by CAD while being correlated with leukocytes and pro-inflammatory cytokines. Our data show an influence of cathelicidin in experimental atherosclerosis, myocardial infarction, as well as in patients with CAD. Further studies are needed to elucidate the pathophysiological mechanism.

Association of Depressive and Anxiety Symptoms With Risk of Cardiovascular Disease in Middle-Aged and Older Chinese Women.

The objective of this study was to estimate the association of depressive and anxiety symptoms with the risk of cardiovascular disease (CVD) in middle-aged and older Chinese women and to further evaluate whether the association was influenced by sociodemographic factors. This cross-sectional study included 9544 women aged 40 to 70 years from the eastern, central, and western regions of China in 2018. Logistic regression models were utilized to examine odds ratios (ORs) and their 95% confidence intervals (CIs) for depressive and anxiety symptoms with CVD risk. Depressive (OR = 1.89) and anxiety symptoms (OR = 1.55) were independently associated with an increased risk of CVD after adjusting for potential confounders. Stratified analyses found that depressive symptoms were only significantly associated with higher risk of CVD in women aged over 50 years and with lower levels of education and household income, whereas anxiety symptoms were only significantly associated with an elevated risk of CVD in women aged 60 to 70 years, and living in rural areas, and with lower levels of education and household income. Our findings emphasize the improvement of recognizing and managing depressive and anxiety symptoms to reduce the risk of CVD in middle-aged and older women, particularly in older women of low socioeconomic status.

Long-Term Ambient Ozone Exposure and Incident Cardiovascular Diseases: National Cohort Evidence in China

BackgroundLong-term ozone exposure has been associated with cardiovascular disease (CVD) mortality in mounting cohort evidence, yet its relationship with incident CVD was poorly understood, especially in low- and middle-income countries (LMICs) experiencing high ambient air pollution. MethodsWe carried out a nationwide perspective cohort study from 2010 through 2018 by dynamically enrolling 36985 participates across Chinese mainland. Warm-season (April–September) ozone concentrations were estimated using satellite-based machine-learning models with national coverage. Cox proportional hazards model with time-varying exposures was employed to evaluate the association of long-term ozone exposure with incident CVD (overall CVD, hypertension, stroke, and coronary heart disease [CHD]). Assuming causality, a counterfactual framework was employed to estimate ozone-attributable CVD burden based on the exposure-response (E-R) relationship obtained from this study. Decomposition analysis was utilized to quantify the contributions of four key direct driving factors (ozone exposure, population size, age structure, and incidence rate) to the net change of ozone-related CVD cases between 2010 and 2018. ResultsA total of 4428 CVD, 2600 hypertension, 1174 stroke, and 337 CHD events were reported during 9-year follow-up. Each 10-μg/m³ increase in warm-season ozone was associated with an incident risk of 1.078 (95% confidence interval [CI]:1.050–1.106) for overall CVD, 1.098 (95% CI:1.062–1.135) for hypertension, 1.073 (95% CI:1.019–1.131) for stroke, and 1.150 (95% CI: 1.038–1.274) for CHD, respectively. We observed no departure from linear E-R relationships of ozone exposure with overall CVD (Pnonlinear= 0.22), hypertension (Pnonlinear=0.19), stroke (Pnonlinear= 0.70), and CHD (Pnonlinear= 0.44) at a broad concentration range of 60–160µg/m3. Compared with rural dwellers, those residing in urban areas were at significantly greater ozone-associated incident risks of overall CVD, hypertension, and stroke. We estimated 1.22 million (10.6% of overall CVD in 2018) incident CVD cases could be attributable to ambient ozone pollution in 2018, representing an overall 40.9% growth (0.36 million) compared to 2010 (0.87 million, 9.7% of overall CVD in 2010). This remarkable rise in ozone-attributable CVD cases was primary driven by population aging (+24.0%), followed by increase in ozone concentration (+10.5) and population size (+6.7%). ConclusionsLong-term ozone exposure was associated with an elevated risk and burden of incident CVD in Chinese adults, especially among urban dwellers. Our findings underscored policy priorities of implementing joint control measures for fine particulate matter and ozone in the context of accelerated urbanization and population aging in China. Environmental ImplicationThis study well depicted spatiotemporal patterns of O3-attributable CVD burden in Chinese mainland and quantify underlying driving factors, which would facilitate dynamic assessments of ozone-related health impacts and development of region-specific ozone policies in China.

