Applicability of non-cholesterol sterols in predicting response in cholesterol metabolism to simvastatin and fluvastatin treatment among hypercholesterolemic men

Background and aimsWe hypothesized that (I) certain features in cholesterol metabolism at baseline could predict a response to statins, (II) good and poor responders to statins have a differential profile of serum and fecal sterols and (III) serum non-cholesterol sterols reflect cholesterol metabolism on statins.Methods and resultsWe examined serum lipids, serum and fecal cholesterol, cholesterol precursors, cholestanol and phytosterols and cholesterol metabolism among 20 hypercholesterolemic men at baseline and on 16-wk simvastatin/fluvastatin treatment.At baseline, the mean of serum cholestanol/cholesterol was 11% lower but those of lathosterol/cholesterol, lathosterol/cholestanol, desmosterol/cholesterol, desmosterol/cholestanol were 36–65% higher among good than poor responders (p < 0.05 for each). On statins, reductions in ratios of serum precursor sterols and increases of absorption sterols were 1.8–2.9 times higher among good than poor responders (p < 0.05 for each). In the whole study group, changes from baseline values of lathosterol/cholestanol were related to those of cholesterol and LDL-C in serum (r = +0.513 and +0.451, p = 0.021 and 0.046, respectively). Serum lathosterol ratios to cholesterol, cholestanol and sitosterol consistently reflected a ratio of cholesterol synthesis (mg/d/kg)/fractional cholesterol absorption (%) (r-range +0.456 to +0.727, p < 0.05 for each).ConclusionsLow serum baseline ratios to cholesterol of lathosterol, cholestenol and desmosterol, but a high ratio of cholestanol predicted a poor response to statins. Good responders were characterized by more profound reductions of serum and fecal (lathosterol) precursor sterols and increases of serum absorption marker sterol ratios on statins. Serum surrogate sterol markers of cholesterol metabolism were applicable in evaluating cholesterol absorption and synthesis also on statins.     

Cholesterol,non-cholesterol sterols and bile acids in paediatric gallstones

BackgroundDepending on underlying aetiopathogenetic factors human gallstones contain various amounts of cholesterol, non-cholesterol sterols and bile acids, which have remained unexplored in paediatric gallstone patients.AimsTo evaluate sterol and bile acids compositions of paediatric gallstones.Patients and methodsStudy group included 21 consecutively cholecystectomised children. Gas–liquid chromatography was used to quantitate gallstone sterols and bile acids. Results were compared to adult gallstones (n = 194).ResultsCholesterol stones (n = 9) had higher proportions of cholestenol and lathosterol, but lower those of lanosterol and phytosterols than pigment stones (n = 12) (p < 0.05 for each). Patients with gallstone cholesterol content over 70% were female. Gallstone cholesterol positively reflected body mass index and, in cholesterol stones-group, age (r = ∼+0.700, p < 0.05). Three patients on parenteral nutrition had brown pigment stones consisting of high amounts of campesterol and sitosterol ranging 483–9303 μg/100 mg of stone. Pigment stones had 13-fold higher amount of bile acids than cholesterol stones (p < 0.05). Black pigment stones contained ∼3-fold higher phytosterol proportions, and pigment stones and cholesterol stones had ∼43% lower proportions of deoxycholic acid than adults (p < 0.05).ConclusionGallstones in patients on parenteral nutrition are rich in phytosterols. With respect to gallstone sterols, gallstone disease of adolescent girls resembles that of adults. Composition of bile acids in paediatric gallstones is different from adults.     

Plant sterols from rapeseed and tall oils: Effects on lipids,fat-soluble vitamins and plant sterol concentrations

Background and aimsData comparing the impact of different sources of plant sterols on CVD risk factors and antioxidant levels is scarce. We evaluated the effects of plant sterols from rapeseed and tall oils on serum lipids, lipoproteins, fat-soluble vitamins and plant sterol concentrations.Methods and resultsThis was a double-blinded, randomized, crossover trial in which 59 hypercholesterolemic subjects consumed 25 g/day of margarine for 4 weeks separated by 1 week washout periods. The two experimental margarines provided 2 g/day of plant sterols from rapeseed or tall oil. The control margarine had no added plant sterols. The control margarine reduced LDL cholesterol by 4.5% (95% CI 1.4, 7.6%). The tall and rapeseed sterol margarines additionally reduced LDL cholesterol by 9.0% (95% CI 5.5, 12.4%) and 8.2% (95% CI 5.2, 11.4%) and apolipoprotein B by 5.3% (95% CI 1.0, 9.6%) and 6.9% (95% CI 3.6, 10.2%), respectively. Lipid-adjusted β-carotene concentrations were reduced by both sterol margarines (P < 0.017). α-Tocopherol concentrations were reduced by the tall sterol compared to the rapeseed sterol margarine (P = 0.001). Campesterol concentrations increased more markedly with the rapeseed sterol versus tall sterol margarine (P < 0.001). The rapeseed sterol margarine increased while the tall sterol margarine decreased brassicasterol concentrations (P < 0.001).ConclusionsPlant sterols from tall and rapeseed oils reduce atherogenic lipids and lipoproteins similarly. The rapeseed sterol margarine may have more favorable effects on serum α-tocopherol concentrations.     

