Physical signs and atherosclerotic cardiovascular disease in familial hypercholesterolemia: the HELLAS-FH Registry.

AIMS: Three physical signs, namely tendon xanthomas, corneal arcus and xanthelasma, have been associated with heterozygous familial hypercholesterolemia (heFH). The prevalence and clinical significance of these signs are not well established among contemporary heFH individuals. This study explored the frequency as well as the association of these physical signs with prevalent atherosclerotic cardiovascular disease (ASCVD) in heFH individuals. METHODS: Data from the Hellenic Familial Hypercholesterolemia Registry were applied for this analysis. The diagnosis of heFH was based on the Dutch Lipid Clinic Network Score. Multivariate logistic regression analysis was conducted to examine the association of heFH-related physical signs with prevalent ASCVD. RESULTS: Adult patients ( n  = 2156, mean age 50 ±â€Š15 years, 47.7% women) were included in this analysis. Among them, 14.5% had at least one heFH-related physical sign present. The prevalence of corneal arcus before the age of 45 years was 6.6%, tendon xanthomas 5.3%, and xanthelasmas 5.8%. Among physical signs, only the presence of corneal arcus before the age of 45 years was independently associated with the presence of premature coronary artery disease (CAD). No association of any physical sign with total CAD, stroke or peripheral artery disease was found. Patients with physical signs were more likely to receive higher intensity statin therapy and dual lipid-lowering therapy, but only a minority reached optimal lipid targets. CONCLUSION: The prevalence of physical signs is relatively low in contemporary heFH patients. The presence of corneal arcus before the age of 45 years is independently associated with premature CAD.

Obesity and atherosclerotic cardiovascular disease in adults with heterozygous familial hypercholesterolemia: An analysis from HELLAS-FH registry.

BACKGROUND: Familial hypercholesterolemia (FH) and obesity are well-established risk factors of atherosclerotic cardiovascular disease (ASCVD). Despite high prevalence, their joint association with ASCVD remains largely unknown. OBJECTIVE: To investigate the association of obesity with prevalent ASCVD in individuals with heterozygous FH (HeFH) enrolled in the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). METHODS: FH diagnosis was based on Dutch Lipid Clinic Network (DLCN) criteria. Adults with at least possible FH diagnosis (DLCN score ≥3) and available body mass index (BMI) values were included. Homozygous FH individuals were excluded. RESULTS: 1655 HeFH adults (mean age 51.0 ± 14.4 years, 48.6% female) were included; 378 (22.8%) and 430 (26.0%) were diagnosed with probable and definite FH, respectively. Furthermore, 371 participants (22.4%) had obesity and 761 (46.0%) were overweight. Prevalence of ASCVD risk factors increased progressively with BMI. Prevalence of coronary artery disease (CAD) was 23.4% (3.2% for stroke and 2.7% for peripheral artery disease, PAD), and increased progressively across BMI groups. After adjusting for traditional ASCVD risk factors and lipid-lowering medication, individuals with obesity had higher odds of established CAD (OR: 1.54, 95% CI: 1.04-2.27, p = 0.036) as well as premature CAD (OR: 1.74, 95% CI: 1.17-2.60, p = 0.009) compared with those with normal BMI. No association was found with stroke or PAD. CONCLUSIONS: Over half of adults with HeFH have overweight or obesity. Obesity was independently associated with increased prevalence of CAD in this population.

Association of Alkaline Phosphatase with Cardiovascular Disease in Patients with Dyslipidemia: A 6-Year Retrospective Study.

BACKGROUND AND AIM: Serum alkaline phosphatase (ALP) activity has been associated with atherosclerotic cardiovascular disease (ASCVD). We aimed to investigate the association of ALP with ASCVD in patients with dyslipidemia. METHODS: We conducted a retrospective cohort study including consecutive adults with dyslipidemia followed-up for ≥3 years (from 1999 to 2022) in the outpatient Lipid Clinic of Ioannina University General Hospital, Greece. The primary endpoint was the association between baseline ALP and incident ASCVD after adjusting for traditional risk factors (i.e., sex, age, hypertension, diabetes, smoking, and dyslipidemia), baseline ASCVD, and lipid-lowering treatment. ALP levels were stratified by tertiles as follows: low: <67 U/L, middle: 67-79 U/L, high: ≥79 U/L. RESULTS: Overall, 1178 subjects were included; 44% were males, and their median age was 57 years (range: 49-65). During a 6-year median follow-up (interquartile range: IQR: 4-9), 78 new ASCVD events (6.6%) occurred. A statistically significant association between baseline ALP levels and incident ASCVD was demonstrated (Odds Ratio, OR: 6.99; 95% Confidence Interval, CI: 2.29-21.03, p = 0.001). Subjects in the highest ALP tertile had the highest odds for ASCVD when compared with those in the lowest tertile (OR: 2.35; 95% CI: 1.24-4.41, p = 0.008). CONCLUSIONS: The present study indicates an association between ALP and the development of ASCVD in patients with dyslipidemia, which underscores the potential of ALP as a predictive tool or a therapeutic target in the realm of ASCVD prevention within this population.

