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Cholesterol  2014 

Effects of Atorvastatin on Resting and Peak Exercise Blood Pressure among Normotensive Men and Women

DOI: 10.1155/2014/720507

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Statins are the most widely prescribed and effective medication for reducing low density lipoprotein cholesterol. Statins may also lower resting blood pressure (BP); however, results are inconsistent. We sought to determine if the maximum dose of atorvastatin reduces resting BP and the peak systolic BP (SBP) achieved on a graded exercise stress test (GEST) among a large sample of 419 healthy men (48%) and women (52%). Subjects (419, ?yr) were double-blinded and randomized to 80?mgd?1 of atorvastatin () or placebo () for 6?mo. Among the total sample, there were no differences in resting BP (SBP, ; diastolic BP [DBP], ; mean arterial pressure (); or peak SBP on a GEST ()) over 6?mo, regardless of drug treatment group. However, among women on atorvastatin, resting SBP/DBP (?mmHg, ?mmHg, ) and peak SBP on a GEST (?mmHg, ) were lower versus men. Atorvastatin lowered resting BP 3-4?mmHg and peak SBP on a GEST ~7?mmHg more among women than men over 6?mo of treatment. The inconsistent findings regarding the antihypertensive effects of statins may be partially explained by not accounting for sex effects. 1. Introduction Statins are the most commonly prescribed and effective medication for reducing low density lipoprotein (LDL) cholesterol and, consequently, lowering cardiovascular disease (CVD) risk [1]. Interestingly, statins may produce other nonlipid, pleiotropic health benefits that may additionally lower CVD risk [2–8]. For example, they may decrease resting blood pressure (BP), which could have a substantial public health impact because hypertension affects one in three U.S. adults and one billion people worldwide [9, 10] and is a major risk factor for heart disease, stroke, congestive heart failure, and kidney disease [11, 12]. Indeed, a recent review has shown that statins lower systolic blood pressure (SBP) up to 8.0?mmHg in patients with dyslipidemia and normal BP; 6.0?mmHg in patients without dyslipidemia and with hypertension; and 13.7?mmHg in patients with dyslipidemia and hypertension [2]. However, other reports have reported no effect of statins on resting BP, and thus results are inconsistent regarding the influence of statin therapy on resting BP [13–15]. These inconsistencies could be attributable to a very small effect of statins on resting BP, such that the benefits of statins on BP may only be apparent during conditions in which BP is augmented, such as exercise. Although a hypertensive response to exercise is predictive of developing future hypertension and increases CVD risk, to the best of our knowledge the effect of statins on the peak


