Vascular Risk Biomarkers Research Articles

High-Polyphenol Fruit and Vegetable Consumption and Cardiovascular Disease (CVD) Risk Factors Among Adults in Jeddah, Saudi Arabia.

Polyphenols found in food is a potential modifiable factor in disease prevention, especially when it comes to cardiovascular diseases (CVDs). This study aimed to determine the total polyphenol intake from fruits and vegetables (FV) in patients at King of Abdulaziz University Hospital, Jeddah, Saudi Arabia, and its association with vascular risk biomarkers. A cross-sectional study was done on 151 adult patients with at least one CVD risk factor. Data about demographics, smoking status, physical activity, height and weight, waist-to-hip ratio (WHR), waist circumference (WC), disease history, current disease (CD), and amount of polyphenol intake (mg/100 g) from rich polyphenol FV sources were collected. Of the participants, 127 (84.1%) were females, 49 (32.5%) had an age ranging from 45 to 54 years, and 110 (72.8%) were married. Of them, 54 (35.8%) had a bachelor's education, and 64 (42.4%) were employed. Moreover, 89 (59.3%) were physically inactive, 18 (11.9%) were smokers, 105 (69.5%) were obese, 116 (76.9%) had high WC, and 103 (68.2%), 109 (72.2%), and 90 (59.6%) had a family history of diabetes mellitus (DM), hypertension (HTN), and hyperlipidemia, respectively. The mean total polyphenol consumption/gm was significantly higher among older and married participants, and patients with HTN had a significantly lower mean total polyphenol consumption/gm. A significant positive correlation was found between the total polyphenol consumption/gm and participants' age. The consumption of polyphenols was associated with age, marital status, and blood pressure. Polyphenols from FV may have a preventive effect against cardiovascular illnesses. Including a range of foods high in polyphenols in a balanced diet is still a potential way to support cardiovascular health.

The association of neighborhood socioeconomic status, cognition, cardiovascular risk factors, and vascular risk biomarkers in the HABS‐HD study

AbstractBackgroundNeighborhood socioeconomic status (NSES) is linked to poorer cognition and physical health, influencing the risk of cardiovascular disease and mortality. Adverse neighborhood conditions have been also associated with higher cardiovascular biomarker levels. This study goal is to examine whether NSES is associated with cognitive function and whether this relationship is explained by associations between NSES and cardiovascular risk and biomarker factors in a sample of non‐Hispanic Whites (NHW) and Mexican American (MA) elders.MethodWe studied 1391 subjects from the Health and Aging Brain Study (HABS‐HD) with signed consent, fasting blood samples, 3T MRI, clinical evaluation, and cognitive testing. Area deprivation index (ADI) was used as a measure NSES. Cardiovascular risk factors (CVRF) were ascertained by self‐ report and medical history, and biomarkers were assayed via a multiple‐plex biomarker assay platform using electrochemiluminescence. Three linear regression models examined the association of ADI with cognitive performance, adjusting for age, sex, and education, CVRF, and vascular risk biomarkers.ResultSixty percent of the sample were female. MA were significantly younger, less educated, and had higher ADI scores than NHW. They also had lower scores in global cognition and executive function measures. MA had a higher prevalence of hypertension, diabetes and obesity (p = <0.0001). After controlling for demographic variables, ADI was associated with SEVLT [NHW (B = ‐0.003, t = ‐2.18, p = 0.02); MA (B = ‐0.005, t = ‐2.96, p = 0.003)] and Trails B [NHW (B = ‐0.006, t = ‐2.55, p = 0.01); MA (B = ‐0.01, t = ‐3.76, p = <0.001)] scores in both ethnic groups. Dyslipidemia influenced the association of ADI with SEVLT in MA, while obesity influenced the association of ADI and trails B in NHW. The association of ADI and trails B was partially influenced by IL6 in MA, and this association was partially influenced by TNF, CRP, and VCAM values in NHW.ConclusionNSES may influence cognitive functioning. This relationship is only partially explained by CVRF and vascular blood biomarkers. Future research is needed on the longitudinal relationships of NSES, cognitive impairment, and vascular factors.

