Pleiotropic beneficial cardiometabolic actions of a high-purity eicosapentaenoic acid product in high cardiovascular risk individuals.

The ideal approach to the secondary dyslipidemia goal of lowering triglycerides (TG) is not well established. The available ω-3 fatty acid products differ from each other in composition and content. The purpose of the present study was to investigate the effect of a highly purified eicosapentaenoic acid (EPA) formulation on cardiometabolic biomarkers in high cardiovascular (CV) risk patients. The study included 226 subjects with high TG and ≥1 of the following CV risk factors: arterial hypertension, diabetes mellitus, ultrasound-documented atheromatosis, peripheral artery disease, previous myocardial infarction, or ischemic stroke. Participants received 2 g EPA twice daily for 3 months, along with typical nutritional counseling. Cardiometabolic hematological parameters (TG, low-density lipoprotein [LDL], high-density lipoprotein [HDL], non-HDL, total cholesterol [TChol], apolipoprotein A1 [Apo A1], apolipoprotein B [Apo B], glucose, glycated hemoglobin [HbA1c], and C-reactive protein [CRP]) were measured at baseline and at 3 months. The mean patients' age was 61.1 ± 1.4 years and the mean baseline TG was 2.97 ± 0.15 mmol/L. Apart from Apo A1, all other biomarkers significantly (p < 0.05) improved at 3 months, regardless of sex (except Apo B) and age: TG 1.75 ± 0.09 versus 2.97 ± 0.15 mmol/L, LDL 2.46 ± 0.08 versus 3.05 ± 0.13 mmol/L, HDL 1.22 ± 0.03 versus 1.11 ± 0.03 mmol/L, non-HDL 3.29 ± 0.10 versus 4.14 ± 0.16 mmol/L, TChol 4.55 ± 0.10 versus 5.15 ± 0.13 mmol/L, Apo A1 26.8 ± 9.3 versus 22.5 ± 8.6 µmol/L, Apo B 1.25 ± 0.23 versus 1.29 ± 0.23 µmol/L, glucose 5.66 ± 0.11 versus 5.99 ± 0.17 mmol/L, HbA1c 5.83 ± 0.1 versus 5.97 ± 0.1% and CRP 1.92 ± 0.2 versus 5.26 ± 2.8 mg/L. In conclusion, adding highly purified EPA product (4 g daily) on nutritional counseling leads to a significant TG reduction. In addition, this treatment appears to have pleiotropic beneficial cardiometabolic actions.

Blood Pressure-Lowering Effect of Newer Antihyperglycemic Agents (SGLT-2 Inhibitors, GLP-1 Receptor Agonists, and DPP-4 Inhibitors).

The prevalence of arterial hypertension is high in patients with diabetes mellitus (DM). When DM and hypertension coexist, they constitute a dual cardiovascular threat and should be adequately controlled. Novel antihyperglycemic agents, including sodium-glucose co-transporter 2 (SGLT-2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and dipeptidyl peptidase-4 (DPP-4) inhibitors, have recently been used in the treatment of DM. Beyond their glucose-lowering effects, these drugs have shown beneficial pleiotropic cardiovascular effects, including lowering of arterial blood pressure (BP), as acknowledged in the 2019 European Society of Cardiology/European Association for the Study of Diabetes guidelines on diabetes, prediabetes, and cardiovascular diseases. The purpose of this review was to summarize the available information on the BP-reducing effects of these new glucose-lowering drug classes and provide a brief report on underlying pathophysiological mechanisms. We also compare the three drug classes (SGLT-2 inhibitors, GLP-1 RAs, and DPP-4 inhibitors) in terms of their BP-lowering effect and show that the greater BP reduction seems to be achieved with SGLT-2 inhibitors, whereas DPP-4 inhibitors have probably the mildest antihypertensive effect.

Sodium Glucose Cotransporter 2 (SGLT2) Inhibitors Across the Spectrum of Hypertension.

Sodium glucose cotransporter 2 (SGLT2) inhibitors represent a novel class of oral antihyperglycemic drugs that have been approved over the last decade for the management of type 2 diabetes mellitus. Except the glucose-lowering effects, robust evidence also suggests that SGLT2 inhibitors confer benefits in cardiovascular system. The purpose of this review was to investigate the effects of SGLT2 inhibitors across the spectrum of arterial hypertension.

Labile hypertension: a new disease or a variability phenomenon?

