Effect Of Lipid-lowering Treatment Research Articles

The effect of lipid-lowering treatment on indices of MASLD in familial hypercholesterolemia patients

Background & AimsThe effect of lipid-lowering treatment (LLT) on metabolic dysfunction associated steatotic liver disease (MASLD) is unclear. This is relevant for patients with familial hypercholesterolemia (FH) who are on lifelong LLT. We aimed to evaluate the effect of LLT on MASLD indices in this population. MethodsPatients with at least possible diagnosis of FH were included into the Hellenic FH Registry (HELLAS-FH) registry. We analyzed the effect of statin monotherapy, statin/ezetimibe and statin/ezetimibe/proprotein convertase subtilisin/kexin 9 inhibitors (PCSK9i) on MASLD indices, i.e., original triglyceride-glucose index (TyGO) and triglyceride-glucose index (TyG). We compared changes of TyG and TyGO before any treatment and after at least one year of stable LLT. ResultsWe included 1289 patients: n=569 in the statin monotherapy group (mean age=51±15 years, 52.7% males), n=629 in the statin/ezetimibe group (52±14 years, 51.8%), and n=91 in the statin/ezetimibe/PCSK9i group (54±13 years, 58.2%). Compared with baseline, TyGO and TyG decreased significantly following statin monotherapy (8.61 vs 8.49 and 4.65 vs 4.59, respectively, both p<0.01), statin/ezetimibe (8.59 vs 8.41 and 4.64 vs 4.55, respectively, both p<0.01) and statin/ezetimibe/PCSK9i (8.79 vs 8.55 and 4.74 vs 4.62, respectively, both p<0.01). There was no difference regarding the change of TyGO and TyG between groups after adjusting for baseline levels. A greater percentage of patients in the statin/ezetimibe and statin/ezetimibe/PCSK9i groups exhibited TyGO-defined MASLD resolution compared with statin monotherapy (p<0.05). After adjustment for possible confounders, LLT was significantly associated with MASLD resolution. ConclusionsMASLD indices were significantly improved in all LLT groups in FH patients. Statin/ezetimibe and statin/ezetimibe/PCSK9i were associated with greater TyGO-defined MASLD resolution compared with statin monotherapy.

Dyslipidemia and lower extremity arterial disease.

Dyslipidemia is an established risk factor for cardiovascular diseases. We aimed to review its role in the pathogenesis of lower extremity arterial disease (LEAD), as well as the effect of lipid-lowering treatment on the progression of LEAD. PubMed/MedLine, EMBASE and Scopus were searched between January 1990 and January 2024 for articles investigating the role of dyslipidemias and hyperlipidemias in the pathogenesis of LEAD. A separate search focused on the effects of lipid-lowering therapy on patients with LEAD. There is evidence that dyslipidemias play a major role in the development of LEAD. All patients with LEAD should receive intensive lipid-lowering therapy for the reduction not only of claudication symptoms and amputation rates, but also of myocardial infarction and cardiovascular event rates. Vascular specialists should keep in mind the pivotal role of dyslipidemia in the pathogenesis and progression of LEAD.

High risk dyslipidemia: can we predict early coronary disease?