Familial Hypercholesterolemia in the Elderly: An Analysis of Clinical Profile and Atherosclerotic Cardiovascular Disease Burden from the Hellas-FH Registry.

BACKGROUND: Familial hypercholesterolemia (FH) carries a high risk of atherosclerotic cardiovascular disease (ASCVD). As the population ages, the age-related influence on clinical characteristics and outcomes becomes increasingly pertinent. This cross-sectional analysis from the HELLAS-FH registry aims to explore potential differences in clinical characteristics, treatment, ASCVD, and goal achievement between those younger and older than 65 years with FH. RESULTS: A total of 2273 adults with heterozygous FH (51.4% males) were studied. Elderly FH patients (n = 349) had a higher prevalence of ASCVD risk factors, such as hypertension (52.1% vs. 20.9%, p < 0.05) and type 2 diabetes (16.9% vs. 6.0%, p < 0.05), compared to younger patients (n = 1924). They also had a higher prevalence of established ASCVD (38.4% vs. 23.1%, p < 0.001), particularly CAD (33.0% vs. 20.2%, p < 0.001), even after adjusting for major ASCVD risk factors. Elderly patients were more frequently and intensively receiving lipid-lowering treatment than younger ones. Although post-treatment LDL-C levels were lower in elderly than younger patients (125 vs. 146 mg/dL, p < 0.05), both groups had similar attainment of the LDL-C target (3.7% vs. 3.0%). CONCLUSIONS: Elderly FH patients have a higher prevalence of ASCVD, particularly CAD. Despite more aggressive treatment, the achievement of LDL-C targets remains very poor. These results emphasize the importance of early FH diagnosis and treatment in reducing ASCVD.

Effects of Lipid-Modifying and Other Drugs on Lipoprotein(a) Levels-Potent Clinical Implications.

The past few years have shown an ongoing interest in lipoprotein(a) (Lp(a)), a lipid molecule that has been proven to have atherogenic, thrombogenic, and inflammatory properties. Several lines of evidence, indeed, have demonstrated an increased risk of cardiovascular disease as well as calcific aortic valve stenosis in patients with elevated Lp(a) levels. Statins, the mainstay of lipid-lowering therapy, slightly increase Lp(a) levels, while most other lipid-modifying agents do not significantly alter Lp(a) concentrations, except for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. The latter have been shown to reduce Lp(a) levels; however, the clinical significance of this effect has not been clearly elucidated. Of note, the pharmaceutical lowering of Lp(a) may be achieved with novel treatments specifically designed for this purpose (i.e., antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs)). Large clinical trials with cardiovascular outcomes with these agents are ongoing, and their results are eagerly awaited. Furthermore, several non-lipid-modifying drugs of various classes may influence Lp(a) concentrations. We have searched MEDLINE, EMBASE, and CENTRAL databases up to 28 January 2023 and summarized the effects of established and emerging lipid-modifying drugs and other medications on Lp(a) levels. We also discuss the potent clinical implications of these alterations.

A step-by-step guide for the diagnosis and management of hyponatraemia in patients with stroke.

