Abstract Patients with chronic inflammatory arthritis experience an increased incidence of cardiovascular (CV) events. In addition to visualizing atherosclerotic plaques, ultrasound examinations ...(USs) of the carotid arteries permit the measurement of subclinical markers of atherosclerosis, such as intima-media thickness (cIMT) and carotid segmental distensibility (cDC). The aims of the study were to identify the determinants of atherosclerosis acceleration (plaques, cIMT and cDC) in a sample of patients suffering from chronic arthritis and to compare these patients with a control group of people with ≤ 1 traditional risk factor (TRF) for CV disease. Methods We recruited 137 patients with rheumatoid arthritis (RA), 43 patients with psoriatic arthritis (PsA), 28 patients with ankylosing spondylitis (AS) and 48 healthy volunteers without histories of previous CV events. These patients underwent carotid artery US examinations using dedicated hardware. Results Regression and multivariate analyses demonstrated that only age ( p < 0.001) was consistently associated with cDC, cIMT and atherosclerotic plaques, both in the entire sample of patients with arthritis and in the subgroup of patients with RA. Among modifiable TRFs for cardiovascular disease, only hypertension, diabetes mellitus and smoking exhibited associations with some carotid phenotypes, with borderline significance. When patients with RA carrying ≤ 1 TRF were compared with control subjects carrying ≤ 1 TRF, only cDC was slightly lower in the RA group than in the control group. Conclusions Age is the major determinant of subclinical atherosclerosis in patients with different types of arthritis, as the contributions of other TRFs and disease activity and duration indices to the disease seem to be limited.
A genetic risk score (GRS) based on 29 single nucleotide polymorpysms (SNPs) associated with high blood pressure (BP) was prospectively associated with development of hypertension, stroke and ...cardiovascular events. The aim of the present study was to evaluate the impact of this GRS on the incidence of aortic disease, including aortic dissection (AD), rupture or surgery of a thoracic (TAA) or abdominal (AAA) aortic aneurysm. More than 25,000 people from the Swedish Malmo Diet and Cancer Study had information on at least 24 SNPs and were followed up for a median ≥ 18 years. The number of BP elevating alleles of each SNPs, weighted by their effect size in the discovery studies, was summed into a BP-GRS. In Cox regression models, adjusted for traditional cardiovascular risk factors including hypertension, we found significant associations of the BP-GRS, prospectively, with incident TAA (hazard ratio (HR) 1.64 (95% confidence interval (CI) 1.081-2.475 comparing the third vs. the first tertile; p = 0.020) but not with either AAA or aortic dissection. Calibration, discrimination and reclassification analyses show modest improvement in prediction using the BP-GRS in addition to the model which used only traditional risk factors. A GRS for hypertension associates with TAA suggesting a link between genetic determinants of BP and aortic disease. The effect size is small but the addition of more SNPs to the GRS might improve its discriminatory capability.
OBJECTIVE:Since childhood, unhealthy dietary habits could trigger the onset of cardiovascular risk factors, such as obesity and hypertension. Aim of this school-based study was to identify the ...possible relation between dietary patterns, physical activity and anthropometric, hemodynamic (blood pressure, BP; pulse wave velocity, PWV) and gluco-lipid parameters.
DESIGN AND METHOD:A validated Food Frequency Questionnaire (FFQ) and a validated questionnaire assessing the degree of physical activity (PAQ-C) were administered to children attending the 3rd and 4th class of 4 primary schools. Children responded with the aid of their parents and a dedicated dietitian. From FFQ, composed by 15 categories for a total of 61 foods, nutritional content in term of energy and macro-nutrients intake was extrapolated. Also dietary patterns obtained by Principal Component Analysis (PCA) were identified. Metabolic Equivalent of Task (MET) were computed for each child from IPAQ.