Prophylactic treatment can modify vascular risk biomarkers in high-frequency episodic and chronic migraine patients: a pilot study

To evaluate whether preventive treatment can modify endothelial and oxidative biomarkers of vascular disease risk in patients with high-frequency episodic and chronic migraine. In this observational, prospective pilot study, 88 prophylactic treatment-naïve patients with episodic and chronic migraine and 56 healthy sex/age matched controls underwent ultrasonography exams and blood tests at baseline, and again in the migraine patients after 3 months’ treatment with metoprolol or topiramate. Biomarkers for endothelial function and oxidative stress were analyzed. At baseline, patients with migraine in the low-frequency episodic group had differences exclusively in nitrates 17.6 versus 27.33 µM; p = 0.046 compared to the controls. However, when comparing the group comprised of patients with high-frequency episodic migraine and chronic migraine versus controls, statistically significant differences appeared in hsCRP 2.68 versus 1.64 mg/dL; p = 0.049, vWF antigen (133% vs. 110%; p = 0.020, vWF activity (111% vs. 90%; p = 0.010) and isoprostane levels (181 vs. 238 µM; p = 0.05). Only in the chronic migraine subgroup did we found statistically significant differences in CIMT (0.60 vs. 0.54 mm; p = 0.042) which were significantly greater than in the controls. After treatment, patients who respond to preventive treatment exhibited significantly higher levels of nitrates (24.2–13.8 µM; p = 0.022) and nitrites (10.4–3.43 µM; p = 0.002) compared than non-responders. Moreover, biomarker levels improved in treatment-responsive patients with migraine; hsCRP levels decreased from 2.54 to 1.69 mg/dL (p < 0.05), vWF activity levels decreased from 124 to 103 IU/dL (p = 0.003) and prothrombin activity decreased from 1.01 to 0.93 (p = 0.01). These differences were also observed in the high-frequency and chronic migraine subgroup and reach statistical significance in the case of hsCRP, which decreased from 2.12 to 0.83 mg/dL (p = 0.048). Patients with migraines have differences in biomarker levels compared to controls, suggesting endothelial and oxidative dysfunction. The greatest differences in biomarker levels compared to controls are observed in migraine patients in the high-frequency and chronic migraine subgroups. Based on our results, preventive treatment is capable of modifying markers of endothelial dysfunction and oxidative stress in migraine patients, even in cases of chronic and high-frequency migraine.

Differential Expression of Vascular-Related MicroRNA in Circulating Endothelial Microvesicles in Adults With Spinal Cord Injury: A Pilot Study.

Spinal cord injury (SCI) is associated with an increased risk and prevalence of cardiopulmonary and cerebrovascular disease-related morbidity and mortality. The factors that initiate, promote, and accelerate vascular diseases and events in SCI are poorly understood. Clinical interest in circulating endothelial cell-derived microvesicles (EMVs) and their microRNA (miRNA) cargo has intensified due to their involvement in endothelial dysfunction, atherosclerosis, and cerebrovascular events. The aim of this study was to determine whether a subset of vascular-related miRNAs is differentially expressed in EMVs isolated from adults with SCI. We assessed eight adults with tetraplegia (7 male/1 female; age: 46±4 years; time since injury: 26±5 years) and eight uninjured (6 male/2 female; age: 39±3 years). Circulating EMVs were isolated, enumerated, and collected from plasma by flow cytometry. The expression of vascular-related miRNAs in EMVs was assessed by RT-PCR. Circulating EMV levels were significantly higher (~130%) in adults with SCI compared with uninjured adults. The expression profile of miRNAs in EMVs from adults with SCI were significantly different than uninjured adults and were pathologic in nature. Expression of miR-126, miR-132, and miR-Let-7a were lower (~100-150%; p < .05), whereas miR-30a, miR-145, miR-155, and miR-216 were higher (~125-450%; p < .05) in EMVs from adults with SCI. This study is the first examination of EMV miRNA cargo in adults with SCI. The cargo signature of vascular-related miRNAs studied reflects a pathogenic EMV phenotype prone to induce inflammation, atherosclerosis, and vascular dysfunction. EMVs and their miRNA cargo represent a novel biomarker of vascular risk and a potential target for intervention to alleviate vascular-related disease after SCI.

Interleukin-6 Signaling and Anti-Interleukin-6 Therapeutics in Cardiovascular Disease.

