ABSTRACT
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 < 0.001) and lower lipoprotein(a) [Lp(a)] (53.4 ± 67.9 vs. 66.6 ± 85.6 mg/dL; p < 0.001) levels with respect to those in the ACVD group. Lp(a) and the presence of ≥3 risk factors were associated with the presence of ACVD.
Subject(s)
Heterozygote , Hyperlipoproteinemia Type II , Humans , Female , Male , Hyperlipoproteinemia Type II/blood , Hyperlipoproteinemia Type II/genetics , Aged , Risk Factors , Cholesterol, LDL/blood , Atherosclerosis/blood , Atherosclerosis/etiology , Atherosclerosis/genetics , Cholesterol, HDL/blood , Lipoprotein(a)/blood , Aged, 80 and overABSTRACT
PURPOSE: Low-density lipoprotein (LDL) cholesterol reduction by statin therapy is dose-dependent, varies among different statins, and has wide inter-individual variability. The present study aimed to compare mean LDL cholesterol reduction and its variability achieved with different doses of the three statins most frequently used in monotherapy or combined with ezetimibe in a real clinical setting. METHODS: Of 5620 cases with primary hypercholesterolemia on the Spanish Arteriosclerosis Society Registry, 1004 with non-familial hypercholesterolemia and complete information on drug therapy and lipid profile were included. RESULTS: The lowest mean percentage LDL cholesterol reduction was observed with simvastatin 10 mg (32.5 ± 18.5%), while the highest mean percentage LDL reduction was obtained with rosuvastatin 40 mg (58.7 ± 18.8%). As to combined treatment, the lowest and highest mean percentage LDL cholesterol reductions were obtained with simvastatin 10 mg combined with ezetimibe (50.6 ± 24.6%) and rosuvastatin 40 mg combined with ezetimibe (71.6 ± 11.1%), respectively. Factors associated with a suboptimal response were male sex, lower age, body mass index, and baseline LDL cholesterol levels. Combined treatment was associated with less variability in LDL cholesterol reduction (OR 0.603, p < 0.001). CONCLUSION: In a real clinical setting, rosuvastatin was superior to the other statins in lowering LDL cholesterol, both as monotherapy or combined with ezetimibe. Factors associated with a suboptimal response in LDL cholesterol decline were male sex, age, body mass index, and baseline LDL cholesterol levels. Combined treatment was associated with less variability in LDL cholesterol improvement.
Subject(s)
Anticholesteremic Agents , Arteriosclerosis , Dyslipidemias , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Hypercholesterolemia , Anticholesteremic Agents/adverse effects , Arteriosclerosis/drug therapy , Cholesterol, LDL , Drug Therapy, Combination , Dyslipidemias/diagnosis , Dyslipidemias/drug therapy , Ezetimibe/adverse effects , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Hypercholesterolemia/diagnosis , Hypercholesterolemia/drug therapy , Male , Registries , Rosuvastatin Calcium/adverse effects , Simvastatin/adverse effectsABSTRACT
BACKGROUND AND AIMS: Cardiovascular risk in heterozygous familial hypercholesterolaemia (HeFH) is driven by LDL cholesterol levels. Since lipid response to statin therapy presents individual variation, this study aimed to compare mean LDL and non-HDL cholesterol reductions and their variability achieved with different types and doses of the most frequently prescribed statins. METHODS AND RESULTS: Among primary hypercholesterolaemia cases on the Spanish Arteriosclerosis Society registry, 2894 with probable/definite HeFH and complete information on drug therapy and lipid profile were included. LDL cholesterol reduction ranged from 30.2 ± 17.0% with simvastatin 10 mg to 48.2 ± 14.7% with rosuvastatin 40 mg. After the addition of ezetimibe, an additional 26, 24, 21 and 24% reduction in LDL cholesterol levels was obtained for rosuvastatin, 5, 10, 20 and 40 mg, respectively. Subjects with definite HeFH and a confirmed genetic mutation had a more discrete LDL cholesterol reduction compared to definite HeFH subjects with no genetic mutation. A suboptimal response (<15% or <30% reduction in LDL cholesterol levels, respectively with low-/moderate-intensity and high-intensity statin therapy) was observed in 13.5% and, respectively, 20.3% of the subjects. CONCLUSION: According to the LDL cholesterol reduction in HeFH patients, the ranking for more to less potent statins was rosuvastatin, atorvastatin and simvastatin; however, at maximum dosage, atorvastatin and rosuvastatin were nearly equivalent. HeFH subjects with positive genetic diagnosis had a lower lipid-lowering response. Approximately 1 in 5 patients on high-intensity statin therapy presented a suboptimal response.
