Hydrophilic or Lipophilic Statins? Climent, Elisenda; Benaiges, David; Pedro-Botet, Juan
Frontiers in cardiovascular medicine,
05/2021, Volume:
8
Journal Article
Peer reviewed
Open access
Drugs can be classified as hydrophilic or lipophilic depending on their ability to dissolve in water or in lipid-containing media. The predominantly lipophilic statins (simvastatin, fluvastatin, ...pitavastatin, lovastatin and atorvastatin) can easily enter cells, whereas hydrophilic statins (rosuvastatin and pravastatin) present greater hepatoselectivity. Although the beneficial role of statins in primary and secondary cardiovascular prevention has been unequivocally confirmed, the possible superiority of one statin or other regarding their solubility profile is still not well-established. In this respect, although some previously published observational studies and clinical trials observed a superiority of lipophilic statins in cardiovascular outcomes, these results could also be explained by a greater low-density lipoprotein cholesterol reduction with this statin type. On the other hand, previous studies reported conflicting results as to the possible superiority of one statin type over the other regarding heart failure outcomes. Furthermore, adverse events with statin therapy may also be related to their solubility profile. Thus, the aim of the present review was to collect clinical evidence on possible differences in cardiovascular outcomes among statins when their solubility profile is considered, and how this may also be related to the occurrence of statin-related adverse effects.
Introduction
Cardiovascular disease is a health concern in ageing population with opioid use disorders (OUD). The study aims to analyse the cardiovascular risk factors in individuals with OUD.
...Methods
An observational study was carried out to compare cardiovascular risk factors of adults >50 years with OUD on methadone therapy from public outpatient drug treatment centres, with that of an age‐ and gender‐matched sample (ratio of 1:5) of subjects from a sample of the Spanish population (REGICOR cohort). High cardiovascular risk (HCVR) at 10 years was defined according to Framingham‐REGICOR and SCORE risk functions.
Results
The individuals studied included 94 people with OUD and 495 from the general population; the mean age was 55.7 ± 4.8 years and 432 (72.7%) were men. Obesity (21.2% vs. 35.2%), hypertension (26.3% vs. 42.1%), total cholesterol (30.3% vs. 65.4%) and LDL‐cholesterol ≥130 mg/dL (27.2% vs. 59.3%) were significantly more prevalent in the general population group, while tobacco smoking (96.0% vs. 25.9%), low HDL‐cholesterol (46.5% vs. 21.2%), hypertriglyceridaemia (39.4% vs. 18.8%) and atherogenic dyslipidaemia (30.3% vs. 10.5%) were significantly higher in individuals with OUD. Differences in abdominal obesity (62.6% vs. 65.3%) were not significant. HCVR was more prevalent in patients with OUD: 15.2% versus 5.8% (Framingham‐REGICOR function) and 21.2% versus 11.3% (SCORE function).
Discussion and Conclusions
Older adults with OUD on methadone therapy have a different prevalence of cardiovascular risk factors and HCVR than the general population. Preventive measures, particularly tobacco smoking cessation and weight control, should be included in the routine care of individuals with OUD.
Sleeve gastrectomy(SG) is a restrictive bariatric surgery technique that was first used as part of restrictive horizontal gastrectomy in the original Scopinaro type biliopancreatic diversion. Its ...good results as a single technique have led to a rise in its use, and it is currently the second most performed technique worldwide. SG achieves clearly better results than other restrictive techniques and is comparable in some aspects to the Roux-en-Y gastric bypass, the current gold standard in bariatric surgery. These benefits have been associated with different pathophysiologic mechanisms unrelated to weight loss such as increased gastric emptying and intestinal transit, and activation of hormonal mechanisms such as increased GLP-1 hormone and decreased ghrelin. The aim of this review was to highlight the salient aspects of SG regarding its historical evolution, pathophysiologic mechanisms, main results, clinical applications and perioperative complications.
Furthermore, neurotensin-deficient mice exhibited reduced intestinal fat absorption and were protected against diet-induced obesity, liver steatosis, and diabetes, despite having similar feeding ...conditions and energy expenditure compared with their wild-type littermates, which further complicates the issue (7). Furthermore, it should be taken into account that recent studies have revealed that within the gastrointestinal tract, neurotensin, peptide YY (PYY), and glucagon-like peptide-1 (GLP-1) are not only coexpressed but also cosecreted in response to a wide range of stimuli, including bile acids (9). ...neurotensin has been shown to act synergistically with GLP-1 and PYY when administered peripherally. ...it is important to recognize stimulus-dependent neurotensin and its possible lack in pathological conditions.
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.
Although statins have a satisfactory safety profile and are well tolerated, many statin-treated patients report muscle symptoms in clinical practice which contribute to drug discontinuation and, ...consequently, adverse cardiovascular outcomes.
This narrative review will cover the definition and prevalence of statin intolerance, the clinical spectrum of statin-associated muscle symptoms (SAMS) with special focus on patients with only mild myalgias, the complexity of statin muscle intolerance diagnosis and provide an overview on the nocebo effect of particular importance for physicians.
Many patients are unable to tolerate statin therapy, with SAMS being the most common cause of statin intolerance. The reported incidence of SAMS was consistently lower in randomized placebo-controlled trials than in observational studies. These results strongly suggested that SAMS were not always due to by the pharmacologic effects of statin therapy. Convincing patients that their muscle symptoms might be due to causes other than statin treatment is sometimes difficult. Furthermore, clinicians should not prematurely discontinue statin therapy before considering other possible causes, including the nocebo effect.
