Antihypertensive treatment and the J-curve.
Unlike the brain, oxygen extraction for the heart is almost maximal at rest, so lowering coronary filling pressure (DBP) below the lower limit of autoregulation with antihypertensive drugs can lead to myocardial ischemia. This situation is exacerbated by the presence of coronary stenosis, which if more than 85% means that coronary flow reserve is virtually zero (particularly in the presence of LVH). Such patients experience a fall in coronary flow and ischemia when DBP is acutely lowered to less than the mid-80s. Ischemic episodes on the 24-hour Holter monitor in treated hypertensives are often immediately preceded by a hypotensive episode. The "J-curve" debate has been going for over 20 years. Those that deny a J-curve relationship between treated DBP and myocardial infarction (MI) quote the continuous DBP/MI relationship seen in the large cohort of MRFIT screenees (with ischemic patients weeded out). However, the actual MRFIT (and similar HDFP) study patients with abnormal ECGs (ischemia or LVH), in contrast to those with normal ECGs, in the special-care group experienced an excess of coronary events associated with a DBP 5 mmHg lower than the referred-care group. Other studies, including the prospective HOT study, have indicated that ischemic hypertensives gain optimal results when DBP is lowered to the mid- to low 80s; below this level, the frequency of MI increases. This treatment-induced J-curve should not be confused with Nature's untreated J-curve, which results from the association of a low DBP (wide pulse-pressure) due to aging, noncompliant arteries, and an increasing frequency of ischemic events. A reasonable conclusion from most treatment studies (including HOT) is that in nonischemic hypertensives there is little point in lowering DBP below the mid- to low 80s in terms of MI prevention--though it is safe to do so. In contrast, ischemic hypertensives should not have their DBP lowered to less than the mid- to low 80s for fear of increasing the risk of MI.
Cruickshank
J M
JM
Oxonian Cardiovascular Consultancy, Long Melford, Suffolk, UK. johndtl@aol.com
D000959:Antihypertensive Agents / Q000009:adverse effects*; D001794:Blood Pressure / Q000187:drug effects*; D002986:Clinical Trials as Topic; D003326:Coronary Circulation / Q000187:drug effects; D016757:Death, Sudden, Cardiac / Q000209:etiology; D004562:Electrocardiography; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced / Q000503:physiopathology; D007022:Hypotension / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology; D009203:Myocardial Infarction / Q000209:etiology* / Q000401:mortality
D000959:Antihypertensive Agents