ABSTRACT
AIM: We aimed to describe clinical and genetic characteristics, lipid-lowering treatment and atherosclerotic cardiovascular disease (ASCVD) outcomes over a long-term follow-up in homozygous familial hypercholesterolemia (HoFH). METHODS: SAFEHEART (Spanish Familial Hypercholesterolaemia Cohort Study) is a long-term study in molecularly diagnosed FH. Data analyzed in HoFH were prospectively obtained from 2004 until 2022. ASCVD events, lipid profile and lipid-lowering treatment were determined. RESULTS: Thirty-nine HoFH patients were analyzed. The mean age was 42 ± 20 years and nineteen (49%) were women. Median follow-up was 11 years (IQR 6,18). Median age at genetic diagnosis was 24 years (IQR 8,42). At enrolment, 33% had ASCVD and 18% had aortic valve disease. Patients with new ASCVD events and aortic valve disease at follow-up were six (15%), and one (3%), respectively. Median untreated LDL-C levels were 555 mg/dL (IQ 413,800), and median LDL-C levels at last follow-up was 122 mg/dL (IQR 91,172). Most patients (92%) were on high intensity statins and ezetimibe, 28% with PCSK9i, 26% with lomitapide, and 23% with lipoprotein-apheresis. Fourteen patients (36%) attained an LDL-C level below 100 mg/dL, and 10% attained an LDL-C below 70 mg/dL in secondary prevention. Patients with null/null variants were youngers, had higher untreated LDL-C and had the first ASCVD event earlier. Free-event survival is longer in patients with defective variant compared with those patients with at least one null variant (p=0.02). CONCLUSIONS: HoFH is a severe life threating disease with a high genetic and phenotypic variability. The improvement in lipid-lowering treatment and LDL-C levels have contributed to reduce ASCVD events.
Subject(s)
Anticholesteremic Agents , Cholesterol, LDL , Homozygote , Hyperlipoproteinemia Type II , Humans , Hyperlipoproteinemia Type II/genetics , Hyperlipoproteinemia Type II/drug therapy , Hyperlipoproteinemia Type II/blood , Hyperlipoproteinemia Type II/complications , Female , Male , Adult , Follow-Up Studies , Middle Aged , Cholesterol, LDL/blood , Treatment Outcome , Anticholesteremic Agents/therapeutic use , Prospective Studies , Young Adult , Spain/epidemiology , Time Factors , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Biomarkers/blood , Phenotype , Proprotein Convertase 9/genetics , Proprotein Convertase 9/metabolism , Ezetimibe/therapeutic useABSTRACT
AIMS: Most heterozygous familial hypercholesterolaemia (FH) patients require intensive lipid-lowering therapy (LLT) including PCSK9 inhibitors (PCSK9is) to reach current low-density lipoprotein cholesterol (LDL-C) goals. Persistence with chronic treatment is important to reduce the burden of atherosclerotic cardiovascular disease. We analysed persistence, efficacy, and impact on quality of life (QoL) of PCSK9i in FH patients in clinical practice setting. METHODS AND RESULTS: Spanish Familial Hypercholesterolaemia Cohort Study (SAFEHEART) is an open, prospective study in genetically defined FH patients in Spain. Patients ≥18 years of age (n = 696, 46% females) on stable LLT treated with PCSK9i were analysed. Median LDL-C at starting PCSK9i was 145 mg/dL [interquartile range (IQR), 123-177], 3.8 mmol/L (IQR 3.2-4.6). After a median follow up of 3.7 years (IQR 2.3-4.8), 27 patients (4%) discontinued PCSK9i treatment: 5 temporarily (0.7%) and 22 permanently (3.2%). Persistence with PCSK9i was 96.1% in the whole period. Median LDL-C levels and % LDL-C reduction attained after 1 year of treatment and in the last follow-up visit were 63 mg/dL (IQR 43-88), 1.6 mmol/L (IQR 1.1-2.23); 61 mg/dL (IQR 44-82), 1.6 mmol/L (IQR 1.1-2.1); 57.6% (IQR 39.5-69); and 58% (IQR 44-68), respectively. 2016 and 2019 ESC/EAS LDL-C goals were attained by 77 and 48% of patients, respectively, at the last follow-up visit (P < 0.001). Mean QoL score increased slightly in the first year and remained stable. CONCLUSION: Long-term persistence with PCSK9i in FH patients is very high, with a good QoL. Effectiveness in LDL-C reduction and LDL-C goal achievement dramatically improved with PCSK9i in this high-risk population in clinical practice setting. TRIAL REGISTRATION: ClinicalTrials.gov number NCT02693548.
