Stratification in Heterozygous Familial Hypercholesterolemia: Imaging, Biomarkers, and Genetic Testing.

PURPOSE OF REVIEW: Heterozygous familial hypercholesterolemia (HeFH) is the most common monogenic autosomal dominant disorder. However, the condition is often underdiagnosed and undertreated. The objective of this review is to provide an update on the risk stratification in patients with HeFH, incorporating new cardiovascular imaging techniques, various biomarkers, and genetic studies. RECENT FINDINGS: The diagnosis of HeFH places patients in a high cardiovascular risk category due to the increased incidence of premature atherosclerotic cardiovascular disease. However, the level of risk varies significantly among different individuals with HeFH. Achieving an optimal stratification of cardiovascular risk is crucial for establishing appropriate and accurate treatment and management strategies. Different new tools such as risk scores have emerged in recent years, aiding physicians in assessing the risk stratification for HeFH using imaging, biomarkers, and genetics. This review emphasizes that not all patients with HeFH face the same cardiovascular risk. By utilizing different assessment tools, we can identify those who require more intensive monitoring, follow-up, and treatment.

Epicardial Adipose Tissue Ceramides Are Related to Lipoprotein Lipase Activity in Coronary Artery Disease: Unfolding a Missing Link.

BACKGROUND: Epicardial adipose tissue (EAT) contributes to coronary artery disease (CAD). EAT presents a specific lipidomic signature, showing increased ceramides and other proinflammatory lipids content. Besides, LPL (lipoprotein lipase) activity in EAT would contribute to its expansion, supplying fatty acids to the tissue. Our aim was to evaluate the relations between LPL activity, regulators of LPL, and ceramides in EAT from CAD patients. METHODS: We studied patients undergoing coronary bypass graft (CAD, n=25) and patients without CAD (no CAD, n=14). EAT and subcutaneous AT (SAT) were obtained, tissue LPL activity and its regulator's expression (ANGPTL4, GPIHBP1 [glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1], and PPARγ [peroxisomal proliferator-activated receptor γ]) were assessed. Tissue lipidomes were evaluated by UHPLC-MS, in positive and negative ionization modes. RESULTS: LPL activity was higher in EAT from CAD (P<0.001), and in EAT than SAT in both groups (P<0.001). ANGPTL4 levels were lower, GPIHBP1 and PPARγ levels were higher in EAT from CAD (P<0.001). In both groups, EAT exhibited more ceramide (P=0.01), directly associated with LPL activity, being the strongest association with Cer18:1/24:1 (P<0.001). EAT Cer18:1/16:0 to Cer18:1/24:0 and Cer18:1/24:1 to 18:1/24:0 ratios were higher in CAD (P=0.03; P<0.001, respectively), the latter directly associated with LPL activity (r=0.63, P<0.001) GPIHBP1 levels (r=0.68, P<0.001), and inversely to EAT ANGPTL4 expression (r=-0.49, P=0.03). Pairwise partial correlation network showed associations among bioactive lipids and LPL and its regulators (P<0.001 in all cases). CONCLUSIONS: The association between LPL activity, total ceramide, and the atherogenic ceramide ratios highlights the importance of the enzyme and these bioactive lipids contributing to the different metabolic profile of EAT in CAD.

Untargeted Lipidomics Reveals a Specific Enrichment in Plasmalogens in Epicardial Adipose Tissue and a Specific Signature in Coronary Artery Disease.