Abstract Funding Acknowledgements Type of funding sources: None. Introduction The AHA/ACC guidelines on the management of blood cholesterol (2013 and 2018) classified the LDL-c &amp;gt;190 mg/dL as high-risk patients, with the indication of high-intensity statins (c-LDL reduction greater than 50%). Recently the 2019 ESC guidelines(1) also classify these patients as high cardiovascular (CV) risk. Objective Determine factors associated with the development of early coronary disease (ECD) in patients with high-risk dyslipidemia (HRD). Methods Observational retrospective cohort of 160 patients with historical maximum LDL-c ≥190 mg/dL without secondary cause. We compared the clinical characteristics, the baseline blood test with maximum LDL-c (BT1), and the effects of lipid-lowering treatment on the last blood test (BT2), between patients with ECD (53 patients Group A) and patients without cardiovascular events (107 patients Group B). Results Group A, presented maximum LDL-c at a younger age, had dyslipidemia of longer evolution time, had a higher proportion of men, smokers, diabetics, and had a higher number of associated risk factor's (Table 1). In the BT1 they presented greater proportion of HDL-c values below 45 mg/dL (35.3% vs 12.3%, p=0.001), and a higher proportion of remnant cholesterol (Non HDLc - LDLc = &amp;gt;30 mg/dL, 51% vs 33.3%, p=0.037). Patients with ECD received high-intensity lipid-lowering treatment, statin + ezetimibe (73.6% vs 29.8%, p&amp;lt;0.0001), IPCSK9 (7.5% vs 2.9%, p=0.18), and achieving LDL-c goals (32.1% vs 13.6%, p=0.006) and Non HDL-c (47.2% vs 14.6%, p&amp;lt;0.0001) according to cardiovascular risk. There were no variation between BT1 and BT2 in HDL-c levels in both groups. In the Cox regression model, male sex (HR 2.8 (1.4-5.7), p=0.003), tobacco (HR 2.5 (1.3-4.7), p=0.005), and the relation between Non HDL-c/HDLc (&amp;gt;4.5 male, &amp;gt;4 female, in primary prevention) in BT1 (HR 1.65, (1.15-1.86) p=0.02) increase independently the risk of ECD in patients with HRD. Conclusion In patients with HRD the presence of male sex, tobacco, increase relation between Non HDLc/HDLc, diabetes, a greater number of cardiovascular risk factors, most atherogenic blood test (HDLc &amp;lt;45 mg/dL and remnant cholesterol) have been associated with the development of ECD. We have had some apreciated 5.45 (± 4) years since the BT1 to prevent ECD.

Consequences of diabetes and high-risk dyslipidemia

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Diabetic patients develop both, microvascular and macrovascular long-term complications, and have double the risk of cardiovascular (CV) disease being the main cause of death. The 97% of diabetic patients are classified as high or very high CV risk. The 2019 ESC guidelines for the managment of dyslipidaemia, classified patients with LDL-c &amp;gt;190 mg/dL as high-risk patients, with the indication of high-intensity statins (LDLc reduction greater than 50% and LDLc below 70 mg/dL). Objective To analyze, in a group of patients with high risk dyslipidaemia (HRD, LDLc &amp;gt;190 mg/dL without secondary cause), the consecuences of its association with type 2 diabetes. Methods Observational retrospective cohort of 153 patients with HRD. We compared 35 diabetic patients (G1) vs 118 non diabetic patients (G2), and we analysed clinical characteristics, cardiovascular risk factor’s (CVRF), tase of cardiovascular disease, the baseline blood test with maximum LDL-c (BT1), lipid profile on the last blood test (BT2) and the effects of lipid-lowering treatment. Results There were no differences in relation to sex. G1 were older (69.2 (±12.8) vs 56.8 (±12.5) years old, p=0.001), had a higher body mass index (BMI) (31.4 (±5.9) vs 28.9 (±4.4) kg/m2, p=0.018), higher number of CVRF (3 CVRF, 54.3% vs 10.2%, p&amp;lt;0.0001, and 4 CVRF, 37.1% vs 0%, p&amp;lt;0.0001). Regarding mayor CV events, 80% develop CV disease vs 38.1% (p&amp;lt;0.0001), and 40% develop early coronary disease (ECD) vs 25% (p&amp;lt;0.0001). In the BT1, G1 presented a more atherogenic lipidogram, lower HDL-c &amp;lt;40-45mg/dL values (22.9% vs 9.3%, p=0.033), higher proportion of triglycerides &amp;gt;150mg/dL (74.3% vs 46.6%, p=0.001), higher proportion of small and dense LDL-c (88.6% vs 62.7%, p=0.004) and a higher proportion of VLDL-c &amp;gt;30mg/dL (74.3% vs 45.8%, p=0.003). There were no differences in lipid-lowering treatment (statin 88.6% vs 86.4%, p= 0.7; ezetimibe 68.6% vs 53.4%, p=0.1) or in the lipid-lowering power of LDL reduction &amp;gt;50% (77.1% vs 70.3%, p=0.4), except for a greater prescription of fibrates in G1 (11.4% vs 1.7%, p=0.027). In BT2, lower rates of HDL-c &amp;lt;40-45mg/dL (34.3% vs 16.1%, p= 0.019) and small and dense LDL-c (80% vs 50.9%) persisted in G1, p=0.002) and a higher proportion of chronic kidney disease (25.8% vs 2.6%, p&amp;lt;0.0001). Conclusions Patients with HRD and diabetes have higher CVRF, a more atherogenic lipid profile that persists despite lipid-lowering treatment, and double the rate of CV disease, were half of these events occurs at early age. This association of CVRF should alert us, implementing an early and agressive prevention treatment of all CVRF.