IL (interleukin)-6 is a pivotal cytokine of innate immunity, which enacts a broad set of physiological functions traditionally associated with host defense, immune cell regulation, proliferation, and differentiation. Following recognition of innate immune pathways leading from the NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome to IL-1 to IL-6 and on to the hepatically derived clinical biomarker CRP (C-reactive protein), an expanding literature has led to understanding of the proatherogenic role for IL-6 in cardiovascular disease and thus the potential for IL-6 inhibition as a novel method for vascular protection. In this review, we provide an overview of the mechanisms by which IL-6 signaling occurs and how that impacts upon pharmacological inhibition; describe murine models of IL-6 and atherogenesis; summarize human epidemiological data outlining the utility of IL-6 as a biomarker of vascular risk; outline genetic data suggesting a causal role for IL-6 in systemic atherothrombosis and aneurysm formation; and then detail the potential role of IL-6 inhibition in stable coronary disease, acute coronary syndromes, heart failure, and the atherothrombotic complications associated with chronic kidney disease and end-stage renal failure. Finally, we review anti-inflammatory and antithrombotic findings for ziltivekimab, a novel IL-6 ligand inhibitor being developed specifically for use in atherosclerotic disease and poised to be tested formally in a large-scale cardiovascular outcomes trial focused on individuals with chronic kidney disease and elevated levels of CRP, a population at high residual atherothrombotic risk, high residual inflammatory risk, and considerable unmet clinical need.

Color Doppler imaging of the retrobulbar circulation and plasmatic biomarkers of vascular risk in age-related macular degeneration: A pilot study.

Purpose:To evaluate preliminarily and compare the level of plasmatic biomarkers of vascular risk in patients with and without exudative age-related macular degeneration (ARMD) and to relate it to vascular resistance alterations in the ophthalmic artery (OA), central retinal artery (CRA), posterior temporal ciliary artery (PTCA), and posterior nasal ciliary artery (PNCA).Methods:Color Doppler imaging of the OA, CRA, PTCA, and PNCA was performed in 30 eyes of 30 cataract patients (control group) as well as in 30 eyes of 30 patients with naive exudative ARMD (study group), measuring the peak systolic velocity, end-diastolic velocity (EDV), and Pourcelot resistive index (RI). Likewise, in both groups, a blood test was performed to determine the plasmatic levels of homocysteine, C-reactive protein (CRP), B12 vitamin, and folic acid.Results:A positive and significant correlation was found between the level of CRP and RI of the OA in the ARMD group (r = 0.498, P = 0.005), with an increased RI in all arteries compared to controls, although differences only reached statistical significance for the PTCA (P = 0.035). Likewise, a significantly lower EDV for the CRA was found in ARMD eyes compared to controls (P = 0.041). In the study group, significantly higher plasmatic levels of homocysteine (P = 0.042) and CRP (P = 0.046) were found. In contrast, no significant differences were found between groups in the levels of folic acid (P = 0.265) and B12 vitamin (P = 0.520).Conclusion:The decrease of the choroidal perfusion related to hyperhomocysteinemia, and increase in the CRP plasmatic levels may play an etiological role on the exudative ARMD. This should be investigated in future studies with larger samples of patients.

Consumption of fish and vascular risk factors: A systematic review and meta-analysis of intervention studies

Background and aimsEpidemiological evidence of the beneficial health effects of fish consumption is strong, but the evidence from intervention trials is less documented. Our aim was to evaluate the state of the evidence on the potential effects of fish consumption on vascular risk factors arising from intervention trials. MethodsA systematic literature search was undertaken in OVID MEDLINE, Scopus, and EMBASE, which were searched from inception to June 2017. A meta-analysis of intervention trials was performed to estimate the effect of fish consumption on vascular risk factors in adults (age >18 years). Primary outcomes included lipid biomarkers such as triglycerides, total cholesterol, HDL cholesterol and LDL cholesterol, and also novel biomarkers of vascular risk. Secondary outcomes were related to feasibility and acceptability aspects of these interventions. Random-effects models were used to determine the pooled effect sizes. Results14 trials, including a total of 1378 individuals, fulfilled the inclusion criteria for this study. Consuming oily fish was associated with significant reductions in plasma triglycerides (−0.11 mmol/L; 95% CI -0.18 to −0.04; p = 0.002). While a significant increase in HDL-cholesterol was observed (0.06 mmol/L, 95% CI 0.02 to −0.11; p = 0.008). No significant effect could be observed on other vascular risk factors. ConclusionsThis study showed that there is evidence indicating that consuming oily fish led to significant improvements in two important biomarkers of cardiovascular risk, such as triglycerides and HDL levels. These results strongly support the important role for oily fish as part of a healthy diet.

