The modern way of life is often associated with an increased prevalence of multiple cardiovascular (C.V.) risk factors. Obesity often lies at the root of this serious problem. Indeed, the coupling of increased caloric intake and decreased physical activity is common, leading to excess body weight. Obesity is associated with numerous adverse effects. Among them the increased prevalence of C.V. disease (C.V.D.), type 2 diabetes mellitus (T2DM) and hypertension increase morbidity and mortality. Moreover, as often seen in metabolic syndrome (Met.S.), these risk factors frequently coexist. Met.S. is a cluster of metabolic risk factors including abdominal obesity, hypertension, impaired glucose metabolism, raised triglyceride levels and decreased levels of high-density lipoprotein cholesterol (H.D.L.-C.). As a result, a comprehensive management of all coexisting C.V.D. risk factors in these patients is important in order to minimize C.V.D. risk. This comprehensive approach often requires multidrug therapy. Indeed, beyond the very important lifestyle modification encouragement, the combination of a statinCitation1 together with an antihypertensive drug is often used in the management of Met.S.
Among the antihypertensive drugs, angiotensin receptor blockers (A.R.B.s) have an established efficacy coupled with a favorable safety profile. As a result, A.R.B.s are among the first choices for hypertension management. Among them, telmisartan may be a unique member of the A.R.B. classCitation2. Its ability to partially activate the peroxisome proliferator activated receptor-γ (PPARγ) gives telmisartan a number of pleiotropic effects beyond blood pressure loweringCitation3. These pleiotropic effects may provide additional benefits, thus rendering the management of multiple coexisting C.V.D. risk factors more efficientCitation4. Indeed, telmisartan has been shown to improve glucose metabolismCitation3. Impaired glucose metabolism plays a central role in Met.S. and may be aggravated by statin treatment. We have shown that the combination of telmisartan with a statin in patients with mixed dyslipidemia, stage 1 hypertension and prediabetes has a beneficial effect on glucose homeostasisCitation5. Not only did telmisartan negate the disadvantageous effects of statin treatment on the homeostasis model assessment insulin resistance (H.O.M.A.-I.R.) index, but it further improved H.O.M.A.-I.R. compared with other A.R.B.s. Moreover, a significant reduction in high sensitivity C-reactive protein levels, a marker of C.V.D., was also only observed in the telmisartan group. Another element contributing to increased C.V.D. risk is high oxidative stressCitation6. The combination of rosuvastatin with telmisartan had a beneficial effect on oxidative stress in hypertensive, prediabetic and dyslipidemic patients as assessed by plasma 8-isoprostane prostaglandin F2a levels when compared with other A.R.B.sCitation7. Furthermore, beyond the quantity of H.D.L.-C., its quality and associated enzymes such as the lipoprotein-associated phospholipase A2 (Lp-PLA2) play an equally important role in the prevention of C.V.D.Citation8,Citation9. H.D.L. associated Lp-PLA2 may significantly contribute to the antiatherogenic effects of H.D.L.Citation10. We have shown that the telmisartan/rosuvastatin combination increased the levels of H.D.L. associated Lp-PLA2 compared with the combination of rosuvastatin with either irbesartan or olmesartanCitation11.
Adipose tissue is not just an energy storing location, it also plays a role in a plethora of metabolic processes through the production of hormones called adipokines. Indeed, adipose tissue affects the development of hypertension, inflammation, oxidative stress and glucose homeostasis thus directly having an impact on C.V.D. development and progressionCitation12. Adipose tissue according to its anatomic distribution is categorized into two major types: the subcutaneous and the visceral adipose tissue. These two categories have distinct functional contrasts which clearly differentiate their effect on metabolic parameters and C.V.D. risk factorsCitation13. Indeed, visceral adiposity has been associated with a more disadvantageous effect on C.V.D. risk when compared with subcutaneous adiposityCitation14–16.
In the present issue of Current Medical Research & Opinion, Choi et al. present the results of a meta-analysis regarding the effects of telmisartan on fat redistribution, lipidemic profile and body weight in hypertensive, obese or overweight patients with Met.S. or glucose intoleranceCitation17. Telmisartan treatment was associated with a decrease in visceral fat while no change in subcutaneous fat was observed. Moreover, body mass index as well as waist circumference remained unaffected. In addition, total cholesterol levels decreased with telmisartan treatment vs. controls, while triglycerides, low density lipoprotein cholesterol and H.D.L.-C. did not change. This meta-analysis provides further corroboration to previous studies associating telmisartan treatment with a favorable redistribution of adipose tissueCitation18,Citation19. The effect of telmisartan on adipose tissue may be associated with its ability to partially activate the PPARγ. This is also the case with thiazolidinediones which are full PPARγ agonists and have been shown to exert a beneficial effect on fat redistributionCitation20,Citation21. Moreover, PPARγ subtypes 1 and 2 are primarily expressed in adipose tissueCitation22 and therefore may play a significant target role in the adipose redistribution effects of both telmisartan and thiazolidinediones. What is more, PPARγ activation can increase adiponectinCitation23,Citation24 which is an adipokine inversely associated with the development of insulin resistance and Met.S.Citation25.
In conclusion, obese or overweight patients often accumulate a number of Met.S. components such as hypertension. The need for lifestyle changes is of paramount importance in the treatment of these patients. However, these changes are often not sufficient for the management of the various C.V.D. risk factors present. Telmisartan provides an attractive option for the treatment of the hypertensive subgroup of these patients. Indeed, beyond safely controlling hypertension, telmisartan may provide further beneficial effects through its multiple pleiotropic effects. As a result, overweight or obese patients with increased visceral adiposity, hypertension, impaired glucose metabolism and dyslipidemia may benefit more with telmisartan treatment compared with other antihypertensive options. Further studies focusing on ‘hard’ clinical endpoints are needed in order to establish whether these pleiotropic effects of telmisartan are translated into C.V.D. benefit for various subgroups of patients.
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The authors state no conflict of interest and have received no payment in preparation of this manuscript. All authors have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this article.
C.M.R.O. peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
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