The burden of cardiovascular disease is particularly high among individuals with diabetes, even when LDL cholesterol is normal or within the therapeutic target. Despite this, cholesterol accumulates ...in their arteries, in part, due to persistent atherogenic dyslipidaemia characterized by elevated triglycerides, remnant cholesterol, smaller LDL particles and reduced HDL cholesterol. The causal link between dyslipidaemia and atherosclerosis in T2DM is complex, and our contention is that a deeper understanding of lipoprotein composition and functionality, the vehicle that delivers cholesterol to the artery, will provide insight for improving our understanding of the hidden cardiovascular risk of diabetes. This narrative review covers three levels of complexity in lipoprotein characterization: 1-the information provided by routine clinical biochemistry, 2-advanced nuclear magnetic resonance (NMR)-based lipoprotein profiling and 3-the identification of minor components or physical properties of lipoproteins that can help explain arterial accumulation in individuals with normal LDLc levels, which is typically the case in individuals with T2DM. This document highlights the importance of incorporating these three layers of lipoprotein-related information into population-based studies on ASCVD in T2DM. Such an attempt should inevitably run in parallel with biotechnological solutions that allow large-scale determination of these sets of methodologically diverse parameters.
In a cohort of women with previous gestational diabetes mellitus (GDM), we aimed to ascertain whether women with abnormal glucose tolerance 1-year postdelivery had a more atherogenic lipid profile ...during and after pregnancy than those with normal glucose tolerance. A prospective cohort study with longitudinal design between January 2004 and March 2016 was conducted. Three hundred and six (56.8%) of 537 women diagnosed with GDM during the studied period attended a control visit during the first year after delivery. Of these, 112 (36.6%) had prediabetes and 16 (5.2%) had type 2 diabetes mellitus. No significant differences during pregnancy were found in total, low-density lipoprotein, high-density lipoprotein (HDL) cholesterol, and triacylglycerol (TAG) concentrations among the three groups. Only HDL cholesterol and TAG levels differed significantly among groups at 2 and 12 months after delivery. Logistic regression analysis revealed pregnancy HDL and glucose metabolism status to be associated with the HDL cholesterol concentration 1-year postdelivery. Furthermore, the only independent factor associated with TAG levels 1 year after delivery was the gestational TAG concentration. In summary, an overweight multiethnic group of women with prior GDM presented a high incidence of postpartum dysglycemia (41.8%). HDL-cholesterol and TAG levels, both components of the metabolic syndrome, differed significantly among the three study groups in the glucose-metabolism status at 2 and 12 months after delivery. Women with previous GDM must be followed up in the postpartum period for early detection and management of lipid and glucose disorders.
Background and Aim
Transient elastography is the reference method for liver stiffness measurement (LSM) in the general population, having lower applicability in obese patients. We evaluated the ...applicability and diagnostic accuracy of the M and XL probes in overweight/obese patients to establish the most appropriate approach.
Methods
From May 2013 to March 2015, we evaluated patients with a body mass index (BMI) ≥ 28 kg/m2. We constructed an algorithm with variables independently related to unreliable LSM with the M probe.
Results
A total of 1084 patients were evaluated. M and XL probe applicability was 88.8% and 98%, respectively. Waist circumference (WC) (OR; 95% CI; P) (0.97; 0.94–0.99; P < 0.001) and skin‐capsule distance (SCD) (0.83; 0.79–0.87; P < 0.001) were independently related to unreliable LSM (M probe). The SCD was > 25 mm in 5.5% of individuals with a BMI ≤ 35 kg/m2 and a WC ≤ 117 cm, with LSM (M probe) applicability rising to 94.3%. In contrast, 36.9% of patients with a BMI > 35 kg/m2 and/or a WC > 117 cm presented an SCD > 25 mm, with M probe applicability being 73.1%. The diagnostic accuracy (area under the receiver operator characteristic) using the M probe to identify significant steatosis (0.76), fibrosis (0.89), and cirrhosis (0.96) was very high in patients with a BMI ≤ 35 kg/m2 and a WC ≤ 117 cm.
Conclusions
The applicability and accuracy of the FibroScan® M probe to identify fibrosis and steatosis was excellent in overweight and obesity grade I (BMI ≤ 35 kg/m2) with a WC ≤ 117 cm. The XL probe increased the applicability of transient elastography in obesity grade II–III (BMI > 35 kg/m2).
Familial hypercholesterolemia (FH) is characterized by high low-density lipoprotein (LDL) cholesterol with co-dominant transmission and high risk of cardiovascular disease (CVD), although with high ...variability among subjects. Currently, CVD stratification tools for heterozygous FH (HeFH) are not available. A definition of severe HeFH has been recently proposed by the International Atherosclerosis Society (IAS), but it has not been validated. Our study aims to see clinical characteristics and prevalence of CVD in subjects defined as severe HeFH by IAS criteria. Probable or definite HeFH introduced in the Dyslipidemia Registry of Spanish Arteriosclerosis Society were analyzed by the IAS criteria. Univariate and multivariate analysis was used to assess the association of CVD with the IAS criteria. About 1,732 HeFH cases were analyzed. Severe HeFH had higher prevalence of familial history of CVD, personal history of tendon xanthomas, LDL cholesterol, and CVD than nonsevere HeFH. A total of 656 (77.1%) and 441 (50.1%) of men and women, respectively, fulfilled the IAS criteria of severe HeFH. In the univariate analysis, subjects defined as severe HeFH showed odds ratio 3.016 (95% CI 3.136 to 4.257, p <0.001) for CVD. However, when traditional risk factors were included in the multivariate analysis, only the presence of cholesterol >400 mg/dl had a statistically significant association with CVD odds ratio 8.76 (95% CI 3.90 to 19.69, p <0.001). In conclusion, the IAS definition of severe HeFH is not significantly associated with CVD when adjusted for classic risk factors. Risk stratification in HeFH is an important issue, but the proposed criteria do not seem to solve this problem.
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