Surrogate Markers Of Cardiovascular Disease Research Articles

Exercise-induced Hypertension and Carotid Intima-media Thickness in Male Marathon Runners.

This study aimed to identify the relationship between exercise-induced hypertension and carotid artery intima-media thickness in long-distance runners. Sixty healthy male runners aged 40 to 60 years were assigned to the following three groups based on resting blood pressure and maximal systolic blood pressure during a maximal exercise test: normal blood pressure response, exercise-induced hypertension, and complex hypertension. An exaggerated systolic blood pressure response was defined as a maximal systolic blood pressure+≥+210 mmHg during the maximal exercise test, while carotid intima-media thickness was measured using B-mode ultrasonography. The carotid intima-media thickness mean values were the highest in the complex hypertension group (0.72±0.11 mm), followed by exercise-induced hypertension (0.62±0.12 mm) and normal blood pressure groups (0.55±0.13 mm), with a significant difference between the groups (p+<+0.002). In linear regression analysis, the mean intima-media thickness was independently associated with age (p=0.015) and maximal systolic blood pressure (p=0.046) but not with resting systolic blood pressure. These results suggest that exercise-induced hypertension is associated with carotid intima-media thickness, a surrogate marker of cardiovascular disease, in long-distance runners. Therefore, evaluating the blood pressure response during exercise is important for the early detection of potential cardiovascular disease risks in long-distance runners.

No correlation between carotid intima-media thickness and long-term glycemic control in individuals with type 1 diabetes

AimsTo determine whether carotid intima-media thickness (CIMT), a surrogate marker of cardiovascular disease (CVD), is associated with long-term blood glucose control in individuals with type 1 diabetes (T1D).MethodsWe recruited 508 individuals (43.4% men; median age 46.1, IQR 37.8–55.9 years) with T1D (median diabetes duration of 30.4, IQR 21.2–40.8 years) in a cross-sectional retrospective sub-study, part of the Finnish Diabetic Nephropathy (FinnDiane) Study. Glycated hemoglobin (HbA1c) data were collected retrospectively over the course of ten years (HbA1c-meanoverall) prior to the clinical study visit that included a clinical examination, biochemical sampling, and ultrasound of the common carotid arteries.ResultsIndividuals with T1D had a median CIMT of 606 μm (IQR 538–683 μm) and HbA1c of 8.0% (7.3–8.8%) during the study visit and HbA1c-meanoverall of 8.0% (IQR 7.3–8.8%). CIMT did not correlate with HbA1c (p = 0.228) at visit or HbA1c-meanoverall (p = 0.063). After controlling for relevant factors in multivariable linear regression analysis, only age was associated with CIMT (p < 0.001). After further dividing CIMT into quartiles, no correlation between long-term glucose control and CIMT (%, 1st 8.1 [IQR 7.2–8.9] vs 4th 7.9 [7.4–8.7], p = 0.730) was found.ConclusionsWe observed no correlation between long-term blood glucose control and CIMT in individuals with T1D. This finding suggests that the development of early signs of macrovascular atherosclerosis is not strongly affected by the glycemic control in people with T1D.

Arterial Stiffness as a Surrogate Marker of Cardiovascular Disease and Atherosclerosis in Patients with Vasculitides: A Literature Review.

Vasculitis, a group of systemic inflammatory diseases that affect the cardiovascular (CV) system, presents with a variety of clinical manifestations that depend on the size of the affected blood vessels. While some types of vasculitis reveal distinct symptoms, others are characterized by more diffuse and nonspecific presentations that can result in delayed diagnosis and treatment initiation. Interestingly, patients with vasculitides share a significant comorbidity: an elevated CV risk, contributing to increased rates of CV events and mortality. This heightened risk is caused by cumulative inflammatory burden, traditional CV risk factors, medication effects, and reduced physical fitness. Traditional risk assessment tools, commonly used in the general population, frequently underestimate the CV risk in patients with inflammatory rheumatic conditions. Consequently, novel approaches are necessary to stratify the precise CV risk in vasculitis patients. A number of surrogate parameters for CV risk have been investigated, with arterial stiffness emerging as a promising marker. Pulse wave velocity (PWV) is a well-established method for assessing arterial stiffness and predicting CV risk across different populations. Among numerous PWV variants, carotid-femoral PWV (cfPWV) stands out as the most extensively studied and accepted reference standard. It has demonstrated its utility as a surrogate CV parameter both in the general population and in patients with systemic inflammatory rheumatic diseases. In recent years, research has expanded to assess arterial stiffness in systemic rheumatic diseases, such as arthritis, connective tissue diseases, rheumatologic overlap syndromes, and chronic pain disorders, using measurements of PWV and other markers of arterial compliance and elasticity. Despite burgeoning research in rheumatologic diseases, data on CV risk markers in vasculitides remain limited and fragmented. This narrative review aims to provide a comprehensive overview of arterial stiffness as a potential screening marker for CV diseases, atheromatosis, and ultimately CV risk among patients with vasculitides.

