ABSTRACT
Background: Hypertension is a main risk factor for premature death. Although blood pressure is a complex trait, we have shown that the activity of the ATP-generating enzyme creatine kinase (CK) is a significant predictor of blood pressure and of failure of antihypertensive drug therapy in the general population. In this report, we systematically review the evidence on the association between this new risk factor CK and blood pressure outcomes. Method: We used a narrative synthesis approach and conducted a systematic search to include studies on non-pregnant adult humans that address the association between plasma CK and blood pressure outcomes. We searched electronic databases and performed a hand search without language restriction. We extracted data in duplo. The main outcome was the association between CK and blood pressure as continuous measures. Other outcomes included the association between CK and blood pressure categories (normotension and hypertension, subdivided in treated controlled, treated uncontrolled, and untreated hypertension). Results: We retrieved 139 reports and included 11 papers from 10 studies assessing CK in 34,578 participants, men and women, of African, Asian, and European ancestry, aged 18 to 87 years. In 9 reports, CK was associated with blood pressure levels, hypertension (vs. normotension), and/or treatment failure. The adjusted increase in systolic blood pressure (mmHg/log CK increase) was reported between 3.3 [1.4 to 5.2] and 8.0 [3.3 to 12.7] and the odds ratio of hypertension with high vs. low CK ranged between 1.2 and 3.9. In addition, CK was a strong predictor of treatment failure in the general population, with an adjusted odds ratio of 3.7 [1.2 to 10.9]. Discussion: This systematic review largely confirms earlier reports that CK is associated with blood pressure and failure of antihypertensive therapy. Further work is needed to address whether this new risk factor is useful in clinical medicine.
ABSTRACT
AIMS/HYPOTHESIS: South Asians have a disproportionately high risk of developing abdominal obesity, insulin resistance and type 2 diabetes. Brown adipose tissue (BAT) has been identified as a possible target to fight obesity and protect against metabolic disturbance. We explored whether lower BAT activity in South Asians compared with Europids may contribute to the high risk of metabolic disturbance. METHODS: We studied 20 healthy men (ten Europids/ten South Asians, BMI 19-25 kg/m(2), age 18-32 years). Following 2 h of cold exposure (16-18°C) after an overnight fast, (18)F-fluorodeoxyglucose ((18)F-FDG) positron-emission tomography-computed tomography (CT) and (123)I-metaiodobenzylguanidine ((123)I-MIBG) single-photon emission computed tomography-CT were performed to visualise metabolic BAT activity and sympathetic stimulation of BAT. Metabolic BAT activity was defined as maximal standardised uptake value (SUV(max)) of (18)F-FDG, and sympathetic stimulation of BAT as semiquantitative uptake value (SQUV) of (123)I-MIBG. We performed hyperinsulinaemic-euglycaemic clamps to assess insulin sensitivity. Spearman's correlations for SUV(max) of (18)F-FDG and both SQUV of (123)I-MIBG and insulin sensitivity were determined. RESULTS: The median (interquartile range) SUV(max) of (18)F-FDG in South Asians (7.5 [2.2-10.6] g/ml) was not different from the median SUV(max) obtained in Europids (4.5 [2.2-8.4] g/ml; p = 0.59). There was no correlation between BAT activity and insulin sensitivity. Correlations between SQUV of (123)I-MIBG and SUV(max) of (18)F-FDG were positive, both in the total population (ρ = 0.80, p < 0.001) and after stratification by ethnicity (Europids, ρ = 0.65, p = 0.04; South Asians, ρ = 0.83, p = 0.01). CONCLUSIONS/INTERPRETATION: This is the first study to prospectively investigate ethnic differences in metabolic BAT activity during cold exposure. We did not find differences in BAT activity between South Asians and Europids. Therefore, it seems unlikely that BAT plays an important role in the development of unfavourable metabolic profiles in South Asians.