OBJECTIVE: Epicardial adipose tissue (EAT) is an active endocrine organ that could contribute to the pathophysiology of coronary artery disease (CAD) through the paracrine release of proatherogenic mediators. Numerous works have analyzed the inflammatory signature of EAT, but scarce informations on its lipidome are available. Our objective was first to study the differences between EAT and subcutaneous adipose tissue (SAT) lipidomes and second to identify the specific untargeted lipidomic signatures of EAT and SAT in CAD. Approach and Results: Subcutaneous and EAT untargeted lipidomic analysis was performed in 25 patients with CAD and 14 patients without CAD and compared with paired plasma lipidomic analysis of isolated VLDL (very low-density lipoprotein) and HDL (high-density lipoprotein). Lipidomics was performed on a C18 column hyphenated to a Q-Exactive plus mass spectrometer, using both positive and negative ionization mode. EAT and SAT had independent lipidomic profile, with 95 lipid species differentially expressed and phosphatidylethanolamine 18:1p/22:6 twenty-fold more expressed in EAT compared with SAT false discovery rate =3×10-4). Patients with CAD exhibited more ceramides (P=0.01), diglycerides (P=0.004; saturated and nonsaturated), monoglycerides (P=0.013) in their EAT than patients without CAD. Conversely, they had lesser unsaturated TG (triglycerides; P=0.02). No difference was observed in the 295 lipid species found in SAT between patients with and without CAD. Fifty-one lipid species were found in common between EAT and plasma lipoproteins. TG 18:0/18:0/18:1 was found positively correlated (r=0.45, P=0.019) in EAT and HDL and in EAT and VLDL (r=0.46, P=0.02). CONCLUSIONS: CAD is associated with specific lipidomic signature of EAT, unlike SAT. Plasma lipoprotein lipidome only partially reflected EAT lipidome.

Phenotypical, Clinical, and Molecular Aspects of Adults and Children With Homozygous Familial Hypercholesterolemia in Iberoamerica.

OBJECTIVE: Characterize homozygous familial hypercholesterolemia (HoFH) individuals from Iberoamerica. Approach and Results: In a cross-sectional retrospective evaluation 134 individuals with a HoFH phenotype, 71 adults (age 39.3±15.8 years, 38.0% males), and 63 children (age 8.8±4.0 years, 50.8% males) were studied. Genetic characterization was available in 129 (96%). The majority (91%) were true homozygotes (true HoFH, n=79, 43.0% children, 46.8% males) or compound heterozygotes (compound heterozygous familial hypercholesterolemia, n=39, 51.3% children, 46.2% males) with putative pathogenic variants in the LDLR. True HoFH due to LDLR variants had higher total (P=0.015) and LDL (low-density lipoprotein)-cholesterol (P=0.008) compared with compound heterozygous familial hypercholesterolemia. Children with true HoFH (n=34) tended to be diagnosed earlier (P=0.051) and had a greater frequency of xanthomas (P=0.016) than those with compound heterozygous familial hypercholesterolemia (n=20). Previous major cardiovascular events were present in 25 (48%) of 52 children (missing information in 2 cases), and in 43 (67%) of 64 adults with LDLR variants. Children who are true HoFH had higher frequency of major cardiovascular events (P=0.02), coronary heart (P=0.013), and aortic/supra-aortic valve diseases (P=0.022) than compound heterozygous familial hypercholesterolemia. In adults, no differences were observed in major cardiovascular events according to type of LDLR variant. From 118 subjects with LDLR variants, 76 (64%) had 2 likely pathogenic or pathogenic variants. In 89 subjects with 2 LDLR variants, those with at least one null allele were younger (P=0.003) and had a greater frequency of major cardiovascular events (P=0.038) occurring at an earlier age (P=0.001). CONCLUSIONS: There was a high frequency of cardiovascular disease even in children. Phenotype and cardiovascular complications were heterogeneous and associated with the type of molecular defect.

Role of SN1 lipases on plasma lipids in metabolic syndrome and obesity.

OBJECTIVE: To assess the phospholipase activity of endothelial (EL) and hepatic lipase (HL) in postheparin plasma of subjects with metabolic syndrome (MS)/obesity and their relationship with atherogenic and antiatherogenic lipoproteins. Additionally, to evaluate lipoprotein lipase (LPL) and HL activity as triglyceride (TG)-hydrolyses to complete the analyses of SN1 lipolytic enzymes in the same patient. APPROACH AND RESULTS: Plasma EL, HL, and LPL activities were evaluated in 59 patients with MS and 36 controls. A trend toward higher EL activity was observed in MS. EL activity was increased in obese compared with normal weight group (P=0.009) and was negatively associated with high-density lipoprotein-cholesterol (P=0.014 and P=0.005) and apolipoprotein A-I (P=0.045 and P=0.001) in control and MS group, respectively. HL activity, as TG-hydrolase, was increased in MS (P=0.025) as well as in obese group (P=0.017); directly correlated with low-density lipoprotein-cholesterol (P=0.005) and apolipoprotein B (P=0.003) and negatively with high-density lipoprotein-cholesterol (P=0.021) in control group. LPL was decreased in MS (P<0.001) as well as in overweight and obese compared with normal weight group (P=0.015 and P=0.004, respectively); inversely correlated %TG-very low-density lipoproteins (P=0.04) and TG/apolipoprotein B index (P=0.013) in control group. These associations were not found in MS. CONCLUSIONS: We describe for the first time EL and HL activity as phospholipases in MS/obesity, being both responsible for high-density lipoprotein catabolism. Our results elucidate part of the remaining controversies about SN1 lipases activity in MS and different grades of obesity. The impact of insulin resistance on the activity of the 3 enzymes determines the lipoprotein alterations observed in these states.