Subject(s)
Atorvastatin/therapeutic use , Cholesterol, HDL/blood , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hyperlipoproteinemia Type II/drug therapy , Rosuvastatin Calcium/therapeutic use , Simvastatin/therapeutic use , Adult , Aged , Biomarkers/blood , Down-Regulation , Drug Therapy, Combination , Ezetimibe/therapeutic use , Female , Genetic Predisposition to Disease , Heterozygote , Humans , Hyperlipoproteinemia Type II/blood , Hyperlipoproteinemia Type II/diagnosis , Hyperlipoproteinemia Type II/genetics , Male , Middle Aged , Phenotype , Registries , Spain , Treatment OutcomeABSTRACT
The irruption of lipoprotein(a) (Lp(a)) in the study of cardiovascular risk factors is perhaps, together with the discovery and use of proprotein convertase subtilisin/kexin type 9 (iPCSK9) inhibitor drugs, the greatest novelty in the field for decades. Lp(a) concentration (especially very high levels) has an undeniable association with certain cardiovascular complications, such as atherosclerotic vascular disease (AVD) and aortic stenosis. However, there are several current limitations to both establishing epidemiological associations and specific pharmacological treatment. Firstly, the measurement of Lp(a) is highly dependent on the test used, mainly because of the characteristics of the molecule. Secondly, Lp(a) concentration is more than 80% genetically determined, so that, unlike other cardiovascular risk factors, it cannot be regulated by lifestyle changes. Finally, although there are many promising clinical trials with specific drugs to reduce Lp(a), currently only iPCSK9 (limited for use because of its cost) significantly reduces Lp(a). However, and in line with other scientific societies, the SEA considers that, with the aim of increasing knowledge about the contribution of Lp(a) to cardiovascular risk, it is relevant to produce a document containing the current status of the subject, recommendations for the control of global cardiovascular risk in people with elevated Lp(a) and recommendations on the therapeutic approach to patients with elevated Lp(a).
Subject(s)
Cardiovascular Diseases , Heart Disease Risk Factors , Lipoprotein(a) , Humans , Lipoprotein(a)/blood , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/etiology , PCSK9 Inhibitors , Spain , Atherosclerosis , Consensus , ArteriosclerosisABSTRACT
BACKGROUND: Recently, an inverse relationship between the blood concentration of lipoprotein(a) (Lp(a)) and triglycerides (TG) has been demonstrated. The larger the VLDL particle size, the greater the presence of VLDL rich in apoliprotein E and in subjects with the apoE2/E2 genotype, the lower Lp(a) concentration. The mechanism of this inverse association is unknown. The objective of this analysis was to evaluate the Lp(a)-TG association in patients treated at the lipid units included in the registry of the Spanish Society of Atherosclerosis (SEA) by comparing the different dyslipidemias. PATIENTS AND METHODS: Five thousand two hundred and seventy-five subjects ≥18 years of age registered in the registry before March 31, 2023, with Lp(a) concentration data and complete lipid profile information without treatment were included. RESULTS: The mean age was 53.0 ± 14.0 years, with 48% women. The 9.5% of subjects (n = 502) had diabetes and the 22.4% (n = 1184) were obese. The median TG level was 130 mg/dL (IQR 88.0-210) and Lp(a) 55.0 nmol/L (IQR 17.9-156). Lp(a) concentration showed a negative association with TG concentration when TG values exceeded 300 mg/dL. Subjects with TG > 1000 mg/dL showed the lowest level of Lp(a), 17.9 nmol/L, and subjects with TG < 300 mg/dL had a mean Lp(a) concentration of 60.1 nmol/L. In subjects without diabetes or obesity, the inverse association of Lp(a)-TG was especially important (p < 0.001). The median Lp(a) was 58.3 nmol/L in those with TG < 300 mg/dL and 22.0 nmol/L if TG > 1000 mg/dL. No association was found between TG and Lp(a) in subjects with diabetes and obesity, nor in subjects with familial hypercholesterolemia. In subjects with multifactorial combined hyperlipemia with TG < 300 mg/dL, Lp(a) was 64.6 nmol/L; in the range of 300-399 mg/dL of TG, Lp(a) decreased to 38. 8 nmol/L, and up to 22.3 nmol/L when TG > 1000 mg/dL. CONCLUSIONS: Our results show an inverse Lp(a)-TG relationship in TG concentrations > 300 mg/dL in subjects without diabetes, obesity and without familial hypercholesterolemia. Our results suggest that, in those hypertriglyceridemias due to hepatic overproduction of VLDL, the formation of Lp(a) is reduced, unlike those in which the peripheral catabolism of TG-rich lipoproteins is reduced.
