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Low grade changes in hypertension

An article from the e-journal of the ESC Council for Cardiology Practice

Physicians are used to classifying target organ damage (TOD) as "normal" or "abnormal" and they will then work out the numerical data only when changes fall outside the "normal" range. However, recent findings have shown that valuable information can be gained from TOD data falling within the "high-normal" range: such TOD data are referred to as "low grade" changes.

Risk Factors and Prevention

The concept of "high-normal" values has been applied to a number of techniques that, in the setting of hypertensive patients, are suggested for routine use. Examples of the techniques for which this concept applies are 1) the electrocardiogram, 2) micro-albuminuria, 3) ankle-brachial index and 4) fundoscopy.

I - The electrocardiogram

The main reason for which to perform an electrocardiogram (ECG) in every hypertensive patient detecting left ventricular hypertrophy (LVH). Of course an ECG will also provide information as to presence of ischemia or not, rhythm and conduction disturbances as well as regarding many other issues - all of which illustrating that this long-standing technique has much to offer the clinician.

Indeed the ECG used in the context of hypertension is a good tool to detect LVH, nevertheless there is a lack of sensitivity associated with its use that may eventually be improved by recording orthogonal leads as done in Vectorcardiography - unfortunately not used as often as it would deserve to be.

An added advantage of ECG is that the data can be expressed numerically, meaning that minor changes can also be detected. In a recent article (1), it was shown that measurements made on lead aVL in an electrocardiogram falling within "normal" limits correlate with long-term events quite well. Such findings highlight the importance of high-normal values (or low grade changes) appearing early in the process of the build-up towards LVH. The data will could most likely indicate a very early stage of TOD and thus play a role in estimating total cardiovascular risk in hypertensive patients.

II - Micro-albuminuria

In the search for renal changes in hypertensive patients, micro-albuminuria offers quite a  helpful tool. However it is greatly underused by clinicians. The normal limit is usually set at 300mg per day; values above 300mg have been shown to correlate with long-term events (2).

As with ECG findings mentioned above, it has been documented that early changes falling within the high-normal values are of obvious importance. A series of studies have indicated that high-normal values varying between 30 and 300mg per day - thus falling between normal limits - correlate very well with long-term events. Again, one can understand the importance of this new concept in hypertension. Moreover, microalbuminuria is a largely available, affordable and easy-to-perform technique.  

III - Ankle-brachial index (ABI)

Measuring ABI is another means to approaching the concept of early changes. In a previous issue of the e-journal of Cardiology Practice (3), we described the great usefulness of this technique in daily practice both for diagnosing peripheral arterial diseases and estimating total cardiovascular risk. A normal limit for ABI is regularly set at 1, with a maximal level at 1.2. Again, high-normal values have been shown to indicate worsened prognosis, at least at a functional level. Values between 1 and 1.2 are accompanied by a short-term decline in walking distance. This is another argument for which physicians should use this easy and affordable technique in the daily clinic and all the more in hypertensive patients in whom PAD is highly prevalent.

IV - Fundoscopy

Changes in retinal vessels as observed by fundoscopy are presently only used to detect advanced impact of high-blood pressure on cerebral vessels. Minor changes are considered less valuable also because there is a large overlap with atherosclerotic alterations. Recently however, Japanese scientists (4) have been able to digitize photographic images of the retinal vessels that allowed them to very accurately quantify  different aspects of the vessels such as diameter and length, characteristics of the wall, etc. By doing so, some very initial changes may be detected and expressed numerically. Here, as was the case with previously mentioned techniques, these early changes seem to contain important prognostic information that allow for the technique to be of help in estimating total cardiovascular risk.


The concept of early "low grade" changes in target organ damage offers a totally different view on estimating TOD and thus calculating total cardiovascular risk. One can understand that diagnosing such low-grade changes would greatly help in daily practice to pinpoint patients that have values falling within "normal" limits but who are at an already increased risk. This concept may well have important implications for treatment of hypertension and prevention of its complications.


1) Verdecchia P. et al. The voltage of R wave in lead aVL improves risk stratification in hypertensive patients without ECG left ventricular hypertrophy J Hypertens. 2009 Aug;27(8):1697-704.

2) Olsen MH, Albuminuria predicts cardiovascular events independently of left ventricular mass in hypertension: a LIFE substudy. J Hypertens. 2009 Aug;27(8):1697-704.

3) Clement D., Measuring the ankle-brachial pressure index. Vol4 N°35
23 May 2006

4) Retinal vessel diameter and cardiovascular mortality: pooled data analysis from two older populations. Wang JJ, Eur Heart J. 2007 Aug;28(16):1984-92. Epub 2007 Jul 10.


Vol8 N°38

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.