Patients with pseudoxanthoma elasticum (PXE) do not have dyslipidemia

Abstract Background Pseudoxanthoma elasticum (PXE) is a rare genetic disease caused by low inorganic pyrophosphate and is characterized by medial arterial calcification, leading to peripheral arterial disease and ischemic cerebral disease. Animal studies and small human studies have reported an association between PXE and dyslipidemia and therefore suggest that atherosclerosis is a second pathway contributing to cardiovascular disease in PXE patients. The association between PXE and dyslipidemia was however not consistent across these studies and there are several biological hypotheses proposed where the affected gene in PXE (ABCC6) could affect the cholesterol pathway: ABCC might influence HMA-CoA reductase – and increase total cholesterol and LDL-c – on one hand, but there is also evidence that points toward influence of ABCC6 on the reversed cholesterol pathway, influencing HDL-c. This study is important to analyze if PXE subjects, from the larges PXE cohort in the world, indeed do have a different a different lipid profile compared to well matched controls. Purpose To evaluate whether PXE patients have a different lipid profile compared to non-PXE patients. Methods A cross-sectional patient-control study was done at the Dutch Expertise Center for PXE in the University Medical Center Utrecht. Patients were all diagnosed conform the Plomp cirteria. The control population consisted of acquaintances of PXE patients, excluding first and second-degree relatives. Total cholesterol, LDL-c, HDL-c and triglycerides were assessed in both patients and controls and if lipid-lowering treatment (LLT) was used pre-treatment levels were calculated using known effects of LLT on lipids. To eliminate the imbalances between patients and controls, we used Coursened Exact Matching (CEM), to investigate the effect of PXE on lipids. Results The study population included 323 PXE patients and 57 controls. Their characteristics are displayed in Figure 1. After CEM 186 patients (weighted means: age 57.8±9.9 years, 58% females, BMI 25.5±2.9 kg/m2) and 52 controls (age 57.3±43.1 years, 58% females, BMI 25.5±17 kg/m2) were left for analyses. The univariate, weighted regression analysis of the effect of having PXE on lipid profile shows that the differences in lipids between patients and controls were 0.22 mmol/L for total cholesterol (p=0.299), 0.15 mmol/L for LDL-c (p=0.524), 0.07 mmol/L for HDL-c (p=0.314) and 0.10 mmol/L for triglycerides (p=0.433). A sensitivity analysis where only the crude values of untreated subjects were included in the analysis showed that LDL-c was sginficantly lower in PXE-patients. Probably due to the fact that only the very healthy PXE patients were included. Conclusion There are no differences in levels of total cholesterol, LDL-c, HDL-c, and triglycerides between PXE patients and matched controls. Funding Acknowledgement Type of funding sources: None.

Nature versus Number: Monocytes in Cardiovascular Disease.

Monocytes play a key role in cardiovascular disease (CVD) as their influx into the vessel wall is necessary for the development of an atherosclerotic plaque. Monocytes are, however, heterogeneous differentiating from classical monocytes through the intermediate subset to the nonclassical subset. While it is recognized that the percentage of intermediate and nonclassical monocytes are higher in individuals with CVD, accompanying changes in inflammatory markers suggest a functional impact on disease development that goes beyond the increased proportion of these ‘inflammatory’ monocyte subsets. Furthermore, emerging evidence indicates that changes in monocyte proportion and function arise in dyslipidemia, with lipid lowering medication having some effect on reversing these changes. This review explores the nature and number of monocyte subsets in CVD addressing what they are, when they arise, the effect of lipid lowering treatment, and the possible implications for plaque development. Understanding these associations will deepen our understanding of the clinical significance of monocytes in CVD.

