Microvascular Inflammation and Cardiovascular Prevention: The Role of Microcirculation as Earlier Determinant of Cardiovascular Risk

The worldwide morbidity and mortality burden of cardiovascular disease (CVD) is overwhelming and caused by increasing life expectancy and an epidemic of risk factors, including hypertension. Therapeutic options targeting different areas of the renin–angiotensin–aldosterone system (RAAS) to disrupt pathophysiological processes along the cardiovascular continuum are available. Angiotensin-converting enzyme (ACE) inhibitors are first-line treatments for CVD and angiotensin receptor blockers (ARBs) are suitable alternatives. Both ACE inhibitors and ARBs prevent CVD by lowering blood pressure (BP). Additionally, several studies have demonstrated that RAAS blockade can reduce cardiovascular risk beyond what might be expected from BP lowering alone. However, the ARBs are not all equally effective. Telmisartan is a long-lasting ARB that effectively controls BP over the full 24-hour period. Recently, the Ongoing telmisartan alone and in combination with ramipril global endpoint trial (ONTARGET) study showed that telmisartan reduces cardiovascular events in high cardiovascular risk patients similarly to the gold standard ACE inhibitor ramipril beyond BP lowering alone, but with a better tolerability. Based on the results of the ONTARGET and Telmisartan randomized assessment study in ACE intolerant subjects with cardiovascular disease (TRANSCEND) studies, telmisartan is indicated for the reduction of cardiovascular morbidity. This article aims to review current guidelines for the management of CVD and consider key data from clinical trials and clinical practice evaluating the role of telmisartan in CVD.

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The Role of Statins in Disease Modification and Cardiovascular Risk in Rheumatoid Arthritis

Frontiers in Medicine ◽

10.3389/fmed.2018.00024 ◽

2018 ◽

Vol 5 ◽

Cited By ~ 20

Author(s):

Stergios Soulaidopoulos ◽

Elena Nikiphorou ◽

Theodoros Dimitroulas ◽

George D. Kitas

Keyword(s):

Rheumatoid Arthritis ◽

Cardiovascular Risk ◽

Disease Modification

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Osteopontin in Cardiovascular Diseases

Biomolecules ◽

10.3390/biom11071047 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1047

Author(s):

Kohsuke Shirakawa ◽

Motoaki Sano

Keyword(s):

Cardiovascular Risk ◽

Cardiovascular Diseases ◽

Therapeutic Target ◽

Gene Mutations ◽

Major Adverse Cardiovascular Event ◽

Matricellular Protein ◽

Pathological State ◽

Adverse Cardiovascular Event ◽

Anti Inflammatory

Unprecedented advances in secondary prevention have greatly improved the prognosis of cardiovascular diseases (CVDs); however, CVDs remain a leading cause of death globally. These findings suggest the need to reconsider cardiovascular risk and optimal medical therapy. Numerous studies have shown that inflammation, pro-thrombotic factors, and gene mutations are focused not only on cardiovascular residual risk but also as the next therapeutic target for CVDs. Furthermore, recent clinical trials, such as the Canakinumab Anti-inflammatory Thrombosis Outcomes Study trial, showed the possibility of anti-inflammatory therapy for patients with CVDs. Osteopontin (OPN) is a matricellular protein that mediates diverse biological functions and is involved in a number of pathological states in CVDs. OPN has a two-faced phenotype that is dependent on the pathological state. Acute increases in OPN have protective roles, including wound healing, neovascularization, and amelioration of vascular calcification. By contrast, chronic increases in OPN predict poor prognosis of a major adverse cardiovascular event independent of conventional cardiovascular risk factors. Thus, OPN can be a therapeutic target for CVDs but is not clinically available. In this review, we discuss the role of OPN in the development of CVDs and its potential as a therapeutic target.

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Role of endometriosis in defining cardiovascular risk: a gender medicine approach for women’s health

Human Fertility ◽

10.1080/14647273.2021.1919764 ◽

2021 ◽

pp. 1-9

Author(s):

Michela Cirillo ◽

Maria Elisabetta Coccia ◽

Felice Petraglia ◽

Cinzia Fatini

Keyword(s):

Cardiovascular Risk ◽

Women’S Health ◽

Women's Health ◽

Gender Medicine

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P1818Descending aortic thoracic diameter: a risk marker for major adverse cardiovascular outcomes in women

European Heart Journal ◽

10.1093/eurheartj/ehz748.0570 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

O L Rueda Ochoa ◽

L R Bons ◽

S Rohde ◽

K E L Ghoud ◽

R Budde ◽

...