Subject(s)
Diabetes Mellitus , Dyslipidemias , Hyperlipoproteinemia Type II , Humans , Female , Adult , Middle Aged , Aged , Male , Lipoprotein(a) , Triglycerides , Obesity/complicationsABSTRACT
Extremely variable prevalence rates of atherogenic dyslipidaemia (AD) in type 2 diabetes (T2DM) subjects have been reported. The primary aim was to assess AD prevalence in Spanish T2DM subjects. Secondary objectives were to evaluate the differential clinical characteristics between T2DM subjects with and without AD, to describe lipid profile evolution and use of lipid-lowering treatment in clinical practice by the Spanish Lipid Units. Data was obtained from the National Registry of Dyslipidaemias of the Spanish Atherosclerosis Society, from a multicentric sub-study focused on AD prevalence in T2DM subjects (PREDISAT study). The inclusion criteria were subjects diagnosed of T2DM with age ≥18 years old. A total of 385 T2DM subjects with a mean age of 61 years and 246 (64%) men were included. The mean follow-up was 22 ± 7.4 months. At baseline, 41.3% of the T2DM subjects presented AD, this percentage decreasing to 34.8% with therapeutic intervention. AD prevalence varied in different age groups and appeared to be more prevalent in younger T2DM subjects. Those with AD had a more atherogenic lipid profile at baseline, with higher total cholesterol, triglyceride and non-(high-density lipoprotein) HDL cholesterol levels at baseline, together with lower HDL cholesterol concentrations, without achieving lipid subfraction goals during follow-up. Although almost 90% of the AD subjects were under lipid-lowering treatment, most were receiving only one drug, being statins the most used treatmentA high AD prevalence in T2DM subjects was observed, being age a determinant factor, with a modest decline during follow-up. Although almost 90% of the AD subjects were under lipid-lowering drugs, most were only receiving monotherapy with statins.
Subject(s)
Atherosclerosis , Diabetes Mellitus, Type 2 , Dyslipidemias , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Male , Humans , Middle Aged , Adolescent , Female , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Cholesterol, HDL , Dyslipidemias/drug therapy , Dyslipidemias/epidemiology , Dyslipidemias/complications , Atherosclerosis/drug therapy , Atherosclerosis/epidemiologyABSTRACT
INTRODUCTION: Statins are used with the understanding that a slightly increased risk of diabetes is outweighed by their cardiovascular benefits. However, it may be necessary to reconsider whether statin therapy really increase this risk mainly in the population with prediabetes. METHODS: A multicenter, cross-sectional, observational study was conducted to assess the relationship between statin therapy and glucose metabolism in 407 patients aged 63.1 years (11SD) diagnosed with dyslipidemia and prediabetes treated in specialized lipid clinics in Spain. RESULTS: Significant differences were found in HbA1c values among treatment groups (p=0.015). Patients treated with pitavastatin (1-4mg/day) showed the lowest HbA1c levels, with significant differences compared to patients treated with atorvastatin 40-80mg/day (p=0.016) and simvastatin 10-40mg/day (p=0.036). By contrast, patients treated with atorvastatin 40-80mg/day showed the highest HbA1c levels compared to those receiving atorvastatin 10-20mg/day (p=0.003), pitavastatin 1-4mg/day (p=0.016), pravastatin 20-40mg/day (p=0.027), rosuvastatin 5-10mg/day (p=0.043), and no statin treatment (p=0.004). Patients treated with simvastatin 10-40mg/day also had higher values than those treated with atorvastatin 10-20mg/day (p=0.016) and pitavastatin 1-4mg/day (p=0.036) or with no statin treatment (p=0.018). CONCLUSIONS: This study suggests that there are differences in the diabetogenic effect of statins. Simvastatin and high doses of atorvastatin may be associated with greater impairment in glucose metabolism than pitavastatin and other statins with less lipid-lowering potency such as pravastatin.
Subject(s)
Diabetes Mellitus , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Prediabetic State , Aged , Atorvastatin/adverse effects , Cross-Sectional Studies , Diabetes Mellitus/chemically induced , Diabetes Mellitus/epidemiology , Glucose , Glycated Hemoglobin , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Middle Aged , Pravastatin/adverse effects , Prediabetic State/epidemiology , Rosuvastatin Calcium/adverse effects , Simvastatin/adverse effects , SpainABSTRACT
BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a codominant autosomal disease characterized by a high risk of cardiovascular disease when not in lipid-lowering treatment. However, there is a large variability in the clinical presentation in heterozygous subjects (HeFH). Maternal hypercholesterolemia has been proposed as a cardiometabolic risk factor later in life. Whether this phenotype variability depends on the mother or father origin of hypercholesterolemia is unknown. The objective of this study was to analyze potential differences in anthropometry, superficial lipid deposits, comorbidities, and lipid concentrations depending on the parental origin of hypercholesterolemia within a large group of HeFH. METHODS: This is a cross-sectional observational, multicenter, nation-wide study in Spain. We recruited adults with HeFH to study clinical differences according to the parental origin. Data on HeFH patients were obtained from the Dyslipidemia Registry of the Spanish Atherosclerosis Society. RESULTS: HeFH patients were grouped in 1231 HeFH-mother-offspring aged 45.7 (16.3) years and 1174 HeFH-father-offspring aged 44.8 (16.7) years. We did not find any difference in lipid parameters (total cholesterol, triglycerides, LDLc, HDLc, and Lp(a)), nor in the comorbidities studied (cardiovascular disease prevalence, age of onset of cardiovascular disease, obesity, diabetes, and hypertension) between groups. Lipid-lowering treatment did not differ between groups. The prevalence of comorbidities did not show differences when they were studied by age groups. CONCLUSIONS: Our research with a large group of subjects with HeFH shows that a potential maternal effect is not relevant in FH. However, due to the size of our sample, potential differences between genders cannot be completely ruled out. This implies that severe maternal hypercholesterolemia during pregnancy is not associated with additional risk in the FH affected offspring.
