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Dr. Luis Ruilope
Dr. César Cerezo
The availability of techniques for ambulatory blood pressure measurements have shown certain aspects of circadian variability of blood pressure - absence of physiological nocturnal dipping, and/or an early morning surge - that must be considered decisive influences on target organ damage and long-term prognosis. Proper management of these factors would positively contribute to the cardiovascular prognosis of hypertensive patients.
Hypertension is one of the most important challenges for public health systems to manage. This relevance is determined by its high prevalence and its association with the risk of cardiovascular and renal disease (1-3). In 2000, approximately a quarter of worldwide adult population had hypertension, and this proportion is expected to rise to 29% of the adult population in 2025, which would amount to 1560 million individuals (4). Biological rhythms Current management of hypertensive patients does not often consider or at least gives little importance to the biological rhythms inherent to the disease process. The development of techniques for ambulatory blood pressure monitoring and home-blood pressure measurements has generated a series of questions directly related to the chronobiology of the cardiovascular system (5). In recent years, research evidence highlights the influence of nocturnal blood pressure (BP) values and, more specifically, the absence of a nocturnal dipping and an increased morning surge of blood pressure, on the development of target organ damage and an increased cardiovascular risk (5). Nocturnal dip
Ambulatory blood pressure monitoring techniques have expanded our knowledge regarding the circadian rhythms of blood pressure. Several studies suggest a relationship between cardiovascular complications such as acute myocardial infarction and cerebrovascular disease with circadian BP changes (6). In fact, many studies suggest that patients who do not show an appropriate nocturnal dip in blood pressure may develop a variety of disorders associated with increased rates of cardiovascular morbidity and mortality (7-9). Ohkubo et al demonstrated that a diminished nocturnal decline in BP is a risk factor for cardiovascular mortality in the general population (10). "Non-dipper" individuals In this regard, Cuspidi et al have shown that the persistence of non-dipper patterns is associated with increased left ventricular mass index, a thicker interventricular septum, and a larger diameter of the left atrium and aortic root in a group of 375 previously untreated hypertensive patients (7). Similarly, non-dipper hypertensive patients show a greater degree of insulin resistance and lower levels of adiponectin, compared to dipper hypertensives (8). These non-dipper hypertensive patients had a more severe impairment of endothelial function as manifested by a reduced ability of endothelium-dependent vasodilation and mediated by a decrease in nitric oxide release (9). In fact, reverse dipper hypertensive patients showed wider pulse pressure at night than any other group, suggesting the potential role of arterial stiffness as an underlying mechanism of impaired cardiovascular risk (11). Long-term prognosis All these changes determine a worsened long-term prognosis for non-dipper. In a meta-analysis including data of 3468 patients from four prospective studies, the dipping pattern and the night-day BP ratio significantly and independently predicted mortality and cardiovascular events in hypertensive patients without a history of major cardiovascular disease (12). In diabetic patients, the loss of the physiological circadian pattern is associated with increased mortality in both type 1 and type 2 diabetes (13). Early morning surge Moreover, there is growing evidence linking an early morning rise in blood pressure with increased cardiovascular risk (14). Although the mechanisms responsible for this relationship are not well known, several factors contribute to hemodynamic and neurohumoral blood pressure (6,14,15). It has been described in patients with coronary disease in which myocardial ischemia may appear transiently in the first two hours after waking (16). Similarly, in reviewing a group of 1167 patients with ischemic stroke, early morning stroke onset as opposed to strokes at any other times of day, have been observed more frequently (17) and the incidence of stroke is directly related to the magnitude of the morning rise in blood pressure (18). Similarly, several meta-analyses have confirmed the relationship between cardiovascular complications (myocardial infarction (19) or stroke (20)) and strokes occuring at highest incidence in the early hours of the morning.
