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1.
Microcirculation and Macrocirculation in Hypertension: A Dangerous Cross-Link?
Laurent, S, Agabiti-Rosei, C, Bruno, RM, Rizzoni, D
Hypertension (Dallas, Tex. : 1979). 2022;(3):479-490
Abstract
Microcirculation and macrocirculation are tightly interconnected into a dangerous cross-link in hypertension. Small artery damage includes functional (vasoconstriction, impaired vasodilatation) and structural abnormalities (mostly inward eutrophic remodeling). These abnormalities are major determinants of the increase in total peripheral resistance and mean blood pressure (BP) in primary hypertension, which in the long term induces large artery stiffening. In turn, large artery stiffening increases central systolic and pulse pressures, which are further augmented by wave reflection in response to the structural alterations in small resistance arteries. Finally, transmission of high BP and flow pulsatility to small resistance arteries further induces functional and structural abnormalities, thus leading to increased total peripheral resistance and mean BP, thus perpetuating the vicious circle. Hyperpulsatility, in addition to higher mean BP, exaggerates cardiac, brain, and kidney damages and leads to cardiovascular, cerebral, and renal complications. The dangerous cross-link between micro and macrocirculation can be reversed into a virtuous one by ACE (angiotensin-converting enzyme) inhibitors, sartans, and calcium channel blockers. These three pharmacological classes are more potent than β-blockers and diuretics for reducing arterial stiffness and small artery remodeling. The same ranking was observed for their effectiveness at reducing left ventricular hypertrophy, preserving glomerular filtration rate, and preventing dementia, suggesting that they can act beyond brachial BP reduction, by breaking the micro/macrocirculation vicious circle.
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2.
Vitamin K2-a neglected player in cardiovascular health: a narrative review.
Hariri, E, Kassis, N, Iskandar, JP, Schurgers, LJ, Saad, A, Abdelfattah, O, Bansal, A, Isogai, T, Harb, SC, Kapadia, S
Open heart. 2021;(2)
Abstract
Vitamin K2 serves an important role in cardiovascular health through regulation of calcium homeostasis. Its effects on the cardiovascular system are mediated through activation of the anti-calcific protein known as matrix Gla protein. In its inactive form, this protein is associated with various markers of cardiovascular disease including increased arterial stiffness, vascular and valvular calcification, insulin resistance and heart failure indices which ultimately increase cardiovascular mortality. Supplementation of vitamin K2 has been strongly associated with improved cardiovascular outcomes through its modification of systemic calcification and arterial stiffness. Although its direct effects on delaying the progression of vascular and valvular calcification is currently the subject of multiple randomised clinical trials, prior reports suggest potential improved survival among cardiac patients with vitamin K2 supplementation. Strengthened by its affordability and Food and Drug Adminstration (FDA)-proven safety, vitamin K2 supplementation is a viable and promising option to improve cardiovascular outcomes.
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3.
Beneficial Effect of Statin Therapy on Arterial Stiffness.
Alidadi, M, Montecucco, F, Jamialahmadi, T, Al-Rasadi, K, Johnston, TP, Sahebkar, A
BioMed research international. 2021;:5548310
Abstract
Arterial stiffness describes the increased rigidity of the arterial wall that occurs as a consequence of biological aging and several diseases. Numerous studies have demonstrated that parameters to assess arterial stiffness, especially pulse-wave velocity, are predictive of those individuals that will suffer cardiovascular morbidity and mortality. Statin therapy may be a pharmacological strategy to improve arterial elasticity. It has been shown that the positive benefits of statin therapy on cardiovascular disease is attributable not only to their lipid-lowering capacity but also to various pleiotropic effects, such as their anti-inflammatory, antiproliferative, antioxidant, and antithrombotic properties. Additionally, statins reduce endothelial dysfunction, improve vascular and myocardial remodeling, and stabilize atherosclerotic plaque. The aim of the present review was to summarize the evidence from human studies showing the effects of statins on arterial stiffness.
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4.
Effects of Lipid Lowering Drugs on Arterial Stiffness: One More Way to Reduce Cardiovascular Risk?
Reklou, A, Katsiki, N, Karagiannis, A, Athyros, V
Current vascular pharmacology. 2020;(1):38-42
Abstract
Arterial stiffness (AS) is considered an independent predictor of cardiovascular disease (CVD) events. Among lipid lowering drugs, statins have a beneficial effect on AS, independent of their hypolipidaemic effect. Based on 3 meta-analyses and other studies, this effect is compound- and doserelated. Potent statins at high doses are more effective than less powerful statins. Ezetimibe (± statin) also seems to decrease AS in patients with dyslipidaemia. Fibrates have no effect on AS. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have data that beneficially affect all AS risk factors, suggesting a beneficial effect on artery compliance. However, there is no direct measurement of their effect on AS indices. In patients with dyslipidaemia, prescribing high dose statins (± ezetimibe) will not only decrease low-density lipoprotein cholesterol levels but also improve AS (in addition to other effects). This effect on AS may contribute to the observed reduction in vascular events.