Cardiovascular Characteristics in Patients with Prader-Willi Syndrome

Abstract The most prevalent type of syndromic obesity is referred to as Prader-Willi Syndrome (PWS), being determined by the lack of expression of paternal genes on chromosome 15q11.2-q13 due to genomic or epigenetic variations, such as DNA and histone methylation or acetylation. The syndrome is frequently associated with behavioral disorders, intellectual deficiencies, short stature, polyphagia, hypogonadism and muscular hypotonia, all stemming from the multiple endocrine dysfunctions characterizing this condition. Cardiovascular (CV) anomalies can manifest even in the early stages of life, and those with PWS have an elevated risk of early onset cardiovascular diseases. The somatic and behavioral aspects of the syndrome interact intricately to cause this increased risk for CV pathologies. Changes in the GH-IGF axis are seen in most Prader-Willi Syndrome (PWS) patients, irrespective of obesity. Specific cardiovascular features of GHD in adult PWS patients include reduced cardiac mass, decreased ejection fraction, and diminished chronotropic response to dobutamine.

Actual and Perceived Risk of Cardiovascular Disease among Sample of Iraqi Patients with Rheumatoid Arthritis

Background: Independent of conventional risk factors, patients with rheumatoid arthritis (RA) have a significantly increased risk of cardiovascular disease (CVD). Aims of the Study: To evaluate the actual and perceived 10-year CVD risk among Iraqi patients with RA as well as their level of knowledge about CVD risk. Patients and methods: This cross-sectional study included 100 RA patients (85 females and 15 males) who visited Baghdad Teaching Hospital/Rheumatology Unit from January 2021 to July 2021. The Framingham Risk Score (FRS) was used to calculate the actual 10-year risk of CVD. The Heart Disease Fact-Rheumatoid Arthritis Questionnaire (HDFQ-RA) was used to assess the subjects' knowledge of cardiovascular disease. Results: Among hundred Iraqi patients with RA, the median age was 51.23 8.4 years. The study's findings revealed that 23% had a high risk for CVD and 27% & 50% had moderate and low risk, respectively, based on the FRS calculator. The risk of CVD was significantly affected by the age of disease onset and seropositivity and steroid use (p-value 0.001). When the perceived risk was compared to the actual risk of cardiovascular disease, there was a weak agreement between them; only 31% had corresponding answers. Conclusions: The study showed an elevated risk of CVD in rheumatoid arthritis patients and a gap between actual and perceived CVD risk.

Association of the trajectory of plasma aldosterone concentration with the risk of cardiovascular disease in patients with hypertension: a cohort study

The purpose of this study was to determine the long-term pattern of plasma aldosterone concentration (PAC) trajectories and to explore the relationship between PAC trajectory patterns and cardiovascular disease (CVD) risk in patients with hypertension. Participants were surveyed three times between 2010 and 2016, and latent mixed modeling was employed to determine the trajectory of PAC over the exposure period (2010–2016). A Cox regression analysis was used to examine the association between PAC trajectory patterns and the risk of CVD (stroke and myocardial infarction). Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were calculated and reported. During a median follow-up of 4.10 (3.37–4.50) years, 82 incident CVD cases (33 myocardial infarction cases and 49 stroke cases) were identified. Among all three PAC models, the high-stability PAC pattern exhibited the highest risk of CVD. After full adjustment for all covariables, HRs were 2.19 (95% CI 1.59–3.01) for the moderate-stable pattern and 2.56 (95% CI 1.68–3.91) for the high-stable pattern in comparison to the low-stable pattern. Subgroup and sensitivity analyses verified this association. The presence of a high-stable PAC trajectory pattern is associated with an elevated risk of CVD in hypertensive patients. Nevertheless, more studies are warranted to confirm these findings.