Hyponatraemia is common in patients with stroke and associated with adverse outcomes and increased mortality risk. The present review presents the underlying causes and provides a thorough algorithm for the diagnosis and management of hyponatraemia in stroke patients. Concomitant diseases and therapies, such as diabetes, chronic kidney disease and heart failure, along with diuretics, antidepressants and proton pump inhibitors are the most common causes of hyponatraemia in community. In the setting of acute stroke, the emergence of hyponatraemia might be attributed to the administration of hypotonic solutions and drugs (ie. mannitol and antiepileptics), poor solute intake, infections, as well as stroke-related conditions or complications, such as the syndrome of inappropriate secretion of antidiuretic hormone, cerebral salt wasting syndrome and secondary adrenal insufficiency. Diagnostically, the initial step is to differentiate hypotonic from non-hypotonic hyponatraemia, usually caused by hyperglycaemia or recent mannitol administration in patients with stroke. Determining urine osmolality, urine sodium level and volume status are the following steps in the differentiation of hypotonic hyponatraemia. Of note, specific parameters, such as fractional uric acid and urea excretion, along with plasma copeptin concentration, may further improve the diagnostic yield. Therapeutic options are based on the duration and symptoms of hyponatremia. In the case of acute or symptomatic hyponatraemia, hypertonic saline administration is recommended. Hypovolaemic chronic hyponatremia is treated with isotonic solution administration. Although fluid restriction remains the first-line treatment for the rest forms of chronic hyponatraemia, therapies increasing renal free water excretion may be necessary. Loop diuretics and urea serve this purpose in patients with stroke, whereas sodium-glucose transport protein-2 inhibitors appear to be a promising therapy. Nevertheless, it is yet unclear whether the appropriate restoration of sodium level improves outcomes in such patients. Randomized trials designed to compare therapeutic strategies in managing hyponatraemia in patients with stroke are required.

Association of Fatty Liver Index with Incident Diabetes Risk in Patients Initiating Statin-Therapy: A 6-Year Retrospective Study.

BACKGROUND: Statins are associated with new-onset type 2 diabetes (T2D), mainly in patients with metabolic syndrome (MetS). The fatty liver index (FLI) is used as a prognostic score for the diagnosis of non-alcoholic fatty liver disease (NAFLD), which is common in patients with MetS. We aimed to investigate the association of FLI with new-onset T2D in patients initiating statin therapy. METHODS: A retrospective observational study including 1241 individuals with dyslipidemia and followed up for ≥3 years. Patients with T2D and those receiving lipid-lowering treatment at the baseline visit were excluded. Models with clinical and laboratory parameters were used to assess the association of FLI with incident T2D. RESULTS: Among the 882 eligible subjects, 11% developed T2D during the follow-up (6 years; IQR: 4-10 years). After adjusting for sex, age and MetS parameters, a multivariate analysis revealed that age (HR:1.05; 95%CI: 1.01-1.09, p < 0.05), fasting plasma glucose (HR: 1.09; 95%CI: 1.06-1.13, p < 0.001) and FLI (HR: 1.02; 95%CI: 1.01-1.04, p < 0.01) were independently associated with T2D risk. The subjects with probable NAFLD (FLI ≥ 60) had a three-fold increased T2D risk compared with the subjects with FLI < 60 (HR: 3.14; 95%CI: 1.50-6.59, p = 0.001). A ROC curve analysis showed that FLI had a significant, although poor, predictive value for assessing T2D risk (C-Statistic: 0.67; 95%CI: 0.58-0.77, p = 0.001). Higher FLI values were associated with reduced T2D-free survival (log-rank = 15.46, p < 0.001). CONCLUSIONS: FLI is significantly and independently associated with new-onset T2D risk in patients initiating statin therapy.

The Effect of Commonly Used Fixed-Dose Single Pill Combinations of Renin-Angiotensin-System Blockers and Calcium Channel Blockers on HOMA-IR Index in Hypertensive Patients with Impaired Fasting Glucose: a 12-Week Randomized Open-Label Prospective Study.