P1565Better adherence to lipid lowering guidelines in secondary prevention may result in substantial reduction in cardiovascular events

Abstract Introduction The preventive effect of lipid lowering treatment in secondary prevention after coronary heart disease (CHD) is well documented. In 2015, regional guidelines recommend an LDL cholesterol of ≤1.8 mmol/L for patients with established CHD but the adherence to these guidelines is low. Purpose Our aim was to predict potential reductions in cardiovascular disease (CVD) events defined as acute myocardial infarction or stroke if patients: 1) with low-dose/less potent or no statin were treated with Atorvastatin 80 mg, or 2) all reached LDL ≤1.8 mmol/L. Methods In total, 37 120 patients with established CHD in a primary care regional register 2015 were studied. Predicted number of CVD events were calculated with actual treatment, with improved treatment and with lowered LDL. For risk estimation we used data from a Cox Proportional Hazards risk estimation model based on patients from 2010 (n=52 042) in combination with data from the literature on effect of statin treatment and LDL reduction. A risk reduction of 22% for CVD events per 1 mmol/L reduction in LDL was used in our model. The risk prediction model included age, sex, diabetes mellitus, a history of heart failure and/or atrial fibrillations, treatment with acetylic salicylic acid and stroke or AMI past year. Smoking and BMI were excluded due to missing data but sensitivity analysis has shown only small differences in results. Results In total, 18% of included patients reached LDL ≤1.8 mmol/L and 32% had no statin treatment. Based on actual LDL levels and treatments, the predicted number of CVD events over 5 years was 9209/37120. If all patients with no statin or less potent statin treatment had been given atorvastatin 80 mg this would lead to a reduction of CVD events by 14% (7901 vs 9209). The largest gain, 33% reduction, occurred when adding statins to patients without previous treatment (1970 vs 2937). Furthermore, if all patients were to reach LDL ≤1.8 mmol/L the predicted number of events would be reduced by 18% (7577 vs 9209). Conclusion There is a substantial potential to reduce the number of CVD events in the large population of patients with established CHD in primary care by improved adherence to lipid treatment guidelines. Acknowledgement/Funding Närhälsan R&amp;D Health Care, R&amp;D Centre Gothenburg and Södra Bohuslän. the Swedish state under the Agreement concerning research and education of doctor

Effect of lipid-lowering treatment in cardiovascular disease prevalence in familial hypercholesterolemia

Background and aimsThe 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. MethodsThis 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. Results1958 HeFH, mean age 49.3 ± 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, p < 0.001). A first CVD event after a mean treatment period of 9.1 ± 7.2 years occurred in 131 out of 1615 (8.1%) HeFH subjects, and 115 (87.8%) of them were on HILLT. ConclusionsCurrent 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.

A Population-Based Study of Cholesterol Measurements in the Oldest Old.

Effect of lipid-lowering treatment in the oldest old is a matter of debate as there is no unequivocal evidence of statins being beneficial among the oldest. The need for cholesterol measurements is therefore also questionable, but the frequency of cholesterol measurements in the oldest old has not been described on a population basis. Therefore, the number of lipid measurements in the period 2002-2012 was evaluated for people aged 85+ years. The Laboratory Information System and the Population Register at Statistics Denmark were used for retrieving data on people aged 85+ living on the Island of Funen. The development in trends for cholesterol measurements was analysed in age groups of 5-years interval using linear regression analysis. A total of 30,424 persons with a cholesterol measurement entered the study. The total number of cholesterol measurements increased by 246% during the observation period. The percentage of people having a cholesterol measurement increased significantly (p < 0.001) from 2002 to 2012 for all groups except males over 100 years of age. The increase was only due to requests from general practitioners, not from hospital units. Despite the uncertainty regarding lipid-lowering treatment in the oldest old, the percentage of people having a cholesterol measurement increased significantly during the study period. Whether this increase in cholesterol measurements leads to increased prescription of lipid-lowering medication in this cohort and/or better outcomes warrants future research.