Monounsaturated fatty acids-rich diets in hypercholesterolemic-growing rats.

The effects of replacing dietary saturated fat by different monounsaturated fatty acid (ω-9MUFA) sources on serum lipids, body fat and bone in growing hypercholesterolemic rats were studied. Rats received one of the six different diets: AIN-93G (control, C); extra virgin olive oil (OO) + C; high-oleic sunflower oil (HOSO) + C or atherogenic diet (AT) for 8 weeks; the remaining two groups received AT for 3 weeks and then, the saturated fat was replaced by an oil mixture of soybean oil added with OO or HOSO for 5 weeks. Rats consuming MUFA-rich diets showed the highest body fat, hepatic index and epididymal, intestinal and perirenal fat, and triglycerides. T-chol and non-HDL-chol were increased in HOSO rats but decreased in OO rats. Bone mineral content and density were higher in both OO and HOSO groups than in AT rats. This study casts caution to the generalization of the benefits of MUFA for the treatment of hypercholesterolemia.

Adiponectin predicts MMP-2 activity independently of obesity.

BACKGROUND: Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9, have been identified in atherosclerotic plaques and have been directly associated with plaque remodelling and vulnerability. Cardiovascular disease (CVD) is related to insulin resistance (IR) and obesity, characterized by changes in plasma levels of inflammatory markers, such as adiponectin and C-reactive protein (CRP). Our aim was to evaluate the impact of both proteins on MMP-2 and MMP-9 behaviour in individuals with IR. MATERIALS AND METHODS: Plasma MMP-2 and MMP-9 activity, adiponectin and hs-CRP concentration and lipoprotein profile were determined in 52 patients with metabolic syndrome (MS) and 27 controls. RESULTS: Patients with MS presented significantly higher MMP-2 activity than controls: 0·95 ± 0·12 vs. 0·77 ± 0·15 relative units (RU) (P < 0·001), while MMP-9 activity was not detectable. MMP-2 activity decreased across quartiles of adiponectin, being significantly reduced in individuals with the highest levels of adiponectin in compared with the lowest levels (0·75 ± 0·17 vs. 0·93 ± 0·09 RU, P < 0·005). This difference persisted significant after adjusting by obesity markers. MMP-2 activity was significantly increased in individuals with the highest levels (G3) compared with those with the lowest levels (G1) of hs-CRP (0·94 ± 0·12 vs. 0·86 ± 0·12, P = 0·041) CONCLUSION: In this study, we observed that adiponectin levels predicted MMP-2 plasma activity independently of obesity. This finding suggests that the inflammatory process, associated with the highest CVD risk, would be involved in MMPs vascular production.

Role of HDL in neutralizing the VLDL effect on endothelial dysfunction.

OBJECTIVE: It has been reported that LDL inhibits endothelium-dependent relaxation (EDR) and that HDL can neutralize this effect. However, the atherogenic properties of VLDL have been so far difficult to demonstrate. Studies on VLDL are controversial, and nothing is known about the role of HDL on potential VLDL vascular actions. We examined the effect of human VLDLs on EDR, and the role of HDL in this system. METHODS: VLDL (n=14) and LDL (n=6) were isolated from volunteer subjects. Normal HDL was obtained from one healthy donor. VLDL ability to inhibit ACh-induced vasorelaxation (10(-9)-10(-5)mM) on aortic rings previously precontracted by noradrenaline (10(-8)mM) was measured in the presence and absence of HDL. RESULTS: ACh-induced maximal relaxation (R%) was mildly, but not significantly attenuated in the presence of VLDL (72±7%), while LDL caused a significant inhibition (60±10%, p<0.05) when compared to incubation in the absence of lipoproteins. VLDLs were subdivided into 2 groups depending on their cholesterol/triglyceride ratio: 0.18-0.22 (n=8) was considered typical and 0.10-0.15, rich in triglycerides (VLDLRT, n=6). Typical VLDL had no effect on EDR (p=0.38), however R% from VLDLRT was lower (54±7%, p<0.01) similar to the one obtained with LDL (p=0.32). HDL showed favorable effects on EDR inhibition induced by the presence of VLDLRT (p<0.05.). CONCLUSION: Although typical VLDL did not cause endothelial dysfunction, triglyceride-enriched VLDL had inhibitory effect on EDR. It is proposed that alterations in VLDL composition would increase its atherogenic capacity. Moreover HDL appears to protect endothelium from VLDL action.