RESULTS:hree-hundred and nine children between 8 and 11 years participated (74,8% response rate) of whose 302 (97,7%) children compiled the FFQ. Significant correlations were found between“junk food” intake and BMI (rs = 0.141, p < 0.05), diastolic BP (rs = 0.114, p < 0.05); PWV (rs = 0.155, p < 0.001), triglycerides (rs = 0.150, p < 0.05); meat intake and diastolic BP (rs = 0.124, p < 0.05); vegetables intake and Z-score of diastolic BP (rs = −0.115, p < 0.05); “animal fats” intake and cholesterol (rs = 0.165, p < 0.05). PCA identifies three dietary patternsone characterized by junk food, meat, sweet, cereals and tubers; one composed by fruits, vegetables and fish and legumes and one characterized by eggs. No significant correlation was found between physical activity and the analyzed parameters.
CONCLUSIONS:The significant correlation between some categories of food and anthropometric, vascular and gluco-lipid parameters in 8-11y children suggests that it is important to begin early with politics to prevent the onset of overt cardiovascular risk factors.
OBJECTIVE:Treatment of obstructive sleep apnoea (OSA) has been shown to reduce blood pressure (BP). However, the effect size is modest and treatment of OSA is not recommended as the only treatment ...target when treating hypertension. Despite the limited effect of continuous positive airway pressure (CPAP) therapy on BP, it is likely that certain phenotypes of OSA patients respond better to CPAP than others. The aim of the present systematic review and meta-analysis was to identify potential predictors for BP response in patients with OSA undergoing CPAP treatment.(Figure is included in full-text article.)
DESIGN AND METHOD:A systematic search was conducted in three databases (MEDLINE, Embase and Web of Science) using terms exploring three domains (obstructive sleep apnoea, CPAP, clinical trial) based on the following inclusion criteriai) randomised controlled clinical trials published between January 1st 1960 to December 31st 2017 including a reasonable control group; iii) OSA diagnosis using polysomnography; iv) age >18 years; v) OSA severity of at least 5 AHI/h. The random effect model was fitted to estimate the pooled BP reductions calculated as the difference between the BP change (end-treatment minus baseline) in the CPAP and control group. Moreover, the original estimates have been stratified according to selected patient characteristics.
RESULTS:Out of 2445 articles, 59 RCTs were included (n = 7,329 subjects) comparing CPAP with control groups. CPAP was associated with a net reduction in systolic BP of −2.12 (95% CI −2.82 to −1.42) mmHg and in diastolic BP of −1.97 (95% CI −2.46 to −1.48) mmHg, favouring treatment of OSA using CPAP (both p-values < 0.001). The subgroup analysis showed that systolic BP reduction was greater in subjects younger than 60 years (−2.88 fro age 40–50, −2.78 for age 50–60 and −0.61 for age more than 60 years, p = 0.007) and in patients with controlled BP at baseline versus uncontrolled BP (−1.45 vs −4.14, p = 0.002) (Figure 1).
CONCLUSIONS:Younger patients (< 60 years) with uncontrolled blood pressure at baseline are more likely to experience significant BP reductions with CPAP therapy. Phenotypisation of specific cohorts of patients can guide clinicians to target OSA treatment and help to optimise patients’ cardiovascular risk.
OBJECTIVE:Epidemiologic and intervention studies suggest that dietary vegetables containing lycopene may associate with a reduction in cardiovascular risk. Lycopene has antioxidant activity, being ...the most efficient carotenoid singlet oxygen quencher. Aim of the present study was to explore the effects of lycopene on the synthesis and release of nitric oxide (NO) in endothelial cells and endothelial cells migration, a key step in angiogenesis.
DESIGN AND METHOD:Cultured human umbilical endothelial cells (HUVECs) were incubated for 30 minutes in the presence or absence of lycopene (2 micromol/L), vascular endothelial growth factor-A (VEGF-A, 10 ng/mL) and the NO-synthase inhibitor L-NAME (300 micromol/L). Confocal microscopy and Diaminofluorescein-FM diacetate (DAF-FM-DA) as NO indicator were used to analyze NO generation. Nitrite/nitrate concentration was measured in the cell culture medium using 2,3-diaminonaphthalene fluorimetric assay after 30 minutes of exposure to agonists and inhibitors. HUVECs migration was quantified by counting the number of migrated cells (10 fields per well) up to 20 hours after the addition of VEGF using the scratch wound healing assay.