The Effects of Pharmacological Urate-Lowering Therapy on Cardiovascular Disease in Older Adults with Gout.

Cardiovascular disease is an important cause of mortality in older patients. In addition to the traditional risk factors for cardiovascular disease, hyperuricemia has been increasingly associated with an elevated risk of cardiovascular disease. Uric acid itself has several unfavorable effects on the cardiovascular system, and hyperuricemia can lead to the development of gout. Gout is the most prevalent inflammatory rheumatic disease. Older patients with gout have an increased risk of cardiovascular morbidity and mortality due toan increased prevalence of traditional risk factors, as well as the inflammatory burden of gout activity. As the prevalence of traditional risk factors and the prevalence of both hyperuricemia and gout are increasing in older adults, cardiovascular risk management in these patients is very important. This risk management consists of, on the one hand, treatment of individual traditional risk factors and, on the other hand, of urate lowering, thereby decreasing inflammatory burden of gout. However, there is insufficient evidence to conclude that urate-lowering therapy reduces the risk of cardiovascular events. Moreover, from a cardiovascular point of view, there is no preference for one urate lowering drug over another in patients with gout, nor is there enough evidence to support a preference in patients with gout with increased cardiovascular risk. Personalized treatment in older patients with gout should be aimed at optimizing serum uric acid levels, as well as targeting traditional cardiovascular risk factors. Further prospective randomized trials are needed to support the hypothesis that urate lowering reduces cardiovascular risk in older patients with gout.

The difference between 2-hour post-challenge and fasting plasma glucose associates with the risk of cardiovascular disease in a normoglycemic population: the Tehran lipid and glucose study

BackgroundElevated fasting plasma glucose (FPG) and 2-hour post-challenge glucose (2hPG) levels are known to be independent risk factors for cardiovascular disease (CVD). However, there is limited data on the association of the difference between these measures and the risk of CVD. This study aims to investigate this association in normoglycemic Iranian adults, particularly in those with low-normal FPG levels.MethodsThis prospective cohort study included 4,594 30-65-year-old participants from the Tehran Lipid and Glucose Study. Using multivariable Cox proportional hazards regression models adjusting for age, sex, body mass index, hypertension, hypercholesterolemia, smoking, education level and FPG, hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated for the association between 2hPG-FPG, both as continuous and categorical variables, and the CVD risk. Analyses of receiver operating characteristic curves were undertaken to determine the optimal 2hPG-FPG cut-off value.ResultsDuring a median of 17.9 years of follow-up, 459 CVD events occurred. A one-unit increase in 2hPG-FPG was significantly associated with an elevated risk of cardiovascular disease in both normoglycemic (HR 1.10, 95% CI (1.01–1.19)) and low-normal FPG individuals (HR 1.16, 95% CI (1.04–1.30)); this association resisted adjustment for Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) among normoglycemic individuals. However, those with 2hPG levels greater than FPG levels had a non-significant increased risk of incident CVD compared to those with 2hPG levels of less than or equal to FPG, with corresponding HR values of 1.18 (95% CI: 0.95–1.46) in normoglycemic and 1.32 (95% CI: 0.98–1.79) in low-normal FPG, respectively. For incident CVD, the optimal cut-off value for the 2hPG-FPG was found to be 1.06 mmol/L, which was applicable for both normoglycemic and low FPG populations; using this criterion, the corresponding risks for incident CVD were 1.36 (95% CI: 1.12–1.64) and 1.57 (95% CI: 1.22–2.03), respectively.ConclusionsThe difference between 2hPG and FPG levels within the normoglycemic range is related to an increased risk of CVD, an issue that was independent of HOMA-IR. A cut-off point for 2hPG-FPG > 1.06 mmol/L may stratify persons at higher risk. These findings were particularly notable in those with low-normal FPG.

Combination Treatment with Verinurad and Allopurinol in CKD: A Randomized Placebo and Active Controlled Trial.