Association between early pregnancy vitamin D status and changes in serum lipid profiles throughout pregnancy

ObjectiveTo evaluate the associations between first trimester 25-hydroxyvitamin D [25(OH)D] status and changes in high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), total cholesterol (TC), triglyceride (TG) concentrations, TG/HDL-c, and TC/HDL-c ratios throughout pregnancy. We hypothesized that first trimester 25(OH)D inadequacy is associated with lower concentrations of HDL-c and higher LDL-c, TC, TG, TG/HDL-c, and TC/HDL-c ratios throughout pregnancy.MethodsA prospective cohort study with 3 visits at 5–13 (baseline), 20–26, and 30–36 gestational weeks, recruited 194 pregnant women attending a public health care center in Rio de Janeiro, Brazil. Plasma 25(OH)D concentrations were measured in the first trimester using liquid chromatography–tandem mass spectrometry. 25(OH)D concentrations were classified as adequate (≥ 75 nmol/L) or inadequate (< 75 nmol/L). Serum TC, HDL-c, and TG concentrations were measured enzymatically. Crude and adjusted longitudinal linear mixed-effects models were employed to evaluate the association between the first trimester 25(OH)D status and changes in serum lipid concentrations throughout pregnancy. Confounders adjusted for in the multiple analysis were age, homeostatic model assessment (HOMA), early pregnancy BMI, leisure time physical activity before pregnancy, energy intake, and gestational age.ResultsAt baseline, 69% of the women had inadequate concentrations of 25(OH)D. Women with 25(OH)D inadequacy had higher mean LDL-c than those with adequate concentrations (91.3 vs. 97.5 mg/dL; P = 0.064) at baseline. TC, HDL-c, LDL-c TG, TG/HDL-c ratios, and TC/HDL-c ratios, increased throughout pregnancy independently of 25(OH)D concentrations (ANOVA for repeated measures P < 0.001). The adjusted models showed direct associations between the first trimester 25(OH)D status and changes in TC (β = 9.53; 95%CI = 1.12–17.94), LDL-c (β = 9.99; 95% CI = 3.62–16.36) concentrations, and TC/HDL-c ratios (β = 0.16; 95% CI = 0.01–0.31) throughout pregnancy.ConclusionsInadequate plasma 25(OH)D concentrations during early pregnancy were associated with more pronounced changes of TC, LDL-c concentrations, and TC/HDL-c ratios throughout pregnancy. Changes in these cardiovascular markers suggest the importance of ensuring adequate vitamin D status at the beginning of pregnancy.     

Association of fructosamine to indices of dyslipidemia in older adults with type 2 diabetes

AimsTo evaluate the association of serum fructosamine values to lipid profiles and to other indices of glycemia both at baseline and over time in adults with type 2 diabetes (T2DM).MethodsForty adults aged 45 or older with T2DM, not taking insulin, and an HbA1c of 6–10% were enrolled in a randomized controlled trial regarding the effects of an 8-week yoga program on glycemia and related cardiovascular disease risk indices in adults with T2DM. Fasting blood was drawn to assess glycemia (HbA1c, glucose, and fructosamine) and dyslipidemia (LDL, HDL, total cholesterol, cholesterol:HDL ratio, LDL:HDL ratio, and triglycerides) pre and post-intervention. Because the relation of fructosamine to other indices of glycemia and to lipid profiles did not differ between treatment groups either at baseline or over time, groups were pooled for analysis.ResultsBaseline fructosamine values were significantly correlated with HbA1c (r = 0.77, P < 0.0001), glucose (r = 0.72, P < 0.0001), LDL:HDL ratio (r = 0.46, P = 0.01), cholesterol:HDL ratio (r = 0.55, P = 0.002), and triglycerides (r = 0.39, P = 0.032), but not to other lipid indices at baseline. Change in fructosamine over 8 weeks was significantly correlated with change in HbA1c (r = 0.63, P = 0.0001), glucose (r = 0.39, P = 0.029), cholesterol (r = 0.65, P < 0.0001), LDL (r = 0.55, P = 0.001), LDL:HDL ratio (r = 0.53, P = 0.003), and cholesterol:HDL ratio (r = 0.52, P = 0.002), and was more strongly related to change in lipid values than were other indices of glycemia.ConclusionsFructosamine was significantly correlated with measures of dyslipidemia and glycemia both at baseline and over time, and may represent a relatively sensitive and low cost index of short to medium term change in both glycemia and certain lipid profiles. However, findings from this small pilot study should be interpreted with caution, and warrant replication in larger prospective studies.     