Relationship between cortisol, life events and metabolic syndrome in men.

Psychological factors and stressful life events (LE) are considered to play a role in the onset of the metabolic syndrome (MS). We tested the association between LE and cortisol, a marker of chronic stress, with the risk of developing MS and their interaction. From a total number of 2906 men who completed a screening for the early detection of prostate cancer, 149 healthy men (mean ± SD age, 58.6 ± 7.7 years) were included in this study. Participants were assessed by the Holmes and Rahe questionnaire about their experience of LE during the previous 1-5 years. MS was diagnosed according to National Cholesterol Education Program-Adult Treatment Panel III (ATP-III) and International Diabetes Federation (IDF) criteria. Serum cortisol was measured at 08:00-09:00 h. Participants with MS (IDF criteria) reported significantly more past LE (p = 0.009) and greater summed weight of LE (p = 0.049) than those without MS. Furthermore, LE interacted with cortisol in relation to MS: in men with increased serum cortisol levels ( ≥ 13.7 µg/dl), number of LE significantly predicted MS-status (relative risk (RR) = 1.16, p = 0.03), whereas in men with low cortisol, LE were unrelated to MS (p = 0.52). We conclude that LE were significantly more prevalent in men with the MS than without the MS, according to IDF criteria, independent of the effects of age and body mass index, especially in men with increased serum cortisol levels.

Endothelial lipase activity predicts high-density lipoprotein catabolism in hemodialysis: novel phospholipase assay in postheparin human plasma.

OBJECTIVE: A novel phospholipase assay was used to measure for the first time the behavior of endothelial and hepatic phospholipase activities in postheparin human plasma of hemodialyzed patients and its relationship with atherogenic and antiatherogenic lipoprotein levels. METHODS AND RESULTS: Endothelial and hepatic phospholipase activity was assessed in a total SN1-specific phospholipase assay, using (1-decanoylthio-1-deoxy-2-decanoyl-sn-glycero-3-phosphoryl) ethylene glycol as the substrate. Hemodialyzed patients presented lower values of total and hepatic phospholipase activity than controls: 4.4 (1.9-9.0) versus 7.5 (3.6-18.0) and 2.6 (0.7-6.2) versus 6.6 (1.3-15.2) µmol of fatty acid released per milliliter of postheparin plasma per hour, respectively (P<0.001); however, endothelial lipase (EL) phospholipase activity was increased in patients: 1.7 (0.8-3.0) versus 1.1 (0.1-2.7) µmol of fatty acid released per milliliter of postheparin plasma per hour (P=0.008). EL was negatively associated with high-density lipoprotein (HDL)-cholesterol (r=-0.427; P=0.001), and apolipoprotein A-I levels, total phospholipase, and hepatic lipase activity were directly associated with low-density lipoprotein-cholesterol and apolipoprotein B. The association of EL and HDL-cholesterol remained significant when adjusting for waist circumference (ß=-0.26; P=0.05), and the effect of hepatic lipase on low-density lipoprotein-cholesterol continued after adjusting for age (ß=0.46; P= 0.001). CONCLUSIONS: Our results support the hypothesis that EL is the predominant enzyme responsible for lipolytic catabolism of HDLs in hemodialyzed patients and resolve the apparent paradox observed between low hepatic lipase activity and decreased HDL-cholesterol levels observed in these patients. In addition, the ability to assess total hepatic lipase and EL phospholipase activity in plasma will increase our knowledge of the mechanisms involved in controlling HDL levels and cardiovascular risk in hemodialyzed patients, as well as other populations with low levels of HDL-cholesterol.

