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Obesity, diabetes, and antidiabetic treatment: blood pressure and vascular effects

Zanchetti, Alberto

doi: 10.1097/HJH.0000000000000834

Istituto Auxologico Italiano and Centro Interuniversitario di Fisiologia Clinica e Ipertensione, Università di Milano, Milan, Italy

Correspondence to Professor Alberto Zanchetti, Centro di Fisiologia Clinica e Ipertensione, Università di Milano, Via F. Sforza, 35, 20122 Milano, Italy. Tel: +39 02 50320484; e-mail:

A number of studies published in the current issue of the Journal of Hypertension are focused on blood pressure (BP) and vascular effects of adiposity, diabetes, and antidiabetic treatment. Park et al. (pp. 282–289) have investigated the effects of diabetes and hyperglycaemia on arterial central haemodynamics, stiffness, and load in a tri-ethnic population-based cohort in the United Kingdom, and found more deleterious effects in south Asians than Europeans, and more favourable arterial function in African Caribbeans.

The BP and vascular effects of the new class of antidiabetic agents, the di-peptidylpeptidase-4 (DPP-4) inhibitors, are the topic of two articles. In a double-blind, randomized, placebo-controlled mechanistic study, Forst et al. (pp. 345–350) report that treatment with linagliptin improved retinal capillary perfusion and reduced the inflammatory marker Transforming Growth Factor ß1. Interestingly, in this group of nondiabetic hypertensive individuals studied by Forst et al., linagliptin did not reduce BP more than placebo. On the other hand, Zhang and Zhao (pp. 167–175), in a systematic review of randomized studies comparing DPP-4 inhibitors with placebo or no antidiabetic treatment (15 trials on 5636 participants), report a modest but significant reduction in both SBPs and DBPs. However, these BP effects are smaller than those induced by another new class of antidiabetic agents, the inhibitors of sodium-glucose cotransporter 2, and similar to those reported with conventional antidiabetic drugs. In an accompanying editorial commentary, Nilsson and Diez (pp. 184–187) remark that there is still a need for more extensive evaluation of ambulatory diurnal BP control with incretin active drugs, as some discrepancy in the cardiovascular results of recent intervention trials that have tested different DPP-4 inhibitors may be explained by a difference in the diurnal BP effect of various DPP-4 inhibitors.

Haemodynamic patterns associated with adiposity have been investigated by Middlemiss et al. (pp. 290–297) in the young adults of the Enigma study: a stronger association was found between SBP and peripheral vascular resistance in overweight individuals, whereas in normal-weight individuals SBP had a stronger association with cardiac output. Commenting these observations, Kotsis and Grassi (pp. 191–192) call attention to the finding that in Middlemiss et al.'s study, higher brachial SBP values were accompanied by higher central BP values, and remark this appears to contradict a widely accepted theory, that systolic hypertension in the youth may be a spurious phenomenon because of excessive peripheral amplification of a normal central BP.

Two other studies are focused on BP in youth. Lurbe and Ingelfinger (pp. 176–183) present their authoritative viewpoint on the importance of measuring BP in childhood and adolescence, a problem that has been debated in recent issues of the journal. Lurbe and Ingelfinger make the point that progress to date in the area should provide an impetus for further research advances that may translate into clinical practice. A study from Brazil (Souza et al., pp. 221–225) confirm current changes in dietary habits adversely influence BP in children, showing that among fifth graders of public schools consumption of soft drinks, and particularly of diet type sodas, is associated with a significant and independent increase in BP.

Two other articles approach dietary problems. Uechi et al. (pp. 204–214) have investigated the most accurate method of estimating 24 h sodium excretion from spot urine samples, and report that the sample-mean method with three spot samples yields the most accurate estimate. In a post hoc analysis of a randomized, double-blind, placebo-controlled crossover trial Riphagen et al. (pp. 215–220) find that potassium supplementation has BP-lowering effects even after sodium restriction, but several counter regulatory mechanisms are activated to mitigate the response.