Brain Perivascular Spaces as Biomarkers of Vascular Risk: Results from the Northern Manhattan Study.

Dilated perivascular spaces in the brain are associated with greater arterial pulsatility. We hypothesized that perivascular spaces identify individuals at higher risk for systemic and cerebral vascular events. Stroke-free participants in the population-based Northern Manhattan Study had brain MR imaging performed and were followed for myocardial infarction, any stroke, and death. Imaging analyses distinguished perivascular spaces from lesions presumably ischemic. Perivascular spaces were further subdivided into lesions with diameters of ≤3 mm (small perivascular spaces) and >3 mm (large perivascular spaces). We calculated relative rates of events with Poisson models and hazard ratios with Cox proportional models. The Northern Manhattan Study participants who had MR imaging data available for review (n = 1228; 59% women, 65% Hispanic; mean age, 71 ± 9 years) were followed for an average of 9 ± 2 years. Participants in the highest tertile of the small perivascular space score had a higher relative rate of all deaths (relative rate, 1.38; 95% CI, 1.01-1.91), vascular death (relative rate, 1.87; 95% CI, 1.12-3.14), myocardial infarction (relative rate, 2.08; 95% CI, 1.01-4.31), any stroke (relative rate, 1.79; 95% CI, 1.03-3.11), and any vascular event (relative rate, 1.74; 95% CI, 1.18-2.56). After we adjusted for confounders, there was a higher risk of vascular death (hazard ratio, 1.06; 95% CI, 1.01-1.11), myocardial infarction (hazard ratio, 2.22; 95% CI, 1.12-4.42), and any vascular event (hazard ratio, 1.04; 95% CI, 1.01-1.08) with higher small perivascular space scores. In this multiethnic, population-based study, participants with a high burden of small perivascular spaces had increased risk of vascular events. By gaining pathophysiologic insight into the mechanism of perivascular space dilation, we may be able to propose novel therapies to better prevent vascular disorders in the population.

Effect of Subtotal Renal Nephrectomy on CYP450-Mediated Metabolism of Arachidonic Acid: A Potential Player in Pathogenesis of Renocardiac Syndrome?

Background/Aims: Cardiovascular events are common in patients with renocardiac syndrome. A direct link between endothelial dysfunction and increased cardiovascular events has not been established for this syndrome; however, a causal role could be attributed to modulations of Cytochrome P450-mediated (CYP450) eicosanoid metabolites including Epoxyeicosatrienoic (EETs), Dihydroxyeicosatrienoic (DHET) and 20-Hydroxyeicosatetraenoic acids (20-HETE). In this study we investigated inter-organ variations in CYP450-mediated eicosanoids in key organs from dogs with renal insufficiency. Methods: Renal insufficiency was induced by two-stage subtotal nephrectomy (SNx). Biochemical markers (serum creatinine, blood urea nitrogen) and cardiac hemodynamics were measured weekly. After 5 weeks, arachidonic acid CYP450-metabolites in heart, remnant kidney and liver biopsies were analyzed. Results: Serum creatinine and blood urea nitrogen were significantly higher in the SNx group (versus timematched sham controls); hematocrit, body weight and creatinine clearance were significantly reduced. The lymphocyte:monocyte ratio, a biomarker of vascular risk, was lower (p=NS) in SNx dogs. Cardiac hemodynamics were similar for both groups. Cardiac levels of 20-HETE were markedly lower (p=0.014) in SNx dogs; however, 14, 15-DHET, a biomarker of soluble epoxide hydrolase levels were unchanged. The 20-HETE/14, 15-DHET ratio was lower in these dogs (p=0.003) and could help to explain a loss of autoregulation in this experimental model. In kidney and liver biopsies from SNx dogs 20-HETE tended to be higher and 14, 15-DHET lower (p=NS) versus time-matched controls; no change was observed for 20-HETE/14, 15-DHET. Conclusion: A marked reduction of cardiac 20-HETE and 20-HETE/14, 15-DHET levels occurred in dogs with kidney injury but no change in these CYP450-metabolites was observed in kidney or liver biopsies. As such, kidney injury appears to trigger significant alterations in CYP450-metabolites that may initiate endothelial dysfunction and vascular inflammation even in distant organs. Manipulating these pathways may eventually constitute a potential pharmacologic target to limit vessel dysfunction in the setting of renocardiac syndrome.