High plasma lecithin:cholesterol acyltransferase activity does not predict low incidence of cardiovascular events: Possible attenuation of cardioprotection associated with high HDL cholesterol

The cholesterol esterifying enzyme, lecithin:cholesterol acyltransferase (LCAT), is crucial in high density lipoprotein (HDL) metabolism. The role of LCAT activity on incident cardiovascular disease (CVD) is unknown. We determined the association of incident CVD with plasma LCAT activity, and evaluated whether LCAT may modify the cardioprotective effect of higher HDL cholesterol. In a community-based prospective nested case-control study (PREVEND cohort), an exogenous substrate assay was used to measure plasma LCAT activity in 116 men who developed CVD (cases) and in 111 male controls. Plasma LCAT activity was 5% higher in cases (P = 0.027) in association with higher total cholesterol, non-HDL cholesterol and triglycerides. Age-adjusted incident CVD was increased with higher LCAT activity (continuous variable: hazard ratio (HR) 1.23; 95% CI 1.01–1.49, P = 0.037; upper quartile vs. lowest 3 quartiles: HR 1.60; 95% CI 1.07–2.39, P = 0.021). This relationship was not significant after adjustment for lipids. Compared to subjects with HDL cholesterol above the median and lower LCAT activity (lowest 3 quartiles) the age-adjusted cardiovascular risk was elevated in subjects with similarly higher HDL cholesterol and higher LCAT activity (HR 2.38; 95% CI 1.27–4.49, P = 0.007), lower HDL cholesterol and lower LCAT activity (HR 2.58; 95% CI 1.64–4.49, P < 0.001) and lower HDL cholesterol and higher LCAT activity (HR 2.76; 95% CI 1.58–4.83, P < 0.001). These HRs were unchanged after non-HDL cholesterol and triglyceride adjustment. In conclusion, high plasma LCAT activity does not predict reduced CVD risk, and may attenuate cardioprotection associated with higher HDL cholesterol.     

Influencia del tratamiento biológico en los factores de riesgo cardiovascular de los pacientes con enfermedad inflamatoria intestinal

IntroductionChronic immune-mediated diseases, including inflammatory bowel disease (IBD), present an increased risk of developing early atherosclerosis and cardiovascular events (CVE) at early age.ObjectiveTo describe the baseline and 1-year cardiovascular profile of patients with IBD according to the biologic treatment received, taking into account the inflammatory activity.Patients and methodsIt is a retrospective, observational study that included 374 patients. Cardiovascular risk factors (CVRF) and CVE were collected at the baseline visit and at one-year follow-up to describe the cardiovascular risk according to the biological treatment received, also assessing clinical and biological remission.ResultsA total of 374 patients were included: 146 (38.73%) were treated with Infliximab, 128 (33.95%) with adalimumab, 61 (16.18%) with ustekinumab and 42 (11.14%) with vedolizumab.The changes in blood glucose levels are [86.31 mg/dL (84.57–88.06) vs. 89.25 mg/dL (87.54–90.96), P=.001] for those treated with antiTNFα and [86.52 mg/dL (83.48–89.55) vs. 89.44 mg/dL (85.77–93.11), P=.11] in the other group.In the group treated with antiTNFα total cholesterol values at baseline visit are [169.40 mg/dL (164.97–173.83) vs. 177.40 mg/dL (172.75–182.05) at one year of treatment, P=<.001], those of HDL [50.22 mg/dL (48.39–52.04) vs. 54.26 mg/dL (52.46–56.07), P=<.001] and those of triglycerides [114.77 mg/dL (106.36–123.18) vs. 121.83 mg/dL (112.11–131.54), P=.054].Regarding weight, an increase was observed, both in those patients treated with antiTNFα [71.39 kg (69.53–73.25) vs. 72.87 kg (71.05–74.70), P<.001], and in the group treated with ustekinumab and vedolizumab [67.59 kg (64.10–71.08) vs. 69.43 kg (65.65–73.04), P=.003].Concerning CVE, no significant differences were observed neither according to the drug used (p = 0.36), nor according to personal history of CVE (P=.23) nor according to inflammatory activity (P=.46).ConclusionsOur results on a real cohort of patients with IBD treated with biologic drugs show a better control of certain cardiovascular parameters such as CRP or HDL, but a worsening of others such as total cholesterol or triglycerides, regardless of the treatment. Therefore, it is possibly the disease control and not the therapeutic target used, the one that affect the cardiovascular risk of these patients.     