Blood pressure (BP) is a physiological parameter with short- and long-term variability caused by complex interactions between intrinsic cardiovascular (CV) mechanisms and extrinsic environmental and behavioral factors. Available evidence suggests that not only mean BP values are important, but also BP variability (BPV) might contribute to CV events. Labile hypertension (HTN) is referred to sudden rises in BP and it seems to be linked with unfavorable outcomes. The aim of this article was to review and summarize recent evidence on BPV phenomenon, unraveling the labile HTN concept along with the prognostic value of these conditions.

The impact of financial crisis on coronary artery disease burden in Greece.

BACKGROUND: Economic crisis poses an immense threat to public health worldwide and has been linked to cardiovascular morbidity and mortality. Greece is facing a distinctive recession over the recent years. However, the exact impact on coronary artery disease (CAD) burden has not been adequately addressed. METHODS: Demographic, clinical, and angiographic data of 3895 hospitalized patients were retrospectively studied. Patients were classified into two groups: those before crisis (2006-2007, n = 1228) and those during crisis (2011-2015, n = 2667). RESULTS: All data before and during crisis were compared. During crisis, patients presented with less acute coronary syndrome (ACS - 45.5% vs. 39.9%, p < 0.001). Subsequently, there were more patients without CAD (23.7% vs. 35.1%, p < 0.001) or one-vessel disease (20.5% vs. 23%, p < 0.001). The prevalence of traditional risk factors decreased significantly or remained stable except obesity (26.3% vs. 31.4%, p = 0.002). A significant increase in the examined females (23.6% vs. 26.7%, p = 0.04) was also observed. CONCLUSIONS: The burden of CAD in Greece was partially affected during the financial crisis. Even though the incidence of ACS was decreased, more women and more patients with no- or single-vessel disease were referred for cardiac catheterization. In addition, the prevalence of traditional risk factors for CAD did not increase except obesity confirming the "obesity paradox." It seems that the impact of traditional risk factors for CAD is not an immediate process and is somewhat related to living conditions or other exogenous and social factors.

The impact of apelin and relaxin plasma levels in masked hypertension and white coat hypertension.

Masked hypertension (HTN) and white coat hypertension represent two reverse forms of clinical HTN with questionable prognostic significance. Recent evidence supports that low apelin and relaxin plasma levels contribute to vascular damage accelerating atherogenesis and predisposing to HTN and cardiovascular (CV) events. The aim of this study was to compare apelin and relaxin plasma levels between patients with masked hypertension (MH) and those with white coat HTN (WCH). Overall, 130 patients not receiving antihypertensive therapy were studied. All patients underwent 24-hour ambulatory BP monitoring (ABPM) and office BP measurements. Plasma apelin and relaxin levels were measured by ELISA method. According to BP recordings, 24 subjects had MH (group A) and 32 had WCH (group B). Apelin (200 ± 111 pg/mL vs 305 ± 127 pg/mL, P < 0.01) and relaxin (35.2 ± 6.7 pg/mL vs 46.8 ± 23.6 pg/mL, P < 0.01) plasma levels were significantly lower in patients with MH compared to those with WCH, respectively. In conclusion, our findings showed that patients with MH had significantly lower apelin and relaxin levels compared to those with WCH. This observation implies an additional prognostic role for adipokines supporting the concept that MH is closer to essential HTN whereas WCH is a more benign condition.

Adherence to Treatment, Safety, Tolerance, and Effectiveness of Perindopril/Amlodipine Fixed-Dose Combination in Greek Patients with Hypertension and Stable Coronary Artery Disease: A Pan-Hellenic Prospective Observational Study of Daily Clinical Practice.