Vitamin D concentrations in familial combined hyperlipidemia: effects of lipid lowering treatment

BackgroundVitamin D deficiency has been linked to several cardiovascular risk factors but information regarding vitamin D concentrations in familial combined hyperlipidemia (FCHL) is lacking. Our objective was to examine vitamin D concentrations in patients with FCHL and to study the effects of lipid-lowering therapy.MethodsWe conducted a cross sectional study on 59 patients with FCHL and 48 healthy controls. We analyzed 25-hydroxyvitamin D (25(OH)D) concentrations and their association with lipid parameters, anthropometric measures, C-reactive protein and homeostasis model assessment (HOMA) index. Twenty-three patients with FCHL were also included in a longitudinal study conducted to analyze 25-hydroxyvitamin D concentrations before and after treatment for dyslipidemia.ResultsAfter adjustment for body mass index and seasonality, patients with FCHL had lower vitamin D concentrations than controls. Adjusted means (standard error of the mean (S.E.M)) for 25(OH)D according to the presence or absence of FCHL were 62.8 (3.6) nmol/L for patients with FCHL and 74.8 (4.1) nmol/L for controls (p = 0.021). In FCHL, hypovitaminosis D was associated with features of atherogenic dyslipidemia. After lipid-lowering therapy, vitamin D concentrations increased (51.0 ± 31.3 to 58.9 ± 24.6 nmol/L (P = 0.022)). However, changes in 25(OH)D concentrations did not correlate with changes in other parameters.ConclusionsOur findings suggest that FCHL is associated with decreased vitamin D concentrations and that treatment for dyslipidemia improves vitamin D status through an unknown mechanism. Further studies are needed to replicate these data in larger populations and to elucidate the mechanisms involved in this association.

Lipid-lowering therapy with statins reduces microparticle shedding from endothelium, platelets and inflammatory cells

Hyperlipidaemia is a causal factor in the ethiopathogenesis of atherosclerosis. Statins are the cornerstone drug therapy for LDL-cholesterol (LDL-c) lowering, that exert beneficial effects beyond lipid lowering. Circulating microparticles (cMPs), microvesicles released by activated cells into the bloodstream, are markers of vascular and inflammatory cell activation with tentative role in disease progression. However, the role of statins on cMPs seems controversial. We aimed at the evaluation of the effects of lipid-lowering treatment (LLT) on cMP generation in patients in primary prevention of atherosclerosis. A case-control study was conducted in hypercholesterolaemic patients receiving LLT with statins and normocholesterolaemic controls (LLT+ and LLT-, respectively, n=37/group), matched by age, gender and LDL-c levels. cMPs were characterised by flow cytometry using annexin-V and cell-specific antibodies. In LLT+-patients overall numbers of cMPs (p<0.005) were lower than in controls. Levels of cMPs carrying parental cell markers from vascular and circulating cell origin (platelet, endothelial cell, pan-leukocyte and specific-leukocyte subsets) were significantly lower in blood of LLT+ compared to LLT--patients. Moreover, MPs from LLT+-patients had reduced markers of activated platelets (αIIbβ3-integrin), activated inflammatory cells (αM-integrin) and tissue factor. The effect of LLT on cMP shedding was found to be accumulative in years. cMP shedding associated to cardiovascular risk in LLT+-patients. In summary, at similar plasma cholesterol levels patients on statin treatment had a significant lower number of cMPs carrying markers of activated cells. These findings indicate that statins protect against vascular cell activation.