Les protéines purifiées à partir de sardines améliorent les chiffres tensionnels,l’équilibre glycémique,les voies métaboliques anti-athérogènes et la capacité anti-oxydante,chez le rat obèse

Aim of the studyThe effects of sardine by-products (SBy-P) and fillet proteins (SF-P) were compared to casein (Cas) ; these effects were assessed on blood pressure, glycemic control, reverse cholesterol transport, lipid peroxidation and total antioxidant capacity in obese rats.Materials and methodsEighteen male Wistar rats were subjected for three months, to a high-fat diet. The obese rats were divided into three groups and consumed the same high-fat diet for 28 days after addition of either, 20% SBy-P, SF-P or Cas.ResultsThe sardine proteins (SBy-P and SF-P) compared respectively to Cas, reduced diastolic (−14%, −11% P < 0.05) and systolic pressures (−12%, −8% P < 0.05), blood glucose (−24%, −21% P < 0.05), glycated hemoglobin (−28%, −21% P < 0.05), insulinemia (−29%, −18% P < 0.05) and HOMA-IR index (−29%, −18% P < 0.05). They improve the reverse cholesterol transport by increasing the lecithin: cholesterol acyltransferase (LCAT) activity (+43%, +30% P < 0.05) and high-density lipoproteins in cholesterol esters (+108%, +88% P < 0.05), and decreasing the atherogenicity ratios and membrane fluidity (P < 0.05). Furthermore, SBy-P and SF-P induced a reduction of reactive thiobarbituric acid substances concentrations in heart (−45%, −25% P < 0.05), aorta (−62%, −41% P < 0.05), liver (−40%, −21% P < 0.05) and adipose tissue (−50%, −37% P < 0.05) with an improvement in antioxidant capacity.ConclusionSardine proteins, in particular those extracted from by-products, because of their hypotensive, hypoglycemic, anti-atherogenic and antioxidant properties, may have protective effects against the cardiovascular risk associated with obesity.     

High triglyceride-to-HDL cholesterol ratio associated with albuminuria in type 2 diabetic subjects

ObjectiveEmerging evidence indicates that metabolic syndrome (MetS) predisposes diabetic subjects to nephropathy. Aside from hypertension and hyperglycemia, it is unclear which component of MetS also contributes to increased urinary albumin excretion (UAE). We compared the MetS profiles of subjects divided into two groups based on their UAE.MethodsThe Asia Pacific Real-Life Effectiveness and Care Patterns of Diabetes Management (AP RECAP-DM) study is a cross-sectional survey in which type 2 diabetic subjects using oral anti-hyperglycemic drugs were enrolled. We analyzed the data of 162 type 2 diabetic subjects with normotension or taking antihypertensive medications.ResultsThere were 123 subjects with normal UAE (< 30 mg/g) and 39 with abnormal UAE (≥ 30 mg/g). MetS was more prevalent in the abnormal UAE group (79.5%) than in the normal UAE group (58.5%) (P = 0.018). Hypertriglyceridemia (odds ratio = 8.65, P < 0.001) and reduced high-density lipoprotein (HDL) cholesterol (odds ratio = 3.27, P = 0.022) were both independently associated with abnormal UAE. Using 3.4 as a cut-off value, a high triglyceride-to-HDL cholesterol ratio was a useful marker (odds ratio = 15.05, P < 0.001) for abnormal UAE.ConclusionsA high triglyceride-to-HDL cholesterol ratio was found to be an important risk factor for nephropathy in type 2 diabetic subjects.     

Fibrinogen-to-albumin ratio is related to the severity of coronary artery disease in chronic kidney disease patients undergoing coronary angiography

ObjectivesThis study was to explore the potential relationship between the fibrinogen-to-albumin ratio (FAR) and the presence and severity of coronary artery disease (CAD) in stage 3–5 predialysis chronic kidney disease (CKD) patients.DesignThis study included 978 patients undergoing coronary angiography (CAG). CAD was defined as the presence of obstructive stenosis > 50% of the lumen diameter in any of the four main coronary arteries. Gensini scores (GSs), left main coronary artery (LMCA) and three-vessel coronary artery disease (TVD) were used to elevate the severity of CAD.ResultsThe adjusted odds ratios of CAD were 3.059 (95% CI: 1.859–5.032) and 2.670 (95% CI: 1.605–4.441) in the third and fourth quartiles of FAR compared with the first quartile, respectively. Among 759 patients diagnosed with CAD, multivariate logistic regression analysis showed that FAR (at the 0.01 level) was significantly positively associated with the presence of LMCA (adjusted OR = 1.177, 95% CI 1.067–1.299, P = 0.001) or TVD (adjusted OR = 1.154, 95% CI 1.076–1.238, P < 0.001), and a higher GS (adjusted OR = 1.152, 95% CI 1.073–1.238, P < 0.001).ConclusionsFAR levels were independently associated with the presence and severity of CAD in stage 3–5 predialysis CKD patients.     