Subject(s)
Anticholesteremic Agents , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Hyperlipoproteinemia Type II , Female , Humans , Male , PCSK9 Inhibitors , Cholesterol, LDL , Anticholesteremic Agents/therapeutic use , Proprotein Convertase 9 , Quality of Life , Cohort Studies , Prospective Studies , Hyperlipoproteinemia Type II/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic useABSTRACT
Due to the COVID-19 pandemic and the consequent restrictions, universities have had to adapt their curricula substantially to new schemes in which remote learning is of the essence. In this study, we assess the feasibility of developing a mobile app supplementary to the distant teaching paradigm for the "Cardiology" module of the "General Pathology" subject in undergraduate Medical Education, and we evaluate its impact and acceptability. A cohort of volunteer second-year medical students (n = 44) had access to the app, and their opinions on its utility (1−10) were collected. Additionally, the students were invited to refer their expected satisfaction (1−10) with a blended learning methodology overlapping this new tool with the traditional resources. The average expected satisfaction had been compared to the average satisfaction obtained by just the traditional methodology in other modules from the same subject. Through a qualitative approach, we defined the strengths and weaknesses of the tool. Seventy-seven percent of the participants rated at 8/10 or more the potential learning value of the application and, if used as a supplement to traditional teaching, it would also statistically improve the satisfaction of students (6.52 vs. 8.70, p < 0.001). Similarly, the qualitative data corroborated the benefits of such innovation. Multidisciplinary collaborations are encouraged to develop teaching innovations, although further research should aim to better define the effectiveness of learning with these resources.
Subject(s)
COVID-19 , Mobile Applications , Students, Medical , COVID-19/epidemiology , Feasibility Studies , Humans , Pandemics/prevention & control , Pilot Projects , SARS-CoV-2ABSTRACT
AIMS: Knowledge of the features of patients with familial hypercholesterolaemia (FH) who are protected from atherosclerotic cardiovascular disease (ASCVD) is important for the clinical and prognostic care of this apparently high-risk condition. Our aim was to investigate the determinant and characteristics of patients with FH who are protected from ASCVD and have normal life expectancy, so-called 'resilient' FH (R-FH). METHODS AND RESULTS: Spanish Familial Hypercholesterolaemia cohort study (SAFEHEART) is an open, multicentre, nation-wide, long-term prospective cohort study in genetically defined patients with heterozygous FH in Spain. Patients in the registry who at the time of analysis were at least 65 years or those who would have reached that age had they not died from an ASCVD event were analysed as a case-control study. Resilient FH was defined as the presence of a pathogenic mutation causative of FH in a patient aged ≥65 years without clinical ASCVD. Nine hundred and thirty registrants with FH met the study criteria. A defective low-density lipoprotein (LDL)-receptor mutation, higher plasma level of high-density lipoprotein cholesterol (HDL-C), younger age, female gender, absence of hypertension, and lower plasma lipoprotein (a) [Lp(a)] concentration were independently predictive of R-FH. In a second model, higher levels of HDL-C and lower 10-year score in SAFEHEART-RE were also independently predictive of R-FH. CONCLUSION: Resilient FH may be typified as being female and having a defective LDL-receptor mutation, higher levels of plasma HDL-C, lower levels of Lp(a), and an absence of hypertension. The implications of this type of FH for clinical practice guidelines and the value for service design and optional care of FH remains to be established. TRIAL REGISTRATION: ClinicalTrials.gov number NCT02693548.
Subject(s)
Atherosclerosis , Hyperlipoproteinemia Type II , Hypertension , Case-Control Studies , Cohort Studies , Female , Follow-Up Studies , Humans , Hyperlipoproteinemia Type II/diagnosis , Hyperlipoproteinemia Type II/genetics , Hyperlipoproteinemia Type II/therapy , Lipoprotein(a) , Male , Prospective StudiesABSTRACT
Non-alcoholic fatty liver disease (NAFLD) is the primary cause of chronic liver disease. The range is extensive, including hepatocellular carcinoma, cirrhosis, fibrosis, fatty liver, and non-alcoholic steatohepatitis (NASH). NASH is a condition related to obesity, overweight, metabolic syndrome, diabetes, and dyslipidemia. It is a dynamic condition that can regress to isolated steatosis or progress to fibrosis and cirrhosis. Statins exert anti-inflammatory, proapoptotic, and antifibrotic effects. It has been proposed that these drugs could have a relevant role in NASH. In this review, we provide an overview of current evidence, from mechanisms of statins involved in the modulation of NASH to human trials about the use of statins to treat or attenuate NASH.