Subject(s)
Hypercholesterolemia , Hyperlipoproteinemia Type II , Adult , Cholesterol, LDL , Cross-Sectional Studies , Female , Humans , Hypercholesterolemia/diagnosis , Hypercholesterolemia/epidemiology , Hypercholesterolemia/genetics , Hyperlipoproteinemia Type II/diagnosis , Hyperlipoproteinemia Type II/epidemiology , Hyperlipoproteinemia Type II/genetics , Male , Maternal Inheritance , Phenotype , Spain/epidemiologyABSTRACT
AIM: To assess the efficacy of sodium-glucose cotransporter-2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptors agonist (GLP-1RA) therapy on liver steatosis measured by fatty liver index (FLI) and hepatic steatosis index (HSI) at 26 weeks in outpatients with diabetes and obesity. METHODS: Observational, prospective, multicenter study. Patients with steatosis determined by FLI (values <30 rule out and >60 indicate steatosis) and HIS (values <30 rule out and >36 indicate steatosis) who received combination therapy were included. Patients were stratified into three groups according to the sequential order of treatment. We used robust statistical methods. RESULTS: In our final report we included 174 patients (58.6% males), mean age 61.9 (10) years. Baseline body mass index, waist circumference and weight were 36.5 (6.8) kg/m2, 117.5 (15.1) cm and 99.4 (20.5) kg, respectively. One hundred percent of patients had altered biomarkers of fatty liver scores (FLI 96 [13] and HSI 49.2 [8.5]). At 26 weeks, significant reductions in FLI (-4.5 [95% CI 3.5-5.9] p < .001) and HSI (-2.4 [95% CI 1.6-3.2] p < .001) were found in the total sample and pre-specified treatment and FLI cut-off point subgroups. CONCLUSION: Our results show a beneficial effect of the combination of GLP-1RAs plus SGLT2is on liver steatosis that goes beyond glucose control, and it is related mainly to weight loss, a decline in biomarkers and reductions in abdominal circumference. For many patients, early detection is essential to improving outcomes in NAFLD and could allow us to select the most efficient treatment options.
Subject(s)
Diabetes Mellitus, Type 2 , Hypoglycemic Agents/therapeutic use , Non-alcoholic Fatty Liver Disease , Obesity , Sodium-Glucose Transporter 2 Inhibitors , Aged , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Female , Humans , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/drug therapy , Obesity/complications , Obesity/drug therapy , Prospective Studies , Sodium-Glucose Transporter 2 Inhibitors/therapeutic useABSTRACT
A low prevalence of type 2 diabetes mellitus has been reported in familial hypercholesterolaemia. Whether a healthier lifestyle could explain it has not been explored. This cross-sectional study determines the prevalence of lifestyle-related cardiovascular risk factors in heterozygous familial hypercholesterolaemia (HeFH) from the Dyslipidaemia Registry of the Spanish Atherosclerosis Society and in the ENRICA study, a representative sample of the adult Spanish general population, weighted to match the age and sex distribution of the HeFH sample. A total of 2185 HeFH patients and 11,856 individuals from ENRICA were included. HeFH had lower body mass index and fewer of them were smokers than in the reference population. A model adjusted for age, sex and body mass index showed that HeFH more frequently had cardiovascular disease (odds ratio (OR) 23.98; 95% confidence interval (CI) 18.40-31.23) and hypertension (OR 1.20; 95% CI 1.07-1.35), and took anti-hypertensive medication (OR 1.36; 95% CI 1.18-1.56) and anti-diabetic medication (OR 1.25; 95% CI 1.00-1.56), but less frequently were smokers (OR 0.79; 95% CI 0.71-0.89). In a HeFH subsample (n = 513) with complete blood glucose information, those patients without cardiovascular disease showed lower prevalence of smoking and type 2 diabetes mellitus, lower body mass index and glucose, and higher diastolic blood pressure than the Spanish population. The differences in type 2 diabetes mellitus were justified mostly by the difference in body mass index. Body mass index adjustment also showed higher prevalence of hypertension and use of anti-hypertensive drugs in HeFH. In summary, HeFH patients had lower body mass index, which may contribute to explaining the lower prevalence of diabetes, and lower current smoking but higher hypertension.