Factors predicting cardiovascular events in statin-treated diabetic and non-diabetic patients with coronary atherosclerosis

ObjectiveWe aimed at identifying which lipid factors drive vascular risk in statin-treated patients with coronary artery disease (CAD).MethodsWe recorded vascular events over 5.6 years in 491 consecutive statin-treated patients with angiographically proven stable CAD, covering 2750 patient-years.ResultsIn the total population, low high-density lipoprotein (HDL) cholesterol (standardized adjusted HR 0.73 [0.60–0.89]; p = 0.001), low apolipoprotein A1 (0.77 [0.65–0.92]; p = 0.003), a small low-density lipoprotein (LDL) particle diameter (0.76 [0.64–0.91]; p = 0.002), and high triglycerides (1.20 [1.05–1.38]; p = 0.007) predicted vascular events, but not total cholesterol, LDL cholesterol, or apolipoprotein B. Factor analysis in the lipid profiles of our patients revealed an HDL-related factor and an LDL-related factor. Concordant with the results for individual lipid parameters, the HDL-related factor (0.69 [0.58–0.83]; p < 0.001) but not the LDL-related factor (p = 0.455) predicted vascular events. Patients with type 2 diabetes (T2DM; n = 116) were at a higher vascular risk than non-diabetic subjects (38.6% vs. 24.1%; p < 0.001), and like in the total population the HDL-related factor (0.59 [0.44–0.77]; p < 0.001) but not the LDL-related factor (p = 0.591) predicted vascular risk in diabetic patients.ConclusionsThe pattern of low HDL cholesterol, low apolipoprotein A1, small LDL particles, and high triglycerides drives vascular risk in statin-treated coronary patients, particularly in those with T2DM.     

Impact of lifestyle intervention on body weight and the metabolic syndrome in home-care providers

AimThe study evaluated the impact of lifestyle intervention on body weight, metabolic syndrome parameters, nutrition and physical activity in home-care providers (HCPs).MethodsOf 551 screened employees of a nursing agency, 173 were eligible to participate and were assigned to either the intervention (n = 129) or the control (n = 44) group. Participants in the intervention group followed an educational programme that encouraged physical activity and healthy nutrition, and were equipped with bicycles free of charge. Anthropometric, biological and lifestyle parameters were assessed at baseline, and after 6 and 12 months.ResultsBody weight, waist circumference and systolic blood pressure significantly decreased at 12 months in both study groups. Incidence of the metabolic syndrome in the intervention group at 12 months was reduced by 50% (from 17 to 9.2%; P = 0.04). There were also decreases in LDL cholesterol (−0.36 mmol/L; P < 0.01), total cholesterol/HDL cholesterol ratio (−0.57; P < 0.01) and fasting glucose (−0.4 mmol/L; P < 0.05), and an increase in HDL cholesterol (+0.22 mmol/L; P < 0.01) in the intervention group. At 12 months, a decrease in daily caloric intake (−391 kcal/day; P < 0.001) and an increase in the percentage of participants engaging in physical activity (+3.4%; P < 0.05) were also observed in the intervention group.ConclusionLifestyle changes among HCPs are possible with relatively modest behavioural education and within a short period of time. Educational strategies and workshops are effective, efficient and easy to perform, and should be encouraged in HCPs to promote the implementation of lifestyle modifications in their patients.     

FTO gene variant and risk of hypertension: A meta-analysis of 57,464 hypertensive cases and 41,256 controls

ObjectivesRecent studies have suggested that fat mass and obesity-associated gene (FTO) may predispose individuals to develop hypertension. However, the results have been inconsistent. We performed a meta-analysis to investigate the relationship of FTO gene variant with risk of hypertension and influence of body mass index (BMI) on this risk.Materials/methodsA systematic literature search in PubMed, Embase and ISI web of science databases was performed to identify eligible published literatures. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.ResultsA total of seven studies comprising 57,464 hypertensive cases and 41,256 controls met the inclusion criteria and were included in the meta-analysis. The FTO gene variant(s) showed significant association with the risk of hypertension (OR = 1.16, 95% CI = 1.07–1.25, P < 0.001) which disappeared on adjustment for BMI (OR = 1.04, 95% CI = 0.98–1.10, P = 0.162). In addition, stratified analysis demonstrated a significant association of the FTO variant with the risk of hypertension in obese subjects (OR = 1.10, 95% CI = 1.01–1.19, P = 0.032) but not in non-obese individuals (OR = 1.00, 95% CI = 0.97–1.03, P = 0.832). Subgroup analysis based on ethnicity showed significant association between FTO variant and hypertension in both European (OR = 1.07, 95% CI = 1.01–1.14, P = 0.028) and Asian populations (OR = 1.37, 95% CI = 1.23–1.53, P < 0.001). However, the association remained significant only in Asians (OR = 1.17, 95% CI = 1.01–1.35, P = 0.035) but not in the Europeans (OR = 1.02, 95% CI = 0.97–1.07, P = 0.390) on adjustment for BMI.ConclusionsThe present meta-analysis confirms that FTO genotype mediates obesity-related hypertension.     