Reference intervals for carotid artery intima-media thickness measurements in the multi-ethnic Asian population: relationship with cardiometabolic risk factors

Abstract Background Carotid artery intima-media thickness (cIMT) is an intermediate surrogate marker for cardiovascular disease (CVD). It has been reported that although the distribution of cIMT values is very heterogeneous and values vary widely between different ethnicity, geographic location, and ultrasound protocol, the prediction of vascular events with study-specific cIMT values is consistent across all ethnicities and regions (1). Hence, Consensus Statement from the American Society of Echocardiography suggests that cIMT greater than or equal to 75th percentile for the patient’s age, sex, and ethnicity is indicative of increased CVD risk (2). Aims We aimed to establish age, sex, and ethnic-specific reference intervals in the multi-ethnic Asian population comprising Chinese, Malays, and Indians. Methods We analysed data from 8762 healthy individuals who had a 3D carotid ultrasonography done as part of the Health for Life in Singapore study. Carotid ultrasonography measurements were taken from the distal common carotid artery (CCA) at both the lateral and posterior angles bilaterally during the end-diastolic phase. The mean of all 4 measurements were taken as average cIMT (avgcIMT). For this analysis, we excluded individuals on treatment for diabetes, hypertension, hyperlipidemia, and ischemic heart disease to derive a healthy population subset comprising of 6522 individuals (Chinese: 69%, Malays: 14%, Indians: 17%). We then assessed the 75th percentile as a marker of cardiovascular risk in all individuals, by testing associations with Framingham risk scores (locally adapted) and with cardiometabolic risk factors (3). Results Ethnic- and sex-specific 75th percentiles (95% CI) of CIMT for our Asian populations are summarised in Table 1. Compared to reference intervals reported in European and African American populations, the 75th centiles are lower in all Asian ethnic subgroups (p&amp;lt;0.05). Framingham risk score, BMI, LDL-C, HbA1c and systolic blood pressure were higher in Asians with cIMT more than 75th percentile (p&amp;lt;0.001), compared to Asians with normal cIMT. Conclusions We estimated race- and sex-specific 75th percentiles of avgcIMT across age in the multi-ethnic Asian population. The thresholds for Asian populations are substantially lower than reported in European and African populations. The 75th centiles identify people with raised cardiovascular risk factors, supporting the validity of cIMT as marker of vascular risk in the population. The 75th centiles will be useful in interpretation of cIMT measures obtained both in research and clinical settings in different ethnic populations in Asia. Longitudinal evaluation is needed to determine the prediction of our Asian specific thresholds for predicting hard cardiovascular outcomes.

Arterial Stiffness as a Surrogate Marker of Cardiovascular Disease and Atherosclerosis in Patients with Arthritides and Connective Tissue Diseases: A Literature Review.

The increased cardiovascular (CV) risk among patients with autoimmune rheumatic diseases, such as arthritides and connective tissue diseases, has been extensively documented. From a pathophysiological standpoint, systemic inflammation in the context of the disease can lead to endothelial dysfunction, accelerated atherosclerosis, and structural changes in vessel walls, which, in turn, are associated with exaggerated CV morbidity and mortality. In addition to these abnormalities, the increased prevalence of traditional CV risk factors, such as obesity, dyslipidemia, arterial hypertension, and impaired glucose metabolism, can further worsen the status of and overall prognosis for CV in rheumatic patients. However, data on appropriate CV screening methods for patients with systemic autoimmune diseases are scarce, and traditional algorithms may lead to an underestimation of the true CV risk. The reason for this is that these calculations were developed for the general population and thus do not take into account the effect of the inflammatory burden, as well as other chronic-disease-associated CV risk factors. In recent years, different research groups, including ours, have examined the value of different CV surrogate markers, including carotid sonography, carotid-femoral pulse wave velocity, and flow-mediated arterial dilation, in the assessment of CV risk in healthy and rheumatic populations. In particular, arterial stiffness has been thoroughly examined in a number of studies, showing high diagnostic and predictive value for the occurrence of CV events. To this end, the present narrative review showcases a series of studies examining aortic and peripheral arterial stiffness as surrogates of all-cause CV disease and atherosclerosis in patients with rheumatoid and psoriatic arthritis, as well as in systemic lupus erythematosus and systemic sclerosis. Moreover, we discuss the associations of arterial stiffness with clinical, laboratory, and disease-specific parameters.