BACKGROUND: Initiation of antihypertensive therapy with a two-drug fixed-dose combination (FDC) in a single tablet may be recommended in patients at high risk of cardiovascular events to improve adherence and effectiveness. Preferred combinations include an angiotensin-converting enzyme inhibitor with a dihydropyridine calcium antagonist. OBJECTIVE: This study assessed adherence to and the safety, tolerance, and effectiveness of the perindopril/amlodipine FDC in Greek patients with hypertension and stable coronary artery disease (CAD) over a 4-month period. METHODS: A total of 1907 patients with hypertension and CAD (59.1% males) who had recently (≤2 weeks) commenced treatment with the perindopril/amlodipine FDC (5/5, 5/10, 10/5, or 10/10 mg) were studied at baseline and at 1 and 4 months. Adherence to treatment was assessed with the Morisky Medication-taking Adherence Scale (MMAS). RESULTS: Seven patients (0.4%) did not attend the scheduled visits. In total, 1607 (84.6%) patients received a constant treatment dose throughout the study. High adherence (MMAS score = 0) was reported by 1592 (83.6%), 1628 (85.7%), and 1477 (77.7%) patients at the second and the third visit and at both visits, respectively. Adverse reactions were reported by only 13 (0.7%) patients, were all minor, and did not result in treatment discontinuation. Office blood pressure (BP) was significantly decreased at the third visit (130.8 ± 8.4/78.2 ± 6.4 mmHg) compared with baseline (156.5 ± 15.0/89.9 ± 9.6 mmHg; p < 0.001), regardless of previous antihypertensive treatment. Patients with grade 1, 2, and 3 hypertension at baseline showed a reduction in BP of 19.3/9.4, 31.5/13.5, and 47.8/22.2 mmHg, respectively (p < 0.001). Uncontrolled hypertension (≥140/90 mmHg) was notably reduced from 90.3% at baseline to 18.5% at the third visit. CONCLUSIONS: The perindopril/amlodipine FDC is characterized by high adherence and effectiveness, regardless of previous treatment. Degree of BP reduction was related to baseline BP levels. Clinical trials registration number (Protocol Number): IC4 - 05985 - 011 - GRC.

Arterial hypertension and aortic valve stenosis: Shedding light on a common "liaison".

Arterial hypertension and aortic valve stenosis are common disorders and frequently present as concomitant diseases, especially in elderly patients. The impact of hypertension on heart haemodynamics is substantial, thus affecting the clinical presentation of any coexisting valvulopathy, especially of aortic stenosis. However, the interaction between these 2 entities is not thoroughly discussed in the European or/and American guidelines on the management of hypertension or/and valvular heart disease. The present review summarizes all available evidence on the potential interplay between hypertension and aortic valve stenosis, aiming to help physicians understand the pathophysiology and select the best diagnostic and therapeutic strategies (medical or/and interventional) for better management of these high-risk patients, taking into account the impact on outcome as well as the risk-benefit-ratio.

Apelin and Visfatin Plasma Levels in Healthy Individuals With High Normal Blood Pressure.

BACKGROUND: High normal blood pressure (BP; 130-139/85-89 mm Hg) is related with increased cardiovascular (CV) risk compared to normal BP (120-129/80-84 mm Hg) or/and optimal BP (<120/80 mm Hg). Low apelin plasma levels have been associated with arterial hypertension and atherosclerosis, while high visfatin plasma levels may promote vascular inflammation and atherosclerotic plaque destabilization and have been evaluated as a marker for identifying stages of essential hypertension. We sought to compare the apelin and visfatin plasma levels between subjects with high normal BP and subjects with normal or optimal BP matched for age, gender, smoking, and body mass index (BMI). METHODS: Twenty-five subjects with high normal BP (office BP 136±3/88±2 mm Hg, age 57±4 years, 76% males, 32% smokers, BMI 24.0±1.7 kg/m2) and 35 subjects with normal or optimal BP (office BP 118±2/78±2 mm Hg, age 55±7 years, 63% males, 29% smokers, BMI 23.2±1.4 kg/m2) were studied. The apelin and visfatin plasma levels were determined with the enzyme-linked immunosorbent assay. RESULTS: Compared to normal or optimal BP subjects, apelin levels were significantly lower (205±108 vs. 325±152 pg/ml, P < 0.001) and visfatin levels significantly higher (11.0±2.0 vs. 7.2±0.9 ng/ml, P = 0.002) in high normal BP subjects. No significant differences were found between the 2 groups (P = NS) regarding the basic clinical characteristics, the glycemic/lipid profile, and the renal function parameters. CONCLUSIONS: The emerging, from the present study, data raise the hypothesis that lower apelin and higher visfatin plasma levels in high normal BP subjects compared to normal or optimal BP individuals could partially explain the higher CV risk of the high normal BP group.

Adiponectin and resistin plasma levels in healthy individuals with prehypertension.