Highly Prevalent Hyperuricaemia is Associated with Adverse Clinical Outcomes Among Ghanaian Stroke Patients: An Observational Prospective Study.

Although a direct causal relationship between hyperuricaemia and stroke continues to be debated, strong associations between serum uric acid (SUA) and cerebrovascular disease exist. Very few studies have been conducted to evaluate the frequency and association between this potentially modifiable biomarker of vascular risk and stroke in sub-Saharan Africa. Therefore the aim of this study was to examine the association between hyperuricaemia and the traditional risk factors and the outcomes of stroke in Ghanaian patients. In this prospective observational study, 147 patients presenting with stroke at a tertiary referral centre in Ghana were consecutively recruited. Patients were screened for vascular risk factors and SUA concentrations measured after an overnight fast. Associations between hyperuricaemia and stroke outcomes were analysed using Kaplan-Meier and Cox proportional hazards regression analysis. The frequency of hyperuricaemia among Ghanaian stroke patients was 46.3%. Non-significant associations were observed between hyperuricaemia and the traditional risk factors of stroke. SUA concentration was positively correlated with stroke severity and associated with early mortality after an acute stroke with unadjusted hazards ratio of 2.3 (1.4 - 4.2, p=0.001). A potent and independent dose-response association between increasing SUA concentration and hazard of mortality was found on Cox proportional hazards regression, aHR (95% CI) of 1.65 (1.14-2.39), p=0.009 for each 100µmol/l increase in SUA. Hyperuricaemia is highly frequent and associated with adverse functional outcomes among Ghanaian stroke patients. Further studies are warranted to determine whether reducing SUA levels after a stroke would be beneficial within our setting.

P3‐065: Association of biomarkers of vascular risk and inflammation to cognitive performance in mexican‐american women: A hable study

P3‐065: Association of biomarkers of vascular risk and inflammation to cognitive performance in mexican‐american women: A hable study

The Impact of APOE Status on Relationship of Biomarkers of Vascular Risk and Systemic Inflammation to Neuropsychiatric Symptoms in Alzheimer's Disease

Research on the link between APOEε4 and neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) has been inconsistent. Previous work has shown a relationship between serum biomarkers of vascular risk and inflammation and NPS in AD. The current study investigated the impact of APOEε4 status on the relationship between biomarkers of cardiovascular risk, systemic inflammation, and NPS. The sample was drawn from the TARCC Longitudinal Research Cohort; the final sample of 190 consisted of 124 females and 66 males meeting the diagnostic criteria for mild to moderate AD. 115 individuals were APOEε4 carriers and 75 were non-carriers. Serum-based clinical biomarkers of vascular risk and biomarkers of inflammation related to AD were analyzed. NPS data was gathered from caretakers/family members using the Neuropsychiatric Inventory. The significant biomarkers differed for carriers and non-carriers with IL15 being a negative biomarker of total NPS accounting for 12% of the variance for carriers and IL18 and TNFα negative predictors for non-carriers (18% of variance). Patterns related to specific symptoms were similar. Stratification by gender revealed significant biomarkers of total NPS for female carriers were negative IL15 and IL1ra (18% of variance) and for female non-carriers were negative IL18 and positive homocysteine. Total cholesterol was a positive biomarker of total NPS for both male carriers (36% of variance) and non-carriers (negative TNFα and total cholesterol, 32% of variance). These findings suggest that dysregulation of inflammatory activity is related to NPS, that cholesterol is a significant factor in the occurrence of NPS, and that gender and APOE status need to be considered.