Pulse pressure strongly predicts cardiovascular disease risk in patients with type 2 diabetes from the Swedish National Diabetes Register (NDR)

ObjectivesTo analyze pulse pressure (PP) as a risk predictor for coronary heart disease (CHD), stroke and cardiovascular disease (CVD; CHD and/or stroke) in type 2 diabetic patients.MethodsA total of 11,128 female and male type 2 diabetic patients with known baseline PP values and no CVD, aged 50–74 years, were followed for a mean duration of 5.6 years (1998–2003). A subgroup of 5521 patients with known mean PP values (mean values at baseline and at the end of the study) was also included.ResultsHazard ratios (HRs) with 95% CI for fatal/nonfatal CHD with baseline or mean PP ≥ 75 mmHg, compared to < 75 mmHg, were 1.23 (1.07–1.40; P = 0.003) and 1.32 (1.07–1.62; P = 0.009), respectively, after adjusting for mean blood pressure (MBP), age, gender, diabetes duration, HbA_1c, body mass index (BMI), lipid-reducing drugs, microalbuminuria > 20 μg/min, antihypertensive drugs and hypoglycaemic treatment, using Cox regression analyses. Fully-adjusted respective HRs for stroke were 1.17 (0.98–1.39) and 1.21 (0.90–1.61) and, for CVD, 1.23 (1.10–1.37; P < 0.001) and 1.28 (1.07–1.52; P = 0.007). Fully-adjusted HRs for baseline PP increased per quartile and, CHD, stroke or CVD, were 1.09 (1.03–1.16; P = 0.004), 1.14 (1.05–1.23; P = 0.002) and 1.11 (1.05–1.17; P < 0.001), respectively. The data suggest that, if a mean PP ≥ 75 mmHg were to be avoided, then 15% and 17% of CHD and or CVD, cases, respectively, in such a cohort might be prevented after multivariable adjustments, with a further 10% of cases avoided if also adjusted for MBP and age. Increasing baseline MBP, age and microalbuminuria were independently and significantly associated (P < 0.001) with increasing baseline or mean PP.ConclusionIncreased PP is a powerful independent risk predictor of CVD in type 2 diabetic patients, and lowering PP can lead to a marked reduction in risk.     

Association of Indoxyl Sulfate With Fibroblast Growth Factor 23 in Patients With Advanced Chronic Kidney Disease

BackgroundProtein-bound uremic toxins–indoxyl sulfate (IS) and p-cresyl sulfate (PCS)–can not only predict clinical outcomes but also may relate to bone-mineral disorders in patients with chronic kidney disease (CKD). However, the relationship between protein-bound uremic toxins and fibroblast growth factor 23 (FGF23) has not been studied before. The objective of this study was to explore the association of IS and PCS with FGF23 in a CKD-based cohort.MethodsThis is a cross-sectional study that enrolled 80 stable CKD stage 3 to 5 patients who met the inclusion criteria in a single medical center. Serum levels of IS, PCS and FGF23 were measured concurrently. General biochemistry and patient background were also investigated.ResultsSerum FGF23 and IS concentrations were elevated commensurately with deteriorating renal function. Pearson's analysis showed that FGF23 levels were significantly associated with blood urea nitrogen (r = 0.381, P < 0.05), creatinine (r = 0.632, P < 0.01), estimated glomerular filtration rate (r = –0.447, P < 0.05), phosphate (r = 0.543, P < 0.01), intact parathyroid hormone (r = 0.543, P < 0.01), IS (r = 0.432, P < 0.01) and PCS (r = 0.318, P < 0.05). After adjusting other confounding factors by stepwise multiple linear regression analysis, only creatinine (β = 0.82, P < 0.01), phosphate (β = 0.28, P = 0.02) and IS (β = 0.39, P = 0.04) retained statistically significant associations with FGF23. Moreover, serum levels of IS were higher in patients with high FGF23 concentration (> 90 pg/mL, median value) than those with lower FGF23 (P < 0.01).ConclusionsResults indicated that only IS but not PCS correlated independently with FGF23 in worsening CKD. IS may be an independent factor involved in regulation of bone-mineral metabolism.     

