Lipoprotein (a) Lp(a) is an independent but moderate, predictor for coronary heart disease (CHD) prevalence and severity. Several established and emerging cardiovascular (CV) risk factors including ...age, gender, ethnicity, smoking, dyslipidemia, hypertension, obesity, type 2 diabetes mellitus, alcohol consumption, arterial stiffness and hyperuricemia have been linked to Lp(a) metabolism. Apart from CHD, Lp(a) has been also associated with non-cardiac vascular diseases and diseases associated with increased CV risk such as chronic kidney disease, metabolic syndrome, non-alcoholic fatty liver disease, erectile dysfunction, obstructive sleep apnea syndrome, inflammatory bowel diseases and human immunodeficiency virus infection. The above data are discussed in the present narrative review. Several guidelines suggest the clinical use of Lp(a) in (re)defining vascular risk, especially in asymptomatic individuals at intermediate or high CV risk and those with a family history of premature CHD. By improving individuals risk stratification, Lp(a) may contribute to a better secondary prevention strategy. However, there is still a need to establish a standardized method to measure Lp(a) as well as selective potent therapies for lowering Lp(a). This will support conducting large randomized trials in order to establish whether lowering circulating Lp(a) levels will result in a significant reduction in CV events.
Highlights • Epilepsy is associated with increased cardiovascular morbidity and mortality. • Certain antiepileptic drugs (AEDs) can have pro-arrhythmic properties. • Polytherapy with AEDs may lead to ...sudden unexpected death in epilepsy. • AEDs may exert different effects on various predictors of vascular risk. • Interactions between AEDs and vascular risk-reducing drugs need to be documented.
Familial chylomicronemia syndrome (FCS) is a rare inherited disease, mainly due to lipoprotein lipase (
) gene mutations, leading to lipid abnormalities. Volanesorsen, a second-generation 2'-
...-methoxyethyl (2'-MOE) chimeric antisense therapeutic oligonucleotide, can decrease plasma apolipoprotein C3 and triglycerides (TG) levels through LPL-independent pathways. The European Medicines Agency has approved volanesorsen as an adjunct to diet in adult FCS patients with an inadequate response to TG-lowering therapy. Areas covered: Available clinical data on volanesorsen efficacy and safety are presented. Furthermore, we discuss the yearly treatment with volanesorsen of a 21-year-old female FCS patient with
mutation. Volanesorsen was well-tolerated and decreased patient's TG levels (from >5000 mg/dL (56 mmol/L) to 350-500 mg/dL (4-5.6 mmol/L)) at 12 months. Lipoprotein apheresis (LA) was stopped and there were no episodes of pancreatitis or abdominal pain. Expert opinion: Severe hypertriglyceridemia can potentially be fatal. Until recently, there was no specific treatment for FCS, apart from hypotriglyceridemic diet, fibrates, omega-3 fatty acids, and LA sessions. Therefore, volanesorsen represents a promising therapeutic solution for these patients. The main side effect of volanesorsen therapy is thrombocytopenia, which should be monitored and treated accordingly. Increasing evidence will further elucidate the clinical implications of volanesorsen use in daily practice.
While microangiopathy is well-documented in systemic sclerosis (SSc), a potential link between SSc and macrovascular disease is highly debated and remains to be established. The aim of the present ...study is to investigate the association between micro- and macrovascular involvement in the setting of SSc.
Consecutive, consenting SSc patients were assessed by nailfold video-capillaroscopy (NVC) to evaluate the microcirculation. The number of capillaries per mm
and the capillaroscopic skin ulcer risk index (CSURI) were measured, and findings were also classified into three scleroderma patterns (i.e., early, active, and late). Carotid intima-media thickness (IMT), aortic augmentation index corrected for a heart rate of 75 beats per minute (AIx-75), carotid-femoral pulse wave velocity (PWV), and central systolic and diastolic blood pressure were also determined to assess macrovascular function.
A total of 37 patients were studied. A significant correlation was observed between AIx and the average number of capillaries per mm
(r = - 0.34, p = 0.047) and between AIx and CSURI (r = 0.35, p = 0.044). Patients with the "early" scleroderma pattern had lower AIx values compared with "active" (20.5 ± 11.4 vs 34.1 ± 11.5%, p = 0.02) and "late" (20.5 ± 11.4 vs 33.4 ± 8.8%, p = 0.05) patterns. No other significant correlations were found between macrovascular biomarkers (PWV, carotid IMT, systolic and diastolic central blood pressure) and the capillaroscopic measurements.
These data suggest that arterial stiffness (as assessed by AIx-75) correlates with microvascular damage in patients with SSc.
Uric acid and diabetes: Is there a link? Katsiki, Niki; Papanas, Nikolaos; Fonseca, Vivian A ...
Current pharmaceutical design,
2013, Letnik:
19, Številka:
27
Journal Article
Recenzirano
Elevated serum uric acid (SUA) levels (i.e. hyperuricaemia) have been associated with metabolic syndrome (MetS) and cardiovascular disease (CVD) morbidity and mortality. Elevated SUA levels predict ...the onset of type 2 diabetes (T2DM). SUA levels are increased during the early stages of impaired glucose metabolism. Furthermore, in diabetic patients, hyperuricaemia has been linked to both micro- and macrovascular complications. The present review considers: (1) SUA levels in patients with MetS, type 1 diabetes and T2DM; (2) the mechanisms that influence SUA levels in these patients; (3) the potential links between SUA and diabetic complications. The effect on SUA levels of drugs commonly prescribed for T2DM and the risk of uric acid nephrolithiasis in patients with MetS or DM are also briefly discussed.