Cardiovascular disease in lupus

With improved management of the classical disease manifestations of systemic lupus erythematosus (SLE), cardiovascular disease (CVD) has emerged as one of the most important causes of morbidity and mortality. This review in particular focuses on progress over the past year in clinical and basic aspects of SLE-driven accelerated atherosclerosis. Both subclinical CVD and CV events continue to be recognized at increased frequency in previously unstudied lupus cohorts and populations. Novel associations have been identified between lupus CVD and cognitive impairment, depression, and low-income status. In terms of pathogenesis, there is an ever-increasing focus on the innate immune system and, in particular, type I interferons (IFNs). Recent studies have drawn connections in both human and murine models between neutrophils, plasmacytoid dendritic cells, type I IFNs, and endothelial dysfunction. Whether treatments such as mycophenolate mofetil or statins have a role in prevention of lupus CVD is an area of intensive study. CVD is a major complication of lupus and is now a leading cause of death among people living with this disease. As such, additional studies are needed in order to identify the most effective preventive strategies and most predictive vascular risk biomarkers. Type I IFNs may play a critical role in lupus CVD pathogenesis, and it is recommended that vascular outcomes be included in ongoing trials testing the efficacy of anti-IFN biologics.

Biomarkers of Vascular Risk, Systemic Inflammation, and Microvascular Pathology and Neuropsychiatric Symptoms in Alzheimer's Disease

Numerous serum and plasma based biomarkers of systemic inflammation have been linked to both neuropsychiatric disorders and Alzheimer's disease (AD). The present study investigated the relationship of clinical biomarkers of cardiovascular risk (cholesterol, triglycerides, and homocysteine) and a panel of markers of systemic inflammation (CRP, TNF-α, IL1-ra, IL-7, IL-10, IL-15, IL-18) and microvascular pathology (ICAM-1, VCAM-1) to neuropsychiatric symptoms in a sample with mild AD. Biomarker data was analyzed on a sample of 194 diagnosed with mild to moderate probable AD. The sample was composed of 127 females and 67 males. The presence of neuropsychiatric symptoms was gathered from interview with caretakers/family members using the Neuropsychiatric Inventory. For the total sample, IL-15, VCAM (vascular adhesion molecule), and triglycerides were significantly and negatively related to number of neuropsychiatric symptoms, and total cholesterol and homocysteine were positively related and as a group accounted for 16.1% of the variance. When stratified by gender, different patterns of significant biomarkers were found with relationships more robust for males for both total symptoms and symptom clusters. A combination of biomarkers of systemic inflammation, microvascular pathology, and clinical biomarkers of cardiovascular risk can account for a significant portion of the variance in the occurrence of neuropsychiatric symptoms in AD supporting a vascular and inflammatory component of psychiatric disorders found in AD. Gender differences suggest distinct impact of specific risks with total cholesterol, a measure of cardiovascular risk, being the strongest marker for males and IL-15, a marker of inflammation, being the strongest for females.

Perceptions of Canadian Primary Care Physicians Towards Cardiovascular Risk Assessment and Lipid Management

Background Cardiovascular (CV) risk stratification remains the cornerstone of preventive cardiology. This study was performed to gain insight into how Canadian primary care physicians (PCPs) incorporate traditional and emerging risk factors in determining risk. Methods Using a tested questionnaire, this cross-sectional survey evaluated the perceptions of 846 PCPs (38% response rate) on CV risk assessment, treatment thresholds, and novel biomarkers of vascular risk. Results Most physicians (74%) perform CV risk assessment in eligible patients annually with 69% using the Framingham Risk Score (FRS). Although 89% of the physicians knew that FRS estimates 10-year risk of coronary heart disease death and myocardial infarction, 30% could not characterize FRS thresholds for high risk. Only 44% correctly used a positive family history to double the FRS. Waist circumference was considered by 79% of the physicians as a vital sign but only 6% reported measuring this routinely. Carotid ultrasound was identified by 55% as the preferred imaging technique for screening in primary prevention. Although 99% had heard of high sensitivity C-reactive protein (hs-CRP), only 49% measured it for the purposes of assessing CV risk and 27% were unsure under what clinical scenarios the test is indicated. Conclusions Our survey suggests that FRS is employed by approximately 2/3 of Canadian PCPs for risk stratification. Family history and central obesity are considered important additional CV risk markers. There are substantial knowledge gaps on the appropriate use of family history and hs-CRP in risk stratification, particularly in patients who may not present with hyperlipidemia.