Key Points The SAPPHIRE trial was designed to assess albuminuria-lowering effects of the urate transporter 1 inhibitor verinurad combined with allopurinol in patients with CKD.Verinurad 3, 7.5, and 12 mg in combination with allopurinol 300 mg did not reduce albuminuria during 34 weeks treatment compared with allopurinol alone or placebo.Verinurad/allopurinol combination dose-dependently reduced serum urate concentrations compared with placebo. Background Hyperuricemia is associated with elevated risks of cardiovascular and chronic kidney disease (CKD). Since inhibition of urate transporter 1 has been suggested to be potentially nephroprotective, we performed a phase 2b study to assess albuminuria-lowering effects of the urate transporter 1 inhibitor verinurad combined with the xanthine oxidase inhibitor allopurinol in patients with CKD and hyperuricemia. Methods In this randomized placebo and active controlled trial, we enrolled participants with serum urate concentrations ≥6.0 mg/dl, eGFR ≥25 ml/min per 1.73 m2, and a urinary albumin-creatinine ratio (UACR) 30–5000 mg/g to one of five treatment arms: placebo, placebo+allopurinol 300 mg/day, verinurad 3 mg+allopurinol 300 mg/day, verinurad 7.5 mg+allopurinol 300 mg/day, or verinurad 12 mg+allopurinol 300 mg/day in a 1:1:1:1:1 ratio. The primary end point was the change in UACR from baseline to 34 weeks. Secondary end points were changes from baseline in UACR at week 60 and changes in serum urate and eGFR at weeks 34 and 60. Results Between August 2019 and November 2021, 861 adults with CKD (mean age 65 years, 33.0% female, mean eGFR 48 ml/min per 1.73 m2, median UACR 217 mg/g) were enrolled. At 34 weeks, the geometric mean percentage change in UACR from baseline did not differ among treatment groups (16.7%, 95% confidence interval [CI], −0.6 to 37.1 in the 3 mg group, 15.0% [95% CI, −1.85 to 34.6] in the 7.5 mg group, 14.0% [95% CI, −3.4 to 34.4] in the 12 mg group versus 9.9% [95% CI, −6.6 to 29.4] in the allopurinol group, and 37.3% [95% CI, 16.6 to 61.8] in the placebo group). UACR and eGFR change from baseline did not differ among treatment groups after 60 weeks. Verinurad/allopurinol combination dose-dependently reduced serum urate concentrations compared with placebo. The proportion of patients with adverse events and serious adverse events was balanced among treatment groups. Conclusions Verinurad in combination with allopurinol did not decrease UACR or eGFR decline, but further reduced serum urate compared with allopurinol alone or placebo. Clinical Trial registry name and registration number: SAPPHIRE Trial registration number, NCT03990363.

HIV Infection Drives Foam Cell Formation via NLRP3 Inflammasome Activation.

Persistent immune activation is linked to an increased risk of cardiovascular disease (CVD) in people with HIV (PWH) on antiretroviral therapy (ART). The NLRP3 inflammasome may contribute to elevated CVD risk in PWH. This study utilized peripheral blood mononuclear cells (PBMCs) from 25 PWH and 25 HIV-negative controls, as well as HIV in vitro infections. Transcriptional changes were analyzed using RNAseq and pathway analysis. Our results showed that in vitro HIV infection of macrophages and PBMCs from PWH had increased foam cell formation and expression of the NLRP3 inflammasome components and downstream cytokines (caspase-1, IL-1β, and IL-18), which was reduced with inhibition of NLRP3 activity using MCC950. Transcriptomic analysis revealed an increased expression of multiple genes involved in lipid metabolism, cholesterol storage, coronary microcirculation disorders, ischemic events, and monocyte/macrophage differentiation and function with HIV infection and oxLDL treatment. HIV infection and NLRP3 activation increased foam cell formation and expression of proinflammatory cytokines, providing insights into the mechanisms underlying HIV-associated atherogenesis. This study suggests that HIV itself may contribute to increased CVD risk in PWH. Understanding the involvement of the inflammasome pathway in HIV atherosclerosis can help identify potential therapeutic targets to mitigate cardiovascular risks in PWH.