Backround: The effect of antihypertensive drugs on glucose homeostasis and insulin resistance remains an issue under investigation. There is evidence that renin-angiotensin system (RAS) blockers may favorably affect glucose metabolism, while treatment with calcium channel blockers (CCBs) is considered to have an overall neutral metabolic effect. However, the effects on glycemic indices may differ among agents within the same class of antihypertensive drugs. Objective: To evaluate the effects of different fixed-dose single pill combinations of RAS blockers with CCBs on homeostatic model assessment for insulin resistance (HOMA-IR). Methods:Drug-naive patients with arterial hypertension (AH) and impaired fasting glucose (IFG) were randomly allocated to open-label fixed, single pill combinations of valsartan 160 mg/day plus amlodipine 5 mg/day (VAL/AMLO group, n = 54), delapril 30 mg/day and manidipine 10 mg/day (DEL/MANI group, n = 53) or telmisartan 80 mg/day and amlodipine 5 mg/day (TEL/AMLO group, n = 51) for 12 weeks. Glycemic indices and HOMA-IR were determined at baseline and post-treatment. Results:A total of 158 patients were included. All treatment combinations effectively reduced blood pressure (systolic and diastolic) to similar levels (all p < 0.001). A decrease in the HOMA-IR index by 22.55% (p <0.01) was noted following treatment with TEL/AMLO, while an increase by 1.4% (p = 0.57) and 12.65% (p = 0.072) was observed in the VAL/AMLO group and the DEL/MANI group, respectively. These changes were significantly different between TEL/AMLO and DEL/MANI (p < 0.05) as well as between TEL/AMLO and VAL/AMLO (p < 0.001). Conclusion:Despite similar antihypertensive action, the effect of fixed, single pill combinations with TEL/AMLO, VAL/AMLO and DEL/MANI on insulin resistance is in favor of TEL/AMLO. Trial registration: The study protocol was published online in https://diavgeia.gov.gr/ (No: ÂÈ6Ó46906Ç-ÁÅÓ) via the Ministry of Digital Governance, after receiving approval from the Scientific Council and Administrative Council of University Hospital of Ioannina (No. of approval: 1/12-06-2014 (issue 150). https://diavgeia.gov.gr/decision/view/%CE%92%CE%986%CE%A346906%CE%97- %CE%91%CE%95%CE%A3 h t t p s : / / d i a v g e i a . g o v . g r / d o c / % C E % 9 2 % C E % 9 8 6 % C E % A 3 4 6 9 0 6 % C E % 9 7 - %CE%91%CE%95%CE%A3?inline=true.

Familial Hypercholesterolemia and Lipoprotein(a): A Gordian Knot in Cardiovascular Prevention.

Familial hypercholesterolemia (FH) is the most frequent genetic disorder resulting in increased low-density lipoprotein cholesterol (LDL-C) levels from childhood, leading to premature atherosclerotic cardiovascular disease (ASCVD) if left untreated. FH diagnosis is based on clinical criteria and/or genetic testing and its prevalence is estimated as being up to 1:300,000−400,000 for the homozygous and ~1:200−300 for the heterozygous form. Apart from its late diagnosis, FH is also undertreated, despite the available lipid-lowering therapies. In addition, elevated lipoprotein(a) (Lp(a)) (>50 mg/dL; 120 nmol/L), mostly genetically determined, has been identified as an important cardiovascular risk factor with prevalence rate of ~20% in the general population. Novel Lp(a)-lowering therapies have been recently developed and their cardiovascular efficacy is currently investigated. Although a considerable proportion of FH patients is also diagnosed with high Lp(a) levels, there is a debate whether these two entities are associated. Nevertheless, Lp(a), particularly among patients with FH, has been established as a significant cardiovascular risk factor. In this narrative review, we present up-to-date evidence on the pathophysiology, diagnosis, and treatment of both FH and elevated Lp(a) with a special focus on their association and joint effect on ASCVD risk.

Hyponatremia in Patients with Heart Failure beyond the Neurohormonal Activation Associated with Reduced Cardiac Output: A Holistic Approach.

BACKGROUND: Heart failure (HF) is considered an epidemic disease with considerable morbidity, mortality, and immense healthcare costs. Electrolyte abnormalities are often encountered in patients with HF, posing a diagnostic and therapeutic challenge for clinicians. Hyponatremia affects up to one-third of HF patients and represents an unfavorable prognostic factor. SUMMARY: Low sodium levels in HF are mainly attributed to the neurohormonal activation secondary to decreased effective circulating volume. However, patients with HF often have several comorbidities which may cause or exacerbate the preexisting hyponatremia. Factors that provoke HF, such as alcohol overconsumption, may also be involved in hyponatremia development. Furthermore, drugs which are frequently prescribed to HF patients, especially diuretics, are potential culprits of hyponatremia and should always be addressed since their withdrawal may reverse hyponatremia. Despite the great prevalence and deleterious effects of hyponatremia in these patients, it is often overlooked and consequently undertreated. In this review, we present the mechanisms involved in the development of hyponatremia focusing on those besides neurohormonal activation. We also discuss the proper management of this electrolyte disorder which is frequently complex in patients with HF. KEY MESSAGES: Hyponatremia in patients with HF is not only the result of neurohormonal activation; several comorbidities and frequently used drugs should also be addressed. Hence, a holistic approach is required both for the diagnosis and optimal treatment.

