The trough: peak ratio and the normalization of blood pressure profiles

Experts from the Food and Drug Administration (FDA) of the USA have assumed that hypertensive patients are likely to achieve greatest benefit from therapy in which the antihypertensive effects do not vary excessively during the course of the day. They suggested that the ratio of the minimal (trough) effect to the maximal (peak) effect of the drug should be no lower than 0.5. The concept of the trough: peak ratio (TPR) raises many practical problems. Using actual data, the effect of a drug often shows erratic fluctuations with several local minima and maxima. Mean blood pressure levels for several hours have been used to estimate the trough and peak effects. Blood pressure averages over 4 h may e a good choice, because blood pressures measured 4 h apart are not correlated. The statistical distribution of the TPR is not Gaussian. Negative and very low or positive and very high individual ratios are frequently observed. Therefore, the individual TPR is of questionable clinical value, except when the ratio is applied for responders only. The TPR can be calculated for a sample. In that case, the bootstrap method can be used to estimate the error of the TPR. Most important is the question of why the TPR should be higher than 0.5. We introduced the concept of 'normalization of the blood pressure profile', namely 'reducing the blood pressure profiles in hypertensives to match those profiles in normotensives'. This concept leads very naturally to the TPR and justifies the lower limit of 0.5 for the TPR.