Associations of cholecystectomy with metabolic health changes and incident cardiovascular disease: a retrospective cohort study

Although some studies conducted about the risk of cholecystectomy and cardiovascular disease, there was a limit to explaining the relationship. We investigated the short-term and long-term relationship between cholecystectomy and cardiovascular disease, and evidence using the elements of the metabolic index as an intermediate step. It was a retrospective cohort study and we used the National Health Insurance Service database of South Korea between 2002 and 2015. Finally, 5,210 patients who underwent cholecystectomy and 49,457 at 1:10 age and gender-matched controls of subjects were collected. The main results was estimated by Multivariate Cox proportional hazard regression to calculate the hazard ratio (HR) with 95% confidence interval (CI) for risk of cardiovascular disease after cholecystectomy. Regarding short-term effects of cholecystectomy, increased risk of cardiovascular disease (aHR 1.35, 95% CI 1.15–1.58) and coronary heart disease (aHR 1.77, 95% CI 1.44–2.16) were similarly seen within 2 years of surgery. When analyzing the change in metabolic risk factors, cholecystectomy was associated with a change in systolic blood pressure (adjusted mean [aMean]: 1.51, 95% CI: [− 1.50 to − 4.51]), total cholesterol (aMean − 14.14, [− 20.33 to 7.95]) and body mass index (aMean − 0.13, [− 0.37 to 0.11]). Cholecystectomy patients had elevated risk of cardiovascular disease in the short-term, possibly due to the characteristics of the patient before surgery. The association of cholecystectomy and cardiovascular disease has decreased after 2 years in patients who underwent cholecystectomy, suggesting that because of improvement of metabolic health, cholecystectomy-associated elevation of cardiovascular disease risk may be ameliorated 2 years after cholecystectomy.

Patients’ views on usefulness and effects of a risk communication tool for cardiovascular disease: a qualitative analysis

BackgroundFailing to comprehend risk communication might contribute to poor treatment adherence. Using hypertension as a case, we investigated how a risk communication tool for patients with an elevated risk of cardiovascular disease was perceived.MethodsAs part of a large project featuring a randomised controlled trial in a general practice setting in the Region of Southern Denmark, we conducted a semi-structured individual interview study. The study included patients with hypertension who had used an intervention comprising a visual and dynamic cardiovascular risk communication tool, along with receiving recurring emails providing advice on a healthy lifestyle. The analyses were based on Malterud’s Systematic Text Condensation.ResultsThis article focuses solely on the results of the interview study, which comprised a total of 9 conducted and analysed interviews. The IT setup had a major impact on adherence to the intervention. A positive impact was found when the IT setup was perceived as easy to use and accessible, while a negative impact was noted when it malfunctioned. The intervention increased patients’ self-reported insight into risk of cardiovascular disease. Patients reported the intervention and their risk of cardiovascular disease to become less important to them when they had more severe comorbidities. The involved health professional was very important for treatment adherence when communicating risk visually. Patients expressed trust in their general practitioners, and the general practitioners’ attitudes toward the intervention affected patients’ perceptions of its usefulness. While the informants reported an increased awareness of their risk of cardiovascular disease, none of them felt more concerned.ConclusionsPatients reported an increase in their perceived insight into the risk of cardiovascular disease but not an increased concern. Our findings align with previous studies emphasizing the importance of patients’ motivation as well as risk perception for adherence. General practitioners have an important role when implementing new tools for patients.

Evolving mechanisms and presentations of cardiovascular disease in people with HIV: implications for management.

SUMMARYPeople with HIV (PWH) are at elevated risk for cardiovascular diseases (CVDs), including myocardial infarction, heart failure, and sudden cardiac death, among other CVD manifestations. Chronic immune dysregulation resulting in persistent inflammation is common among PWH, particularly those with sustained viremia and impaired CD4+ T cell recovery. This inflammatory milieu is a major contributor to CVDs among PWH, in concert with common comorbidities (such as dyslipidemia and smoking) and, to a lesser extent, off-target effects of antiretroviral therapy. In this review, we discuss the clinical and mechanistic evidence surrounding heightened CVD risks among PWH, implications for specific CVD manifestations, and practical guidance for management in the setting of evolving data.