Current Vascular Pharmacology - Volume 14, Issue 5, 2016

Background: Chronic kidney disease (CKD) accounts for a significant proportion of the morbidity and mortality in the United States. CKD is defined as glomerular filtration rate (GFR) <60ml/min/1.73m2 or clear evidence of renal damage from biopsy. All-cause cardiovascular risk increases with decreasing GFR. Clinically, detection of CKD is through changes in creatinine clearance which estimates GFR, an indicator of kidney function. We reviewed conventional and nonconventional cardiovascular risk factors associated with CKD. Clinically, we reviewed the status of statins as a treatment option for CKD-induced dyslipidemia. Objective: CKD has dramatic consequences on cardiovascular risk profile due to a complex pathophysiologic response to declining kidney function. In this review, we explored new, more accurate methods of detecting decreasing kidney function, discerned risk factors for the development of cardiovascular events, and examined the controversial use of statins for renoprotection. Results: Detection of declining renal function by monitoring creatinine has been the clinical gold standard, but it substantially fluctuates with muscle mass, sex, and ethnicity. Newer methods using cystatin C have been at the forefront as the next substance that will be used for detection of CKD. Traditional and non-traditional risk factors contribute to the cardiovascular risk profile of patients with declining renal function. Statins, along with angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB)s, have been used for renoprotection, but evidence shows only modest benefits in non-dialysis patients. Conclusion: Cardio-renal interaction involves multiple risk factors that contribute significantly to the CKD-induced development of accelerated atherosclerosis, an inflammatory state that causes cardiovascular events.

Cardiovascular (CV) disease is the most common cause of morbidity and mortality worldwide, particularly in the presence of the metabolic syndrome (MetS). Classifications and treatment of the MetS have recently been redefined. While the majority of the cardiac components such as hypertension, diabetes mellitus (DM) and dyslipidemia (DLD) are objectively measurable elements, a few disparities among the definitions have to be considered that can variably modify diagnosis, treatment and prevention. Non-cardiac factors such as liver disease (including, but not limited to, alcoholic and non-alcoholic steatosis/hepatitis), renal disease, severe obesity, polycystic ovarian syndrome and obstructive sleep apnea (OSA), may have independent or synergistic relationship with complementary cardiac MetS elements, and these additional risk factors may have an incremental adverse impact on CV outcome. The combination of all these factors potentiates the adverse significance on CV events. MetS not only increases morbidity and mortality but also has economic ramifications for the healthcare system. Prevention of CV disease includes primary and secondary aspects. Besides overall advances to provide optimal care for hypertension, diabetes, and dyslipidemia, early-targeted inventions to diagnose, treat and prevent OSA, and severe obesity, are needed.

Cardiovascular disease remains a significant cause of mortality and morbidity despite relentless ongoing research all over the world. The different cardiovascular societies and research organizations are in a constant effort to improve overall cardiovascular (CV) outcome by conducting trials and establishment of guidelines. The ever growing health care costs have enforced governmental agencies to develop quality performance measures which are addressed towards increasing quality, safety, efficiency of patient care and to curtail the cost of health care. Clinical registries are observational databases which provide detailed information about patient population, a specific disease or a clinical condition, therapy or procedure. These can be utilized in estimating appropriateness of health care delivery and providing feedback to providers and health care organizations for gauging their performance at regional and national level. The introduction of electronic health records (EHR) has immensely helped the workflow and maintenance of clinical registries with their integrated software.

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.

Cardiovascular Disease (CVD) remains the leading cause of death and disability worldwide, with increased hospital discharge rates, causing a serious public health issue and an economic burden. Recent demographic transitions, including ageing of the population, low fertility, urbanization and shift towards unhealthy behaviours have resulted in an increase in the prevalence of cardiometabolic disorders (i.e. hypertension, obesity, diabetes). According to the reports of international organisations, a substantial number of heart attacks could have been prevented through lifestyle modifications (i.e. diet, physical activity, smoking cessation). Regarding secondary prevention, it is well documented that effective cardiovascular rehabilitation requires a multidisciplinary approach, including medical treatment, as well as lifestyle changes. Diet has been recognised as one of the most important modifiable and preventable factors, being undoubtedly beneficial in primary prevention, as well as among cardiac patients. However, studies among CVD patients are scarce, and with inconclusive results. The most studied dietary pattern is the Mediterranean-type diet, with several observational studies and clinical trials demonstrating its protective role against recurrent cardiac events, whereas evidence regarding other well-known models, including Western-type, Vegetarian, Asian-type and Dietary Approaches to Stop Hypertension (DASH) diet, are more limited. The aim of this review was to present an overview of the most prevalent dietary patterns and their role in the secondary CVD prevention and management.

Coronary heart disease (CHD) is the leading cause of death for women worldwide, most of which is believed to be preventable. Numerous risk factors for CHD are well described, and understanding these risk factors is the first step to reducing the burden of CHD. There are clear differences in risk factors between women and men. The incidence of myocardial infarction is much lower among women under the age of 50 years compared with men, but after menopause, the incidence in women dramatically increases to approach that of men. For this reason, estrogen is postulated to be cardioprotective but results of recent randomized clinical trials challenge this hypothesis. The significance of cardiovascular risk factors appears to vary between women and men, the reasons for which remain elusive but could include the interaction of these risk factors with hormones. Confounding this observation is that most early studies of cardiovascular risk factors enrolled primarily men. This review will focus solely on the differences in cardiovascular risk factors in women and men including the current role of hormone therapy in CHD prevention, sex differences in established CHD risk factors and emerging risk factors for CHD in women.