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5.
Vitamin K-Dependent Matrix Gla Protein as Multifaceted Protector of Vascular and Tissue Integrity.
Wei, FF, Trenson, S, Verhamme, P, Vermeer, C, Staessen, JA
Hypertension (Dallas, Tex. : 1979). 2019;(6):1160-1169
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Abstract
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6.
Potential Mechanisms of Sodium-Glucose Co-Transporter 2 Inhibitor-Related Cardiovascular Benefits.
Verma, S
The American journal of cardiology. 2019;:S36-S44
Abstract
The findings of recent clinical trials have shown that sodium-glucose co-transporter 2 (SGLT2) inhibitors produce effects beyond glucose lowering and have demonstrated beneficial cardiovascular effects that have been observed across a broad range of patients with type 2 diabetes mellitus. In particular, the cardiovascular benefit results largely from substantial and early effects of SGLT2 inhibition on cardiovascular death and hospitalization for heart failure. Recent cardiovascular outcomes trials (CVOTs) have also shown that relative risk reductions in cardiovascular outcomes were observed with SGLT2 inhibition both in patients with current and prior heart failure. Since the observed reductions of cardiovascular outcomes with SGLT2 inhibitor therapy were observed much earlier than would be expected by an anti-atherosclerotic effect, these results have led to speculation about the potential underlying pathways. Suggested mechanisms include natriuresis and osmotic diuresis; reductions in inflammation, oxidative stress, and arterial stiffness; reductions in blood pressure and body weight; and possible renoprotective effects. These effects could produce cardiovascular benefits through a range of cardiac effects, including reduction in left ventricular load, attenuation of cardiac fibrosis and inflammation, and improved myocardial energy production. Other possible mechanisms include inhibition of sodium-hydrogen exchange, increases in erythropoietin levels, and reduction in myocardial ischemia or reperfusion injury. It is likely that a range of mechanisms underlie the observed cardiovascular benefits of SGLT2 inhibitors; further elucidation of these mechanisms will be answered by ongoing research.
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7.
A systematic review of arterial stiffness, wave reflection and air pollution.
Zanoli, L, Lentini, P, Granata, A, Gaudio, A, Fatuzzo, P, Serafino, L, Rastelli, S, Fiore, V, D'Anca, A, Signorelli, SS, et al
Molecular medicine reports. 2017;(5):3425-3429
Abstract
Arterial stiffening is associated with increased cardiovascular risk. Whether exposure to relatively high levels of air pollution is associated with arterial stiffening is unclear. We aimed to assess the association between exposure to major air pollutants and arterial stiffening. PubMed, SCOPUS and Web of Science databases (through 31 January 2017) were searched using a combination of terms related to exposure to gaseous [nitrogen dioxide (NO2), nitrogen oxides (NOx) and sulphur dioxide (SO2)] or particulate matter pollutants (PM2.5, PM10 and PM10-2.5), arterial stiffness (pulse wave velocity) and reflected waves (augmentation index, augmentation pressure). Pertinent information were extracted from selected studies. In this systematic review were included 8 studies with available data on air pollution and arterial stiffness/reflected waves parameters (8 studies explored the effects of exposure to particulate matter pollutants, 3 studies the effects of exposure to gaseous pollutants); seven of them reported increased arterial stiffness/reflected waves after exposure to air pollution (6 of 8 studies after particulate matter pollutants; 2 of 3 studies after gaseous pollutants). Arterial stiffness and reflected waves were increased in the majority of the studies after both short- and long-term exposure to air pollutants. In conclusion, available evidence supports an association of main air pollutants with increased arterial stiffness and reflected waves. This finding may have implications for population-based strategies for the reduction of arterial stiffness, a vascular biomarker and an intermediate endpoint for cardiovascular disease.
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8.
Uric Acid, Vascular Stiffness, and Chronic Kidney Disease: Is There a Link?