RESULTS:An increase in DAF-FM-DA fluorescence was observed in HUVECs with a perinuclear pattern after exposure to lycopene (486.5 ± 142.0 Arbitrary Units, M ± SD, n = 7, p < 0.01), VEGF (472.7 ± 103.4 AU, p < 0.01) or the combination of the two agents with no synergistic effect (460.4 ± 183.2 AU, p < 0.05) compared to controls (293.5 ± 110.9 AU). Nitrite/nitrate concentration in HUVECs culture medium was higher in the presence of lycopene (35.9 ± 25.0 nmol/L, n = 4, P < 0.05), compared to controls (10.4 ± 1.0 nmol/L) and VEGF-A which had no effects. Nitrite/nitrate concentration was reduced by L-NAME (8.6 ± 2.6 nmol/L), demonstrating their generation via NO-synthase. HUVECs migration was stimulated by VEGF-A (967 ± 235 Cells/Field, control652.9 ± 118.5, n = 8, p < 0.05) and inhibited by the addition of lycopene (676.1 ± 204.8 C/F, p < 0.01 vs VEGF alone).
CONCLUSIONS:The present data demonstrate that lycopene increases NO generation and release, as shown by the increase in NO and nitrite/nitrate concentrations, by preventing peroxynitrite formation. Lycopene has biological activity, blunting the increase in cell migration induced by VEGF-A, possibly through NO-depended modulation of VEGF signaling system. The potential of lycopene bioactivity should be further investigated in the setting of vascular inflammation and pathological angiogenesis.
Essentials
The reliability of platelet tests as markers of the variable bioavailability of clopidogrel is not yet defined.
Kinetics of clopidogrel active metabolite (CAM) and platelet response were ...studied in ischemic heart disease.
CAM plasma maximum concentration (Cmax) predicted vasodilator‐stimulated phosphoprotein (VASP‐P).
Timely performed VASP‐P, not an aggregation‐based test, may be a surrogate for clopidogrel bioavailability.
Summary
Background
The high inter‐individual variability in the inhibition of platelet function by clopidogrel is mostly explained by high variability in its transformation to an active metabolite (CAM).
Objective
We investigated the relations between pharmacokinetics and pharmacodynamics of CAM by comparing two methods of platelet function.
Methods
We enrolled 14 patients undergoing percutaneous coronary interventions for non‐ST‐segment elevation acute coronary syndrome or inducible myocardial ischemia. Plasma concentrations of clopidogrel and CAM, phosphorylation of vasodilator‐stimulated phosphoprotein (VASP‐P), expressed as a platelet reactivity index (PRI) and whole‐blood platelet aggregation (multiple electrode aggregometer, MEA) were measured before and after a 600‐mg clopidogrel loading dose (nine time‐points) and before and after 75‐mg maintenance doses on days 2, 7 and 30.
Results
Plasma concentrations of clopidogrel and CAM were highly variable. CAM reached maximal concentration (Cmax) (median, 110.8 nm; range, 41.9–484.8) 0.5–2 h after the loading dose. A sigmoid dose‒response curve defined the relations between CAMCmax and PRI after 3 to 24 h (IC50, 459.6 nm; 95% confidence interval, 453.4–465.7; R2 = 0.82). PRI was unchanged from baseline in patients with the lowest CAMCmax (< 83 nm, n = 7), indicating low sensitivity of VASP‐P. PRI values were also predicted by CAMCmax at days 2, 7 and 30. Platelet aggregation measured by MEA did not show significant relations with either PRI or with CAM pharmacokinetics at any time‐point.
Conclusions
After 600 mg clopidogrel, VASP‐P, but not whole‐blood platelet aggregation measured by MEA, is almost entirely predicted by CAMCmax. VASP‐P could be useful in studies aimed at investigating relations between CAM bioavailability and clinical events.
OBJECTIVE:Overweight and obesity lead to the clustering of cardiovascular (CV) risk factors and the metabolic syndrome (MetS) not only in adults but also in children and are often accompanied by ...non-alcoholic fatty liver disease. Quality of dietary fat, beyond the quantity, can influence CV risk profile and in particular omega-3 fatty acids (FA) have been proposed as beneficial.