ABSTRACT
BACKGROUND: PCSK9 inhibitors are a treatment option for patients with familial hypercholesterolemia not on low-density lipoprotein cholesterol goals despite the use of maximally tolerated high intensity-statins dose. OBJECTIVE: To evaluate the efficacy of alirocumab and evolocumab in LDL-C reduction and targets attainment in patients with heterozygous familial hypercholesterolemia in clinical practice setting. METHODS: SAFEHEART is an open, long-term prospective study of a cohort of subjects with molecular diagnosis of familial hypercholesterolemia. This study analyze subjects ≥ 20 years of age on stable lipid-lowering therapy, who received PCSK9 inhibitors during the period 2016 to January 2020. RESULTS: 433 patients (mean age 55 years, 53% male, 39% with cardiovascular disease) were included and followed-up for a median of 2.5 years (IQR 1.6-3.0). Median LDL-C level prior to PCSK9 inhibitors was 145 mg/dL (IQR 125-173). The addition of PCSK9 inhibitors (211 alirocumab, 222 evolocumab) reduced LDL-C by 58% (IQR 41-70) p<0.001, in men and women, achieving a median LDL-C level of 62 mg/dL (IQR 44-87) without differences between both PCSK9 inhibitors. Out of them 67% with and 80% without cardiovascular disease reached 2016 ESC/EAS LDL-C targets, and 46% very high risk and 50% high risk patients achieved 2019 ESC/EAS LDL-C goals. Independent predictor factors for attainment of 2019 ESC/EAS LDL-C goals were to be male, smoking and the use of statins with ezetimibe. Both inhibitors were well tolerated. CONCLUSIONS: PCSK9 inhibitors on top of maximum lipid-lowering treatment significantly reduced LDL-C levels in patients with familial hypercholesterolemia and improved the achievement of LDL-C targets.
Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Hyperlipoproteinemia Type II/blood , Hyperlipoproteinemia Type II/drug therapy , PCSK9 Inhibitors/administration & dosage , Aged , Cholesterol, LDL/antagonists & inhibitors , Cholesterol, LDL/blood , Cohort Studies , Female , Follow-Up Studies , Humans , Hyperlipoproteinemia Type II/diagnosis , Injections, Subcutaneous , Male , Middle Aged , Prospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: The impact of statins on COVID-19 outcomes is important given the high prevalence of their use among individuals at risk for severe COVID-19. Our aim is to assess whether patients receiving chronic statin treatment who are hospitalized with COVID-19 have reduced in-hospital mortality if statin therapy is maintained during hospitalization. METHODS: This work is a cross-sectional, observational, retrospective multicenter study that analyzed 2921 patients who required hospital admission at 150 Spanish centers included in the nationwide SEMI-COVID-19 Network. We compared the clinical characteristics and COVID-19 disease outcomes between patients receiving chronic statin therapy who maintained this therapy during hospitalization versus those who did not. Propensity score matching was used to match each statin user whose therapy was maintained during hospitalization to a statin user whose therapy was withdrawn during hospitalization. RESULTS: After propensity score matching, continuation of statin therapy was associated with lower all-cause mortality (OR 0.67, 0.54-0.83, p < 0.001); lower incidence of acute kidney injury (AKI) (OR 0.76,0.6-0.97, p = 0.025), acute respiratory distress syndrome (ARDS) (OR 0.78, 0.69- 0.89, p < 0.001), and sepsis (4.82% vs 9.85%, p = 0.008); and less need for invasive mechanical ventilation (IMV) (5.35% vs 8.57, p < 0.001) compared to patients whose statin therapy was withdrawn during hospitalization. CONCLUSIONS: Patients previously treated with statins who are hospitalized for COVID-19 and maintain statin therapy during hospitalization have a lower mortality rate than those in whom therapy is withdrawn. In addition, statin therapy was associated with a decreased probability that patients with COVID-19 will develop AKI, ARDS, or sepsis and decreases the need for IMV.
Subject(s)
COVID-19/complications , COVID-19/epidemiology , Hospital Mortality/trends , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Aged , Aged, 80 and over , COVID-19/mortality , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Propensity Score , Retrospective Studies , Risk Assessment , SARS-CoV-2 , Spain/epidemiologyABSTRACT
BACKGROUND: Limited evidence exists on the role of glucose-lowering drugs in patients with COVID-19. Our main objective was to examine the association between in-hospital death and each routine at-home glucose-lowering drug both individually and in combination with metformin in patients with type 2 diabetes mellitus admitted for COVID-19. We also evaluated their association with the composite outcome of the need for ICU admission, invasive and non-invasive mechanical ventilation, or in-hospital death as well as on the development of in-hospital complications and a long-time hospital stay. METHODS: We selected all patients with type 2 diabetes mellitus in the Spanish Society of Internal Medicine's registry of COVID-19 patients (SEMI-COVID-19 Registry). It is an ongoing, observational, multicenter, nationwide cohort of patients admitted for COVID-19 in Spain from March 1, 2020. Each glucose-lowering drug user was matched with a user of other glucose-lowering drugs in a 1:1 manner by propensity scores. In order to assess the adequacy of propensity score matching, we used the standardized mean difference found in patient characteristics after matching. There was considered to be a significant imbalance in the group if a standardized mean difference > 10% was found. To evaluate the association between treatment and study outcomes, both conditional logit and mixed effect logistic regressions were used when the sample size was ≥ 100. RESULTS: A total of 2666 patients were found in the SEMI-COVID-19 Registry, 1297 on glucose-lowering drugs in monotherapy and 465 in combination with metformin. After propensity matching, 249 patients on metformin, 105 on dipeptidyl peptidase-4 inhibitors, 129 on insulin, 127 on metformin/dipeptidyl peptidase-4 inhibitors, 34 on metformin/sodium-glucose cotransporter 2 inhibitor, and 67 on metformin/insulin were selected. No at-home glucose-lowering drugs showed a significant association with in-hospital death; the composite outcome of the need of intensive care unit admission, mechanical ventilation, or in-hospital death; in-hospital complications; or long-time hospital stays. CONCLUSIONS: In patients with type 2 diabetes mellitus admitted for COVID-19, at-home glucose-lowering drugs showed no significant association with mortality and adverse outcomes. Given the close relationship between diabetes and COVID-19 and the limited evidence on the role of glucose-lowering drugs, prospective studies are needed.