Association between lipoprotein(a) concentrations and atherosclerotic cardiovascular disease risk in patients with familial hypercholesterolemia: an analysis from the HELLAS-FH.

AIMS: Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) in the general population. However, such a role in patients with familial hypercholesterolemia (FH) is less documented. The purpose of this study was to evaluate the association between Lp(a) concentrations and ASCVD prevalence in adult patients with FH. METHODS: This was a cross-sectional study from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). Patients were categorized into 3 tertiles according to Lp(a) levels. RESULTS: A total of 541 adult patients (249 males) with possible/probable/definite FH heterozygous FH (HeFH) were included (mean age 48.5 ± 15.0 years at registration, 40.8 ± 15.9 years at diagnosis). Median (interquartile range) Lp(a) concentrations in the 1st, 2nd and 3rd Lp(a) tertile were 6.4 (3.0-9.7), 22.4 (16.0-29.1) and 77.0 (55.0-102.0) mg/dL, respectively. There was no difference in lipid profile across Lp(a) tertiles. The overall prevalence of ASCVD was 9.4% in the first, 16.1% in the second and 20.6% in the third tertile (p = 0.012 among tertiles). This was also the case for premature ASCVD, with prevalence rates of 8.5, 13.4 and 19.8%, respectively (p = 0.010 among tertiles). A trend for increasing prevalence of coronary artery disease (8.3, 12.2 and 16.1%, respectively; p = 0.076 among tertiles) was also observed. No difference in the prevalence of stroke and peripheral artery disease was found across tertiles. CONCLUSIONS: Elevated Lp(a) concentrations are significantly associated with increased prevalence of ASCVD in patients with possible/probable/definite HeFH.

Early Investigational and Experimental Therapeutics for the Treatment of Hypertriglyceridemia.

Hypertriglyceridemia has been identified as a risk factor for cardiovascular disease and acute pancreatitis. To date, there are only few drug classes targeting triglyceride levels such as fibrates and ω-3 fatty acids. These agents are at times insufficient to address very high triglycerides and the residual cardiovascular risk in patients with mixed dyslipidemia. To address this unmet clinical need, novel triglyceride-lowering agents have been in different phases of early clinical development. In this review, the latest and experimental therapies for the management of hypertriglyceridemia are presented. Specifically, ongoing trials evaluating novel apolipoprotein C-III inhibitors, ω-3 fatty acids, as well as fibroblast growth 21 analogues are discussed.

Prevalence of Diabetes and Its Association with Atherosclerotic Cardiovascular Disease Risk in Patients with Familial Hypercholesterolemia: An Analysis from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH).

Familial hypercholesterolemia (FH) and type 2 diabetes mellitus (T2DM) are both associated with a high risk of atherosclerotic cardiovascular disease (ASCVD). Little is known about the prevalence of T2DM and its association with ASCVD risk in FH patients. This was a cross-sectional analysis from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH) including adults with FH (n = 1719, mean age 51.3 ± 14.6 years). Of FH patients, 7.2% had a diagnosis of T2DM. The prevalence of ASCVD, coronary artery disease (CAD), and stroke was higher among subjects with T2DM compared with those without (55.3% vs. 23.3%, 48.8% vs. 20.7%, 8.3% vs. 2.7%, respectively, p < 0.001). When adjusted for age, systolic blood pressure, smoking, body mass index, hypertension, waist circumference, triglyceride levels, high-density lipoprotein cholesterol levels, and gender, T2DM was significantly associated with prevalent ASCVD [OR 2.0 (95% CI 1.2−3.3), p = 0.004]. FH patients with T2DM were more likely to have undergone coronary revascularization than those without (14.2% vs. 4.5% for coronary artery bypass graft, and 23.9% vs. 11.5% for percutaneous coronary intervention, p < 0.001). T2DM is associated with an increased risk for prevalent ASCVD in subjects with FH. This may have implications for risk stratification and treatment intensity in these patients.

An overview of diagnosis and management of drug-induced hypomagnesemia.