Altering dietary lysine:arginine ratio has little effect on cardiovascular risk factors and vascular reactivity in moderately hypercholesterolemic adults

BackgroundInformation is scarce regarding the effect of dietary protein type, with specific focus on the lysine-to-arginine (Lys:Arg) ratio, on cardiovascular risk factors and vascular reactivity in humans.ObjectiveDetermine the effect of dietary Lys:Arg ratio on cardiovascular risk factors and vascular reactivity in moderately hypercholesterolemic adults.DesignRandomized cross-over design of two 35-day diet phases; thirty adults (21 females and 9 males, ≥50 years, LDL cholesterol ≥120 mg/dL). Diets had 20% energy (E) protein, 30% E fat, 50% E carbohydrate and were designed to have low (0.7) or high (1.4) Lys:Arg ratio. Measures included fasting and postprandial lipid, lipoprotein, apolipoprotein concentrations; fasting high sensitivity C-reactive protein (hsCRP), small dense LDL (sdLDL) cholesterol, remnant lipoprotein cholesterol (RemLC), glycated albumin, adiponectin and immunoreactive insulin concentrations, endogenous cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyl transferase (LCAT) activities; cholesterol fractional synthesis rate (FSR); and flow mediated dilation (FMD) and peripheral artery tonometry (PAT).ResultsNo differences were observed in fasting and/or postprandial total, LDL, HDL and sdLDL cholesterol, RemLC, Lp(a) or apo B concentrations, LCAT and CETP activities, FSR, glycated albumin, immunoreactive insulin, FMD or PAT. The low, relative to the high, Lys:Arg ratio diet resulted in lower postprandial VLDL cholesterol (?24%, P = 0.001) and triglycerides (?23%, P = 0.001), and small but significant differences in fasting (?3%, P = 0.003) and postprandial (?3%, P = 0.018) apo AI, and fasting adiponectin concentrations (+7%, P = 0.035). Fasting and postprandial hsCRP concentrations were 23% lower after the low Lys:Arg ratio diet (P = 0.020 for both).ConclusionsDiets differing in Lys:Arg ratios had no or small effects on cardiovascular risk factors and vascular reactivity.     

Twenty-one year tracking of serum non-cholesterol sterols. The Cardiovascular Risk in Young Finns study

Background and aimTo show tracking of cholesterol metabolism, the ratios to cholesterol of e.g. serum cholestenol, desmosterol, and lathosterol, reflecting cholesterol synthesis, and cholestanol, campesterol, avenasterol and sitosterol, reflecting cholesterol absorption, were measured 21 years apart.Methods and resultsIn random population samples initially comprising 12- (n = 162), 15- (n = 158), and 18-year-old (n = 148) males participating in the Cardiovascular Risk in Young Finns Study, serum sterols and squalene were measured with gas–liquid chromatography in 1980 and 2001. Quartiles of cholestanol, indicating low to high cholesterol absorption, were defined from the cholestanol values in 1980.Serum cholesterol increased in the oldest age group only, but synthesis markers (except desmosterol) increased in all age groups after the follow-up (e.g. lathosterol, total population +47.3 ± 2.6% (SE), P < 0.001). Campesterol (+69.0 ± 3.0%, P < 0.001) and sitosterol increased, avenasterol was unchanged, and cholestanol decreased (−6.2 ± 0.7%, P < 0.001), respectively. The 1980 synthesis and absorption markers were interrelated with respective values 21 years later in all age groups and quartiles (e.g. lathosterol, total population 1980 vs. 2001 r = 0.460, cholestanol 1980 vs. 2001 r = 0.593, P < 0.001 for both). Synthesis markers were highest in the first and lowest in the fourth quartile both in 1980 and 2001 (e.g. 2001, desmosterol, quartile 1, 99 ± 9, quartile 4, 83 ± 2 μg/mg of cholesterol, P < 0.05).ConclusionsCholesterol metabolism is significantly tracked in adolescent males over the follow-up of 21 years. Thus, high cholesterol synthesis and low absorption characterize subjects with the lowest cholestanol quartile, while those with the highest quartile have low synthesis and high absorption in both adolescence and later in young adult life.     