Effect of dietary calcium (Ca) on body composition and Ca metabolism during growth in genetically obese (ß) male rats.

INTRODUCTION: Obese ß rats may be a suitable model to evaluate the association between calcium intake (CaI) and obesity during growth. OBJECTIVE: The present study comparatively evaluated Ca absorption and retention, and changes in body composition in spontaneously genetically obese (ß) male rats fed three different dietary Ca levels: high 0.9% (HCa); normal: 0.5% (NCa); low: 0.2% (LCa). METHODS: Pregnant rats were fed isocaloric diets which varied in Ca content only. Male pups continued feeding the same maternal diet until postnatal day 60. The percentage of Apparent Ca absorption (CaA %), Ca balance (CaB), body composition, glucose, triglycerides (TGL), and insulin levels were evaluated. RESULTS: Food consumption and body weight (BW) were higher in Group LCa than in Groups NCa and HCa (p < 0.01); no differences were observed between the latter two groups. Group LCa presented the highest body fat, liver weight, perigonadal and retroperitoneal fat (p < 0.05); conversely, body ashes and total skeleton bone mineral content were significantly lower compared with animals in both the NCa (p < 0.01) and HCa groups (p < 0.01). CaB (mg/day) reached a plateau at the highest CaI (mg/day) value (r = 0.985, p < 0.001). CaA%, serum glucose, insulin, and TGL levels rose as CaI decreased (p < 0.01). CONCLUSIONS: Although further studies are required, low Ca consumption in this strain of rats could modulate BW inducing changes in several lipid metabolism parameters, which in turn lead to an increase in body fat.

APOE -491 T allele may reduce the risk of atherosclerotic lesions among middle-aged women.

Genetic variability of the APOE gene confers susceptibility to coronary artery disease (CAD). Beyond variability on the coding region, polymorphisms in the regulatory region of the APOE gene have been associated with variation on plasma cholesterol levels. It has also been demonstrated a complex and multifactorial association between, APOE gene polymorphisms, gender, plasma lipids levels and risk of CAD. In the present case-control study, we examined polymorphisms -427 T/C and -491 A/T in the promoter region of APOE in relation to lipid profile and the coronary atherosclerosis, in a sample of Argentinean adults with (cases) and without (controls) atherosclerotic injuries regarding gender and age. In females below 60 years APOE -491 T allele was less prevalent in cases than in controls (OR 0.12, 95% CI 0.04-0.76). Among females cases the T allele was more frequent with increasing age (OR 0.49, 95% CI 0.27-0.90). Female up to 45 years who were carriers of the T allele showed lower levels of total (P = 0.01) and LDL cholesterol (P = 0.02) compared with non-carriers. Levels of total and LDL cholesterol increased with the age only in female carriers (P < 0.01 and P < 0.01). No differences were observed for HDL and TG levels. Allele C of polymorphism APOE -427 was associated with higher levels of triglycerides (P < 0.01). We conclude that, in middle-aged women, APOE -491 T allele contributes keeping lower levels of LDL cholesterol in the population studied, and would have a putative protective effect for the development of CAD.

Elevated Lipoprotein(a) prevalence and association with family history of premature cardiovascular disease in general population with moderate cardiovascular risk and increased LDL cholesterol.

