Natural History of Treated and Untreated Hypertension

Elevated blood pressure is the most prevalent and relevant risk factor for death and disability worldwide. Hypertension occurs in more than one billion individuals causing an estimated 9.4 million deaths every year [1]. Overall the prevalence of hypertension appears to be around 40% of the general population, with a steep increase with aging from 7% in individuals age 18–39 to 65% in individuals over age 59 [2]. There are clear differences in the average blood pressure levels across countries, with no systematic trends toward blood pressure changes in the past decade [3]. During middle and older age, blood pressure is strongly and directly related to cardiovascular and overall mortality [4]. This association seems to exist across large and diverse population groups aged 40–89 years, including men and women from different ethnicities, with and without established vascular disease [4–6]. Prospective cohort studies have reported a continuous log-linear association between blood pressure and vascular events over a wide range, apparently beginning at values of 115 mmHg for systolic and 75 mmHg for diastolic with no apparent threshold [4]. Notably, taking into account the continuous and direct relationship between blood pressure and cardiovascular disease, most blood pressure-associated cardiovascular complications occur in individuals with prehypertension. In the Framingham Heart Study, compared with the subjects with optimal blood pressure, those with high-normal blood pressure showed a significantly increased risk of cardiovascular disease independent of other risk factors, and a nonsignificant trend toward an increased incidence of events was also shown in the group with normal blood pressure [7]. About half of hypertensive patients develop related end-organ damage if blood pressure is left untreated over 7–10 years. The remaining patients exhibit a less impactful course with hypertensive complications occurring slowly. Fewer than 5% of people with hypertension enter a very rapid, sometimes malignant course with rapid deterioration in cardiac, renal, and neurologic function. Tissue- and organ-deteriorating and remodeling processes induced by the hypertensive status may impair the physiology and the structure of the heart, large- and medium-sized arteries, kidneys, and brain. Thus, the presentation of the target organ complications in hypertensive patients may reflect different pathophysiological abnormalities including diastolic and systolic dysfunction, left ventricular hypertrophy, endocardial scarring, congestive heart failure (39% of cases in men and 59% in women), and coronary disease; accelerated atherosclerosis and aneurysm formation (with or without dissection); stroke (both hemorrhagic and thrombotic infarction); and nephrosclerosis (with and without renal failure) [8]. Stroke mortality is often viewed as a surrogate of hypertension consequences, because hypertension is regarded as the most important cause of this event. A close relationship between prevalence of hypertension and mortality for stroke has been reported [9]. Nowadays, Western European countries exhibit a downward trend, in contrast to Eastern European countries which show an increase in death rates from stroke [10]. It should be noted that only a small fraction of the hypertensive population presents with an elevation of blood pressure alone, whereas the majority of the patients have additional cardiovascular risk factors. Population studies have clearly shown that the total cardiovascular risk exceed the sum of its individual components when blood pressure elevation is concomitantly associated with other cardiovascular risk factors. Therefore, international guidelines emphasize that prevention of coronary heart disease should be related to quantification and target of global cardiovascular risk [3, 11–16]. Several methods and tools have been developed for estimating total cardiovascular risk, although all currently available models for cardiovascular risk assessment have some methodological and conceptual limitations [3, 17–25]. Based on those methods, for more than a decade, international guidelines for the management of hypertension have stratified cardiovascular risk in different categories, based on blood pressure values, the presence of other cardiovascular risk factors, diabetes or asymptomatic organ damage, as well as symptomatic cardiovascular disease or chronic kidney disease or cardiovascular events [3, 11–16]. The large number of patients with hypertension is identified at low, moderate, high, or very high risk. The estimation of total cardiovascular risk may be easy to evaluate in specific subgroups of patients, especially those at high or very high cardiovascular risk, such as patients with diabetes or with severely elevated single risk factors or with established cardiovascular disease. Those are the patients that require intensive cardiovascular risk-reducing measures. It should be emphasized that for the management of hypertensive patients, the recognition of target organ damage is crucial, even when asymptomatic, in view of the fact that the presence of target organ damage is the expression of organ abnormalities promoted by hypertension (i.e., heart, kidney, brain) which markedly increases the cardiovascular risk in the cardiovascular continuum. If the blood pressure elevation is identified and properly managed early in the natural history of hypertension and adequate antihypertensive strategies (i.e., lifestyle changes, drugs) are timely initiated together with the control of the other cardiovascular risk factors, the reduction of cardiovascular risk and/or normalization of target organ damage may be achieved and the prognosis obviously improved [3, 17–25].