Ramirez-Sandoval, JC, Sanchez-Lozada, LG, Madero, M
Blood purification. 2017;(1-3):189-195
Abstract
Controversy exists with regard to the causal role of hyperuricemia in chronic kidney disease. Vascular stiffness may be the link that explains the relation between hyperuricemia and kidney disease. Hyperuricemia is associated with a number of effects on the vascular endothelium and vascular smooth muscle cells, including an increase in oxidative stress, production of vasoconstrictors, and changes on the structural properties of the large artery wall. Observational evidence in large epidemiological cross-sectional studies suggests that there is an independent association between uric acid and arterial stiffness. The limited evidence from cohort studies or clinical trials does not support treatment of hyperuricemia to reduce vascular stiffness in order to prevent kidney disease. Nevertheless, vascular stiffness may be a valid, reproducible, and useful surrogate endpoint. At this point there seems to be sufficient evidence to warrant larger clinical trials to determine whether lowering uric acid concentrations would be useful for prevention or treatment of vascular stiffness and, subsequently, of cardiovascular and kidney diseases. Video Journal Club 'Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=452726.
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9.
Effects of statin therapy on augmentation index as a measure of arterial stiffness: A systematic review and meta-analysis.
Sahebkar, A, Pećin, I, Tedeschi-Reiner, E, Derosa, G, Maffioli, P, Reiner, Ž
International journal of cardiology. 2016;:160-8
Abstract
OBJECTIVE To evaluate the effects of statin therapy on augmentation index (AIx) as a measure of arterial stiffness using a meta-analysis of clinical trials. METHODS The search included PubMed-Medline, Embase, SCOPUS, Web of Science and Google Scholar databases to identify randomized controlled trials investigating the effects of statin therapy on arterial stiffness measured as AIx. A random-effects model and generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. Random-effects meta-regression was performed using unrestricted maximum likelihood method to evaluate the impact of potential confounders. RESULTS 18 trials examining the effects of statin therapy on arterial stiffness were included. A significant reduction in aortic AIx following statin therapy was proven (WMD: -2.40%, 95% CI: -4.59, -0.21, p=0.032; I(2): 51.20%). HR-adjusted AIx 75% values also revealed a significant improvement by statin therapy (WMD: -5.04%, 95% CI: -7.81, -2.27, p<0.001; I(2): 0%), but not when analysis was restricted to unadjusted AIx values (WMD: -2.30%, 95% CI: -4.83, 0.23, p=0.075; I(2): 53.83%). There was no significant change in carotid (WMD: -2.75%, 95% CI: -8.06, 2.56, p=0.309; I(2): 26.86%) and peripheral (WMD: 0.25%, 95% CI: -3.31, 3.82, p=0.889; I(2): 72.19%) AIx due to statin treatment. There was also no difference in the effect size calculated for different statins subgroups. The impact of statins on AIx was independent of LDL-cholesterol level (slope: 0.05; 95% CI: -0.02, 0.13; p=0.181). CONCLUSION Statin therapy causes a significant reduction in aortic AIx which is independent of LDL-cholesterol changes.
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10.
Effect of vitamin D supplementation on measures of arterial stiffness: a systematic review and meta-analysis of randomized controlled trials.
Rodríguez, AJ, Scott, D, Srikanth, V, Ebeling, P
Clinical endocrinology. 2016;(5):645-57
Abstract
BACKGROUND Low vitamin D has been associated with poor arterial compliance in observational studies. Arterial stiffness has prognostic value for cardiovascular disease risk. The aim of this systematic review was to clarify the literature surrounding the use of vitamin D to ameliorate arterial stiffness. METHODS We conducted a systematic review of the MEDLINE, Scopus and EMBASE databases for randomized controlled clinical trials investigating the effect of vitamin D supplementation on pulse wave velocity (PWV) and/or augmentation index (AI) as indicators of arterial stiffness. We meta-analysed data and calculated standardized mean difference (SMD) and 95% confidence intervals (CI) using inverse-variance models on RevMan v5.3 software. Study quality was assessed using a modified Jadad scale. RESULTS A total of 607 unique records were identified, of which 18 satisfied our inclusion and exclusion criteria. Study quality was high, ranging from 9 to 12 (of 13). Study design in terms of vitamin D dosing protocol (range: 1000-5700 IU/day), follow-up times (range: 1-12 months), sample size (range: n = 29-183) and recruitment strategies varied markedly. Thirteen studies had data for meta-analysis. Vitamin D was associated with nonsignificant reductions in PWV [SMD = -0·10; 95% CI: -0·24, 0·04; P = 0·17; n = 806 from ten studies] and AI [-0·15; -0·32, 0·02; 0·08; n = 551 from eight studies]. DISCUSSION There is inconsistent evidence to suggest that vitamin D supplementation improves indicators of arterial stiffness. This may be attributable to the heterogeneity in study design. Therefore, large and well-designed randomized studies are required to determine the casual relationships between vitamin D and arterial stiffness and cardiovascular risk.