MicroRNAs represent a class of small (19-25 nucleotides) single-strand pieces of RNA that are noncoding ones. They are synthesized by RNA polymerase II from transcripts that fold back on themselves. ...They mostly act as gene regulatory agents that pair with complementary sequences on mRNA and produce silencing complexes, which, in turn, suppress coding genes at a post-transcriptional level. There is now evidence that microRNAs may affect insulin secretion or insulin action, as they can alter pancreatic beta cells development, insulin production, as well as insulin signaling. Any molecular disorder that affects these pathways can deteriorate insulin resistance and lead to type 2 diabetes mellitus (T2DM) onset. Furthermore, the expression of several microRNAs is up- or down-regulated in the presence of diabetic microvascular complications (i.e., peripheral neuropathy, nephropathy, retinopathy, foot ulcers), as well as in patients with coronary heart disease, stroke, and peripheral artery disease. However, more evidence is needed, specifically regarding T2DM patients, to establish the use of such microRNAs as diagnostical biomarkers or therapeutic targets in daily practice.
Lipids, Statins and Heart Failure: An Update Katsiki, Niki; Doumas, Michael; Mikhailidis, Dimitri P
Current pharmaceutical design,
01/2016, Letnik:
22, Številka:
31
Journal Article
Recenzirano
Heart failure (HF) is characterized by cardiac functional and structural alterations, progressively leading to clinical symptoms and signs. Certain neurohormonal systems (i.e. the sympathetic nervous ...system, the reninangiotensin-aldosterone system and the natriuretic peptide system) as well as interactions between endothelial, monocytes/macrophages and myocardial cells are involved in the process.
The present narrative review discusses the relationships between lipids, statins and HF.
Lipid metabolism is involved in cardiac function. Inflammation, oxidative stress, endothelial and platelet dysfunction, activation of neurohormonal systems, adverse cardiac remodeling, haemodynamic disorders and arrhythmogenesis predispose to HF development and progression. Statins have been shown to reduce HF incidence possibly via their pleiotropic actions on the above mentioned mechanisms. Other cardiovascular (CV) risk factors affecting HF prevalence and outcomes include metabolic syndrome, non-alcoholic fatty liver disease, chronic kidney disease, hyperuricaemia, epicardial fat and increased arterial stiffness that are improved following statin therapy.
Lipid disorders are involved in HF development and progression. Statins may beneficially affect these disorders as well as other CV risk factors linked to HF. However, the impact of statins in patients with established HF has yet to be determined. Further studies are needed to unveil potential benefits of statin therapy (or some statins) in specific groups of HF patients.
Adipose tissue, a major endocrine organ, consists of brown and white adipocytes. Brown fat may play a beneficial role in cardiometabolic disorders. Brown adipose tissue can also improve glucose and ...lipid metabolism. In contrast, the expansion of white adipose tissue has been related to obesity, type 2 diabetes mellitus and cardiovascular disease (CVD). Both the quantity and the quality of the white adipose tissue as well as its distribution may affect CVD risk. In this context, the link between adiposity and CVD risk is greater for visceral than subcutaneous fat. Apart from these fat depots, there are other adipose tissues that are either systemically (i.e. in the liver, muscle or neck) or mainly locally acting (i.e. pericardial/epicardial, perivascular and perirenal). These fat depots can affect the nearby anatomic organs via lipid accumulation and cytokine secretion. In the present narrative review, the associations of excessive peri-organ adipose tissue, namely intrahepatic, epicardial/ pericardial, perivascular, intramuscular, peripancreatic and perirenal fat, with cardiometabolic and CVD risk factors are discussed. The effects of drugs that target vascular risk and/or different fat depots are also considered.
Inflammation is implicated in the development and severity of the coronavirus disease 2019 (COVID-19), as well as in the pathophysiology of diabetes. Diabetes, especially when uncontrolled, is also ...recognized as an important risk factor for COVID-19 morbidity and mortality. Furthermore, certain inflammatory markers i.e. C-reactive protein (CRP), interleukin-6 (IL-6) and ferritin were reported as strong predictors of worse outcomes in COVID-19 positive patients. The same biomarkers have been associated with poor glycemic control. Therefore, achieving euglycemia in patients with diabetes is even more important in the era of the COVID-19 pandemic.
Based on the above, it is clinically interesting to elucidate whether antidiabetic drugs may reduce inflammation, thus possibly minimizing the risk for COVID-19 development and severity. The present narrative review discusses the potential anti-inflammatory properties of certain antidiabetic drugs (i.e. metformin, pioglitazone, sitagliptin, linagliptin, vildagliptin, alogliptin, saxagliptin, liraglutide, dulaglutide, exenatide, lixisenatide, semaglutide, empagliflozin, dapagliflozin, canagliflozin), with a focus on CRP, IL-6 and ferritin.
•Inflammation is implicated in the development and severity of the coronavirus disease 2019 and diabetes.•C-reactive protein, interleukin-6 and ferritin were linked to poor glycemic control and worse COVID-19 outcomes.•There are limited and, in many cases, inconsistent data on the potential anti-inflammatory actions of antidiabetic drugs.•The most suggestive data are those on ferritin for the sodium glucose co-transporter-2 inhibitors.•Multiethnic trials are required to determine whether certain antidiabetic drugs exert inherent anti-inflammatory actions.
PDF