Effects of lipid-lowering treatment on platelet reactivity and platelet-leukocyte aggregation in diabetic patients without and with chronic kidney disease: a randomized trial

Diabetes mellitus (DM) is associated with hyperreactive platelets and increased platelet-leukocyte aggregation (PLA), but the impact of concomitant chronic kidney disease (CKD) has been much less studied. Lipid-lowering treatment (LLT) may have favorable effects on platelet activation and inflammation. The objective of this mechanistic study was to investigate the impact of CKD on platelet function and inflammatory parameters in patients with DM and the effects of LLT. After a placebo run-in period, the effects of simvastatin alone (S) or simvastatin + ezetimibe (S + E) were compared in a randomized, double-blind, cross-over study on platelet reactivity, PLA formation and inflammatory parameters. Eighteen DM patients with estimated glomerular filtration rate (eGFR) 15-59 mL/min × 1.73 m(2) (CKD stages 3-4) (DM-CKD) and 21 DM patients with eGFR >75 mL/min (DM-only) were included. PLAs were elevated at baseline in DM-CKD compared with DM-only (P = 0.04). S + E reduced PLAs among total leukocytes and neutrophils in DM-CKD patients (P = 0.01 for both) but not in the DM-only group. Platelet reactivity did not differ between patient groups or with LLT. Plasma levels of sCD40L (P < 0.001), elastase (P < 0.01) and von Willebrand factor (VWF) (P < 0.001) were elevated in DM-CKD compared with DM-only. S + E reduced sCD40L in DM-CKD patients (P = 0.01), but LLT did not influence VWF or elastase. DM patients with CKD stages 3-4 had increased PLA and inflammatory activity compared with DM patients with normal GFR. Simvastatin + ezetimbe decreased PLAs and plasma sCD40L in DM patients with concomitant CKD. Clinical Trial registration http://www.clinicaltrials.gov. Identifier NCT01035320.

Effect of Treatment on Lipid Profile and Body Fat Composition in the Patients of Coronary Artery Diseases (CAD)

Introduction: CAD patients are aggressively treated for lipid lowering. However, CAD risk people remain untreated. We aim to compare lipids and body fat composition of these two groups and study the effect of lipid lowering treatment. Methods: 477 subjects divided in three groups: documented CAD (n = 153), CAD risk (n = 174) and control (n = 150). CAD patients: documented CAD with prior high dose lipid lowering treatment for minimum six weeks. CAD risk: those with metabolic syndrome (based on NCEP-ATPIII) or with Framingham 10 year risk > 10%. We measured body fat percentage (BF%), visceral fat rating (VFR) by bioelectrical impedance using InnerScanV (TANITA Inc, Tokyo) & lipid profile; trigylcerides (TG), total cholesterol (TC), low and high density lipoprotein (LDL, HDL). Groups were compared by one way ANOVA and Tukey's test. Results: TG, TC, and LDL were raised and HDL reduced in risk group while lipid profile was similar in CAD patients and control apart from HDL which was lower in CAD patients. BF% was higher in risk group and not different between CAD patients and control. VFR of CAD patients was higher from risk and control.Tabled 1VariablesControl (n = 153)CAD Risk (n = 174)CAD Patients (n = 150)TG (mg/dl)136.76 ± 5.37204.09 ± 6.63ap<0.05 as compared to control group.140.63 ± 4.65bp<0.05 as compared to risk group.TC (mg/dl)158.21 ± 3.42194.19 ± 3.84ap<0.05 as compared to control group.160.83 ± 3.22bp<0.05 as compared to risk group.HDL (mg/dl)39.48 ± 0.9731.28 ± 0.87ap<0.05 as compared to control group.35.65 ± 0.64ap<0.05 as compared to control group.,bp<0.05 as compared to risk group.LDL (mg/dl)91.38 ± 3.08122.58 ± 3.78ap<0.05 as compared to control group.97.06 ± 2.83bp<0.05 as compared to risk group.BF%23.92 ± 0.7530.72 ± 0.64ap<0.05 as compared to control group.25.44 ± 0.76bp<0.05 as compared to risk group.VFR7.77 ± 0.2610.03 ± 0.23ap<0.05 as compared to control group.11.30 ± 0.38ap<0.05 as compared to control group.,bp<0.05 as compared to risk group.a p < 0.05 as compared to control group.b p < 0.05 as compared to risk group. Open table in a new tab Conclusion: As a result of aggressive lipid lowering treatment, TG, TC, LDL and BF% were significantly lower in CAD patients; similar to control. Minimal effect of treatment was seen on HDL and VFR. There is need of more aggressive treatment in CAD risk population.