Diagnostic performance of different anthropometric indices among Iranian adolescents for intima media thickness in early adulthood: A prospective study and literature review.

There is debate regarding which anthropometric indices is the most appropriate predictor of cardiovascular disease (CVD) among adolescents. The purpose of this study was to investigate the association of body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) in adolescents with high carotid intima-media thickness (cIMT) in early adulthood, as the surrogate marker of CVD in a cohort study. A total of 875 Iranian adolescents (female = 421) aged 10-17 years old were entered the study. The cIMT was measured in early adulthood (20-38 years old) after 18.2 (median) years of follow-up and defined as > 90th percentile for sex and age groups. The gender specific association between a 1-SD increase in each anthropometric measures with high cIMT was examined using multivariate logistic regression analysis adjusted for age, smoking, family history of CVD, systolic blood pressure, total cholesterol, and fasting blood sugar. In the multivariable analysis, the interaction between sex and age groups with anthropometric measures were significant (all p-values < 0.05). Among males, all anthropometric measures including BMI, WC, WHR, and WHtR were associated with high cIMT; the corresponding odds ratios were 1.43 (1.05-1.94), 1.63 (1.22-2.19), 1.33 (1.03-1.71), and 1.41 (1.07-1.87), respectively. However, after considering the related adulthood anthropometric measurements, the association remained significant for WC 1.48 (1.04-2.10) and WHR [1.28 (0.99-1.66), P = 0.06]. Moreover, among early adolescent boys aged 10-14 years, all of the anthropometric measures were significantly associated with high cIMT in the multivariate analysis that included the related adulthood anthropometric measures. The area under the curve (AUC) for the anthropometric measurements among males ranged from 0.576 for WHtR up to 0.632 for WC, without any superiority between them. Among females, only in linear regression analysis, a significant association were found between the higher value of WC and WHtR with cIMT measurement in adulthood; however, the risk reached to null after considering adult anthropometric measures. General and central obesity measures were significantly associated with high cIMT only among Iranian male adolescents, the relationship that were more prominent among pre-pubertal males.

Abstract 11647: Association of Breast Arterial Calcification With Clinical Outcomes and Mortality

Introduction: Breast arterial calcification (BAC), seen on mammography, has emerged as a risk stratification tool and surrogate marker of cardiovascular disease (CVD). Studies evaluating the association of BAC with clinical outcomes are limited. Methods: This single-center, retrospective study included 14,544 women who had a digital mammogram from 2008-2016. BAC was quantified with the Bradley score using an automated algorithm based on a trained, deep neural network (CureMetrix). The presence of BAC was defined as Bradley score &gt;10. Clinical outcomes were collected via medical records using ICD-10 diagnoses. Cox regression models were used to evaluate the association between BAC (continuous and binary) and clinical outcomes including mortality and composite outcome (mortality, stroke, and myocardial infarction). Models were adjusted for age, diabetes, medications, race, current smoking, systolic blood pressure, total &amp; HDL cholesterol, and prior CVD diagnosis. Results: The mean age was 54.7 ±11.0 years with 8% diabetes, 30% hypertension, 30% hyperlipidemia and 5% smokers. BAC was present in 13%. Over a mean follow-up of 4.2 years, there were 1,687 deaths (6.8%) and 2,113 composite outcomes (8.5%). On multivariable analysis, each 10-point increase in BAC score was significantly associated with clinical outcomes: mortality (aHR 1.05 [95% CI 1.02-1.08], p &lt; 0.001) and composite outcome (aHR 1.07 [95% CI 1.04-1.09], p &lt; 0.001). With BAC as a binary variable, women with BAC had a 1.52 (95% CI 1.22-1.89) higher risk of mortality and a 1.72 (95% CI 1.40-2.11) higher risk of composite outcome compared to those without BAC. Conclusion: BAC is significantly associated with clinical outcomes, including mortality and CVD. Further study is needed to confirm these findings.

Skin microcirculation dynamics are impaired in patients with rheumatoid arthritis and no cardiovascular comorbidities.

