Familial Hypercholesterolemia : Do HDL Play a Role?

Cardiovascular disease (CVD) in heterozygous familial hypercholesterolemia (HeFH), the most frequent monogenic disorder of human metabolism, is largely driven by low-density lipoprotein (LDL) cholesterol concentrations. Since the CVD rate differs considerably in this population, beyond the lifetime LDL cholesterol vascular accumulation, other classical risk factors are involved in the high cardiovascular risk of HeFH. Among other lipoprotein disturbances, alterations in the phenotype and functionality of high-density lipoproteins (HDL) have been described in HeFH patients, contributing to the presence and severity of CVD. In fact, HDL are the first defensive barrier against the burden of high LDL cholesterol levels owing to their contribution to reverse cholesterol transport as well as their antioxidant and anti-inflammatory properties, among others. In this context, the present narrative review aimed to focus on quantitative and qualitative abnormalities in HDL particles in HeFH, encompassing metabolic, genetic and epigenetic aspects

Atherogenic Ratios in Patients with Recurrent Acute Coronary Syndrome and Receiving Statin Therapy: Clinical Usefullness as Cardiovascular Predictors

Patients who have already suffered a vascular event require more and better control of cardiovascular risk factors. Different atherogenic indexes such as TC/HDLc, LDLc/HDLc, apoB/apoA-I, LDLc/apoB and non-HDLc/HDLc have been used to follow-up the patients because of their predictive capacity of the lipid profile. The aim of this study was to evaluate atherogenic ratios as a marker of the lipid residual risk in high-risk patients receiving statin therapy and to know the changes produced by previous lipid-lowering drugs treatment for a previous coronary event. The study including patients admitted to coronary care units of six Spanish tertiary hospitals for Acute Coronary Syndrome (ACS). A total of 633 ACS patients were included; of these, 478 (75.8%) had presented a myocardial infarction and 153 (24.2%) angina. A previous ACS had occurred in 43.1% of cases, and was the first episode in 56.9% of the studied patients. Among patients with known ischemic heart disease, 187 (52.2%) were receiving lipid-lowering drugs, mainlystatins (182 patients, 50.7%). Of those with a first ACS, 59 (21.7%) were on lipid-lowering drugs: 55 (20.1%) statins and 4 (1.7%) fibrates. Patients with recurrent ACS had similar triglyceride and HDLc levels, but significantly lower total cholesterol and LDLc concentrations compared with those presenting the first ACS. Patients with recurrent ACS had significantly lower non-HDLc levels, TC/HDLc and LDLc/HDLc, but higher HDLc/TC and HDLc/LDLc ratios compared with first ACS patients. In patients taking statins the lipid residual vascular risk was related with the persistence of cardiovascular risk factors, and related with lipid profile with dyslipemia no-LDL dependent. So, we can conclude that the correction of lipid profile by statin is not per se sufficient to control cardiovascular risk

Cataract Surgery in Elderly Subjects with Heterozygous Familial Hypercholesterolemia in Prolonged Treatment with Statins

Background: Cataracts are the main cause of blindness and represent one fifth of visual problems worldwide. It is still unknown whether prolonged statin treatment favors the development of cataracts. We aimed to ascertain the prevalence of cataract surgery in elderly subjects with genetically diagnosed heterozygous familial hypercholesterolemia (HeFH) receiving statin treatment for ≥5 years, and compare this with controls. Methods: This is an observational, multicenter, case–control study from five lipid clinics in Spain. We collected data with the following inclusion criteria: age ≥65 years, LDL cholesterol levels ≥220 mg/dL without lipid-lowering drugs, a pathogenic mutation in a candidate gene for HeFH (LDLR, APOB, or PCSK9) and statin treatment for ≥5 years. Controls were selected from relatives of HeFH patients without hypercholesterolemia. Linear and logistic regressions based on generalized linear models and generalized estimating equations (GEE) were used. Cataract surgery was used as a proxy for cataract development. Results: We analyzed 205 subjects, 112 HeFH, and 93 controls, with a mean age of 71.8 (6.5) and 70.0 (7.3) years, respectively. HeFH subjects presented no difference in clinical characteristics, including smoking, hypertension, and type 2 diabetes mellitus, compared with controls. The mean duration of lipid-lowering treatment in HeFH was 22.5 (8.7) years. Cataract surgery prevalence was not significantly different between cases and controls. The presence of cataracts was associated neither with LDLc nor with the length of the statin therapy. Conclusion: In the present study, HeFH was not a risk factor for cataract surgery and prolonged statin treatment did not favor it either. These findings suggest that statin treatment is not related with cataracts