Background: Elevated Lipoprotein(a) [Lp(a)] is independently associated with increased cardiovascular disease (CVD) risk. There are discrepancies regarding its epidemiology due to great variability in different populations. This study aimed to evaluate the prevalence of elevated Lp(a) in people with moderate CVD risk and increased LDL-c and to determine the association between family history of premature CVD and elevated Lp(a). Methods: Random subjects from the CESCAS population-based study of people with moderate CVD risk (Framingham score 10-20 %) and LDL-c ≥ 130 mg/dL, were selected to evaluate Lp(a) by immunoturbidimetry independent of the Isoforms variability. The association between family history of premature CVD and elevated Lp(a) was evaluated using multivariate logistic regression models. Elevated Lp(a) was defined as Lp(a) ​​≥ 125 nmol/L. Results: Lp(a) was evaluated in 484 samples; men = 39.5 %, median age = 57 years (Q1-Q3: 50-63), mean CVD risk = 14.4 % (SE: 0.2), family history of premature CVD = 11.2 %, Lp(a) median of 21 nmol/L (Q1-Q3: 9-42 nmol/L), high Lp(a) = 6.1 % (95 % CI = 3.8-9.6). Association between family history of premature CVD and elevated Lp(a) in total population: OR 1.31 (95 % CI = 0.4, 4.2) p = 0.642; in subgroup of people with LDL-c ≥ 160 mg%, OR 4.24 (95 % CI = 1.2, 15.1) p = 0.026. Conclusions: In general population with moderate CVD risk and elevated LDL-c from the Southern Cone of Latin America, less than one over ten people had elevated Lp(a). Family history of premature CVD was significantly associated with the presence of elevated Lp(a) in people with LDL-c ≥ 160 mg/dL.

Remnant cholesterol levels are associated with severity and death in COVID-19 patients.

Coronavirus disease-19 (COVID-19) patients with severe complications present comorbidities like cardiovascular-disease, hypertension and type-2 diabetes mellitus (DM), sharing metabolic alterations like insulin resistance (IR) and dyslipidemia. Our objective was to evaluate the association among different components of the lipid-lipoprotein profile, such as remnant lipoprotein (RLP)-cholesterol, in patients with COVID-19, and to analyze their associations with the severity of the disease and death. We studied 193 patients (68 (29-96) years; 49.7% male) hospitalized for COVID-19 and 200 controls (46 (18-79) years; 52.5% male). Lipoprotein profile, glucose and procalcitonin were assessed. Patients presented higher glucose, TG, TG/HDL-cholesterol and RLP-cholesterol levels, but lower total, LDL, HDL and no-HDL-cholesterol levels (p < 0.001). When a binary logistic regression was performed, age, non-HDL-cholesterol, and RLP-cholesterol were associated with death (p = 0.005). As the COVID-19 condition worsened, according to procalcitonin tertiles, a decrease in all the cholesterol fractions (p < 0.03) was observed with no differences in TG, while levels of RLP-cholesterol and TG/HDL-cholesterol increased (p < 0.001). Lower levels of all the cholesterol fractions were related with the presence and severity of COVID-19, except for RLP-cholesterol levels and TG/HDL-cholesterol index. These alterations indicate a lipid metabolic disorder, characteristic of IR states in COVID-19 patients. RLP-cholesterol levels predicted severity and death in these patients.

Cardiometabolic risk factors as apolipoprotein B, triglyceride/HDL-cholesterol ratio and C-reactive protein, in adolescents with and without obesity: cross-sectional study in middle class suburban children.

BACKGROUND: The prevalence of obesity (OB), overweight (OW), and metabolic syndrome (MS) has increased worldwide. That imposes a substantial risk for type 2 diabetes and premature cardiovascular disease. However, to date no unified criteria exist to asses risk or outcomes in children and adolescents. OBJECTIVES: To establish the presence of OB/OW and MS and risk factors for cardiovascular disease in adolescents. DESIGN AND SUBJECTS: Male (n = 514) and female (n = 429) adolescents from high school were studied (11-14 yr). Weight, height, body mass index (BMI), waist circumference (WC), and blood pressure were determined in all subjects. Glucose, lipoprotein profile, apolipoprotein B (apoB), and high-sensitivity C-reactive protein (hs-CRP) levels were measured. Triglyceride/high-density lipoprotein-cholesterol (TG/HDL-cholesterol) ratio was calculated. RESULTS: The frequency of OB/OW and MS were 22.2 and 3.7%, respectively. In comparison to healthy adolescents, TG/HDL-cholesterol ratio was increased in OB/OW (2.9 ± 2.5 vs. 1.6 ± 1.0) and MS groups (4.0 ± 2.5 vs. 1.6 ± 0.9), p < 0.001. OB/OW adolescents presented higher values of hs-CRP in comparison to non-obese, median (range): 1.9 (0.1-9.4) vs. 1.4 (0.1-9.9), mg/L, p < 0.001. ApoB (mean ± SD) was 71 ± 21 mg/dL in MS group and 59 ± 17 mg/dL in those without MS (p < 0.001). TG/HDL-cholesterol ratio positively correlated with BMI (r = 0.18, p < 0.001), WC (r = 0.24, p < 0.001), and apoB (r = 0.24, p < 0.001); hs-CRP correlated with WC (r = 0.14, p < 0.001) and BMI (r = 0.17, p < 0.001). CONCLUSIONS: Even when the frequency of OB, OW, and MS in adolescents was low, those subjects presented an atherogenic lipoprotein. These findings emphasize the importance to evaluate cardiovascular risk factors in adolescents to assess strategies to prevent future disease.