Rheumatoid arthritis (RA) is associated with increased cardiovascular disease (CVD) risk. Microvascular endothelial dysfunction contributes to the development of vascular injury and subsequent CVD. We hypothesised that RA patients exhibit blunted microvascular reactivity regardless of CVD risk factors and investigated potential associations with coronary microvascular perfusion and surrogate markers of CVD. This case-control study recruited RA patients and non-RA individuals in the absence of cardiovascular comorbidities. Skin microvascular reactivity was dynamically assessed using laser speckle contrast imaging coupled with post-occlusive reactive hyperaemia protocol. Applanation tonometry was applied to assess subendocardial viability ratio, an index of myocardial microvascular perfusion, and central arterial stiffness [carotid-femoral pulse wave velocity (PWV), augmentation index]. Peripheral arterial stiffness (carotid PWV, β-stiffness index) and carotid atherosclerosis (intima-media thickness) were assessed with carotid ultrasound software. Skin microvascular responses before and following reperfusion [baseline flux, occlusion flux, time-to-peak, peak magnitude, peak-to-baseline magnitude, baseline cutaneous vascular conductance (CVC), and percentage increase in CVC] were significantly impaired in RA patients (n=35) compared to controls (n=35). Presence of RA independently predicted altered microvascular reactivity in multivariate analysis. Skin microcirculation dynamics significantly correlated with coronary microvascular perfusion and peripheral arterial stiffness, yet not carotid atherosclerosis, even after adjustment for CVD risk factors. Patients with RA present impaired microvascular reactivity regardless of CVD risk factors at a preclinical stage preceding CVD. Assessment of skin microvascular dysfunction may reflect a state of generalised vasculopathy, including myocardial microvascular abnormalities, and serve as a non-invasive surrogate indicator of CVD risk in RA.

Cardiorenal benefits of mineralocorticoid antagonists in CKD and type2 diabetes : Lessons from the FIGARO-DKD trial.

Diabetic kidney disease (DKD) develops in almost half of all patients with diabetes and is the most common cause of chronic kidney disease (CKD) worldwide. Despite the high risk of chronic renal failure in these patients, only few therapeutic strategies are available. The use of renin-angiotensin system blockers to reduce the incidence of kidney failure in patients with DKD was established years ago and remains the hallmark of therapy. The past 2years have seen adramatic change in our therapeutic arsenal for CKD. Sodium-glucose co-transporter‑2 inhibitors (SGLT2s) have been successfully introduced for the treatment of CKD. Afurther addition is anovel compound antagonizing the activation of the mineralocorticoid receptor: finerenone. Finerenone reduces albuminuria and surrogate markers of cardiovascular disease in patients who are already on optimal therapy. In the past, treatment with other mineralocorticoid receptor antagonists was hampered by asignificantly increased risk of hyperkalemia. Finerenone had amuch smaller effect on hyperkalemia. Together with areduced effect on blood pressure and no signs of gynecomastia, this therapeutic strategy had amore specific anti-inflammatory effect and a smaller effect on the volume/electrolyte axis. In the FIDELIO-DKD study comparing the actions of the non-steroidal mineralocorticoid receptor antagonist finerenone with placebo, finerenone reduced the progression of DKD and the incidence of cardiovascular events, with arelatively safe adverse event profile. In this article, we summarize the available evidence on the cardioprotective and nephroprotective effects of finerenone and analyze the molecular mechanisms involved. In addition, we discuss the potential future role of mineralocorticoid receptor inhibition in the treatment of patients with diabetic CKD.

A panel of plasma microRNAs improves the assessment of surrogate markers of cardiovascular disease in rheumatoid arthritis patients.

Patients with RA present increased risk of cardiovascular (CV) disease compared with the general population. Moreover, CV risk factors that have a causal relationship with atherosclerosis do not seem to fully explain the accelerated process that they exhibit. We evaluated the association of a 10 microRNAs panel with surrogate markers of subclinical arteriosclerosis [carotid intima-media thickness (cIMT), carotid plaque presence (cPP), pulse wave velocity (PWV) and distensibility] in a cohort of RA patients. A total of 199 patients with RA were included. Surrogate markers of arteriosclerosis were measured with My Lab 60 X-Vision sonographer. MicroRNAs were extracted from plasma and quantified with qPCR. Multivariate models and classification methods were performed. Multivariate models showed that microRNAs-24 (β = 15.48), 125a (β = 9.93), 132 (β = 11.52), 146 (β = 15.12), 191 (β = 13.25) and 223 (β = 13.30) were associated with cIMT globally. MicroRNA-24 [odds ratio (OR) = 0.41], 146 (OR = 0.36) and Let7a (OR = 0.23) were associated with cPP in men. Including the microRNAs in a partial least square discriminant analysis model properly classified men with and without cPP. MicroRNA-96 (β = -0.28) was associated with PWV in male patients. Finally, several miRNAs were also associated with cIMT, cPP and arterial stiffness in the high DAS28 group and in the earlier tertile groups of disease duration. Plasmatic expression of microRNA-24, 96, 103, 125a, 132, 146, 191, 223 and Let7a were associated with surrogate markers of CV disease and could be predictors of CV risk in patients with RA.

Exercise training and vascular function in postmenopausal individuals: a systematic review and meta-analysis.