Subject(s)
Behavior , Cardiovascular Diseases/psychology , Cholesterol, LDL/blood , Diabetes Mellitus, Type 2/ethnology , Risk Assessment/methods , Biomarkers , Cardiovascular Diseases/complications , Cross-Sectional Studies , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/etiology , Female , Humans , Hyperlipoproteinemia Type II/blood , Hyperlipoproteinemia Type II/complications , Hyperlipoproteinemia Type II/psychology , Male , Middle Aged , Prevalence , Risk Factors , Spain/epidemiologyABSTRACT
INTRODUCTION AND OBJECTIVES: The lower prevalence of type 2 diabetes mellitus (T2DM) in patients with heterozygous familial hypercholesterolemia (HeFH) could explain why T2DM has not always been identified as an independent predictor of cardiovascular disease (CVD) in different familial hypercholesterolemia cohort studies. The aim of the present study was to evaluate clinical and genetic aspects of HeFH patients with T2DM in the dyslipidemia registry of the Spanish Arteriosclerosis Society. METHODS: HeFH patients were classified according to the presence or absence of T2DM. The clinical, biochemical and genetic characteristics of the 2 groups were compared. RESULTS: Of the 2301 patients with primary hypercholesterolemia included in the registry, 1724 with a probable or definite diagnosis according to the Dutch Lipid Clinic Network score were finally included. HeFH patients with T2DM had a higher rate of CVD and a less favorable lipid profile, with higher total cholesterol (366.9±86.7mg/dL vs 342.0±74.7mg/dL; mean difference 24.894; 95%CI, 5.840-43.949) and non-high-density lipoprotein cholesterol (316.9±87.8mg/dL vs 286.4±75.4mg/dL; mean difference 30.500; 95%CI, 11.211-49.790) levels. No significant differences were found between the groups concerning the specific type of HeFH-causing mutation (P=.720). After adjustment for major risk factors, logistic regression analysis confirmed a relationship between T2DM and the presence of CVD (OR, 2.01; 95%CI, 1.18-3.43; P=.010). CONCLUSIONS: HeFH patients with T2DM have a higher rate of CVD and a less favorable lipid profile, regardless of genetic mutation type. In these patients, T2DM is associated with the presence of CVD.
Subject(s)
Diabetes Mellitus, Type 2 , Hypercholesterolemia , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/genetics , Heterozygote , Humans , Hyperlipoproteinemia Type II/complications , Hyperlipoproteinemia Type II/diagnosis , Hyperlipoproteinemia Type II/epidemiology , Risk FactorsABSTRACT
The Spanish Arteriosclerosis Society has accredited more than 70 lipid units across the country. The main criteria for patients to be referred to these units are presented. These are not only grouped by the type of dyslipidaemia or the lipid levels, but also on certain clinical characteristics suggesting primary hyperlipidaemia, a complex diagnosis, or difficult management due to inefficacy, or side effects.
Subject(s)
Atherosclerosis/therapy , Dyslipidemias/therapy , Hyperlipidemias/therapy , Societies, Medical/organization & administration , Accreditation , Atherosclerosis/diagnosis , Dyslipidemias/diagnosis , Humans , Hyperlipidemias/diagnosis , Lipids/blood , Referral and Consultation/organization & administration , SpainABSTRACT
BACKGROUND AND AIMS: The impact on heterozygous familial hypercholesterolemia (HeFH) health led by high-intensity lipid-lowering therapy (HILLT) is unknown, and the question remains if there is still an unacceptably high residual risk to justify treatment with new lipid-lowering drugs. METHODS: This observational, retrospective, multicenter, national study in Spain, whose information was obtained from a national dyslipemia registry, was designed to establish the current prevalence of cardiovascular disease (CVD) in HeFH and to define the impact of HILLT on CVD in this population. Odds were estimated using several logistic regression models with progressive adjustment. RESULTS: 1958 HeFH, mean age 49.3⯱â¯14.3 years, were included in the analysis. At inclusion in the registry, 295 patients (15.1%) had suffered CVD and 164 (55.6%) had suffered the first event before the onset lipid-lowering treatment. Exposition to treatment associated more than ten times lower odds for CVD than in subjects naïve to treatment (OR 0.085, 95% CI 0.063-0.114, pâ¯<â¯0.001). A first CVD event after a mean treatment period of 9.1⯱â¯7.2 years occurred in 131 out of 1615 (8.1%) HeFH subjects, and 115 (87.8%) of them were on HILLT. CONCLUSIONS: Current prevalence of CVD among HeFH is one third of that reported before the statins era. Early initiation and prolonged lipid-lowering treatment was associated with a reduction in CVD. New cases of CVD, in spite of HILLT, appeared mostly among patients accumulating risk factors and probably they may be considered for further lipid-lowering drugs.