DESIGN AND METHOD:The aim of this observational study was to evaluate the associations of individual CV risk factors, characterizing the MetS, with erythrocyte membrane FA (by gas-chromatography), markers of average intake, in a group of obese children.
RESULTS:We enrolled 70 children (BMI = 29.4 ± 4.4 Kg/m; percentile of BMI = 98.0 ± 1.7), aged 5–17 years. Mean content of Omega-3 FA was low (Omega-3 Index = 4.7 ± 0.8%). Omega-3 FA were not associated with MetS characteristics, whereas omega-6 FA, in particular arachidonic acid (AA), were inversely associated with several features of the MetSAA resulted inversely correlated with waist circumference (rS = −0.352), waist/hip ratio (rS = −0.311), Waist/height ratio (rS = −0.248), triglycerides (rS = −0.366), fasting insulin (rS = −0.337), 24-hour-SBP (rS = −0.313), daytime-SBP (rS = −0.267), nighttime-SBP (rS = −0,245) and nighttime DBP (rS = −0.344). On the opposite, total amount of saturated FA (SFA) and specifically, palmitic acid, correlated positively with waist circumference (rS = 0.254), waist/hip ratio (rS = 0.247), total cholesterol (rS = 0.258), triglycerides (rS = 0.373) and fasting insulin (rS = 0.287).Thirty-five children (50%) had hepatic steatosis detected by ultrasounds. Fatty Liver Index (FLI), a predictive score of steatosis based on GGT, triglycerides and anthropometric indexes, was directly correlated to SFA (rS = 0.479), palmitic acid (rS = 0.515) and inversely to omega-6 FA (rS = −0.435) and AA (rS = −0.472). AA was inversely correlated with ALT (rS = −0.331) and palmitic acid directly with GGT (rS = 0.339).
CONCLUSIONS:Omega-6 FA, and especially AA, may be protective toward CV risk factors featuring the MetS and also to indexes of hepatic steatosis in obese children, whereas SFA seems to exert opposite effects.
OBJECTIVE:In a retrospective study, the prevalence of preeclampsia in patients with renal FMD was estimated to 52% (Vance et al., 2015). The aim of our study was to assess the prevalence and nature ...of pregnancy-related complications in patients with FMD.
DESIGN AND METHOD:A call for participation was sent to all centres contributing to the European/International FMD registry (EIFR). Eleven centres volunteered to participate. All patients with at least one pregnancy were included. Data on pregnancy and/or peripartum complications were collected through medical files and/or patient interviews. Data on FMD characteristics were collected through the FMD registry.
RESULTS:Data from 446 pregnancies were obtained in 197 patients (age at FMD diagnosis48 ± 14 years, 90% renal, 77% multifocal). Forty% of women (n = 78) experienced pregnancy-related complications. However, the latter mostly corresponded to hypertension during pregnancy (22%) and preterm birth (20%), while preeclampsia was reported in only 6%. Preeclampsia occurred at a median of 31 weeks (27–34). Of 12 patients, intra-uterine fetal death occurred in 8 and placenta abruption in 3. Only one patient presented with HELLP syndrome and one experienced arterial dissection. When compared to patients without pregnancy-related complications, patients with complicated pregnancies were younger at FMD diagnosis (43 vs. 52 yo, p < 0.000), had lower prevalence of multivessel FMD (30 vs. 45%, p = 0.037) and cerebrovascular FMD (16 vs. 52%, p < 0.001), but underwent more often renal revascularization (62 vs. 32%, p < 0.000).
CONCLUSIONS:The prevalence of pregnancy-related complications such as hypertension during pregnancy and preterm birth in the EIFR is high, probably related to severity of renal FMD. However, the prevalence of preeclampsia and other severe complications was low. Our findings emphasize the need to screen hypertensive women of childbearing age for FMD in order to ensure renal artery angioplasty before pregnancy if indicated and proper follow-up during pregnancy, without discouraging patients with FMD to consider pregnancy.