Keyword(s):

Heart Failure ◽

Cardiovascular Risk ◽

Cardiovascular Mortality ◽

Total Mortality ◽

Population Based ◽

Cardiovascular Outcomes ◽

Increased Risk ◽

Almost All

Abstract Background Thoracic aortic diameters have been associated with cardiovascular risk factors and atherosclerosis. However, limited evidence regarding the role of thoracic aortic diameters as risk markers for major cardiovascular outcomes among women and men exist. Purpose To evaluate the independent associations between crude and indexed ascending and descending aortic (AA and DA) diameters with major cardiovascular outcomes among women and men and to provide optimal cutoff values associated with increased cardiovascular risk. Methods and results 2178 women and men ≥55 years from the prospective population-based Rotterdam Study underwent multi-detector CT scan of thorax. Crude diameters of the AA and DA were measured and indexed by height, weight, body surface area (BSA) and body mass index (BMI). Incidence of stroke, coronary heart disease (CHD), heart failure (HF), cardiovascular and all-cause mortality were evaluated during 13 years of follow-up. Weight-, BSA-, or BMI-indexed AA diameters showed significant associations with total or cardiovascular mortality in both sexes and height-indexed values showed association with HF in women. Crude AA diameters were associated with stroke in men and HF in women. For DA, crude and almost all indexed diameters showed significant associations with either stroke, HF, cardiovascular or total mortality in women. Only weight-, BSA- and BMI-indexed values were associated with total mortality in men. For crude DA diameter, the risk for stroke increased significantly at the 75th percentile among men while the risks for HF and cardiovascular mortality increased at the 75th and 85th percentiles respectively in women. Conclusions Our study suggests a role for descending thoracic aortic diameter as a marker for increased cardiovascular risk, in particular for stroke, heart failure and cardiovascular mortality among women. The cut points for increased risk for several of cardiovascular outcomes were below the 95th percentile of the distribution of aortic diameters.

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THU0081 Assessing the cardiovascular risk burden in patients with rheumatoid arthritis: Role of annual review clinic

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2012-eular.2046 ◽

2013 ◽

Vol 71 (Suppl 3) ◽

pp. 180.1-180

Author(s):

V. Patel ◽

U. Karjigi ◽

R. Abernethy ◽

J. Dawson ◽

A. Clewes ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Cardiovascular Risk ◽

Annual Review

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Residual cardiovascular risk in patients with dyslipidemia receiving multifactorial cardiovascular prevention therapy

Atherosclerosis ◽

10.1016/j.atherosclerosis.2021.06.451 ◽

2021 ◽

Vol 331 ◽

pp. e150

Author(s):

F. Barkas ◽

G. Anastasiou ◽

G. Liamis ◽

I. Gartzonikas ◽

H. Milionis ◽

...

Keyword(s):

Cardiovascular Risk ◽

Cardiovascular Prevention ◽

Residual Cardiovascular Risk ◽

Prevention Therapy

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Characterization of TNF receptor subtype expression and signaling on pulmonary endothelial cells in mice

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00326.2010 ◽

2011 ◽

Vol 300 (5) ◽

pp. L781-L789 ◽

Cited By ~ 17

Author(s):

Szabolcs Bertok ◽

Michael R. Wilson ◽

Anthony D. Dorr ◽

Justina O. Dokpesi ◽

Kieran P. O'Dea ◽

...

Keyword(s):

Flow Cytometry ◽

Adhesion Molecules ◽

Surface Expression ◽

Tnf Receptor ◽

Wild Type ◽

Tnf Receptors ◽

Pulmonary Endothelial Cells ◽

Microvascular Inflammation

TNF plays a crucial role in the pathogenesis of acute lung injury. However, the expression profile of its two receptors, p55 and p75, on pulmonary endothelium and their influence on TNF signaling during lung microvascular inflammation remain uncertain. Using flow cytometry, we characterized the expression profile of TNF receptors on the surface of freshly harvested pulmonary endothelial cells (PECs) from mice and found expression of both receptors with dominance of p55. To investigate the impact of stimulating individual TNF receptors, we treated wild-type and TNF receptor knockout mice with intravenous TNF and determined surface expression of adhesion molecules (E-selectin, VCAM-1, ICAM-1) on PECs by flow cytometry. TNF-induced upregulation of all adhesion molecules was substantially attenuated by absence of p55, whereas lack of p75 had a similar but smaller effect that varied between adhesion molecules. Selective blockade of individual TNF receptors by specific antibodies in wild-type primary PEC culture confirmed that the in vivo findings were due to direct effects of TNF receptor inhibition on endothelium and not other cells (e.g., circulating leukocytes). Finally, we found that PEC surface expression of p55 dramatically decreased in the early stages of endotoxemia following intravenous LPS, while no change in p75 expression was detected. These data demonstrate a crucial in vivo role of p55 and an auxiliary role of p75 in TNF-mediated adhesion molecule upregulation on PECs. It is possible that the importance of the individual receptors varies at different stages of pulmonary microvascular inflammation following changes in their relative expression.

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