Subject(s)
Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Hyperlipoproteinemia Type II/drug therapy , Hypolipidemic Agents/therapeutic use , Adult , Aged , Cardiovascular Diseases/etiology , Female , Humans , Hyperlipoproteinemia Type II/complications , Male , Middle Aged , Prevalence , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND AND OBJECTIVE: Patients with polyvascular disease have an increased rate of cardiovascular events and death. Their identification would define a subgroup of the population at very high risk, who would be candidates to intensified preventive measures. The objective of the present study was to evaluate the prevalence of subclinical peripheral artery disease in subjects with a previous diagnosis of vascular disease in other territories. PATIENTS AND METHOD: Subjects with a coronary or a cerebrovascular event between 3 months and 5 years, and who were attended at internal medicine outpatient clinics from Spain were included in the study. All patients had a clinical history, a physical examination, a blood and urine analysis, and a measurement of the ankle-brachial index (ABI). RESULTS: A total of 1203 patients (64% males; mean age: 74.3 years), were included in the study. A previous coronary event was reported in 55.4% of the participants, cerebrovascular disease in 38%, and a clinical history of disease in both territories in 6.7%. The prevalence of a low ABI (< 0,9) was 33.8%, 32.4% and 53.9% for each group, respectively. In a multivariate analysis, factors associated with a low ABI were age, smoking habit, diabetes, a reduced glomerular filtration rate, systolic blood pressure and the presence of clinical disease in both territories upon inclusion. The sensitivity of both, the Edinburgh questionnaire and pulse palpation for detecting and ABI below 0.9, were low. CONCLUSIONS: Prevalence of a low ABI is elevated in asymptomatic patients with coronary or cerebrovascular disease, particularly if there are clinical manifestations in both territories.
Subject(s)
Ankle Brachial Index , Peripheral Vascular Diseases/diagnosis , Peripheral Vascular Diseases/epidemiology , Aged , Cardiovascular Diseases/complications , Female , Humans , Male , Peripheral Vascular Diseases/etiology , Prevalence , Prospective StudiesABSTRACT
BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a high cardiovascular risk condition. Less than 20% of patients achieve the LDL targets. Although PCSK9 inhibitors improve control and reduce cardiovascular events, official recommendations for their use are restrictive. We aim to assess the number of FH patients suitable for PCSK9 inhibition according to the European guidelines. METHODS: A total of 2685 FH patients, with a minimum follow-up of 6 months, included in the Dyslipidemia Registry of the Spanish Arteriosclerosis Society, were sorted according to the intensity of their lipid-lowering therapy (LLT) and LDL cholesterol levels achieved. The number of patients who met the recommendations for PCSK9 inhibition treatment according to the European Atherosclerosis Society (ESC/EAS), Spanish Arteriosclerosis Society and the European Medicines Agency was calculated. RESULTS: In total, 1573 patients were on high-intensity LLT; 607 were on moderate-intensity statins; 82 were on low-intensity LLT, and 423 were neither on statins nor on ezetimibe in the last visit registered. The mean LDL reduction among those on high-intensity LLT was 54%. Ninety-one percent of patients on high-intensity LLT had an LDL below 5.2 mmol/L, 53% below 3.4 mmol/L, and 23% below 2.6 mmol/L. Only 12% of FH patients with cardiovascular disease achieved 1.8 mmol/L. Despite this, only 17% of patients qualified for PCSK9 inhibition according to ESC/EAS guidelines. CONCLUSIONS: For patients with a condition that exposes them to high cardiovascular risk and who have extreme difficulties in achieving LDL targets, wider access to PCSK9 inhibitor therapy is warranted.