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality for menopausal individuals. Flow-mediated dilation (FMD), a surrogate marker of CVD, improves with aerobic exercise training in healthy and nonhealthy cohorts. However, systematic evaluation and precise estimate of this effect for menopausal individuals are unknown. We conducted a systematic review with meta-analysis to evaluate the influence of exercise training on FMD in postmenopausal individuals. Studies were identified from systematic search of major electronic databases (PubMed, ScienceDirect, and Cochrane Library) from inception to February 2021. Healthy, postmenopausal individuals were included, following an aerobic exercise intervention assessing FMD. A random-effects meta-analysis was used to calculate a pooled effect size (mean difference [MD]) with 95% confidence interval. Heterogeneity was assessed using I2 statistics. Metaregression was used to assess the association between changes in FMD and physical characteristics (eg, blood pressure, age, baseline FMD) and intervention details (metabolic equivalents and change in maximal oxygen uptake [∆V˙ o2max ]). For variables that significantly correlated, a multiple metaregression model was used to assess the accounted variance in between-study ∆FMD%. Study quality was assessed using the National Heart, Lung, and Blood Institute assessment tool. Nine studies, including 11 interventions (6 controlled interventions and 5 pre-post interventions; N = 182), with age range of 52 ± 4 to 64 ± 7 years underwent quantitative pooling of data. Exercise training significantly improved ∆FMD% (MD, 0.99; 95% confidence interval, 0.46-1.52; P < 0.001). Between-study heterogeneity was large and statistically significant ( I2 = 93.8%, P < 0.001). Post hoc analysis based on study design identified significant heterogeneity in the MD in ∆FMD% between controlled and pre-post study interventions ( P < 0.05). According to multiple metaregression, diastolic and systolic blood pressure and ∆V˙ o2max significantly predicted ∆FMD% ( Q = 15.74, df = 3, P < 0.01, R2 = 0.72). Aerobic exercise training improves FMD for postmenopausal individuals, and this observation was greater among controlled versus pre-post interventions. A higher resting blood pressure and the greatest ∆V˙ o2max yielded the largest improvements in FMD.

The Roles of Neutrophils Linking Periodontitis and Atherosclerotic Cardiovascular Diseases.

Inflammation plays a crucial role in the onset and development of atherosclerosis. Periodontitis is a common chronic disease linked to other chronic inflammatory diseases such as atherosclerotic cardiovascular disease (ASCVD). The mechanistic pathways underlying this association are yet to be fully understood. This critical review aims at discuss the role of neutrophils in mediating the relationship between periodontitis and ASCVD. Systemic inflammation triggered by periodontitis could lead to adaptations in hematopoietic stem and progenitor cells (HSPCs) resulting in trained granulopoiesis in the bone marrow, thereby increasing the production of neutrophils and driving the hyper-responsiveness of these abundant innate-immune cells. These alterations may contribute to the onset, progression, and complications of atherosclerosis. Despite the emerging evidence suggesting that the treatment of periodontitis improves surrogate markers of cardiovascular disease, the resolution of periodontitis may not necessarily reverse neutrophil hyper-responsiveness since the hyper-inflammatory re-programming of granulopoiesis can persist long after the inflammatory inducers are removed. Novel and targeted approaches to manipulate neutrophil numbers and functions are warranted within the context of the treatment of periodontitis and also to mitigate its potential impact on ASCVD.

PATIENTS WITH PSORIASIS PRESENT IMPAIRED MICROVASCULAR REACTIVITY INDEPENDENTLY OF TRADITIONAL CARDIOVASCULAR RISK FACTORS