Volume of white matter hyperintensities in healthy adults: Contribution of age, vascular risk factors, and inflammation-related genetic variants

Aging is associated with appearance of white matter hyperintensities (WMH) on MRI scans. Vascular risk and inflammation, which increase with age, may contribute to white matter deterioration and proliferation of WMH. We investigated whether circulating biomarkers and genetic variants associated with elevated vascular risk and inflammation are associated with WMH volume in healthy adults (144 volunteers, 44–77 years of age). We examined association of WMH volume with age, sex, hypertension, circulating levels of total plasma homocysteine (tHcy), cholesterol (low-density lipoprotein), and C-reactive protein (CRP), and four polymorphisms related to vascular risk and inflammation: Apolipoprotein ε ( ApoE ε2,3,4), Angiotensin-Converting Enzyme insertion/deletion ( ACE I/D), methylenetetrahydrofolate reductase ( MTHFR) C677T, C-reactive protein ( CRP)-286C>A>T, and interleukin-1β ( IL-1β) C-511T. We found that larger WMH volume was associated with advanced age, hypertension, and elevated levels of homocysteine and CRP but not with low-density lipoprotein levels. Homozygotes for IL-1β-511T allele and carriers of CRP-286T allele that are associated with increased inflammatory response had larger WMH than the other allelic combinations. Carriers of the APOE ε2 allele had larger frontal WMH than ε3 homozygotes and ε4 carriers did. Thus, in healthy adults, who are free of neurological and vascular disease, genetic variants that promote inflammation and elevated levels of vascular risk biomarkers can contribute to brain abnormalities. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.

Endothelial progenitor cells: novel biomarker and promising cell therapy for cardiovascular disease

Bone-marrow-derived EPCs (endothelial progenitor cells) play an integral role in the regulation and protection of the endothelium, as well as new vessel formation. Peripheral circulating EPC number and function are robust biomarkers of vascular risk for a multitude of diseases, particularly CVD (cardiovascular disease). Importantly, using EPCs as a biomarker is independent of both traditional and non-traditional risk factors (e.g. hypertension, hypercholesterolaemia and C-reactive protein), with infused ex vivo-expanded EPCs showing potential for improved endothelial function and either reducing the risk of events or enhancing recovery from ischaemia. However, as the number of existing cardiovascular risk factors is variable between patients, simple EPC counts do not adequately describe vascular disease risk in all clinical conditions and, as such, the risk of CVD remains. It is likely that this limitation is attributable to variation in the definition of EPCs, as well as a difference in the interaction between EPCs and other cells involved in vascular control such as pericytes, smooth muscle cells and macrophages. For EPCs to be used regularly in clinical practice, agreement on definitions of EPC subtypes is needed, and recognition that function of EPCs (rather than number) may be a better marker of vascular risk in certain CVD risk states. The present review focuses on the identification of measures to improve individual risk stratification and, further, to potentially individualize patient care to address specific EPC functional abnormalities. Herein, we describe that future therapeutic use of EPCs will probably rely on a combination of strategies, including optimization of the function of adjunct cell types to prime tissues for the effect of EPCs.

Association of Vascular Risk Factors With Carotid Intima Media Thickness After Kidney Transplant

Background. Vascular risk remains the greatest cause of mortality after kidney transplant (KTX). Carotid intima media thickness (CIMT) has not been studied after KTX. We have analyzed a cross section of KTX recipients to determine which risk factors best correlate with CIMT, representing vascular risk. Methods. All recipients 6 or more months after KTX with estimated glomerular filtration rate (GFR) ≥30 mL/min were invited to participate. Biomarkers of vascular risk were compared with CIMT. Results. A total of 342 recipients (192 men/150 women) with mean age of 52.3±0.6 years (±standard error of the mean) were studied 5.9±0.3 years since KTX (range: 0.5-33.7 years). Diabetes (P<0.01), smoking (P=0.01), and donor status (deceased vs. living) (P=0.04) were associated with CIMT. Age (P<0.0001), body mass index (BMI, P=0.0026), systolic blood pressure (P=0.0013), and pulse pressure (P<0.0001) were positively and diastolic pressure was negatively correlated with CIMT (P=0.0002) and pulse pressure (P=0.007). In multivariate analysis, race/ethnicity, GFR, as well as age, BMI, diabetes status, systolic and diastolic blood pressures, and pulse pressure were all independently associated with CIMT (P<0.05). There was no correlation between CIMT and lipids, homocysteine, high-sensitive C-reactive protein, 25-hydroxyvitamin D, or parathyroid hormone (PTH). Conclusions. In the largest study of CIMT after KTX, diastolic blood pressure was negatively correlated with vascular risk, whereas age, diabetes, BMI, systolic blood pressure, race/ethnicity, and GFR independently correlated with CIMT after KTX confirming the value of CIMT as a noninvasive means to assess vascular risk and factors unique to this patient population.

