Treatment with statins substantially reduces cardiovascular morbidity and mortality both in patients with and without established cardiovascular disease. Accordingly, statins represent the ...cornerstone of lipid-lowering treatment. However, there are still unmet clinical needs in the management of dyslipidemia. Indeed, it is difficult to achieve low-density lipoprotein cholesterol (LDL-C) targets in many patients, particularly in those at very high cardiovascular risk or in those with very high baseline LDL-C levels e.g. with heterozygous familial hypercholesterolemia (FH). Moreover, a sizable proportion of patients are not able to tolerate high doses of statins, mostly due to muscle-related adverse effects. In these patient populations, inhibition of proprotein convertase subtilisin-kexin type 9 (PCSK9) with monoclonal antibodies appears to represent a useful tool for achieving LDL-C targets.
In the present review, we summarize the current knowledge on the effects of the PCSK9 inhibitors alirocumab and evolocumab on lipid levels in various populations and discuss the role of these agents in the management of dyslipidemia.
In addition to a substantial reduction in LDL-C levels (by 50-60%), PCSK9 inhibitors also lower triglyceride, non-high-density lipoprotein cholesterol (non-HDL-C) and lipoprotein (a) levels and increase HDL-C levels. Preliminary data suggest that PCSK9 inhibitors are safe. However, ongoing randomized, placebo-controlled trials will provide definitive evidence on the safety of these novel agents and on their effects on cardiovascular morbidity and mortality.
Given the high cost of PCSK9 inhibitors, their use should be restricted to carefully selected, veryhigh risk patients until the results of these trials are available.
It is estimated that 5-10% of hypertensive patients have secondary hypertension. The main causes of secondary hypertension are parenchymal renal disease, primary aldosteronism and renovascular ...hypertension. The identification of these patients is important because it enables the etiological management of the underlying disease and in some cases leads to blood pressure control without antihypertensive medications. On the other hand, diagnostic evaluation for secondary hypertension often includes complex and expensive tests and should be performed only in patients with a strong clinical suspicion for its presence. If preliminary screening tests suggest the presence of secondary hypertension, these patients should be referred to specialized centers for further diagnostic evaluation and comprehensive management.
Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease. The pathogenesis of DKD is multifactorial, with several molecular pathways implicated. Recent data suggest that histone ...modification plays an important role in the development and progression of DKD. Histone modification appears to induce oxidative stress, inflammation and fibrosis in the diabetic kidney. In the present review, we summarize the current knowledge on the association between histone modification and DKD.
The polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in women of reproductive age and shows substantial phenotypic variability. According to the presence of the three diagnostic ...criteria of PCOS, i.e. oligo- and/or anovulation, hyperandrogenemia and/or clinical signs of high androgen levels, and polycystic ovaries, four different phenotypes of PCOS are identified. It appears that these phenotypes differ in the prevalence of several established and emerging cardiovascular risk factors.
We searched the literature for studies that compared the cardiovascular risk profile of patients with the different phenotypes of PCOS.
Patients with both anovulation and hyperandrogenemia have more pronounced insulin resistance and higher levels of proinflammatory and prothrombotic mediators than patients with polycystic ovaries and either anovulation or hyperandrogenemia.
Given that these differences appear to be mainly driven by the more pronounced obesity of the former patients, diet and exercise aiming at weight loss should constitute the cornerstone of management of PCOS and should be particularly emphasized in patients with the higher risk phenotypes of the syndrome.
Nonalcoholic fatty liver disease (NAFLD) affects a substantial proportion of the general population and is even more prevalent in obese and diabetic patients. NAFLD, and particularly the more ...advanced manifestation of the disease, nonalcoholic steatohepatitis (NASH), increases the risk for both liver-related and cardiovascular morbidity. The pathogenesis of NAFLD is complex and multifactorial, with many molecular pathways implicated. Emerging data suggest that microsomal prostaglandin E synthase-1 and -2 might participate in the development and progression of NAFLD. It also appears that targeting these enzymes might represent a novel therapeutic approach for NAFLD. In the present review, we discuss the association between microsomal prostaglandin E synthase-1 and -2 and NAFLD.
Diabetic nephropathy is the leading cause of end-stage renal disease. Patients with diabetic nephropathy have a high cardiovascular risk, comparable to patients with coronary heart disease. ...Accordingly, identification and management of risk factors for diabetic nephropathy as well as timely diagnosis and prompt management of the condition are of paramount importance for effective treatment. A variety of risk factors promotes the development and progression of diabetic nephropathy, including elevated glucose levels, long duration of diabetes, high blood pressure, obesity, and dyslipidemia. Most of these risk factors are modifiable by antidiabetic, antihypertensive, or lipid-lowering treatment and lifestyle changes. Others such as genetic factors or advanced age cannot be modified. Therefore, the rigorous management of the modifiable risk factors is essential for preventing and delaying the decline in renal function. Early diagnosis of diabetic nephropathy is another essential component in the management of diabetes and its complications such as nephropathy. New markers may allow earlier diagnosis of this common and serious complication, but further studies are needed to clarify their additive predictive value, and to define their cost-benefit ratio. This article reviews the most important risk factors in the development and progression of diabetic nephropathy and summarizes recent developments in the diagnosis of this disease.
Hormone-dependent cancers are a major cause of morbidity and mortality in both genders. Accumulating evidence suggest that adiponectin, an adipokine with multifaceted functions, is implicated in the ...pathogenesis of several malignancies. In the present review, we discuss the existing data regarding this relationship. Several observational studies showed that low adiponectin levels are associated with higher risk for breast, cervical, endometrial, ovarian and prostate cancer. A relationship between adiponectin and the aggressiveness of some of these tumors has also been reported.
studies reported that adiponectin inhibits the proliferation and induces apoptosis of breast, cervical, endometrial, ovarian and prostate cancer cells. Given the high prevalence of these cancers and the substantial associated morbidity and mortality, the role of agents that increase adiponectin levels and/or stimulate its activity should be evaluated for the prevention and management of these common tumors.
Nonalcoholic fatty liver disease(NAFLD) is the most common chronic liver disease in developed countries and is associated not only with increased risk for liver disease-related complications but also ...with higher cardiovascular morbidity. Accordingly, lipid-lowering agents are frequently considered in these patients to reduce cardiovascular risk. However, there have been concerns regarding the safety of these agents in patients with chronic liver diseases. In the present review, we discuss the safety of lipid-lowering agents in patients with NAFLD as well as their effects on both cardiovascular and liver disease in this population. Accumulating data suggest that statins are safe in patients with NAFLD and that they reduce the increased cardiovascular morbidity of this population. However, it is still unclear whether statins are also useful as a treatment for NAFLD per se, since there are very limited and conflicting data on their effects on liver histology. There is also very scarce evidence regarding the safety and efficacy of other lipid-lowering agents in patients with NAFLD. Randomized controlled studies are needed to evaluate the role of lipid-lowering agents and particularly statins for the prevention of both cardiovascular and liver disease-related complications in this high-risk population.
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