Subject(s)
Coronavirus Infections/mortality , Diabetes Mellitus, Type 2/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Hypoglycemic Agents/standards , Insulin/therapeutic use , Metformin/therapeutic use , Pneumonia, Viral/mortality , Respiration, Artificial/statistics & numerical data , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Aged , Aged, 80 and over , Betacoronavirus , COVID-19 , Cohort Studies , Coronavirus Infections/complications , Coronavirus Infections/therapy , Diabetes Mellitus, Type 2/complications , Drug Therapy, Combination , Female , Hospital Mortality , Hospitalization , Humans , Hypoglycemic Agents/therapeutic use , Intensive Care Units , Length of Stay/statistics & numerical data , Logistic Models , Male , Noninvasive Ventilation/statistics & numerical data , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/therapy , Prospective Studies , SARS-CoV-2 , SpainABSTRACT
Worldwide health policies are trying to implement physical activity on prescription (PAP) at healthcare settings. However, there is not a proper methodology to analyze PHC organizational staff factors. This study aims to validate two questionnaires to assess the self-perception of nurses and general practitioners to implement PAP at primary healthcare (PHC) settings. The designed choice-modeling Google-form questionnaire was sent to 11 expert nurses and 11 expert sports medicine physicians. Experts evaluated each question on a 1-5 points Likert-type scale according to their expertise. Aiken's V coefficient values ≥0.75 were used to validate separately each question using the Visual Basic-6.0 software. A total of 10 sports medicine physicians and 10 nurses with 28.4 ± 5.1 y and 16.3 ± 11.8 y of PAP experience, respectively, validated the questionnaire. One expert in each group was not considered for offering 3 ± SD answers in ≥2 questions respect to the mean of the rest of experts. Final Aiken's V coefficient values were 0.89 (0.77-1.00) for the nurses' questionnaire and 0.84 (0.77-0.95) for the physicians' one. The questionnaires designed to assess the PAP self-perception of PHC nurses and physicians were validated. This methodology could be used to analyze PHC organizational staff factors in order to achieve an efficient PAP implementation in other PHC contexts.
Subject(s)
Exercise , Prescriptions , Primary Health Care , Attitude of Health Personnel , Feasibility Studies , Humans , Surveys and QuestionnairesABSTRACT
OBJECTIVE: Healthy lifestyle habits are the cornerstone in the management of familial hypercholesterolaemia (FH). Nevertheless, dietary studies on FH-affected populations are scarce. The present study analyses dietary habits, adherence to a Mediterranean diet pattern and physical activity in an adult population with FH and compares them with their non-affected relatives. DESIGN: Cross-sectional study. SETTING: Data came from SAFEHEART, a nationwide study in Spain.ParticipantsIndividuals (n 3714) aged ≥18 years with a genetic diagnosis of FH (n2736) and their non-affected relatives (n 978). Food consumption was evaluated using a validated FFQ. RESULTS: Total energy intake was lower in FH patients v. non-affected relatives (P<0·005). Percentage of energy from fats was also lower in the FH population (35 % in men, 36 % in women) v. those non-affected (38 % in both sexes, P<0·005), due to the lower consumption of saturated fats (12·1 % in FH patients, 13·2 % in non-affected, P<0·005). Consumption of sugars was lower in FH patients v. non-affected relatives (P<0·05). Consumption of vegetables, fish and skimmed milk was higher in the FH population (P<0·005). Patients with FH showed greater adherence to a Mediterranean diet pattern v. non-affected relatives (P<0·005). Active smoking was lower and moderate physical activity was higher in people with FH, especially women (P<0·005). CONCLUSIONS: Adult patients with FH report healthier lifestyles than their non-affected family members. They eat a healthier diet, perform more physical activity and smoke less. However, this patient group's consumption of saturated fats and sugars still exceeds guidelines.