Objective: Psoriasis is associated with increased rates of cardiovascular complications. Altered microvascular responses in divergent vascular beds are considered as an early precursor of cardiovascular disease and have been well-described in patients with cardiovascular risk factors and chronic inflammatory diseases. Laser Speckle Contrast Imaging (LSCI) has emerged as a novel, non-invasive and highly reproducible technique for the in vivo, real-time evaluation of microvascular perfusion. Design and method: We aimed to assess real-time skin microvascular function in patients with psoriasis free from established cardiovascular disease, in comparison with controls matched for cardiovascular risk factors. Microvascular function was evaluated dynamically using LSCI coupled with a post-occlusive reactive hyperaemia (PORH) protocol. Well-established markers of arterial stiffness, i.e. pulse wave velocity (PWV) and augmentation index (AIx), were assessed as surrogate markers of cardiovascular disease through a whole 24 h period using the Mobil-O-Graph device. Results: We studied 90 patients with psoriasis and 45 control individuals. Traditional cardiovascular risk factors and surrogate markers of cardiovascular disease did not differ between groups. By contrast, several indices of microvascular responses assessed with LSCI were found impaired in patients with psoriasis compared to controls, specifically baseline flux [45.7 (11.7) vs 36.2 (7.5) LSPUs, p &lt; 0.001], occlusion flux [11.6 (7.1) vs 7.4 (4.6) LSPUs, p &lt; 0.001], peak-to-baseline magnitude [128.9 (46.4) vs 179.0 (62.0) %, p &lt; 0.001], and baseline cutaneous vascular conductance (0.50 ± 0.13 vs 0.39 ± 0.10 LSPUs/mmHg, p &lt; 0.001). 24 h PWV significantly correlated with nearly all LSCI parameters, including time-to-peak flux, baseline perfusion, occlusion flux, peak flux, peak-to-baseline magnitude, and baseline cutaneous vascular conductance (p &lt; 0.05 for all). 24 h AIx significantly correlated only with occlusion flux (r = 0.223, p = 0.011). The latter was significantly associated with psoriasis duration (r = 0.300, p = 0.015). Conclusions: Our study shows for the first-time impaired microcirculation dynamics in patients with psoriasis using LSCI, in the absence of established cardiovascular disease and regardless of cardiovascular risk factors. A cross-talk between micro-macrovascular dysfunction apparently exists even at these early stages, before the establishment of clinically evident cardiovascular manifestations.

Assessment of Surrogate Markers for Cardiovascular Disease in Familial Mediterranean Fever-Related Amyloidosis Patients Homozygous for M694V Mutation in MEFV Gene.

Cardiovascular disease (CVD) remains underestimated in familial Mediterranean fever-associated AA amyloidosis (FMF-AA). We aimed to compare early markers of endothelial dysfunction and atherosclerosis in FMF-AA with a homozygous M694V mutation (Group 1 = 76 patients) in the Mediterranean fever (MEFV) gene and in patients with other genotypes (Group 2 = 93 patients). Measures of increased risk for future CVD events and endothelial dysfunction, including flow-mediated dilatation (FMD), pentraxin-3 (PTX3), and carotid intima-media thickness (cIMT), and fibroblast growth factor 23 (FGF23) as a marker of atherosclerotic vascular disease were compared between groups. The frequency of clinical FMF manifestations did not differ between the two groups apart from arthritis (76.3% in Group 1 and 59.1% in Group 2, p < 0.05). FMD was significantly lower in Group 1 when compared with Group 2 (MD [95% CI]: −0.6 [(−0.89)–(−0.31)]). cIMT, FGF23, and PTX3 levels were higher in Group 1 (cIMT MD [95% CI]: 0.12 [0.08–0.16]; FGF23 MD [95% CI]: 12.8 [5.9–19.6]; PTX3 MD [95% CI]: 13.3 [8.9–17.5]). In patients with FMF-AA, M694V homozygosity is associated with lower FMD values and higher cIMT, FGF23, and PTX3 levels, suggesting increased CVD risk profiles. These data suggest that a genotype–phenotype association exists in terms of endothelial dysfunction and atherosclerosis in patients with FMF-AA.

IDF21-0540 HbA1c as a marker of HDL cholesterol in Indian subjects with type 2 diabetes

Background: HbA1c is the gold standard means of accessing long term glycemia and for diagnosing diabetes. Cardiovascular disease (CVD) is the leading cause of death in type 2 diabetes (T2DM). HDL‐c has been considered as a surrogate marker of CVD. Aim: In this study we aimed to find the relationship between HbA1c and HDL‐c in Odia subjects with T2DM. Method: T2DM adults, who visited Diabetic OPD were requested to participate. Subjects with type 1 diabetes, secondary diabetes, GDM, nourishing mothers, pregnant women, as well as individuals who were on lipid lowering medicines, thyroid hormone therapy, steroids, immunosupressants were excluded. Comprehensive medical and drug history were recorded. After consent, participants underwent overnight fasting for estimation of HbA1c and lipid panel measurement. Results: Mean age and duration of diabetes for the sample (n = 1352, M/F = 832/520) were 51.8 ± 10.5 and 9.8 ± 6.0 years respectively. Mean HbA1c and HDL‐c values were 8.7 ± 2.4% and 40.6 ± 8.7mg/dl in order. The prevalence of low HDL (n = 697, 51.6%) and hypertriglyceridemia (n = 689, 51.0%) were almost similar. Uncontrolled HbA1c (≥7%) was documented in two third (66.7%) of persons with low HDL. While HDL was seen to be inversely related to HbA1c values, triglyceride level was found to be proportionate to HbA1c. Discussion: The study shows that elevated HbA1c is associated with low HDL and high triglyceride levels in Odia T2DM subjects and warrants the use of statins for prevention of cardiovascular events in this resource restricted community.

