Metabolic Vascular Syndrome: New Insights into a Multidimensional Network of Risk Factors and Diseases

Abstract

<b><i>Background:</i></b> Since 1981, we have used the term metabolic syndrome to describe an association of a dysregulation in lipid metabolism (high triglycerides, low high-density lipoprotein cholesterol, disturbed glucose homeostasis (enhanced fasting and/or prandial glucose), gout, and hypertension), with android obesity being based on a common soil (overnutrition, reduced physical activity, sociocultural factors, and genetic predisposition). We hypothesized that main traits of the syndrome occur early and are tightly connected with hyperinsulinemia/insulin resistance, procoagulation, and cardiovascular diseases. <b><i>Methods:</i></b> To establish a close link between the traits of the metabolic vascular syndrome, we focused our literature search on recent original work and comprehensive reviews dealing with the topics metabolic syndrome, visceral obesity, fatty liver, fat tissue inflammation, insulin resistance, atherogenic dyslipidemia, arterial hypertension, and type 2 diabetes mellitus. <b><i>Results:</i></b> Recent research supports the concept that the metabolic vascular syndrome is a multidimensional and interactive network of risk factors and diseases based on individual genetic susceptibility and epigenetic changes where metabolic dysregulation/metabolic inflexibility in different organs and vascular dysfunction are early interconnected. <b><i>Conclusion:</i></b> The metabolic vascular syndrome is not only a risk factor constellation but rather a life-long abnormality of a closely connected interactive cluster of developing diseases which escalate each other and should continuously attract the attention of every clinician.

High-Risk Atherosclerosis and Metabolic Phenotype: The Roles of Ectopic Adiposity, Atherogenic Dyslipidemia, and Inflammation

“…1G). 47 The procoagulatory state associated with diabetes has been linked to higher concentrations of plasminogen activator inhibitor-1, which reflects a state of fibrinolytic dysfunction in this phenotype. This provides biological plausibility for the increased predisposition of individuals with MetS to develop atherothrombosis.…”

“…30 Endothelial dysfunction results in decreased bioavailability of the vascular protective vasodilatory molecule nitric oxide. 47 Furthermore, hyperinsulinemia affects kidney function in a way that promotes uric acid and sodium retention and hypertension. 50 T2DM constitutes the tip of the iceberg of this vicious cycle of insulin resistance and compensatory hyperinsulinemia.…”

The vicious circle of hypometabolism in neurodegenerative diseases: Ways and mechanisms of metabolic correction

“…Major preconditioning risk factors such as cardio‐vascular dysfunction, diabetes, metabolic syndrome, traumatic brain injury, and stroke are shared by the sporadic AD (Biessels and Reagan, ; Chakrabarti et al, ; de la Torre, ; Patterson et al, ) and PD (Athauda and Foltynie ; Daneshvar et al, ; Jabir et al, ; Jha et al, ; Santiago and Potashkin, ; Santiago and Potashkin, ), in addition to being associated with AE (Chou et al, ; Kalra et al, ; Ono and Galanopoulou, ; Pitkanen et al, ; Verrotti et al, ; Waldbaum and Patel, ). These factors are characterized by common brain pathologies such as chronic hypoperfusion (Scholz and Hanefeld, ; Zlokovic, ), neuro‐inflammation, and insulin resistance (Rosales‐Corral et al, ; Straub ; Yamagata et al, ), all leading to energy deficiency and oxidative stress. At the same time, the major genetic risk factors for sporadic AD, APOE ε4 allele (Liu et al, ; Zlokovic, ), and TREM2 mutations (Guerreiro et al, ; Jonsson et al, ), and a‐synuclein gene, MAPT, LRRK2, and GBA for PD (Deleidi and Gasser, ; Kalinderi et al, ) also lead to neurovascular dysfunction and neuro‐inflammation.…”

“…In AD, for instance, such main hypotheses are genetic inheritance (Liu et al, ), the cholinergic hypothesis (Francis et al, ), the amyloid hypothesis (Hardy, ; Karran et al, ), the tau hypothesis (Arendt et al, ; Maccioni et al, ), the neurovascular hypothesis (Zlokovic, ), and others. The wide diversity of causes and manifestations of the disease development resulted in an increasingly popular view that each of these disorders represents not a single disease but rather a syndrome (Blass, ; Dexter and Jenner, ; Khachaturian et al, ; Korczyn and Hassin‐Baer, ), in analogy to the metabolic syndrome (Scholz and Hanefeld, ; Sperling et al, ). However, analysis of the risk factors shared among these diseases reveals that disrupted glucose metabolism associated with oxidative stress and neuro‐inflammation is the common end state of most, if not all, risk factors preceding the neurodegenerative disease initiation.…”

Metabolic syndrome in peri - and postmenopausal women performing intellectual work

“…The risk of sudden cardiovascular events is increased in people with MS, cardiovascular disease or type 2 diabetes, compared to healthy subjects. It is currently believed that one metabolic disorder in MS increases the severity of one or more associated disorders [4].…”