However, what was not mentioned was that patients in that trial who had a BP <120/70 mmHg (the level below which the risk of adverse outcomes seemed to rise) were older and had a history of more MI, coronary artery bypass grafting or percutaneous coronary intervention, stroke or transient ischemic attack, diabetes mellitus, HF, and cancer, all confounding factors. After adjustment for these and other comorbidities, there was no increased risk down to a DBP of A different nadir for a J-shaped relationship of BP with outcome, 146.3/81.4 mmHg, was identified in another sec- ondary analysis, this time of the Treating to New Targets Trial (TNT) in patients with clinically evident CAD.142 The Secondary Manifestations of Arterial Disease (SMART) study of patients with manifest arteriosclerotic disease had a nadir of The implication of these trials is that there is a higher risk of coronary events if the SBP is <146.3 or 143 mmHg, which is clearly at odds with the mass of data from clinical trials over many decades, which show that SBPs <140 mmHg are cardioprotective. There are much debate and disagreement about the meth- odological assumptions and pitfalls, and several reports have articulated how confounding variables, especially age and comorbidities, including late-stage HF, could have affected In none of the retrospective analyses was it possible to control adequately for the many interact- ing comorbid conditions that accompany and confound low DBP or for the complex relationships among age, DBP, and CVD risk. Age, DBP, and cardiovascular risk are positively associated until 50 years of age. For the remainder of life, DBP decreases and pulse pressure widens, whereas car- diovascular risk increases exponentially. 