Arterial stiffness in rheumatoid arthritis: Current knowledge and future perspectivess

Rheumatoid arthritis (RA) is characterized by the excess cardiovascular risk that remains essentially unaltered despite current medical advances. The introduction of reliable markers towards early identification and subsequently effective management of high-risk patients with RA are urgently needed. Arterial stiffness represents an early indicator of cardiovascular morbidity and mortality and has emerged as a surrogate marker of cardiovascular disease. From a pathophysiological perspective, it is significantly accelerated by the accumulation of cardiovascular risk factors and is considered an intermediate process towards the development and progression of atherosclerotic cardiovascular disease. The aim of this review is to critically upraise current knowledge on arterial stiffness in patients with RA. Although not all studies concur, increased Pulse Wave Velocity (PWV) has been repeatedly reported in patients with RA. However, results need to be interpreted with caution as most studies enrolled patients with multiple cardiovascular risk factors and/or established cardiovascular disease, or with uncontrolled RA with high levels of systemic inflammation. Whether and to which extent increased arterial stiffness among patients with RA is associated with the disease per se, or rather represents the composite effect of hypertension and other classical cardiovascular risk factors, warrants further investigation. The impact of antirheumatic drugs on arterial stiffness is also discussed. Considering the well-established predictive value of increased PWV both in the general population and patients at high cardiovascular risk, future studies need to focus on the clinical utility of this surrogate risk marker specifically in patients with RA.

Cardiovascular Diseases and Periodontitis.

Periodontitis is a chronic inflammatory disease of the tooth-supporting connective tissue and alveolar bone that is initiated by a bacterial biofilm in periodontal pockets. It affects about half of adults in the Western world, and is associated with a range of systemic comorbidities, e.g., cardiovascular disease (CVD), diabetes and rheumatoid arthritis, and these diseases share overlapping systemic and target tissue inflammatory mechanisms. Indeed, mounting evidence has indicated that their association is causal and built on the presence of systemic low-grade inflammation (LGI). Prior research linking periodontitis to CVD has mainly been derived from experimental studies, observational data, and small interventional trials with surrogate markers of CVD, e.g., endothelial dysfunction. However, recent data from randomised studies have demonstrated that intensive treatment of periodontitis can reduce blood pressure in patients with hypertension in conjunction with reduction of systemic inflammatory markers. Furthermore, targeted anti-inflammatory therapy has been shown to reduce recurrent events in patients with established CVD and LGI. Along this line, the concept of residual inflammatory risk has emerged as an independent new risk factor for atherothrombotic CVD. The present review summarizes translational evidence indicating that periodontitis is a risk factor for CVD dependent on LGI, and we conclude that treatment of periodontitis is likely to contribute importantly to reduction of residual inflammatory risk.

Effect of amlodipine versus bisoprolol in hypertensive patients on maintenance hemodialysis: A randomized controlled trial.

Background:Left ventricular hypertrophy and asymmetric dimethylarginine (ADMA) are surrogate markers of cardiovascular disease (CVD) in the dialysis population. This study aimed to evaluate the effect of a calcium channel blocker-based antihypertensive regimen compared to a beta-blocker-based antihypertensive regimen on left ventricular mass index (LVMI) and ADMA levels in hypertensive patients on hemodialysis (HD).Methods:This was a parallel-design, open-label, single-center randomized controlled trial on 46 hypertensive patients on maintenance HD, with no history of CVD. Patients were randomly assigned to receive amlodipine 10 mg/d (n = 23) or bisoprolol 10 mg/d (n = 23). Office-based blood pressure (BP) was targeted to ≤ 140/ 90 mm Hg. The outcome was the change in LVMI and ADMA from baseline to 6 months.Results:Baseline demographic and clinical characteristics did not vary between groups. After 6 months of treatment, amlodipine-based therapy induced a greater reduction in LVMI from baseline than bisoprolol-based treatment (35 ± 34.2 vs 9.8 ± 35.9 gm/m2; P = .017). A similar reduction in the mean BP occurred with treatment in both groups. ADMA concentration decreased significantly from baseline in the amlodipine group (0.75 ± 0.73 to 0.65 ± 0.67 nmol/mL; P = .001), but increased nonsignificantly in the bisoprolol group (0.64 ± 0.61 to 0.78 ± 0.64 nmol/mL; P = .052).Conclusion:This study showed that compared to a bisoprolol-based regimen, an amlodipine-based antihypertensive regimen resulted in a significantly greater reduction in LVMI and ADMA levels from baseline in hypertensive patients on HD despite similar BP reduction in both groups. These findings support the re-evaluation of amlodipine as a potential first-line antihypertensive treatment in patients on HD without previous CVD.Trial Registration:Clinicaltrials.gov Identifier: NCT04085562, registered September 2019.