Subject(s)
Anticholesteremic Agents/therapeutic use , Cardiovascular Diseases/prevention & control , Eligibility Determination , Hyperlipoproteinemia Type II/drug therapy , PCSK9 Inhibitors , Serine Proteinase Inhibitors/therapeutic use , Adult , Aged , Cardiovascular Diseases/blood , Cardiovascular Diseases/enzymology , Ezetimibe/therapeutic use , Female , Guideline Adherence , Health Services Accessibility , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hyperlipoproteinemia Type II/blood , Hyperlipoproteinemia Type II/diagnosis , Hyperlipoproteinemia Type II/enzymology , Male , Middle Aged , Practice Guidelines as Topic , Proprotein Convertase 9/metabolism , Registries , Risk Assessment , Risk Factors , Spain , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND AND OBJECTIVES: Statins are safe but have a significant potential for pharmacological interactions. The objective of the study was to evaluate the prevalence of potential interactions throughout the cytochrome P450 isoenzyme 3A4 (CYP3A4) system in a large sample of statin-treated subjects and to determine which factors, from the patient and the physician, were associated with a higher risk of interactions. PATIENTS AND METHODS: This is an observational, cross-over, population study that included 7,880 subjects treated with statins. Both data from patients and from the1,681 participating physicians were recorded and analyzed. RESULTS: Fifty-nine percent of the participants were receiving a statin metabolized by the CYP3A4, and 21.5% of all participants received a drug, different from a statin, metabolized by the CYP3A4. There were no differences in the frequency of utilization of statins metabolized or not by the CYP3A4 in relation to the simultaneous prescription of drugs metabolized by the same pathway (22 vs. 21%, respectively). Globally, 12.9% of all participants were at risk of an interaction. These patients were older, received a higher number of drugs and had more comorbidity. Sixty percent of the physicians mentioned that the possibility of an interaction greatly conditioned their selection of a particular statin. Likewise, 56% of them had software that alerted of possible interactions. These aspects, however, did not influence the number of patients at risk of interactions. CONCLUSION: The proportion of statin-treated patients at risk of interaction is elevated. Physicians do not usually pay attention to this possibility despite having available alert software and therapeutic alternatives.
Subject(s)
Cytochrome P-450 CYP3A/metabolism , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Polypharmacy , Practice Patterns, Physicians'/statistics & numerical data , Adult , Age Distribution , Aged , Aged, 80 and over , Biotransformation , Cross-Over Studies , Cross-Sectional Studies , Decision Making, Computer-Assisted , Drug Interactions , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/metabolism , Isoenzymes/metabolism , Logistic Models , Male , Middle Aged , Risk Assessment , SpainABSTRACT
Introduction:Statins are used with the understanding that a slightly increased risk of diabetes is outweighed by their cardiovascular benefits. However, it may be necessary to reconsider whether statin therapy really increase this risk mainly in the population with prediabetes.Methods:A multicenter, cross-sectional, observational study was conducted to assess the relationship between statin therapy and glucose metabolism in 407 patients aged 63.1 years (11SD) diagnosed with dyslipidemia and prediabetes treated in specialized lipid clinics in Spain.Results:Significant differences were found in HbA1c values among treatment groups (p=0.015). Patients treated with pitavastatin (14mg/day) showed the lowest HbA1c levels, with significant differences compared to patients treated with atorvastatin 4080mg/day (p=0.016) and simvastatin 1040mg/day (p=0.036). By contrast, patients treated with atorvastatin 4080mg/day showed the highest HbA1c levels compared to those receiving atorvastatin 1020mg/day (p=0.003), pitavastatin 14mg/day (p=0.016), pravastatin 2040mg/day (p=0.027), rosuvastatin 510mg/day (p=0.043), and no statin treatment (p=0.004). Patients treated with simvastatin 1040mg/day also had higher values than those treated with atorvastatin 1020mg/day (p=0.016) and pitavastatin 14mg/day (p=0.036) or with no statin treatment (p=0.018).Conclusions:This study suggests that there are differences in the diabetogenic effect of statins. Simvastatin and high doses of atorvastatin may be associated with greater impairment in glucose metabolism than pitavastatin and other statins with less lipid-lowering potency such as pravastatin. (AU)
