European Heart Journal Advance Access originally published online on November 6, 2007
European Heart Journal 2007 28(23):2832-2833; doi:10.1093/eurheartj/ehm494
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High-normal blood pressure and future risks—a new concern for clinicians?
Department of Clinical Sciences Medicine, Lund University, University Hospital, S-205 02 Malmö, Sweden
* Corresponding author. Tel: +46 40 33 24 15; fax: +46 40 92 32 72.E-mail address: Peter.Nilsson{at}med.lu.se
This editorial refers to ‘Blood pressure and risk of developing type 2 diabetes mellitus: the Women's Health Study’ by D. Conen et al., on page 2937
Footnotes
The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.
The fact that hypertension (>140/ > 90 mmHg) is a well established cardiovascular risk factor in numerous studies has led epidemiologists to expand their interest also to the risks associated with high-normal blood pressure (130–139/85–89 mmHg). As blood pressure is documented to show properties of tracking over time,1 it is no wonder that people in the high-normal range tend to develop established hypertension after a follow-up period more frequently than subjects with a normal (120–129/80–84 mmHg) or even optimal (<120/ < 80 mmHg) blood pressure. Furthermore, as blood pressure is most often a part of a cardiovascular risk factor syndrome, whether called metabolic syndrome or even cardiometabolic syndrome,2 it is reasonable to believe that the tracking phenomenon could also influence other long-term risks, e.g. for type 2 diabetes and cardiovascular disease.
In two recent publications from the Women's Health Study of 38 172 health professionals followed for 10.2 years,3,4 it has now been shown that subjects in the high-normal blood pressure range run an increased risk of type 2 diabetes3 as well as established hypertension and cardiovascular disease,4 when compared with other women in the normal or optimal blood pressure range at baseline. The risk is, however, less pronounced than in established hypertension. This indicates that the screening of subjects for a high-normal blood pressure could result in the detection of subjects who should be followed-up for other risk conditions and also screened for the cluster of risk factors included in the metabolic syndrome, most notably increased waist to hip circumference, plasma glucose, dyslipidaemia, and (micro)-albuminuria. On the other hand, it has been argued that this would label a very large group of non-hypertensive subjects for future control, and it is doubted whether any health care system could handle such vast numbers of potential patients. Therefore, other and more feasible public health-based solutions have to be found. A parallel could me made to a similar cardiovascular risk condition, e.g. impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) regarded as a pre-diabetic state. Currently, subjects with IGT/IFG receive lifestyle advice but are rarely treated with drugs, even if some anti-diabetes drugs have indeed been documented for diabetes prevention, or rather diabetes postponement, in subjects screened with an oral glucose tolerance test (OGTT) for IGT, for example by use of acarbose,5 metformin,6 or rosiglitazone.7
Should antihypertensive drugs be used for this large group of subjects at future risk? In pre-hypertension, or high-normal blood pressure, a drug intervention study using the angiotensin-2 receptor blocker candesartan celexitil vs. placebo was recently published by Julius et al.8 The study showed that early drug treatment could postpone the development of established hypertension, an effect that vanished after discontinuation of the study drug after a few years.
The study of Conen et al.3 is focused on the risk of diabetes in women with self-report of a high-normal blood pressure. This self-report of blood pressure is subject to recall bias, but the authors argue that previous studies have shown a good correlation with measured office blood pressure. Also the ascertainment of the end-point diabetes mellitus was self-reported, but as annual screening of blood glucose was extremely prevalent in the cohort (85–90%), most cases would have been detected in this way. Every new diabetes case was also validated in a medical record review. In addition, blood pressure was a strong predictor of diabetes within each category of body mass index (BMI), a well-known confounder for any such associations. No data on waist to hip circumference were available, but the authors argue that BMI is an acceptable proxy for abdominal obesity. The overall hazard ratio for new diabetes in the high-normal blood pressure group of women compared with the normal blood pressure group (reference) was 1.47 (95% confidence interval: 1.24–1.75). It thus seems well proven that a high-normal blood pressure is in fact a true predictor of type 2 diabetes. Possible causes of this association include not only tracking of components clustering in the metabolic syndrome,2 but also the putative effect of early life programming in the developmental origin hypothesis of adult disease, as recently reviewed, based on the proceedings of a Berzelius symposium in Stockholm, Sweden.9
Finally, based on new data from a whole genome scan (WGS) of type 2 diabetes, several genetic polymorphisms have been detected as predictors of type 2 diabetes.10 Some of these, or related polymorphisms, could also be suspected to have links to other aspects of the metabolic syndrome, including haemodynamic regulation, for example based on the influence of variations in insulin sensitivity. Future mapping of the genetics of hypertension will hopefully increase knowledge of this potential link. Such studies are underway, for example within the InGenious HyperCare EU-Project (http://www.hypercare.eu). The goal of the InGenious HyperCare Network of Excellence is that of integrating complementary but still fragmented experience of the mechanisms of blood pressure control and hypertension development, in phenotyping initiation and progression of organ damage, and in exploring genetics, genomics, and proteomics of proneness to hypertension and hypertension-related cardiovascular disease. A better prevention of hypertension and its cardiovascular consequences is an essential public health goal in Europe, where cardiovascular diseases are the major cause of mortality and morbidity. It is obvious that links with diabetes mellitus, and its genetic risk factors based on WGS data, could hopefully be made through inter-project collaboration in the future.
In summary, the present data from the Women's Health Study indicate that a high-normal blood pressure in women confers increased future risk for type 2 diabetes3 as well as established hypertension and cardiovascular disease.4 However, the study could neither compare its data with corresponding risks in men, nor give any recommendation on interventions due to the observational design of the study. Lifestyle advice should nevertheless be given to all subjects with a high-normal blood pressure, to increase physical activity, keep their weight stable or achieve weight reduction, and to eat a healthy diet including sodium restriction, based on current European guidelines.11,12 There are at present no intervention studies with cardiovascular end-points to support early drug intervention in these subjects. This should, however, ideally be tested in a randomized clinical study. If such a study were to be carried out, many clinicians and researchers would ask the question of whether lifestyle advice is superior, equal, or inferior to drug therapy for cardiovascular prevention. However, this is very costly, time-consuming and a high-risk study in itself due to foreseen compliance problems in, per definition, healthy individuals followed for many years. Will we ever get the answer?
Conflict of interest: none declared.
Footnotes
The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.
doi:10.1093/eurheartj/ehm400 
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Related articles in EHJ:
- Blood pressure and risk of developing type 2 diabetes mellitus: The Women's Health Study
- David Conen, Paul M. Ridker, Samia Mora, Julie E. Buring, and Robert J. Glynn
EHJ 2007 28: 2937-2943.[Abstract] [FREE Full Text]
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