Magnesium (Mg) is commonly addressed as the "forgotten ion" in medicine. Nonetheless, hypomagnesemia should be suspected in clinical practice in patients with relevant symptomatology and also be considered a predisposing factor for the development of other electrolyte disturbances. Furthermore, chronic hypomagnesemia has been associated with diabetes mellitus and cardiovascular disease. Hypomagnesemia as a consequence of drug therapy is relatively common, with the list of drugs inducing low serum Mg levels expanding. Culprit medications linked to hypomagnesemia include antibiotics (e.g. aminoglycosides, amphotericin B), diuretics, antineoplastic drugs (cisplatin and cetuximab), calcineurin inhibitors, and proton pump inhibitors. In recent years, the mechanisms of drug-induced hypomagnesemia have been unraveled through the discovery of key Mg transporters in the gut and kidney. This narrative review of available literature focuses on the pathogenetic mechanisms underlying drug-induced hypomagnesemia in order to increase the insight of clinicians toward early diagnosis and effective management.

Prevalence of Non-coronary Heart Disease in Patients with Familial Hypercholesterolemia: An Analysis from the HELLAS-FH.

AIMS: Despite the established link between familial hypercholesterolemia (FH) and increased risk of coronary heart disease (CHD), its association with other common atherosclerotic and metabolic diseases has not been extensively studied. The aim of this study was to report the prevalence of peripheral arterial disease (PAD) [i.e., common carotid artery disease (CCAD) and lower extremity arterial disease (LEAD)], aortic valve stenosis, chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) in patients with FH. MATERIALS & METHODS: This was a cross-sectional study retrieving data from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). RESULTS: A total of 1,633 adult patients (850 males) with heterozygous FH (HeFH) were included (mean age 51.3±14.6 years at registration and 44.3±15.9 years at diagnosis). Any common carotid artery stenosis (CCAS) was diagnosed in 124 out of 569 patients with available related data (21.8%), while the prevalence of CCAD (defined as a CCAS ≥50%) was 4.2%. The median (interquartile range - IQR) CCAS was 30% (20-40), whereas the median (IQR) carotid intima-media thickness (CIMT) was 0.7 (0.1-1.4) mm. LEAD was reported in 44 patients (prevalence 2.7%). The prevalence of aortic valve stenosis and CKD was 2.0% and 6.4%, respectively. NAFLD was present in 24% of study participants. CONCLUSION: HeFH is associated with a relatively high prevalence of any CCAS and CCAD. The prevalence of LEAD, CKD and aortic valve stenosis was relatively low, whereas the prevalence of NAFLD was similar to that of the general population.

Statin-associated side effects in patients attending a lipid clinic: evidence from a 6-year study.

Introduction: There is conflicting evidence regarding the actual incidence of statin-associated side effects in clinical practice. We aimed to record the incidence of statin-associated side effects in the setting of a lipid clinic. We focused on clinically relevant liver enzyme increase and statin-associated muscle symptoms (SAMS). Material and methods: This was a retrospective study including adult patients with dyslipidemia followed up for ≥ 3 years in a university hospital lipid clinic in Greece. We recorded the incidence of clinically relevant liver enzyme increase (> 3 × upper limit of normal (ULN) on 2 occasions) and SAMS (muscle crumps, creatine kinase (CK) increase > 10 × ULN and rhabdomyolysis) during follow-up. Results: Among study participants (n = 1,334), 3.1% and 2.8% presented with clinically relevant liver enzyme increase and SAMS at least once during a median follow-up of 6 years (4-10). Only 11% (n = 5) of subjects with a clinically relevant liver enzyme increase and 6% (n = 2) of those with SAMS did not tolerate any statin at any dose. Most subjects with a history of a clinically relevant liver enzyme increase or SAMS were eventually treated with a moderate- or high-intensity statin (76% and 80%, respectively) or with combination treatment of a statin plus another lipid-lowering drug (15% and 36%, respectively). No risk factors for these statin-associated side effects were identified. Conclusions: The incidence of statin-associated side effects is low in the setting of a lipid clinic. The vast majority of these individuals were still able to tolerate statin treatment.

Lipoprotein(a): A Concealed Precursor of Increased Cardiovascular Risk? A Real-World Regional Lipid Clinic Experience.