Abstract 10905: Breast Arterial Calcification as a Novel Predictor of Cardiovascular Disease Risk: A Systematic Review and Meta-Analysis

Introduction: Mammographically detected breast arterial calcification (BAC) is purported as a surrogate marker for cardiovascular disease (CVD). We conducted a systematic review and meta-analysis to determine the prevalence of BAC and its association with CVD risk and disease. Methods: Online databases were searched until March 2021 for studies reporting BAC. Four endpoints were evaluated: (1) BAC prevalence, (2) association with CVD risk factors, (3) prevalent and incident vascular disease and (4) BAC prevalence based on estimated CVD risk. Random-effects models were used. Data was analysed as odds ratio (OR), hazard ratio (HR) or effect size (ES) obtained through data transformation for differentially reported data. A CVD-specific risk metric was calculated as the product of CVD risk factor proportion and HR risk estimate from the CAD Consortium Risk Calculator and summed for all risk factors. Meta-regression modelling with predicted BAC prevalence stratified by age was performed. Results: There were 77 studies (104,710 patients) included. Pooled BAC prevalence was 22% (95%CI: 19-25%) with cumulatively increasing prevalence annually. Significant BAC predictors were age, hypertension, diabetes, hypercholesterolemia (p&lt;0.01). BAC was associated with CAD (OR 2.65, 95%CI: 2.17-3.23, p&lt;0.01) and non-coronary vascular disease (ES 0.80, 95%CI: 0.51-1.09, p&lt;0.01). BAC associated with incident cardiovascular events (HR 1.61, 95%CI: 1.11-2.32, p=0.001). Predicted BAC prevalence associated significantly with increasing CVD risk regardless of age (Figure). Conclusions: BAC is significantly associated with prevalent and incident vascular disease affecting intimal and medial arterial beds. BAC is highly prevalent and associated with CVD risk factors individually and cumulatively. Routine assessment of BAC should be considered in screening mammography to potentially trigger CVD risk consultation.

Can cholesterol be too low? A retrospective correlation of cholesterol lab values to other markers of cardiovascular disease risk

Abstract Introduction/Objective Most recommendations for lipid panel reference ranges are one-sided (desirable total cholesterol is &amp;lt;200 mg/dL, optimal LDL cholesterol [LDL-C] is &amp;lt;100 mg/dL). However, recent studies suggest risks for cardiovascular diseases or mortality at very low cholesterol values. In this retrospective study, we investigated the association between lipid panel results and surrogate markers of cardiovascular disease to test the hypothesis that very low cholesterol levels are associated with increases in cardiovascular risk. Methods/Case Report Patients with lipid panels reported from April 2020-March 2021 at LAC+USC Medical Center were included. Lipid panels (total cholesterol, LDL-C, HDL-C, triglycerides) and laboratory results representing risk factors for cardiovascular disease (troponin T (TnT), NT-pro brain natriuretic peptide (BNP), hemoglobin A1c (HbA1c), high sensitivity C-reactive protein (CRP)) were collated. Lipid panel values were compared against the percentage of patients with non-optimal laboratory results for the cardiovascular risk markers. Results (if a Case Study enter NA) Decreasing total cholesterol levels vs. the percentage of patients with high TnT or BNP showed a U-curve with a nadir at 200-240 mg/dL (elevated TnT: 15%, BNP: 49%) and further increased with lower cholesterol levels &amp;lt;60 mg/dL (TnT: 56%, BNP: 92%); HbA1c (U-curve, nadir: 160-180 mg/dL); and CRP (90% at cholesterol &amp;lt;60 mg/dL; 43% at 220-240 mg/dL). Decreasing HDL-C against all markers of cardiovascular disease demonstrated a continued downtrend below optimal HDL-C levels. Decreasing LDL-C vs. the percentage of high TnT showed a U-curve with a nadir at 120-140 mg/dL; BNP (uptrends in the optimal range of LDL-C); HbA1c (U-curve, nadir: 90-100 mg/dL); and CRP (uptrends with decreasing LDL-C). TnT and BNP decreased with increasing triglycerides, while HbA1c increased with increasing triglycerides. Data points (TnT: n &amp;gt; 5,000; BNP: n &amp;gt; 3,000; HbA1c: n &amp;gt; 29,000; CRP: n &amp;gt; 4,500). Conclusion Very low concentrations of total cholesterol and LDL-cholesterol are associated with elevated markers of cardiovascular risk. Laboratories may wish to consider incorporating low ends to total cholesterol and LDL-cholesterol reference ranges.