Subject(s)
Diet, Mediterranean/psychology , Family/psychology , Feeding Behavior/psychology , Healthy Lifestyle , Hyperlipoproteinemia Type II/psychology , Adult , Cross-Sectional Studies , Diet Surveys , Exercise/psychology , Female , Humans , Hyperlipoproteinemia Type II/therapy , Male , Middle Aged , Patient Compliance/psychology , Patient Compliance/statistics & numerical dataABSTRACT
The purpose of this study was to compare the predictive ability of waist-to-height ratio (WHtR) compared with other anthropometric indicators in the incidence of metabolic syndrome (MetS) and to propose cutoff values for its early detection in nursing practice. A longitudinal cohort study was conducted on a sample of 630 workers (137 exposed and 493 nonexposed), free of MetS at baseline. WHtR was compared with body mass index (BMI), waist circumference (WC), and the percentage of body fat (BF%). In the Cox regression, the adjusted values of hazard ratio (HR) were 5.4 (confidence interval [CI] = [3.1, 9.5]) for WHtR and 7.4 (CI = [3.7, 14.9]) for components of MetS. WHtR obtained the largest area under the curve 0.82 (CI = [0.76, 0.88]), and with a cutoff value of 0.54, values were obtained for sensitivity (70%) and specificity (77%). WHtR was the best predictor of incidence of MetS, with a cutoff value of 0.54. Nursing can improve the early detection of MetS by measuring WHtR.
Subject(s)
Mass Screening , Metabolic Syndrome/epidemiology , Waist-Height Ratio , Adult , Body Mass Index , Female , Humans , Incidence , Longitudinal Studies , Male , Metabolic Syndrome/diagnosis , Occupational Health , Retrospective Studies , Waist CircumferenceABSTRACT
OBJECTIVES: A non-invasive method for the early detection of metabolic syndrome (NIM-MetS) using only waist-to-height ratio (WHtR) and blood pressure (BP) has recently been published, with fixed cut-off values for gender and age. The aim of this study was to validate this method in a large sample of Spanish workers. DESIGN: A diagnostic test accuracy to assess the validity of the method was performed. SETTING: Occupational health services. PARTICIPANTS: The studies were conducted in 2012-2016 on a sample of 60 799 workers from the Balearic Islands (Spain). INTERVENTIONS: The NCEP-ATP III criteria were used as the gold standard. NIM-MetS has been devised using classification trees (the χ2 automatic interaction detection method). MAIN OUTCOME MEASURES: Anthropometric and biochemical variables to diagnose MetS. Sensitivity, specificity, validity index and Youden Index were determined to analyse the accuracy of the diagnostic test (NIM-MetS). RESULTS: With regard to the validation of the method, sensitivity was 54.7%, specificity 94.9% and the Validity Index 91.2%. The cut-off value for WHtR was 0.54, ranging from 0.51 (lower age group) to 0.56 (higher age group). Variables more closely associated with MetS were WHtR (area under the curve (AUC)=0.85; 95% CI 0.84 to 0.86) and systolic BP (AUC=0.79; 95% CI 0.78 to 0.80)). The final cut-off values for the non-invasive method were WHtR ≥0.56 and BP ≥128/80 mm Hg, which includes four levels of MetS risk (very low, low, moderate and high). CONCLUSIONS: The analysed method has shown a high validity index (higher than 91%) for the early detection of MetS. It is a non-invasive method that is easy to apply and interpret in any healthcare setting. This method provides a scale of MetS risk which allows more accurate detection and more effective intervention.
Subject(s)
Anthropometry , Early Diagnosis , Metabolic Syndrome/diagnosis , Adult , Age Factors , Aged , Body Mass Index , Cross-Sectional Studies , Female , Humans , Logistic Models , Male , Middle Aged , Occupational Health Services , ROC Curve , Sensitivity and Specificity , Sex Factors , Spain , Waist Circumference , Waist-Hip Ratio , Young AdultABSTRACT
BACKGROUND: Although risk factors for atherosclerotic cardiovascular disease (ASCVD) in familial hypercholesterolemia (FH) have been described, models for predicting incident ASCVD have not been reported. Our aim was to use the SAFEHEART registry (Spanish Familial Hypercholesterolemia Cohort Study) to define key risk factors for predicting incident ASCVD in patients with FH. METHODS: SAFEHEART is a multicenter, nationwide, long-term prospective cohort study of a molecularly defined population with FH with or without previous ASCVD. Analyses to define risk factors and to build a risk prediction equation were developed, and the risk prediction equation was tested for its ability to discriminate patients who experience incident ASCVD from those who did not over time. RESULTS: We recruited 2404 adult patients with FH who were followed up for a mean of 5.5 years (SD, 3.2 years), during which 12 (0.5%) and 122 (5.1%) suffered fatal and nonfatal incident ASCVD, respectively. Age, male sex, history of previous ASCVD, high blood pressure, increased body mass index, active smoking, and low-density lipoprotein cholesterol and lipoprotein(a) levels were independent predictors of incident ASCVD from which a risk equation with a Harrell C index of 0.85 was derived. The bootstrap resampling (100 randomized samples) of the original set for internal validation showed a degree of overoptimism of 0.003. Individual risk was estimated for each person without an established diagnosis of ASCVD before enrollment in the registry by use of the SAFEHEART risk equation, the modified Framingham risk equation, and the American College of Cardiology/American Heart Association ASCVD Pooled Cohort Risk Equations. The Harrell C index for these models was 0.81, 0.78, and 0.8, respectively, and differences between the SAFEHEART risk equation and the other 2 were significant (P=0.023 and P=0.045). CONCLUSIONS: The risk of incident ASCVD may be estimated in patients with FH with simple clinical predictors. This finding may improve risk stratification and could be used to guide therapy in patients with FH. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT02693548.