European Atherosclerosis Society Screening Recommendations for Lipoprotein(a) and High-Sensitivity C-Reactive Protein: Double Standard or Failure of Evidence-Based Medicine?

While remaining silent on the role of high sensitivity C-Reactive Protein (hsCRP),2) the European Atherosclerosis Society (EAS) has issued a new consensus statement endorsing routine measurement of lipoprotein(a) [Lp(a)] among patients at moderate to high risk of cardiovascular disease (1). The EAS took an even larger step in this consensus document and recommended prescription of niacin therapy (1–3 g) to lower Lp(a) concentrations to less than 50 mg/dL. This recommendation is exceptionally broad, because as many as 1 in 5 adults may have an LP(a) concentration that exceeds 50 mg/dL. Therefore, the EAS recommendations urging healthcare providers to screen for high concentrations of Lp(a) and advising treatment of high concentrations with niacin mark radical changes in policy. The role of Lp(a) as an independent biomarker of vascular risk has been investigated for more than 20 years. Problems with standardization and reporting of Lp(a) assays have persisted without resolution. Therefore, it is reasonable to inquire what new evidence has emerged to explain this seismic shift in thinking and to justify these new and far-reaching recommendations for screening and treatment in the field of cardiovascular disease prevention. Surprisingly, the impetus and rationale for these changes stem largely from recent observational studies using the techniques of mendelian randomization, which refers to the random assortment of gene variants passed from parents to offspring. Mendelian randomization is a method used by some epidemiologists in an attempt to understand causal pathways for intermediate phenotypes. With regard to Lp(a), results of 2 recently reported studies demonstrated that polymorphism in the lipoprotein, Lp(a) ( LPA ) gene is associated both with plasma Lp(a) concentrations and with subsequent vascular risk (2, 3). Proponents have suggested that these data define a causal relationship between Lp(a) and cardiovascular disease (4). However, the technique of mendelian randomization is itself highly controversial, and …

Inflammatory Biomarkers of Vascular Risk as Correlates of Leukoariosis

Inflammatory biomarkers, including lipoprotein-associated phospholipase A2 (Lp-PLA2), myeloperoxidase (MPO), and high-sensitivity C-reactive protein (hsCRP) are associated with ischemic stroke risk. White matter hyperintensities (WMH) seen on brain MRI scans are associated with vascular risk factors and an increased risk of incident stroke, but their relation to inflammatory biomarkers is unclear. The Northern Manhattan Study includes a stroke-free community-based sample of Hispanic, black, and white participants with quantitative measurement of WMH volume (WMHV) and inflammatory biomarkers. We measured the association between Lp-PLA2, MPO, and hsCRP levels, and log-transformed WMHV after adjusting for sociodemographic and vascular risk factors. The hsCRP (median, 2.42 mg/L; IQR, 1.04, 5.19), Lp-PLA2 (median, 220.97 ng/mL; IQR, 185.77, 268.05), and MPO (median, 15.14 ng/mL; IQR, 12.32, 19.69) levels were available in 527 The Northern Manhattan Study participants with WMHV data but no subclinical infarcts. Those with hsCRP in the upper quartile (Q4 >4.92 mg/L or >3 mg/L), Lp-PLA2 in Q4 (>or=264.9 ng/mL), or MPO levels in Q3 (15.04-19.39 ng/mL) or Q4 (>19.39 ng/mL) each had greater WMHV, adjusting for sociodemographic and vascular risk factors. Adjusting for all biomarkers simultaneously, WMHV was 1.3-fold greater for Lp-PLA2 levels in Q4 compared to Q1 (beta=0.28; P=0.008) and 1.25-fold greater for MPO levels above the median compared to below (beta=0.22; P=0.02), but hsCRP was not associated with WMHV. Relative elevations of the inflammatory markers Lp-PLA2 and MPO were associated with a greater burden of WMH independent of hsCRP.