A number of studies on prospective cohorts shed light on several mechanisms leading to development of hypertension or cardiovascular disease. In the large community-based cohort of the Atherosclerosis Risk in Community study, Yao et al. (pp. 196–203) have found that parathyroid hormone levels were not independently associated with the risk of developing hypertension, though some possible association was found in blacks. In the population sample of the Dallas Heart Study, Velasco et al. (pp. 226–234) have estimated the alerting response to BP measurement as isolated hypertension during the first of five consecutive measurements and report an independent association of this type of alerting response with increased cardiovascular and renal complications. Retrospectively analysing a very large prospective cohort of patients with chronic kidney disease of the Kaiser Permanente, Chang et al. (pp. 244–252) report that indices of visit-to-visit BP variability appear to be independently associated with higher rates of death and haemorrhagic stroke, but not with heart failure, acute coronary syndrome, ischaemic stroke, and end-stage renal disease. In a thoughtful accompanying editorial Redon (pp. 188–190) comments that electronic health records, such as those used in this research, provide unique opportunities to analyse real life data, but the question remains as to whether high visit-to-visit BP variability is cause or consequence of the higher cardiovascular risk, and whether it mostly reflects a lower level of patients’ adherence to drug treatment. In another prospective study, Hu et al. (pp. 332–337) report that serum bisphenol A appears to be a predictor of chronic kidney disease in patients with hypertension. Benezet-Mazuecos et al. (pp. 338–344) have followed-up hypertensive patients with an implanted cardiac electronic device, and found that episodes of high-rate atrial fibrillations are rather frequent in these patients and associated with a high proportion of ischaemic brain lesions on computer tomography scans. Finally, a cross-sectional study in a geriatric population (Press et al., pp. 351–358) reports a very high prevalence of orthostatic hypotension, and indicates the drugs more strongly associated with this phenomenon.

A group of studies is focused on pathophysiological mechanisms of blood vessel alterations: Aguado et al. (pp. 253–265) find that NOX-1 regulation by NOX-4 and the RNA-binding protein HuR contributes to vascular smooth muscle cell migration, a phenomenon important in vascular inflammation and remodeling. Trinity et al. (pp. 266–273) show that endothelin-1, acting through the ETA receptors, exerts a powerful age-specific vasoconstriction, but that removal of this vasoconstrictive stimulus does not augment the decreased shear rate in the old. Norman et al. (pp. 274–281) report that the adipokine, resistin, the role of which in mediating aortic stiffness is debated, is indeed independently and directly associated with aortic stiffness, and this association is independent of BP, insulin resistance and general inflammation. Another pathophysiological study is focused on the role of podoplanin as an antiapoptotic prosurvival factor in angiotensin II-induced injury in human podocytes (Eisenreich et al., pp. 323–331).

Further interesting research contributions can be found in the present issue. Booth et al. (pp. 235–243) have investigated different methods for precise estimation of night-time and daytime ambulatory BP periods, and show self-reports to define diurnal period have a high agreement with actigraphy. Koton et al. (pp. 316–322) have examined the National Acute Stroke Israeli Registry, and found admission SBP in patients with acute stroke decreased from 2004 to 2010 and parallelly rate of disability at discharge or in-hospital death decreased supporting the concept that elevated BP during acute stroke is associated with unfavourable outcome. Frederiksen-Møller et al. (pp. 298–306) present novel data showing that levels of prostasin, a serine protease, are increased in the urine of women with preeclampsia and this increase is correlated with urinary albumin excretion; however, the authors do not find any changes in prostasin or its associated inhibitory molecules in placental samples at delivery. In their commentary, Small et al. (pp. 193–195) remark that the beauty of prostasin lies in its involvement in many of the key mechanisms that are dysregulated in the development of preeclampsia, and conclude we need to know more about its regulation on a genetic and epigenetic level, and whether prostasin has a causal role in the development of preeclampsia or if changes in prostasin levels are secondary to other phenomena in this multifactorial condition. Griffin et al. (pp. 307–315) have investigated whether β-blocker therapy interferes in a dose-related way with the aldosterone/renin ratio as a diagnostic test for primary aldosteronism, and report an increased risk of false positive aldosterone/renin ratio tests irrespective of the β-blocker dose. Redon et al. (pp. 359–367) present the results of a randomized comparison of the combinations olmesartan/amlodipine and perindropril/amlodipine and conclude both combinations are equally safe, well tolerated, and effective in the control of hypertension in patients with diabetes, and that a missed dose does not leave the patients unprotected in both treatments. Finally, Pietilä-Effati et al. (pp. 368–370) report a case of renal sympathetic denervation in a drug-resistant hypertension of a patient on haemodialysis.

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Conflicts of interest

There are no conflicts of interest.

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