A multi-center, open label, crossover designed prospective study evaluating the effects of lipid lowering treatment on steroid synthesis in patients with Type 2 diabetes (MODEST Study)

It has been suggested that lipid-lowering treatment with the use of statins adversely affects the steroid hormones. However, the safety of lipid lowering treatment targeting very low levels of LDL with respect to the steroid hormones has not been established. A prospective, randomized, multicenter trial was conducted involving 98 patients. The patients were randomized into 2 groups: group-I received 10 mg of atorvastatin plus 10 mg of ezetimibe and group-II 80 mg of atorvastatin for the first 3 months. After crossover, the first group received 80 mg of atorvastatin and the second group 10 mg of atorvastatin plus 10 mg of ezetimibe for the following 3 months. Cortisol, DHEAS, testosterone, and estradiol levels were measured at the enrollment and at the end of the 1st, 2nd, 3rd, and 6th months. Along with a decrease in LDL level, the levels of DHEAS, testosterone, and estradiol decreased in both groups (p<0.001). While cortisol levels were maintained in the group given 10 mg of atorvastatin plus 10 mg of ezetimibe, it decreased significantly after the crossover to 80 mg of atorvastatin (p<0.001). The group initially given 80 mg of atorvastatin measured a lower level of cortisol for the first 3 months and it returned to normal levels after switching to 10 mg of atorvastatin plus 10 mg of ezetimibe. Eighty milligrams of atorvastatin decreased all adrenal and gonadal steroids, whereas 10 mg of ezetimibe combined with 10 mg of atorvastatin had at least no impact on cortisol levels.

A 005 Early Effects of Lipid Lowering Treatment in Subjects with Metabolic Syndrome and Acute Coronary Syndromes

A 005 Early Effects of Lipid Lowering Treatment in Subjects with Metabolic Syndrome and Acute Coronary Syndromes

Plasma Lipid Levels in the Elderly Are Not Associated with the Risk of Mild Cognitive Impairment

Background: There are conflicting data relating plasma lipids to the risk of Alzheimer‘s disease (AD). We explored the association of plasma lipids to mild cognitive impairment (MCI), a transitional stage between normal cognition and dementia, in a prospective community-based cohort study among randomly sampled Medicare recipients ≧65 years. Baseline data were collected from 1992 to 1994, follow-up data were collected at 18-month intervals. Methods: Multivariate proportional hazards regression was used to relate plasma lipid levels to incident total MCI, amnestic MCI and nonamnestic MCI in 854 persons without MCI or dementia at baseline. Results: There were 324 cases of incident MCI, 153 cases of amnestic MCI and 171 cases of nonamnestic MCI during 4,189 person-years of follow-up. Higher levels of total cholesterol and LDL were associated with a decreased risk of total MCI in models adjusting for age and sex. However, these associations were attenuated after adjusting for ethnicity, education, APOEΕ4 and vascular risk factors. There was no association between lipids and the risk of amnestic or nonamnestic MCI, and there was no effect of lipid-lowering treatment on MCI risk. Conclusions: Plasma lipid levels or lipid-lowering treatment in the elderly are not associated with the risk of MCI.

Pharmacogenetic study of cholesteryl ester transfer protein gene and simvastatin treatment in hypercholesterolaemic subjects

Objective: To examine the effect of the I405V and TaqIB polymorphisms of cholesteryl ester transfer protein (CETP) on the lipid response after simvastatin treatment in 180 hypercholesterolaemic patients. Methods: Hypercholesterolaemic patients (n = 180) attending the lipid clinic at the Onassis Cardiac Surgery Center were genotyped and their response to simvastatin was evaluated. Results: Sequence variations in the CETP gene influenced the effect of lipid-lowering treatment. Specifically, the I allele of the I405V polymorphism was associated with a greater reduction in triglyceride (TG; p = 0.04) and a significant increase in high-density lipoprotein cholesterol (HDL-C) levels (p = 0.05) after treatment compared with the V allele. Conclusions: The authors' findings suggest that CETP I405V polymorphism modifies the effect of simvastatin on TG reduction and HDL-C elevation; the carriers of the I allele responded better to treatment. These findings need to be confirmed in larger studies.

