Free Leptin Predicts Incident (Clinic) Hypertension in a Danish Cohort

Abstract

Study" 1 that investigated the independent effects of leptin and adiponectin on incident hypertension in a large Danish populationbased cohort. The authors have elegantly shown that leptin, but not adiponectin, was an independent predictor of new-onset (clinic) hypertension.An issue not taken into account by the Danish study is that participants were not screened for obstructive sleep apnea syndrome (OSAS), a well-associated comorbidity with both free leptin and new-onset hypertension. Although the exclusion of OSAS is not definitive by using clinical measures alone (i.e., sleep history and assessment of daytime sleepiness by validated questionnaires), 2 it would have contributed to a better confounding risk factor subset of the predictor variable (i.e., leptin) on the outcome (i.e., new-onset hypertension).Furthermore, it is known that hyperleptinemia and hypoadiponectinemia are closely associated with metabolic syndrome.However, in the article by Asferg et al., 1 no analysis is provided for the predictive value of leptin and adiponectin on incident hypertension in those with and without metabolic syndrome. Last but not least, although authors reported the level of triglycerides as a surrogate estimate of insulin resistance, we feel that this approach is by far insufficient to replace the traditional measures of insulin resistance, namely fasting insulin and oral glucose tolerance testing.One aspect partly emphasized by the authors is that blood pressure (BP) measurement was performed only once and thus white-coat hypertension was inevitably included in the outcome. We acknowledge that by the design of the study it was difficult to perform ambulatory BP monitoring, but it is obvious that at least three BP measurements, even in the context of the same visit, would have alleviated the eventuality of the white-coat phenomenon. In two different outpatient samples, we have previously demonstrated that white-coat hypertension was not associated with either free leptin or adiponectin; however, both of these adipokines were associated with sustained and masked hypertension. 3,4 Consequently, we believe that white-coat phenomenon might not have affected the results of the Danish prospective study, 1 and this is further supported when harder criteria for the definition of the outcome were implemented (i.e., systolic BP ≥160 mm Hg and/or diastolic BP ≥95 mm Hg). In contrary, masked hypertension phenomenon would have diminished and convicted as not significant of the predictive value of leptin and adiponectin on incident hypertension, respectively. By summarizing our concerns for this Danish study, first, screening for high clinical suspicion of OSAS was not performed; second, insulin resistance was not assessed properly; third, it would have been interested to know the impact of metabolic syndrome on the investigated relationship; and last, measurement of the main outcome could be more accurate. Nonetheless, the present study provides enough evidence for the relative predictive value of leptin over adiponectin in the predi...

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“…observed that free leptin predicts incident hypertension in a Danish cohort. 39 Leptin may regulate blood pressure through sympathetic activation. 40 In our study, we found elevated plasma leptin level was associated with systemic hypertension: mean leptin was significantly higher in hypertensive than normotensive individuals ( P = 0.014) (Figure 1), as well as in subjects with positive family history of hypertension ( P = 0.035) (Figure 1).…”