Introducción:Las estatinas son utilizadas de acuerdo con el entendimiento de que el pequeño riesgo de incremento de diabetes se ve compensado por sus beneficios cardiovasculares. Sin embargo, puede resultar necesario reconsiderar si la terapia con estatinas incrementa realmente el riesgo, principalmente en la población con prediabetes.Métodos:Se realizó un estudio multicéntrico, transversal y observacional para evaluar la relación entre la terapia con estatinas y el metabolismo de la glucosa en 407 pacientes de 63,1 años (11 DE) diagnosticados de dislipidemia y prediabetes tratados en clínicas especializadas en lípidos en España.Resultados:Se encontraron diferencias significativas en los valores de HbA1c entre los grupos de tratamiento (p=0,015). Los pacientes tratados con pitavastatina (1-4mg/día) reflejaron los menores niveles de HbA1c, con diferencias significativas en comparación con los pacientes tratados con atorvastatina 40-80mg/día (p=0,016) y simvastatina 10-40mg/día (p=0,036). Por contra, los pacientes tratados con atorvastatina 40-80mg/día reflejaron los mayores niveles de HbA1c en comparación con los pacientes que recibieron atorvastatina 10-20mg/día (p=0,003), pitavastatina 1-4mg/día (p=0,016), pravastatina 20-40mg/día (p=0,027), rosuvastatina 5-10mg/día (p=0,043) y los que no recibieron estatinas (p=0,004). Los pacientes tratados con simvastatina 10-40mg/día tuvieron también valores más elevados que aquellos pacientes tratados con atorvastatina 10-20mg/día (p=0,016) y pitavastatina 1-4mg/día (p=0,036) que no recibieron estatinas (p=0,018).Conclusiones:El presente estudio sugiere que existen diferencias en cuanto al efecto diabetógeno de las estatinas. Simvastatina y las altas dosis de atorvastatina pueden guardar relación con un mayor deterioro del metabolismo de la glucosa que pitavastatina y demás estatinas con menor potencia de reducción de lípidos, tales como pravastatina. (AU)
Subject(s)
Humans , Atorvastatin/adverse effects , Diabetes Mellitus/chemically induced , Diabetes Mellitus/epidemiology , Glycated Hemoglobin , Pravastatin/adverse effects , Cross-Sectional Studies , Glucose , SpainABSTRACT
INTRODUCCIÓN Y OBJETIVOS: La menor prevalencia de diabetes mellitus tipo 2 (DM2) en pacientes con hipercolesterolemia familiar heterocigota (HFHe) podría explicar por qué la DM2 no siempre se ha descrito como un predictor de enfermedad cardiovascular (ECV) en estos pacientes. El objetivo del presente estudio fue evaluar los aspectos clínicos y genéticos de pacientes con HFHe y DM2 del registro de dislipidemias de la Sociedad Española de Arteriosclerosis. MÉTODOS: Los pacientes con HFHe se clasificaron según la presencia/ausencia de DM2. Se compararon las características clínicas, bioquímicas y genéticas de ambos grupos. RESULTADOS: De los 2.301 casos de hipercolesterolemia primaria del registro, se incluyeron 1.724 casos con el diagnóstico cierto o probable según la Dutch Lipid Clinic Network para la hipercolesterolemia familiar. Los pacientes con HFHe y DM2 presentaron una tasa más elevada de ECV y un perfil lipídico menos favorable, con niveles más elevados de colesterol total (366,9±86,7 mg/dl frente a 342,0±74,7 mg/dl; diferencia media 24,894; IC95%, 5,840-43,949) y colesterol no-unido a lipoproteínas de alta densidad (316,9±87,8 mg/dl frente a 286,4±75,4 mg/dl; diferencia media 30,500; IC95%, 11,211-49,790). No se encontraron diferencias significativas entre los grupos con respecto al tipo de mutación (p = 0,720). Después de ajustar por los principales factores de riesgo, el análisis de regresión logística confirmó una relación entre la DM2 y la ECV (OR=2,01; IC95%, 1,18-3,43; p = 0,010). CONCLUSIONES: Los pacientes con HFHe y DM2 presentan una tasa más elevada de ECV y un perfil lipídico menos favorable, independientemente del tipo de mutación. La diabetes mellitus es un factor asociado a la presencia de ECV en estos pacientes
INTRODUCTION AND OBJECTIVES: The lower prevalence of type 2 diabetes mellitus (T2DM) in patients with heterozygous familial hypercholesterolemia (HeFH) could explain why T2DM has not always been identified as an independent predictor of cardiovascular disease (CVD) in different familial hypercholesterolemia cohort studies. The aim of the present study was to evaluate clinical and genetic aspects of HeFH patients with T2DM in the dyslipidemia registry of the Spanish Arteriosclerosis Society. METHODS: HeFH patients were classified according to the presence or absence of T2DM. The clinical, biochemical and genetic characteristics of the 2 groups were compared. RESULTS: Of the 2301 patients with primary hypercholesterolemia included in the registry, 1724 with a probable or definite diagnosis according to the Dutch Lipid Clinic Network score were finally included. HeFH patients with T2DM had a higher rate of CVD and a less favorable lipid profile, with higher total cholesterol (366.9±86.7mg/dL vs 342.0±74.7mg/dL; mean difference 24.894; 95%CI, 5.840-43.949) and non-high-density lipoprotein cholesterol (316.9±87.8mg/dL vs 286.4±75.4mg/dL; mean difference 30.500; 95%CI, 11.211-49.790) levels. No significant differences were found between the groups concerning the specific type of HeFH-causing mutation (P=.720). After adjustment for major risk factors, logistic regression analysis confirmed a relationship between T2DM and the presence of CVD (OR, 2.01; 95%CI, 1.18-3.43; P=.010). CONCLUSIONS: HeFH patients with T2DM have a higher rate of CVD and a less favorable lipid profile, regardless of genetic mutation type. In these patients, T2DM is associated with the presence of CVD