Use and persistence of lipid-lowering therapy in patients with severe hypercholesterolemia: A prospective study. / Estudio prospectivo sobre uso y persistencia de tratamiento hipolipidemiante en pacientes con hipercolesterolemia severa.

INTRODUCTION: Statins are the first line of treatment in patients with severe hypercholesterolemia (SH). However, despite the knowledge regarding its effectiveness and security for preventing cardiovascular diseases, treatment is a major challenge. MATERIAL AND METHODS: A prospective observational study was conducted by telephone survey to determine cardiovascular risk factors, annual monitoring, statins use and persistence and new-onset cardiovascular events (CVE) after 5 years in patients with SH including in a program for detection of familial hypercholesterolemia. RESULTS: 115 participants were analysed, the median age was 56 ±10 being 74% females. 63.4% of women and 43% of men had been correctly controlled in the last year. Patients on lipid lowering drugs stratified by sex was 38.8% in women and 26.7% in men, however, only 22 participants (31.8%) were persistence with statins since 2015.Overall, 48% of the patients presented a CVE and 3.4% died. Multivariate analysis did not reveal predictors for CVE. CONCLUSIONS: In our population with SH we found a high risk to present a CVE and a dramatic low use and persistence with the treatment.

Role of matrix metalloproteinase-2 in the cardioprotective effect of ischaemic postconditioning.

The activation of matrix metalloproteinases (MMPs) contributes to myocardial injury at the onset of reperfusion; however, their role in ischaemic postconditioning is unknown. The aim of the present study was to examine the effects of ischaemic postconditioning on MMP activity in isolated rabbit hearts. The isolated rabbit hearts were subjected to 30 min of global ischaemia followed by 180 min of reperfusion (I/R group; n = 8). In the ischaemic postconditioning group (n = 8), a postconditioning protocol was performed (2 cycles of 30 s reperfusion-ischaemia). In other experiments, we added doxycycline, an MMP inhibitor, at 25 (n = 7) or 50 micromol l(1) (n = 8) during the first 2 min of reperfusion. Coronary effluent and left ventricular tissue were collected during pre-ischaemic conditions and at different times during the reperfusion period to measure MMP-2 activity and cardiac protein nitration. We evaluated ventricular function and infarct size. In the I/R group, infarct size was 32.1 +/- 5.2%; Postcon reduced infarct size to 9.5 +/- 3.8% (P < 0.05) and inhibited MMP-2 activity during reperfusion. The administration of doxycycline at 50 micromol l(1) inhibited MMP-2 activity and cardiac protein nitration and reduced the infarct size to 9.7 +/- 2.8% (P < 0.05). A lower dose of doxycycline (25 micromol l(1)) failed to inhibit MMP-2 activity and did not modify the infarct size. Our results strongly suggest that ischaemic postconditioning may exert part of its cardioprotective effects through the inhibition of MMP-2 activity.

Exposure to zinc deficiency in fetal and postnatal life determines nitric oxide system activity and arterial blood pressure levels in adult rats.

We had previously shown that prenatal exposure to Zn-deficient diets induces an increase in blood pressure and impairs renal function in adult rats. The aim of the present study was to investigate if moderate Zn restriction during early growth periods, fetal life and lactation would induce impairment in the vascular and renal NO system and alterations in plasma lipid profile. We also investigated if these effects persisted into adult life, even when a Zn-replete diet was provided after weaning. Pregnant rats were fed control (30 parts per million (ppm)) or low (8 ppm) Zn diets throughout gestation up to weaning. Afterwards, male offspring from low-Zn mothers were assigned to low- or control-Zn diets during 60 d. Male offspring from control mothers were fed a control diet. Animals exposed to Zn restriction showed low birth weight, increased systolic blood pressure and serum TAG levels, and decreased glomerular filtration rate in adulthood. Zn restriction induced a decrease in vascular and renal NO synthase activity and a reduced expression of the endothelial NO synthase isoform in aorta. A control-Zn diet during post-weaning growth returned TAG levels to normal but was unsuccessful in normalising systolic blood pressure, glomerular filtration rate or NO system activity in Zn-deficient offspring. Zn restriction during fetal life, lactation and/or post-weaning growth induced alterations in the vascular and renal NO system and in lipid metabolism that could contribute to the programming of hypertension and renal dysfunction in adulthood.