Effects of pioglitazone on beta-cell function in metabolic syndrome patients with impaired glucose tolerance

ObjectiveTo determine the potential effects of pioglitazone on beta-cell function in metabolic syndrome patients with impaired glucose tolerance and probe into the possible mechanisms.Research design and methodsTwenty-two subjects were treated with pioglitazone 30 mg/day for 4 months. At baseline and after treatment, each subject underwent an IVGTT. The acute insulin response (AIRg), the glucose disappearance rates (coefficients K) and the ratio of Δinsulin/Δglucose (ΔI/ΔG) were calculated according to IVGTT results. Hyperglycemic clamp study was conducted to determine the second-phase insulin response, insulin sensitivity index (ISI) and glucose infusion rate (GIR). Euglycemic–hyperinsulinemic clamp study was made to measure the glucose disposal rate (GDR). Plasma glucose, free fatty acids (FFAs), serum insulin and proinsulin levels were measured.ResultsAIRg unchanged (P = 0.25) after treatment, whereas the values of coefficients K (P < 0.01) and ΔI/ΔG increased (P < 0.05). The second-phase insulin response and GIR were both demonstrated marked increments (P < 0.01 and P < 0.01, respectively). Pioglitazone therapy also resulted in improvement of ISI value (P < 0.05). And the increment of GDR during the euglycemic–hyperinsulinemic clamp was also significant (P < 0.01). Furthermore, a decrease in fasting proinsulin level was observed (P < 0.001). And plasma glucose, FFAs and serum insulin levels all declined. The increase of ΔI₁/ΔG₁ was positively correlated with the improvement of GDR (r = 0.536, P = 0.089). And a positive relationship was observed between the change in the second-phase insulin response and change in K value (r = 0.682, P = 0.021).ConclusionsShort-term pioglitazone therapy improved beta-cell dysfunction, the mechanism might involve the attenuation of insulin resistance.     

Recours à l’automédication chez l’hypertendu noir africain : ses facteurs et ses conséquences

IntroductionSelf-medication practice is under-evaluated among black African hypertensive patients.AimTo assess the level of self-medication among black African hypertensive patients and to determine the factors favoring this practice and their consequences.MethodsProspective study during a 3-month period including 612 hypertensive patients followed in Abidjan cardiology institute.ResultsMean age was 55.1. The patients had a self-medication use in 60.1% of cases. Medicinal plants and derived products were commonly involved. Self-medication use reasons were: influence of relatives (89.8%) and the fear of antihypertensive drugs adverses effects (54.9%). Multivariate analysis shows that factors of self-medication were age (56.6 years vs. 50.3 years, P < 0.001), income less than 762 euros/month (88% vs. 75.4%; OR = 2.73; 95% CI: 1.62–4.6; P < 0,0001), obesity (70.4% vs. 35.6%; OR = 1.24; 95% CI: 0.75–1.15; P = 0.037), dyslipidemia (40.8% vs. 27.9%; OR = 6.72; 95% CI: 0.57–2.13; P = 0.043), antihypertensive association therapy (61.7% vs. 51.4%; OR = 2.27; 95% CI: 0.25–0.97; P = 0.037). Poor control of high blood pressure (HBP) was a consequence of self-medication (6.5% vs. 47.1%; OR = 10.27; 95% CI: 4.65–56.4; P = 0.034), repercussions of HBP on major organ (75% vs. 17.2%; OR = 12.9; 95% CI: 8.5–19.6; P = 0.0001).ConclusionSelf-medication is a common practice in African hypertensive patients. It has many consequences.     

Disección coronaria espontánea en España: un estudio sobre bases administrativas realizado a partir del Conjunto Mínimo Básico de Datos español

Introduction and objectivesSpontaneous coronary artery dissection (SCAD) is a rare cause of acute myocardial infarction (AMI). We sought to compare the results on in-hospital mortality and 30-day readmission rates among patients with AMI-SCAD vs AMI due to other causes (AMI-non-SCAD).MethodsRisk-standardized in-hospital mortality (rIMR) and risk-standardized 30-day readmission ratios (rRAR) were calculated using the minimum dataset of the Spanish National Health System (2016-2019).ResultsA total of 806 episodes of AMI-SCAD were compared with 119 425 episodes of AMI–non-SCAD. Patients with AMI-SCAD were younger and more frequently female than those with AMI–non-SCAD. Crude in-hospital mortality was lower (3% vs 7.6%; P < .001) and rIMR higher (7.6 ± 1.7% vs 7.4 ± 1.7%; P = .019) in AMI-SCAD. However, after propensity score adjustment (806 pairs), the mortality rate was similar in the 2 groups (AdjOR, 1.15; 95%CI, 0.61-2,2; P = .653). Crude 30-day readmission rates were also similar in the 2 groups (4.6% vs 5%, P = .67) whereas rRAR were lower (4.7 ± 1% vs 4.8% ± 1%; P = .015) in patients with AMI-SCAD. Again, after propensity score adjustment (715 pairs) readmission rates were similar in the 2 groups (AdjOR, 1.14; 95%CI, 0.67–1.98; P = .603).ConclusionsIn-hospital mortality and readmission rates are similar in patients with AMI-SCAD and AMI–non-SCAD when adjusted for the differences in baseline characteristics. These findings underscore the need to optimize the management, treatment, and clinical follow-up of patients with SCAD.