1. Neaton JD, Wentworth D. Serum cholesterol blood pressure, cigarette smoking, and death from coronary heart disease. Overall findings and differences by age for 316.099 white men. Multiple Risk Factor Intervention Trial Research Group. Arch Intern Med 1992; 152: 56-64. 2. Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002; 360: 1903-1913. 3. Weiner DE, Tighiouart H, Amin MG, Stark PC, MacLeod B, Griffith JL, Salem DN, Levey AS, Sarnak MJ. Chronic kidney disease as a risk factor for cardiovascular disease and all-cause mortality: a pooled analysis of community-based studies. J Am Soc Nephrol 2004;15: 1307-1315. 4. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton P, He J. Global burden of hypertension: analysis of worldwide data. Lancet 2005; 365: 217-223. 5. Hassler C, Burnier M. Circadian variations in blood pressure: implications for chronotherapeutics. Am J Cardiovasc Drugs 2005; 5: 7-15. 6. Giles T. Relevance of blood pressure variation in the circadian onset of cardiovascular events. J Hypertens 2005; 23 (Suppl 1): S35-S39. 7. Cuspidi C, Meani S, Salerno M, Valerio C, Fusi V, Severgnini B, et al. Cardiovascular target organ damage in essential hypertensives with or without reproducible nocturnal fall in blood pressure. J Hypertens 2004; 22: 273-280. 8. Della Mea P, Lupia M, Bandolin V, Guzzon S, Sonino N, Vettor R, et al. Adiponectin, insulin resistance, and left ventricular structure in dipper and nondipper essential hypertensive patients. Am J Hypertens 2005; 18: 30-35. 9. Higashi Y, Nakagawa K, Kimura M, Noma K, Hara K, Sasaki S, et al. Circadian variation of blood pressure and endothelial function in patients with essential hypertension: a comparison of dippers and non-dippers. J Am Coll Cardiol 2002; 40: 2039-2043. 10. Ohkubo T, Hozawa A, Yamaguchi J, Kikuya M, Ohmori K, Michimata M, et al. Prognostic significance of the nocturnal decline in blood pressure in individuals with and without high 24-h blood pressure: the Ohasama study. J Hypertens 2002; 20: 2183-2189. 11. Jerrard-Dunne P, Mahmud A, Feely J. Circadian blood pressure variation: relationship betweendipper status and measures of arterial stiffness. J Hypertens 2007; 25: 1233-1239. 12. Fagard RH, Thijs L, Staessen JA, Clement DL, De Buyzere ML, De Bacquer DA. Night-day blood pressure ratio and dipping pattern as predictors of death and cardiovascular events in hypertension. J Hum Hypertens 2009; 23: 645-653. 13. Sturrock ND, George E, Pound N, Stevenson J, Peck GM, Sowter H. Non-dipping circadian blood pressure and renal impairment are associated with increased mortality in diabetes mellitus. Diabet Med 2000; 17: 360-364. 14. Weber MA. The 24-hour blood pressure pattern: does it have implications for morbidity and mortality? Am J Cardiol 2002; 89(suppl 2A):27A–33A. 15. Kario K. Morning surge and variability in blood pressure: a new therapeutic target? Hypertension 2005; 45: 485-486. 16. Rocco MB, Barry J, Campbell S, Nabel E, Cook EF, Goldman L, et al. Circadian variation of transient myocardial ischemia in patients with coronary artery disease. Circulation 1987; 75:395–400. 17. Marler JR, Price TR, Clark GL, Muller JE, Robertson T, Mohr JP, et al. Morning increase in onset of ischemic stroke. Stroke 1989; 20:473–476. 18. Kario K, Pickering TG, Umeda Y, Hoshide S, Hoshide Y, Morinari M, et al. Morning surge in blood pressure as a predictor of silent and clinical cerebrovascular disease in elderly hypertensives: a prospective study. Circulation 2003; 107: 1401–1406. 19. Cohen MC. Meta-analysis of the morning excess of acute myocardial infarction and sudden cardiac death. Am J Cardiol 1997; 79: 1512–1516. 20. Elliott WJ. Circadian variation in the timing of stroke onset – a meta-analysis. Stroke 1998; 29:992–996.
Cerezo C., Segura J., García-Donaire J.A., Ruilope L.M. Hypertension Unit. Hospital 12 de Octubre. Madrid. Spain.
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