Endothelial function, arterial stiffness and lipid lowering drugs

The endothelium is a dynamic organ that plays a pivotal role in cardiovascular homeostasis. Alteration in endothelial function precedes the development of atherosclerosis and contributes to its initiation, perpetuation and clinical manifestations. It has been suggested that the assessment of endothelial function could represent a barometer of vascular health that could be used to gauge cardiovascular risk. This review summarises the various methods used to assess endothelium-dependent vasodilatation and their potential prognostic implications. In addition, the techniques used to evaluate arterial stiffness are discussed. The latter is to some extent controlled by the endothelium and has been the subject of considerable research in recent years. This paper also discusses the effects of lipid lowering treatment on both endothelial function and arterial stiffness.

Estimation of Effect of Lipid Lowering Treatment on Total Mortality Rate and Its Cost-Effectiveness Determined by Intervention Study of Hypercholesterolemia

Total cholesterol (TC) level reduction decreases coronary heart disease (CHD) risk, but it is also associated with an increase in non-CHD mortality rate. Our objectives are to estimate the effect of TC level reduction on total mortality and other mortalities in the Japanese population using published data and to analyze the cost-effectiveness of drug therapy. We analyzed three data sets for the estimation. The first data set comprised Japanese mortality rates of cardiac diseases, cerebrovascular/other vascular diseases, malignancy, and all causes according to sex and age. The second data set comprised the distributions of serum TC levels in the Japanese population. The third data set comprised the relative risks of mortality rates for the above causes according to the TC level classified into discrete intervals of 20 mg/dl from an intervention study. We estimated the mortality rates of people aged 30-69, with each TC level classification group on the basis of each cause. On the assumption that TC level decreases from 240-259 mg/dl to 160-179 mg/dl or 180-199 mg/dl with drug therapy, we calculated the differences between the mortalities of the classification. When we found a positive effect of TC level reduction, we performed cost-effectiveness analyses of Number Needed to Treat (NNT). TC level reduction increased the mortality rates except for that of cardiac diseases, and the NNT for cardiac diseases was in the range of 4,202-17,533. The cost of simvastatin, for example, was 0.25-1.05 billion yen per year. TC level reduction from 240-259 mg/dl to 160-199 mg/dl leads to an increase in total mortality rate in the Japanese population. The treatment should be reevaluated from both viewpoints of risk benefit and cost-effectiveness.

Pharmacological treatment of severe dyslipidaemia in patients with schizophrenia.

Mortality rates in patients with schizophrenia are double compared with the general population, with cardiovascular disease causing 50% of the excess. Lowering low-density lipoprotein cholesterol is recognized as a primary target for the prevention of cardiovascular mortality. The effects of lipid-lowering treatment were evaluated in patients with schizophrenia. Forty-six patients with schizophrenia and with severe dyslipidaemia were identified. All were treated with antipsychotics. Patients were screened for cardiovascular risk factors and examined at baseline when statin therapy was initiated. The effects of lipid-lowering medication on lipid profile, glucose homeostasis and components of metabolic syndrome were evaluated at 3 months follow-up. After 3 months of statin therapy, a significant decrease in triglycerides, total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and, in associated ratios, low-density lipoprotein/high-density lipoprotein, cholesterol/high-density lipoprotein was observed. No significant changes occurred in high-density lipoprotein cholesterol, body mass index, waist circumference or glucose homeostasis. The only component of metabolic syndrome affected by statin therapy has been the serum triglyceride level. Statins proved effective in the management of dyslipidaemia in patients with schizophrenia treated with antipsychotics. More complex treatment may be required for associated metabolic disturbances.