Exercise therapy, especially when supervised on-site in a clinical facility or directed off-site for a home-based program, is an essential component of the management of coronary artery disease (CAD) and peripheral arterial disease (PAD). In the case of both atherosclerotic diseases, it can decrease adverse cardiovascular (CV) events. There has been a recent push toward invasive management of both CAD and PAD but accumulating clinical experience has shown the limitation of invasive management and emphasized the importance of medications, CV risk reduction, conditioning, and exercise, especially when supervised. Exercise results in increased peak oxygen consumption (V02), improvement of wellestablished CV risk factors such as plasma lipids, and an improvement in indicators of inflammation and of various metabolic factors. Fortunately, there is generally good third-party coverage of medications and vascular interventions but unfortunately, poor insurance coverage for supervised or directed exercise programs for which significant patient benefit has been established.

Objectives: Hypercholesterolaemia is associated with increased plasma levels of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8). We studied the effect of rosuvastatin monotherapy or its combination at a lower dose with omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in the VEGF and IL-8 plasma levels in patients with mixed dyslipidaemia. Methods: Fifty patients with mixed dyslipidaemia were recruited. Fifty-five normolipidaemic, apparently healthy, ageand sex- matched subjects acted as controls. Patients were randomized to 40 mg/day rosuvastatin (R group, n=26) or 10 mg/day rosuvastatin plus 2 g/day of ω-3 PUFAs (R+O group, n=24). The levels of VEGF and IL-8 in plasma, were assessed at baseline and 3 months post-treatment. Results: At baseline, both plasma VEGF and IL-8 levels were significantly higher in the R and R+O groups compared with controls (p<0.04, p<0.03 and p<0.02, p<0.03, respectively). Post-treatment levels of VEGF were decreased in the R group while a significant increase was observed in the R+O group, compared with baseline levels (p<0.02 and p<0.03, respectively). Post-treatment IL-8 levels were decreased in both R and R+O groups (p<0.03 and p<0.04, respectively). Conclusions: We show for the first time that either rosuvastatin monotherapy or its combination at a lower dose with ω-3 PUFAs reduces IL-8 levels in mixed dyslipidaemic patients. High-dose rosuvastatin monotherapy reduces VEGF values, whereas a significant increase is observed in patients receiving lower dose rosuvastatin with ω-3 PUFAs. The clinical significance of the above findings regarding cardiovascular risk remains to be established.

Objective: Chronic heart failure (CHF) remains a major health problem, with high levels of morbidity and mortality and a low health-related quality of life (HRQoL). We assessed the impact on HRQoL of adding the If channel blocker, ivabradine, to a standard treatment regimen of patients with ischaemic CHF (I-CHF) and heart rate (HR) ≥70 beats/min (bpm). & Methods: A randomized prospective study of 100 consecutive patients presenting with stable I-CHF, left ventricular ejection fraction (LVEF) <40% and a sinus HR ≥70 bpm. New York Heart Association (NYHA) class, overall summary score (OSS) and clinical summary score (CSS) of the Kansas City Cardiomyopathy Questionnaire (KCCQ) were used to assess HRQoL. The patients were randomized into 2 groups: carvedilol only (group I (n=50)) and carvedilol + ivabradine (group II (n=50)). The patients were followed up for 12 weeks and their HRQoL scores were monitored and compared. & Results: The overall mean age of the cohort was 63±10 years with 70% (n=70) males. HRQoL scores had significantly improved in group II after 12 weeks of follow-up. The net proportion of patients with a 5-point improvement in CSS was 30% higher in group II (p=0.002), whereas that for the OSS, it was 24% (p=0.001), when compared with group I. These improvements were accompanied by a significant HR reduction (69 vs 78 bpm; p=0.002). & Conclusion: Adding ivabradine to the standard drug regimen, currently advocated by guidelines for CHF with a heart rate ≥70 bpm, resulted in a significant improvement in HRQoL. &

Background: Ticagrelor may exert pleiotropic actions, beyond platelet inhibition, which are possibly adenosine-mediated. It has been suggested that in patients with coronary artery disease (CAD) ticagrelor may influence endothelial function. Objective: We aimed to assess the possibility of endothelial function deterioration following ticagrelor treatment cessation. Methods: This was a prospective, observational study, in stable CAD patients with prior percutaneous coronary intervention (PCI) for acute coronary syndrome manifested 1 year earlier, under ticagrelor maintenance dose (90 mg bid) and due to discontinue ticagrelor. Endothelial function was assessed by Peripheral Arterial Tonometry (EndoPat 2000 system, Itamar Medical, Caesarea, Israel) immediately after receiving the last tablet of ticagrelor (Day 0) and at Day 2 and Day 5 post-ticagrelor cessation. Reactive hyperaemia index (RHI) was calculated by automated software and endothelial dysfunction (ED) was defined as a RHI <1.67. Results: We identified 30 eligible patients with endothelial function assessment pre- and post-ticagrelor cessation (86.7% men, 13.3% with diabetes and 33.3% current smokers; mean age: 63.6±11.5 years). The study’s primary endpoint of RHI at Day 5 did not differ significantly compared with RHI at Day 0, 1.69 (1.45-2.23) vs 1.81 (1.59-2.13). ED rate did not differ significantly between Day 5 and Day 0, 40 vs 33.3%, p=0.8, respectively. No differences in RHI or ED rate were observed between Day 2 and Day 0, 1.64 (1.54-2.04) vs 1.8 1(1.59-2.13), p=0.3 and 53.3 vs 33.3%, p=0.2, respectively. In stable CAD patients there is no evidence of deterioration in endothelial function after discontinuing ticagrelor.