Subject(s)
Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Hyperlipoproteinemia Type II/diagnosis , Hyperlipoproteinemia Type II/epidemiology , Registries , Adult , Cohort Studies , Female , Humans , Longitudinal Studies , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Risk Factors , Spain/epidemiologyABSTRACT
BACKGROUND AND AIMS: We aimed to assess whether elevated PCSK9 and lipoprotein (a) [Lp(a)] levels associate with coronary artery calcification (CAC), a good marker of atherosclerosis burden, in asymptomatic familial hypercholesterolemia. METHODS: We selected 161 molecularly defined FH patients treated with stable doses of statins for more than a year. CAC was measured using the Agatston method and quantified as categorical variable. Fasting plasma samples were collected and analyzed for lipids and lipoproteins. PCSK9 was measured by ELISA, Lp(a) and apolipoprotein (a) concentrations by inmunoturbidimetry and LC-MS/MS, respectively. RESULTS: Circulating PCSK9 levels were significantly reduced in patients without CAC (n = 63), compared to those with CAC (n = 99). Patients with the highest CAC scores (above 100) had the highest levels of circulating PCSK9 and Lp(a). In multivariable regression analyses, the main predictors for a positive CAC score was age and sex followed by circulating PCSK9 and Lp(a) levels. CONCLUSIONS: In statin treated asymptomatic FH patients, elevated PCSK9 and Lp(a) levels are independently associated with the presence and severity of CAC, a good predictor of coronary artery disease.
Subject(s)
Calcinosis/blood , Coronary Vessels/pathology , Hyperlipoproteinemia Type II/blood , Lipoprotein(a)/blood , Proprotein Convertase 9/blood , Adult , Aged , Calcium/blood , Coronary Artery Disease/blood , Coronary Artery Disease/genetics , Coronary Vessels/metabolism , Enzyme-Linked Immunosorbent Assay , Female , Humans , Hyperlipoproteinemia Type II/genetics , Male , Middle Aged , Multivariate Analysis , Mutation , Phenotype , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder associated with very high levels of cholesterol, accelerated atherosclerosis and very premature death, often secondary to occlusion of the coronary ostia by supravalvular atheroma in untreated individuals. OBJECTIVE: To describe molecular and clinical characteristics of HoFH enrolled at SAFEHEART registry and to evaluate the role of the type of mutation in clinical expression. METHODS: SAFEHEART is a registry of molecularly defined familial hypercholesterolemia patients. A standardized phone call is made every year for the follow-up. Patients with confirmed HoFH were selected. Molecular and clinical characteristics were analyzed. RESULTS: Thirty-four HoFH patients (27 true HoFH, 4 compound heterozygous familial hypercholesterolemia, and 3 autosomal recessive hypercholesterolemia) have been enrolled in the period 2004-2015. Twenty different mutations in LDLR gene have been detected. Sixteen patients carry defective mutations (DMs), and 15 carry null mutations (NMs). Only patients with NMs met low-density lipoprotein cholesterol (LDL-C) criteria for clinical diagnosis. Patients with NMs had higher untreated LDL-C levels (P < .0001), more aortic valve stenosis (P < .05), and lower age at first cardiovascular event (P < .05) compared to patients with DMs. In the follow-up, 1 liver transplant patient died and 3 cases underwent revascularization procedures. Eight cases started LDL apheresis and 1 case had a liver transplant. CONCLUSIONS: HoFH phenotypic expression is highly variable. These patients have high atherosclerotic coronary artery disease risk including aortic valve stenosis and do not achieve the LDL-C treatment goals with standard therapy.
Subject(s)
Hyperlipoproteinemia Type II/epidemiology , Hyperlipoproteinemia Type II/genetics , Registries/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Cohort Studies , Female , Follow-Up Studies , Humans , Hyperlipoproteinemia Type II/blood , Hyperlipoproteinemia Type II/drug therapy , Hypolipidemic Agents/pharmacology , Hypolipidemic Agents/therapeutic use , Infant , Lipids/blood , Male , Middle Aged , Mutation , Phenotype , Receptors, LDL/genetics , Spain/epidemiology , Young AdultABSTRACT
[This corrects the article DOI: 10.1371/journal.pone.0153096.].
