The findings show that blood pressure is influenced by the metabolic syndrome, irrespective of the presence or absence of diabetes mellitus. This finding was not a reflection of the antihypertensive treatments received by the patients, as those with metabolic syndrome alone and those with diabetes alone were receiving a similar number of treatments. Other factors may be more important for conferring resistance to antihypertensive treatment, since patients with diabetes mellitus alone, without accompanying metabolic syndrome, showed much lower blood pressure than patients with metabolic syndrome with or without diabetes mellitus. In addition, resistance to antihypertensive treatment may also reflect some doubts about target blood pressure values and low physician compliance in prescribing further therapy for patients with metabolic syndrome.
As disturbed glucose metabolism is present in both metabolic syndrome and diabetes mellitus, other factors of the metabolic syndrome are likely to be responsible for the tendency towards higher blood pressure in patients with metabolic syndrome. Indeed, when we evaluated the other components of the metabolic syndrome with respect to their impact on blood pressure, it was BMI and waist circumference which showed the closest association with blood pressure, both systolic and diastolic. On the other hand, the presence or absence of diabetes mellitus was not a major determinant of blood pressure. The above analyses were based on blood pressure values instead of blood pressure control rates. This seemed appropriate since blood pressure control rates were much lower in patients with diabetes mellitus than in patients with metabolic syndrome due to the fact that in patients with metabolic syndrome without diabetes mellitus the blood pressure target was < 140/90 mm Hg, but in patients with diabetes mellitus with or without metabolic syndrome the blood pressure target was < 130/80 mm Hg. Due to the different blood pressure targets, blood pressure control rates differed markedly depending on the presence or absence of diabetes mellitus.
These findings suggest that among the components of the metabolic syndrome, it is central obesity which affects blood pressure most. These findings are in line with the newer concepts on the pathophysiology of hypertension. The role of adipocytokines in the pathogenesis of hypertension has been of increasing interest in the last decade, and has markedly extended our view on the humoral mechanisms of hypertension [3–6]. Among the adipocytokines involved in the pathogenesis of hypertension, adiponectin and leptin have been most extensively studied. Recently, in a 5-year prospective study, serum adiponectin levels have been shown to be independent predictors of incident hypertension in a population normotensive at baseline .
Adiponectin, besides its effects on insulin sensitivity, may also act on the vasculature directly. Hypoadiponectinemia was found to be associated with an impaired endothelium-dependent vasodilation in humans and mice [8–10]. Conversely, adiponectin is a stimulator of nitric oxide (NO) production in endothelial cells [11, 12]. In addition to adiponectin, other adipocytokines, such as leptin, have also been linked with the development of hypertension. Leptin increases peripheral sympathetic tone, and leptin-deficient mice show lower arterial blood pressure [13, 14]. Among the many known adipocytokines, angiotensinogen has been found to be produced by adipocytes, and angiotensinogen can promote the development of hypertension by stimulating the production of angiotensin II [15, 16].
There is also ample epidemiological evidence that obesity is one of the major causes of essential hypertension. Excess weight gain has been repeatedly shown to be one of the best predictors for the development of hypertension [17–19]. Moreover, from the Framingham Heart study it has been estimated that about 65% to 75% of the risk for hypertension can be attributed to excess weight .
Recent results from the National Health and Nutrition Examination Survey (NHANES) support the eminent role of obesity in the development of hypertension : between NHANES II (1988-1994) and NHANES 1999-2004, the age-standardized hypertension prevalence increased from 24.4% to 28.9%. Depending on gender and ethnicity, between 20% and 80% of this increase could be attributed to increasing BMI. Although the authors did not report control rates depending on BMI, blood pressure distribution within the population was shifted towards higher values with increasing BMI.
The relative contributions of subcutaneous and visceral fat to the development of hypertension have been elucidated in further studies. It is visceral fat which has been identified as the more prominent factor inducing hypertension : quantification of adipose tissue in different locations by computer tomography revealed that, in a group of 300 Japanese Americans, the amount of visceral fat, but not subcutaneous fat, conferred a risk of incident hypertension during the follow-up of up to 11 years.
Blood pressure is also associated with humoral components of the metabolic syndrome. Low HDL levels are known to confer an increased cardiovascular risk. Moreover, a direct association between low serum HDL levels and blood pressure has been shown in elderly hypertensive patients . The mechanistic background of this association may be that HDL contains important lipid mediators such as sphingosine-1-phosphate, sphingosylphosphorylcholine, and lysosulphatide which induce NO-dependent vasorelaxation via the lysophospholipid receptor S1P3 . Thereby HDL restores endothelial function by improving NO availability and hence favours vasorelaxation.
As in the present survey we studied patients receiving antihypertensive treatment, the results do not imply a higher prevalence of hypertension with increasing BMI, but show less effective blood pressure control in obese patients. This finding infers that in obesity-related hypertension other pathogenetic mechanisms may be involved than occur in other forms of essential hypertension.
The data in this survey show that metabolic syndrome is not only associated with higher blood pressure but also with the poor response to treatment. Interestingly, among the components of the metabolic syndrome, it is not impaired glucose tolerance which is associated with the response to antihypertensive treatment. Instead, both visceral obesity and the dyslipidemia of the metabolic syndrome, i.e. hypertriglyceridemia and low HDL cholesterol levels, are associated with resistance to antihypertensive treatment.
There have been few studies addressing the relative contributions of single components of the metabolic syndrome to the development of hypertension and vascular disease . The GOOD registry offers an appropriate database to answer these questions. Earlier publications of the GOOD data focused on the control of blood pressure depending on the co-occurrence of the metabolic syndrome  and on regional differences in blood pressure control . The DIG study addressed a similar question as the present study; Hanefeld et al.  studied the relative contributions of the different components of the metabolic syndrome to the development of atherosclerotic vascular disease. In contrast to the present study, the DIG study did not assess the impact of the components of the metabolic syndrome on the development of hypertension. Similarly to the present study, diabetes mellitus alone did not contribute significantly to the development of atherosclerotic vascular disease, whereas the combination of diabetes mellitus with hypertension and dyslipidemia was closely associated with vascular disease.