Lipoproteins, sex hormones and inflammatory markers in association with prostate cancer.

OBJECTIVE: To evaluate lipoprotein profile and sex hormones in patients with prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and their possible associations with some inflammatory markers linked to PCa. METHODS: A total of 150 men (50-65 years), matched by age and body mass index (BMI), included in this study and divided into three groups according to total prostate specific antigen (PSA), digital rectal examination and prostate biopsy: 50 PCa, 50 BPH and 50 controls. Total cholesterol (Chol), HDL-chol, LDL-chol, triglycerides (TG), total testosterone (T), free T (FT), bioavailable T (BioT), estradiol and SHBG were measured. The free androgen index (FAI) and TG/HDL-chol were calculated. In 25 PCa and 25 controls, C-reactive protein (hs-CRP), adiponectin and insulin were determined. RESULTS: Patients with PCa showed higher TG/HDL-chol and diminished HDL-chol than Controls and BPH. PSA correlated inversely with HDL-chol and directly with TG/HDL-chol. FAI, FT, BioT and estradiol levels were higher, and SHBG and adiponectin were lower in PCa than in Controls. No differences were found in androgens between BPH and PCa. CONCLUSION: Our most novel findings are that the patients with PCa presented lower total Chol and HDL-chol and higher TG/HDL-chol than BPH and Controls. Patients with PCa showed higher androgens and lower adiponectin than Controls.

[Relation between paraoxonase activity, other HDL components and inflammatory state in hemodialyzed patients]. / Relación entre paraoxonasa, otros componentes de HDL y estado inflamatorio en hemodiálisis.

Advanced Chronic Renal Disease (CKD) is closely associated with a pro-inflammatory condition, with an increase in triglyceride-rich lipoproteins and decrease in HDL level. HDL contains antioxidant enzymes such as paraoxonase (PON), whose activity is diminished in CKD. The aim of our study was to evaluate the relationship between PON activity with HDL cholesterol, apo A1 and hs-CRP levels, which are known to be inflammatory markers in hemodialyzed patients. Forty-two patients were studied; age, median (range) = 50 (25-67) years old, gender M/F = 22/20, duration of hemodialysis = 4.4 ± 0.5 years, BMI: 23 ± 0.5 kg/m2. After a 12 h fast, a blood sample was obtained and classic components of lipid profile were determined, as well as apoproteins A1 and B, PON by means of its arylsterase activity and hs-CRP levels. On the basis of the latter, patients were divided into two groups: hs-CRP ≤ 1 (low risk, range: 0.1 to 1.0 mg/l) and > 1 mg/l (moderate and high risk, 1.1 to 10.7 mg/l). No difference was found in triglycerides, LDL cholesterol and apo B in the groups. Patients with hs-CRP > 1 showed lower HDL cholesterol (40 ± 2 mg/dl) and apo A1 (118 ± 4 mg/dl) than patients with hs-CRP ≤ 1 (50 ± 4 and 133 ± 5, respectively); p < 0.05. PON was lower in hs-CRP > 1 = 90.5 ± 24.0 µmol/ml.min than in hs-CRP ≤ 1 = 105.2 ± 18.0. Consequently, inverse correlations were obtained between apo A1 and hs-CRP, r = -0.381, p = 0.013 and between PON and hs-CRP, r = -0.32, p = 0.042. Furthermore, increase in hs-CRP correlated positively with BMI r = 0.318, p = 0.042. Since apo A1 has an anti-inflammatory role and PON an antioxidant activity, the decrease in HDL and its components, cholesterol, apo A1 and PON, in subjects with higher chronic inflammatory condition might explain, in part, the increased cardiovascular risk in these patients.