ABSTRACT
BACKGROUND: Recent data suggest that the presence of associated metabolic abnormalities may be important modifiers of the association of obesity with a poorer prognosis in coronary heart disease. We determined the influence of isolated overweight and obesity on carotid intima media thickness (IMT-CC), and also assessed whether this influence was determined by the presence of metabolic abnormalities. METHODS: 1002 participants from the CordioPrev study were studied at entry. We determined their metabolic phenotypes and performed carotid ultrasound assessment. We evaluated the influence of obesity, overweight and metabolic phenotypes on the IMT-CC. RESULTS: Metabolically sick participants (defined by the presence of two or more metabolic abnormalities) showed a greater IMT-CC than metabolically healthy individuals (p = 4 * 10(-6)). Overweight and normal weight patients who were metabolically healthy showed a lower IMT-CC than the metabolically abnormal groups (all p<0.05). When we evaluated only body weight (without considering metabolic phenotypes), overweight or obese patients did not differ significantly from normal-weight patients in their IMT-CC (p = 0.077). However, obesity was a determinant of IMT-CC when compared to the composite group of normal weight and overweight patients (all not obese). CONCLUSIONS: In coronary patients, a metabolically abnormal phenotype is associated with a greater IMT-CC, and may be linked to a higher risk of suffering new cardiovascular events. The protection conferred in the IMT-CC by the absence of metabolic abnormality may be blunted by the presence of obesity. TRIAL REGISTRATION: ClinicalTrials.gov NCT00924937.
Subject(s)
Carotid Artery Diseases/etiology , Coronary Artery Disease/complications , Metabolic Diseases/physiopathology , Obesity/physiopathology , Overweight/physiopathology , Adult , Aged , Body Mass Index , Body Weight , Carotid Intima-Media Thickness , Female , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Risk Factors , Young AdultABSTRACT
BACKGROUND: We propose a new method for the early detection of metabolic syndrome in the working population, which was free of biomarkers (non-invasive) and based on anthropometric variables, and to validate it in a new working population. METHODS: Prevalence studies and diagnostic test accuracy to determine the anthropometric variables associated with metabolic syndrome, as well as the screening validity of the new method proposed, were carried out between 2013 and 2015 on 636 and 550 workers, respectively. The anthropometric variables analysed were: blood pressure, body mass index, waist circumference, waist-height ratio, body fat percentage and waist-hip ratio. We performed a multivariate logistic regression analysis and obtained receiver operating curves to determine the predictive ability of the variables. The new method for the early detection of metabolic syndrome we present is based on a decision tree using chi-squared automatic interaction detection methodology. RESULTS: The overall prevalence of metabolic syndrome was 14.9%. The area under the curve for waist-height ratio and waist circumference was 0.91 and 0.90, respectively. The anthropometric variables associated with metabolic syndrome in the adjusted model were waist-height ratio, body mass index, blood pressure and body fat percentage. The decision tree was configured from the waist-height ratio (⩾0.55) and hypertension (blood pressure ⩾128/85 mmHg), with a sensitivity of 91.6% and a specificity of 95.7% obtained. CONCLUSIONS: The early detection of metabolic syndrome in a healthy population is possible through non-invasive methods, based on anthropometric indicators such as waist-height ratio and blood pressure. This method has a high degree of predictive validity and its use can be recommended in any healthcare context.
Subject(s)
Anthropometry , Metabolic Syndrome/diagnosis , Body Mass Index , Cross-Sectional Studies , Humans , Waist Circumference , Waist-Hip RatioABSTRACT
Introducción y objetivos: Estimar el coste-efectividad de rosuvastatina frente a simvastatina, atorvastatina y pitavastatina en España, de acuerdo con las guías europeas de tratamiento de las dislipidemias, en pacientes con alto y muy alto riesgo cardiovascular. Métodos: Modelo de Markov de coste-efectividad a largo plazo de rosuvastatina versus simvastatina, atorvastatina y pitavastatina, en pacientes de alto y muy alto riesgo cardiovascular definido por 5 factores (sexo, edad, hábito tabáquico, nivel de colesterol inicial, presión arterial sistólica) según el sistema SCORE. La ratio coste-efectividad incremental se expresa en euros por año de vida ajustado por calidad y se calcula desde la perspectiva del Sistema Nacional de Salud. Resultados: Los resultados indican que rosuvastatina se asocia a un beneficio mayor que las otras estatinas en todos los perfiles considerados. Rosuvastatina es más coste-efectiva con respecto a simvastatina en pacientes con riesgo SCORE ≥ 8% en mujeres y ≥ 6% en hombres, mientras que entre 5% y los valores indicados su coste-efectividad depende del nivel basal de c-LDL del paciente. Rosuvastatina resulta más coste-efectiva frente a atorvastatina a partir de un riesgo SCORE de 11% en mujeres y 10% en hombres. Rosuvastatina resulta dominante frente a pitavastatina, tanto en mujeres como en hombres con riesgo alto y muy alto en el sistema SCORE. Conclusiones: Rosuvastatina es una terapia coste-efectiva en el tratamiento de la hipercolesterolemia, frente a simvastatina, atorvastatina y pitavastatina, especialmente en determinados perfiles de pacientes con factores de riesgo cardiovascular alto y muy alto según el sistema SCORE en España