Prehypertension seems to be related to increased cardiovascular risk in healthy subjects, while hypoadiponectinemia and hyperresistinemia may contribute to insulin resistance and accelerated atherogenesis. This study investigated whether plasma levels of adiponectin (known to increase insulin sensitivity) and resistin (a protein possibly involved in inflammatory activities) are affected in healthy individuals with prehypertension, and to compare the findings to those of healthy normotensives matched for age, gender, and body mass index. Twenty-six (14 men and 12 women) healthy individuals with prehypertension (mean age, 52+/-5 years; mean body mass index, 23+/-1.5 kg/m2) and 24 healthy normotensives (13 men and 11 women; mean age 53+/-6 years; body mass index 23.2+/-1.4 kg/m2) were studied. The adiponectin and resistin plasma levels were determined by the enzyme-linked immunosorbent assay method. Plasma resistin levels were significantly higher, while adiponectin plasma levels were significantly lower, in prehypertensive subjects compared with normotensive subjects (10.62+/-3.17 ng/mL vs. 6.72+/-3.15 ng/mL and 6.26+/-2.18 mg/mL vs. 12.12+/-4.8 mg/mL; p < 0.01, respectively). The findings suggest that healthy individuals with prehypertension have significantly higher resistin plasma levels and significantly lower adiponectin plasma levels compared with healthy normotensives. These findings may represent another possible mechanism that may increase the cardiovascular risk in this special group of patients, needing further investigation.

Changes in metalloproteinases in healthy normotensive patients with high-normal blood pressure.

INTRODUCTION: High-normal blood pressure (HNBP) seems to be related to increased cardiovascular risk in healthy, normotensive subjects, while essential hypertension is associated with an increase in extracellular matrix content, especially fibrillar collagen type I. The aim of our study was to investigate whether collagen degradation is altered in healthy normotensives with HNBP, and whether this alteration could be related to disturbances in the matrix metalloproteinases plasma concentration, and to compare the findings to those of healthy normotensives with normal blood pressure (NBP) levels, matched for age, sex and BMI. METHODS: Twenty six (14 males, 12 females) healthy, normotensive patients with HNBP, mean age 52 +/- 5 yrs, and BMI 23 +/- 1.5 kg/m(2) (group A), and 24, healthy normotensive patients (13 males, 11 females) with NBP, mean age 53 +/- 6 yrs, and BMI 23.2 +/- 1.4 kg/m(2) (group B), were studied. The two groups were matched for age, sex and BMI. Plasma levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitors (TIMP-1) and (TIMP-4) were determined by relevant ELISA in the study population. RESULTS: Plasma MMP-9 levels were significantly higher, while TIMP-1 and TIMP-4 levels were significantly lower in group A compared to group B, (MMP-9 579 +/- 147 versus 294 +/- 111 ng/mL, TIMP-1 178 +/- 45 versus 237 +/- 35 ng/mL p < 0.01, and TIMP-4 2.2 +/- 1.4 versus 4.4 +/- 2.1 p < 0.04 respectively). CONCLUSIONS: Our findings suggest that healthy normotensives with high-normal blood pressure have significantly increased MMP-9 and decreased TIMP-1 and TIMP-4 plasma levels compared to healthy normotensives with normal blood pressure. These findings need further investigation.

Human soluble leptin receptor number in healthy normotensive individuals with high normal blood pressure.

BACKGROUND: High normal blood pressure (BP) seems to be related to increased cardiovascular risk in healthy normotensive subjects, whereas hyperleptinemia enhances both sympathetic tone and arterial BP. The aim of our study was to determine the human soluble leptin receptor number in healthy normotensive subjects with high normal BP and to compare these findings to those of healthy normotensive individuals with normal BP levels. METHODS: We studied 36 healthy normotensive individuals with high normal BP (19 men and 17 women, mean age 42+/-8 years, body mass index [BMI] 23+/-1.5 kg/m2) and 40 healthy normotensive individuals with normal BP (23 men and 17 women, mean age 43+/-7 years, BMI 23.2+/-1.4 kg/m2). The two groups are matched for age, sex, and BMI. The human soluble leptin receptor number and immunoreactive leptin levels were determined in the study population by enzyme-linked immunoassay and radioimmunoassay, respectively. RESULTS: Mean plasma leptin levels were significantly higher, whereas mean human soluble leptin receptor numbers were lower in the group with high normal BP compared with the normotensive group (10+/-4.8 v 6+/-2.7 ng/mL, P<.001 and 18+/-7 v 27+/-9 IU/mL, P<.001, respectively). CONCLUSIONS: Our findings indicate that normotensive individuals with high normal BP have statistically significantly higher plasma leptin levels and lower numbers of human soluble leptin receptors. This observation may play a important role in the pathogenesis of cardiovascular events in this special group of patients and needs further investigation.