Resilient Older Subjects with Heterozygous Familial Hypercholesterolemia, Baseline Differences and Associated Factors

Despite elevated low-density lipoprotein (LDL) cholesterol levels, some older subjects with heterozygous familial hypercholesterolemia (HeFH) do not develop atherosclerotic cardiovascular disease (ACVD) during their lifetime. The factors related to this resilient state have not been fully established. The aim of this study was to evaluate differential characteristics between older HeFH subjects with and without ACVD and factors associated with the presence of ACVD. Subjects were part of the Spanish Atherosclerosis Society Dyslipidemia Registry, and those >= 70 years old and with HeFH were included. Baseline characteristics of these subjects with and without ACVD were compared. A multivariate analysis was performed to assess factors associated with the presence of ACVD. A total of 2148 subjects with HeFH were included. Resilient subjects were mostly female, younger and presented fewer comorbidities with respect to the ACVD group. Subjects without ACVD had higher baseline high-density lipoprotein (HDL) cholesterol (55.8 +/- 17.1 vs. 47.9 +/- 15.4 mg/dL; p = 3 risk factors were associated with the presence of ACVD

Decreased paraoxonase-1 activity is associated with alterations of high-density lipoprotein particles in chronic liver impairment

<p>Abstract</p> <p>Background</p> <p>Paraoxonase-1 (PON1), a lactonase synthesized by the liver, circulates in blood bound to high-density lipoproteins (HDL). This enzyme is thought to degrade oxidized phospholipids and play an important role in the organism's antioxidant and anti-inflammatory system. Chronic liver diseases are characterized by decreased serum PON1 activity. The aim of the present study was to investigate the compositional changes in HDL that could influence PON1 activity in liver impairment.</p> <p>Methods</p> <p>The study was performed in samples from five patients with advanced liver cirrhosis and with preserved renal function, chosen on the basis of having low serum PON1 activity and high serum PON1 concentration. As a control group, we accessed five healthy volunteers from among our hospital staff. Lipid and protein compositional analysis of lipoprotein particles were done by high-performance liquid chromatography, gel electrophoresis, and Western-Blot.</p> <p>Results</p> <p>HDL particles from cirrhotic patients had an increased phospholipid content that was inversely correlated to PON1 activity. The HDL particles contained high levels of PON1 that corresponded, in part, to an immunoreactive protein of high molecular weight (55 kDa) not present in control subjects. This protein was identified as glycosylated PON1 and was also present in biopsies from patients with steatosis and from rats with CCl₄-induced hepatic impairment. These changes were associated with an increased plasma concentration of markers of oxidative stress, inflammation and fibrogenesis.</p> <p>Conclusion</p> <p>Abnormalities in the composition of lipids and proteins of HDL particles, including PON1 glycosylation, are associated with the decrease in serum PON1 activity in patients with liver disease. These alterations may adversely affect the protective role of HDL against oxidative stress and inflammation in these patients.</p

Golpe de calor : Estudio clínico-epidemiológico durante el período 2003-2010

El diagnòstic de cop de calor és clínic: hipertermia, alteració neurològica y exposició ambiental. Es presenten 25 casos de cop de calor. S'identifiquen els següents factors de risc: gènere masculí, hipertensió arterial i/o malaltia psiquiàtrica. A l'analítica destaca disminució del temps de protrombina, elevació de creatinin-quinasa i transaminases. La mortalitat global fou del 36%. Es van identificar com a factors associats a major mortalitat la edat, APACHE II, antecedent de malaltia cardiovascular i el SOFA. Aconseguir una ràpida davallada de la temperatura corporal 37,5ºC va millorar el pronòstic.El diagnóstico de golpe de calor es clínico: hipertermia, alteración neurológica y exposición ambiental. Se presentan 25 casos de golpe de calor. Se identifican como factores de riesgo: ser varón, tener hipertensión arterial y/o enfermedad psiquiátrica. En la analítica destaca disminución del tiempo de protrombina, elevación de creatinin-quinasa y de transaminasas. La mortalidad global fue del 36%. Se identificaron como factores asociados a mayor mortalidad la edad, APACHE II, tener enfermedad cardiovascular y el SOFA. El conseguir un rápido descenso de la temperatura corporal 37,5ºC mejoró el pronóstico