OBJECTIVE: Lipoprotein(a) [Lp(a)] is an independent cardiovascular risk factor. We present real-life characteristics of patients with increased Lp(a) levels attending a University Lipid Clinic. METHODS: We retrospectively studied patients attending the University of Ioannina Hospital Lipid Clinic with Lp(a) levels ≥30 mg/dL who were followed-up for a median of 22 months. RESULTS: One hundred eight patients (median age 59 years, 49% females) were included with median Lp(a) levels 67 mg/dL (30-320). Of patients, 25.1% had established atherosclerotic cardiovascular disease (ASCVD): 11.1 and 5.6% positive personal history of myocardial infarction (MI) and stroke, respectively, 6.5% carotid artery disease and 1.9% lower extremities arterial disease (LEAD). In addition, 35.2% of participants had heterozygous familial hypercholesterolemia (heFH), 37.9% positive family history of premature ASCVD, 29.6% hypertension, 12.0% diabetes and 5.5% chronic kidney disease (CKD). Of patients, 67.6% were receiving statin therapy and 16.6% additional ezetimibe at baseline visit, and 83 and 35% were receiving statin treatment and additional ezetimibe, respectively, during follow-up. Low-density cholesterol (LDL-C) levels and LDL-Ccorrected for Lp(a) levels were significantly reduced in lipid-lowering therapy naive patients by 37 and 40% (p <0.05), in lipid-lowering therapy intensified patients by 31 and 36% (p <0.05), and in patients on stable lipid-lowering treatment by 15% (p <0.05) and 10% (p >0.05), respectively, during follow-up. Lp(a) levels increased by 9% (p <0.05). CONCLUSION: Our data confirm the high prevalence of established ASCVD, hFH and positive familial history of premature ASCVD in patients with elevated Lp(a) levels. Lp(a) levels slightly increased during follow-up.

Hyperemesis Gravidarum: A Benign Condition of Pregnancy or a Challenging Metabolic Disorder?

Hyperemesis gravidarum (HG) is a complication mainly of the first trimester of pregnancy, which sometimes leads to metabolic disorders such as hypovolemia and acute kidney injury (AKI). Herein, we present the case of a 25-year-old woman at week 10 of gestation who exhibited a constellation ofsevere abnormalities, namely AKI (serum creatinine 6.15 mg/dl), transaminasemia (serum aminotransferases >1,000 IU/l), alkalemia (arterial pH7.667), hyponatremia (serum sodium 117 mEq/l), hypochloremia (serum chloride 54 mEq/l), hypokalemia (serum potassium 2.2 mEq/l) and hyperuricemia (serum uric acid 20 mg/dl). Despite a thorough work-up, no other disorder was found apart from HG. All symptoms and metabolic abnormalities resolved with targeted administration of intravenous fluids. The differential diagnosis of these disorders and therapeutic challenges are discussed. LEARNING POINTS: Hyperemesis gravidarum is a severe form of vomiting during pregnancy that typically occurs in the first trimester.It may lead to severe metabolic abnormalities including acute kidney injury (AKI), and electrolyte and acid-base disturbances.Early detection, thorough diagnostic evaluation and prompt management with fluid resuscitation are essential for the well-being of both the mother and the fetus.

Hyponatremia in Patients with Hematologic Diseases.

Hyponatremia is the most common electrolyte disorder in clinical practice and is associated with increased morbidity and mortality. It is frequently encountered in hematologic patients with either benign or malignant diseases. Several underlying mechanisms, such as hypovolemia, infections, toxins, renal, endocrine, cardiac, and liver disorders, as well as the use of certain drugs appear to be involved in the development or the persistence of hyponatremia. This review describes the pathophysiology of hyponatremia and discusses thoroughly the contributing factors and mechanisms that may be encountered specifically in patients with hematologic disorders. The involvement of the syndrome of inappropriate antidiuretic hormone (SIADH) secretion and renal salt wasting syndrome (RSWS) in the development of hyponatremia in such patients, as well as their differential diagnosis and management, are also presented. Furthermore, the distinction between true hyponatremia and pseudohyponatremia is explained. Finally, a practical algorithm for the evaluation of hyponatremia in hematologic patients, as well as the principles of hyponatremia management, are included in this review.

Metabolic consequences of immune checkpoint inhibitors: A new challenge in clinical practice.

Treatment of oncologic patients has progressed greatly the last few years with the development of immune checkpoint inhibitors (ICPIs). These drugs are associated with the immune system and, thus, may cause side effects of immune origin, the so called immune related adverse events (irAEs). Immune related AEs may actually affect all organs and systems and frequently resemble clinical entities commonly encountered in clinical practice. As ICPIs have improved both quality of life and life expectancy, clinicians of various specialties may need to deal with irAEs in their everyday practice. Therefore, they should be able to recognize them timely and treat them accordingly. Herein, we review the pathophysiology, clinical manifestations and treatment of irAEs.