Gitelmańs syndrome (GS) is an inherited recessive disorder caused by homozygous or compound heterozygous loss of function mutations of the NaCl cotransporter (NCCT) gene encoding the kidney-expressed ...NCCT, the pharmacological target of thiazide diuretics. An observational study estimated the prevalence of GS to 19/1 000 000, in Sweden, suggesting that ∼1% of the population carries one mutant NCCT allele. As the phenotype of GS patients, who always carry two mutant alleles, is indistinguishable from that seen in patients treated with high-dose thiazide diuretics, we aimed at investigating whether subjects carrying one mutated NCCT allele have a phenotype resembling that of treatment with low-dose thiazide diuretics. We screened first-degree relatives of 18 of our patients with an established clinical end genetic diagnosis of GS for NCCT loss of function mutations and identified 35 healthy subjects carrying one mutant allele (GS-heterozygotes). Each GS-heterozygote was assigned a healthy control subject matched for age, BMI and sex. GS-heterozygotes had markedly lower blood pressure (systolic 103.3 ± 16.4 versus 123.2 ± 19.4 mmHg; diastolic 62.5 ± 10.5 versus 73.1 ± 9.4 mmHg; P < 0.001) than controls. There was no significant difference between the groups either in plasma concentration or urinary excretion rate of electrolytes, however, GS-heterozygotes had higher fasting plasma glucose concentration. Similar to patients being treated with low-dose thiazide diuretics, GS-heterozygotes have markedly lower blood pressure and slightly higher fasting plasma glucose compared with control subjects. Our findings suggest that GS-heterozygotes, the prevalence of which can be estimated to 1%, are partially protected from hypertension through partial genetic loss of function of the NCCT. However, as our study had a case–control design, it is important to underline that any potential effects on population blood pressure and risk of future cardiovascular disease need to be examined in prospective and population-based studies.
OBJECTIVE:Between genetic variants pinpointed in genome wide association study there is the rs1378942 near the CYP1A1/CYP1A2 locus. Coffee consumption has been associated with blood pressure (BP) but ...with sometimes contrasting evidences. A part of BP-coffee relationship could be mediated by genetic mechanismsthat is single nucleotide polymorphisms (SNPs) nearby the CYP1A2 gene, which metabolize caffeine, could influence BP. Indeed, smoking habit induces the expression of the CYP1A2 enzyme whereas coffee consumption itself could increase CYP1A2 activity. The aim of the present study was to explore if coffee consumption and/or smoking habit may affect BP and BP change over time (delta-BP), considering the rs1378942A > C polimorphysm.
DESIGN AND METHOD:Coffee intake was collected by a modified diet history method and the rs1378942 was genotyped by Taqman in > 28,000 participant of the Malmö Diet and Cancer (MDC). We performed a replication in 3381 participants that were rescreened after a period (13–20 years) of follow-up (MDC-FU) and in the Malmö Preventive Project (MPP; n > 17,000).
RESULTS:In MDC, both systolic and diastolic BP were positively associated with the rs1378942A > C, suggesting that carrying the C variant could increase BP (for SBP β = 0.397 ± 0.185, p = 0.031; for DBP β = 0.220 ± 0.100, p = 0.028). Coffee consumption as well as smoking were negatively associated with both SBP and DBP (p < 0.0001 for coffee consumption; p < 0.05 for smoke). A significant interaction between smoke and coffee was found, and both coffee and smoke interact with the rs1378942A > C (pinteraction < 0.05 for all). After stratification, in non-smokers who drink at least 600 gr/day of coffee, carriers of the rs1378942C variant had a higher BP (p_trend < 0.01 for SBP and DBP). At MDC-FU, only in non-smokers who drink less than 300 gr/day, a lesser delta-DBP was shown for rs1378942C carriers (ptrend < 0.01). In the MPP we found an interaction between the rs1378942A > C and smoking (pinteraction < 0.05; data on coffe consumption not available).
CONCLUSIONS:This study demonstrates that the effect of some genetic loci on BP could be highly influenced by voluptuary habits. In particular, coffee and smoke could influence the effect of the CYP1A1/CYP1A2 locus probably due to the metabolic action of the CYP1A2.
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