Trends in Prevalence of Diabetes among Twin Pregnancies and Perinatal Outcomes in Catalonia between 2006 and 2015 : the DIAGESTCAT Study

The aims of our study were to evaluate the trends in the prevalence of diabetes among twin pregnancies in Catalonia, Spain between 2006 and 2015, to assess the influence of diabetes on perinatal outcomes of twin gestations and to ascertain the interaction between twin pregnancies and glycaemic status. A population-based study was conducted using the Spanish Minimum Basic Data Set. Cases of gestational diabetes mellitus (GDM) and pre-existing diabetes were identified using ICD-9-CM codes. Data from 743,762 singleton and 15,956 twin deliveries between 2006 and 2015 in Catalonia was analysed. Among twin pregnancies, 1088 (6.82%) were diagnosed with GDM and 83 (0.52%) had pre-existing diabetes. The prevalence of GDM among twin pregnancies increased from 6.01% in 2006 to 8.48% in 2015 (p < 0.001) and the prevalence of pre-existing diabetes remained stable (from 0.46% to 0.27%, p = 0.416). The risk of pre-eclampsia was higher in pre-existing diabetes (15.66%, p = 0.015) and GDM (11.39%, p < 0.001) than in normoglycaemic twin pregnancies (7.55%). Pre-existing diabetes increased the risk of prematurity (69.62% vs. 51.84%, p = 0.002) and large-for-gestational-age (LGA) infants (20.9% vs. 11.6%, p = 0.001) in twin gestations. An attenuating effect on several adverse perinatal outcomes was found between twin pregnancies and the presence of GDM and pre-existing diabetes. As a result, unlike in singleton pregnancies, diabetes did not increase the risk of all perinatal outcomes in twins and the effect of pre-existing diabetes on pre-eclampsia and LGA appeared to be attenuated. In conclusion, prevalence of GDM among twin pregnancies increased over the study period. Diabetes was associated with a higher risk of pre-eclampsia, prematurity and LGA in twin gestations. However, the impact of both, pre-existing diabetes and GDM, on twin pregnancy outcomes was attenuated when compared with its impact on singleton gestations

Toward a new clinical classification of patients with familial hypercholesterolemia: One perspective from Spain

The introduction of singular therapies, such as proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), to lower high cholesterol levels requires better classification of patients eligible for intensive lipid lowering therapy. According to the European Medicines Administration, PCSK9i are recommended in primary prevention in familial hypercholesterolemia (FH) patients. Therefore, an FH diagnosis is not simply an academic issue, because it has many clinical implications. The bases of a diagnosis of FH are not entirely clear. The availability of genetic testing, including large genome-wide association analyses and whole genome studies, has shown that some patients with a clinical diagnosis of definite FH have no mutations in the genes associated with the disease. This fact does not exclude the very high cardiovascular risk of these patients, and an early and intensive lipid lowering therapy is recommended in all FH patients. Because an FH diagnosis is a cornerstone for decisions about therapies, a precise definition of FH is urgently required. This is an expert consensus document from the Spanish Atherosclerosis Society. We propose the following classification: familial hypercholesterolemia syndrome integrated by (1) heterozygous familial hypercholesterolemia: patients with clinically definite FH and a functional mutation in one allele of the LDLR, ApoB:100, and PCSK9 genes; (2) homozygous familial hypercholesterolemia: mutations affect both alleles; (3) polygenic familial hypercholesterolemia: patients with clinically definite FH but no mutations associated with FH are found (to be distinguished from non-familial, multifactorial hypercholesterolemia); (4) familial hypercholesterolemia combined with hypertriglyceridemia: a subgroup of familial combined hyperlipidaemia patients fulfilling clinically definite FH with associated hypertriglyceridemia

Nutrients and Dietary Approaches in Patients with Type 2 Diabetes Mellitus and Cardiovascular Disease: A Narrative Review

Cardiovascular disease (CVD) is the most common cause of morbidity and mortality in developed countries. The prevalence of CVD is much higher in patients with type 2 diabetes mellitus (T2DM), who may benefit from lifestyle changes, which include adapted diets. In this review, we provide the role of different groups of nutrients in patients with T2DM and CVD, as well as dietary approaches that have been associated with better and worse outcomes in those patients. Many different diets and supplements have proved to be beneficial in T2DM and CVD, but further studies, guidelines, and dietary recommendations are particularly required for patients with both diseases