Introduction and objectives: To estimate the cost-effectiveness of rosuvastatin versus simvastatin, atorvastatin and pitavastatin in Spain, according to the European guidelines for the treatment of dyslipidemias in patients with high and very high cardiovascular risk.Methods: A Markov long-term cost-effectiveness model of rosuvastatin versus simvastatin, atorvastatin and pitavastatin in patients with high and very high cardiovascular risk defined according to 5 factors (sex, age, smoking habit, baseline cholesterol level, and systolic blood pressure) using the SCORE system. The incremental cost-effectiveness ratio is expressed in euros per quality adjusted life years and is calculated according to the perspective of the Spanish National Health System. Results: Rosuvastatin is associated with a greater health benefit than the other statins across the considered profiles. Rosuvastatin is cost-effective compared to simvastatin in patients with SCORE risk ≥8% in females and ≥6% in males, while between 5% and the indicated values its cost-effectiveness is conditional to the patient baseline c-LDL level. Rosuvastatin is more cost-effective versus atorvastatin in female profiles associated with a SCORE risk≥11% and male profiles with SCORE risk ≥10%. Rosuvastatin is superior versus pitavastatin in both female and male profiles with high and very high cardiovascular risk. Conclusions: Rosuvastatin is a cost-effective therapy in the treatment of hypercholesterolemia versus simvastatin, atorvastatin and pitavastatin, especially in specific profiles of patients with high and very high cardiovascular risk factors, according to the SCORE system, in Spain
Subject(s)
Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Cardiovascular Diseases/prevention & control , Dyslipidemias/drug therapy , Anticholesteremic Agents/economics , Simvastatin/therapeutic use , Risk Factors , 50303 , Coronary Disease/prevention & controlABSTRACT
La hipercolesterolemia familiar (HF) es un trastorno genético frecuente que se manifiesta desde el nacimiento y que causa un aumento en los niveles plasmáticos de colesterol-LDL (cLDL), xantomas y enfermedad coronaria prematura. Su detección y tratamiento precoz reduce la morbimortalidad coronaria. A pesar de la disponibilidad de un tratamiento eficaz, la HF está poco diagnosticada y tratada. La identificación de los casos índices y la posterior detección en cascada familiar utilizando los niveles de cLDL y la detección genética es la estrategia más coste-efectiva para la detección de nuevos casos. El tratamiento crónico con estatinas ha disminuido el riesgo cardiovascular a los niveles de la población general. Los objetivos en cLDL son < 130 mg/dl en los niños y adultos jóvenes, < 100 mg/dl en los adultos y < 70 mg/dl en los adultos con enfermedad coronaria conocida o diabetes. En la mayoría de los pacientes es difícil conseguir estos objetivos, por lo que puede ser necesario el tratamiento combinado con ezetimiba u otros fármacos. Cuando no se alcanzan los objetivos con el máximo tratamiento farmacológico tolerado, una reducción de cLDL ≥ 50% puede ser aceptable. La LDL-aféresis es útil en los pacientes homocigotos y en los heterocigotos graves resistentes al tratamiento. Este documento proporciona recomendaciones para el diagnóstico, cribado y tratamiento de la HF en niños y adultos, así como consejos específicos para los especialistas clínicos y médicos de atención primaria con el objetivo de mejorar el cuidado de los pacientes y reducir su carga de enfermedad cardiovascular (AU)
Familial hypercholesterolemia (FH) is a common genetic disorder, clinically manifested since birth, and associated with very high levels of plasma LDL-cholesterol (LDL-c), xanthomas, and premature coronary heart disease. Its early detection and treatment reduces coronary morbidity and mortality. Despite effective treatment being available, FH is under-diagnosed and under-treated. Identification of index cases and cascade screening using LDL-c levels and genetic testing are the most cost-effective strategies for detecting new cases and starting early treatment. Long-term treatment with statins has decreased the vascular risk to the levels of the general population. LDL-c targets are < 130 mg/dL for children and young adults, < 100 mg/dL for adults, and < 70 mg/dL for adults with known coronary heart disease or diabetes. Most patients do not to reach these goals, and combined treatments with ezetimibe or other drugs may be necessary. When the goals are not achieved with the maximum tolerated drug treatment, a reduction ≥ 50% in LDL-c levels can be acceptable. Lipoprotein apheresis can be useful in homozygous, and in treatment-resistant severe heterozygous, cases. This Consensus Paper gives recommendations on the diagnosis, screening, and treatment of FH in children and adults, and specific advice to specialists and general practitioners with the objective of improving the clinical management of these patients, in order to reduce the high burden of coronary heart disease (AU)