[1]  Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, “Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III),” Journal of the American Medical Association, vol. 285, no. 19, pp. 2486–2497, 2001.
[2]  M. S. Kostapanos, H. J. Milionis, and M. S. Elisaf, “Current role of statins in the treatment of essential hypertension,” Expert Opinion on Pharmacotherapy, vol. 11, no. 16, pp. 2635–2650, 2010.
[3]  S. Mangat, S. Agarwal, and C. Rosendorff, “Do statins lower blood pressure?” Journal of Cardiovascular Pharmacology and Therapeutics, vol. 12, no. 2, pp. 112–123, 2007.
[4]  A. Briasoulis, V. Agarwal, A. Valachis, and F. H. Messerli, “Antihypertensive effects of statins: a meta-analysis of prospective controlled studies,” Journal of Clinical Hypertension, vol. 15, no. 5, pp. 310–320, 2013.
[5]  B. A. Golomb, J. E. Dimsdale, H. L. White, J. B. Ritchie, and M. H. Criqui, “Reduction in blood pressure with statins: results from the UCSD statin study, a randomized trial,” Archives of Internal Medicine, vol. 168, no. 7, pp. 721–727, 2008.
[6]  S. Hashimoto, H. Urushihara, S. Hinotsu, S. Kosugi, and K. Kawakami, “Effect of HMG-CoA reductase inhibitors on blood pressure in hypertensive patients treated with blood pressure-lowering agents: retrospective study using an anti-hypertensive drug database,” European Review for Medical and Pharmacological Sciences, vol. 16, no. 2, pp. 235–241, 2012.
[7]  C. A. Feldstein, “Statins in hypertension: are they a new class of antihypertensive agents?” The American Journal of Therapeutics, vol. 17, no. 3, pp. 255–262, 2010.
[8]  K. K. Koh, M. J. Quon, and M. A. Waclawiw, “Are statins effective for simultaneously treating dyslipidemias and hypertension?” Atherosclerosis, vol. 196, no. 1, pp. 1–8, 2008.
[9]  World health Organization, A World health Organization Global Brief on Hypertension. Silent killer, Global Public Health Crisis, World health Organization, Geneva, Switzerland, 2013.
[10]  Centers for Disease Control and Prevention (CDC), “Vital signs: prevalence, treatment, and control of hypertension—United States, 1999–2002 and 2005–2008,” Morbidity and Mortality Weekly Report, vol. 60, no. 4, pp. 103–108, 2011.
[11]  P. A. James, S. Oparil, B. L. Carter et al., “2014 Evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8),” Journal of the American Medical Association, vol. 311, no. 5, pp. 507–520, 2014.
[12]  A. S. Go, D. Mozaffarian, V. L. Roger et al., “Executive summary: heart disease and stroke statistics—2014 update: a report from the american heart association,” Circulation, vol. 129, no. 3, pp. 399–410, 2014.
[13]  M. Tonelli, F. Sacks, M. Pfeffer, F. Lopez-Jimenez, G. S. Jhangri, and G. Curhan, “Effect of pravastatin on blood pressure in people with cardiovascular disease,” Journal of Human Hypertension, vol. 20, no. 8, pp. 560–565, 2006.
[14]  M. Banach, S. Nikfar, R. Rahimi et al., “The effects of statins on blood pressure in normotensive or hypertensive subjects—a meta-analysis of randomized controlled trials,” International Journal of Cardiology, vol. 168, no. 3, pp. 2816–2824, 2013.
[15]  L. Paulsen, C. Holm, J. N. Bech, J. Starklint, and E. B. Pedersen, “Effects of statins on renal sodium and water handling: acute and short-term effects of atorvastatin on renal haemodynamics, tubular function, vasoactive hormones, blood pressure and pulse rate in healthy, normocholesterolemic humans,” Nephrology Dialysis Transplantation, vol. 23, no. 5, pp. 1556–1561, 2008.
[16]  A. N. Syme, B. E. Blanchard, M. A. Guidry et al., “Peak systolic blood pressure on a graded maximal exercise test and the blood pressure response to an acute bout of submaximal exercise,” American Journal of Cardiology, vol. 98, no. 7, pp. 938–943, 2006.
[17]  P. Thompson, B. Parker, P. Clarkson et al., “A randomized clinical trial to assess the effect of statins on skeletal muscle function and performance: rationale and study design,” Preventive Cardiology, vol. 13, no. 3, pp. 104–111, 2010.
[18]  B. A. Parker, J. A. Capizzi, A. S. Grimaldi, et al., “Effect of statins on skeletal muscle function,” Circulation, vol. 127, no. 1, pp. 96–103, 2013.
[19]  L. Pescatello, R. Arena, D. Riebe, and P. Thompson, ACSM’s Guidelines for Exercise Testing and Prescription, Lippincott Williams & Wilkins, Baltimore, Md, USA, 9th edition, 2013.
[20]  W. T. Friedewald, R. I. Levy, and D. S. Fredrickson, “Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge,” Clinical Chemistry, vol. 18, no. 6, pp. 499–502, 1972.
[21]  T. G. Pickering, J. E. Hall, L. J. Appel et al., “Recommendations for blood pressure measurement in humans: an AHA scientific statement from the council on high blood pressure research professional and public education subcommittee,” Journal of Clinical Hypertension, vol. 7, no. 2, pp. 102–109, 2005.
[22]  L. S. Pescatello, B. A. Franklin, R. Fagard, W. B. Farquhar, G. A. Kelley, and C. A. Ray, “American college of sports medicine position stand. exercise and hypertension,” Medicine and science in sports and exercise, vol. 36, no. 3, pp. 533–553, 2004.
[23]  H. J. Milionis, E. N. Liberopoulos, A. Achimastos, M. S. Elisaf, and D. P. Mikhailidis, “Statins: another class of antihypertensive agents?” Journal of Human Hypertension, vol. 20, no. 5, pp. 320–335, 2006.
[24]  G. Nickenig, A. T. B?umer, Y. Temur, D. Kebben, F. Jockenh?vel, and M. B?hm, “Statin-sensitive dysregulated AT1 receptor function and density in hypercholesterolemic men,” Circulation, vol. 100, no. 21, pp. 2131–2134, 1999.
[25]  C. Ott, M. P. Schneider, M. P. Schlaich, and R. E. Schmieder, “Rosuvastatin improves pulse wave reflection by restoring endothelial function,” Microvascular Research, vol. 84, no. 1, pp. 60–64, 2012.
[26]  P. J. Millar and J. S. Floras, “Statins and the autonomic nervous system,” Clinical Science, vol. 126, no. 5, pp. 401–415, 2014.
[27]  M. Fischer, A. Baessler, and H. Schunkert, “Renin angiotensin system and gender differences in the cardiovascular system,” Cardiovascular Research, vol. 53, no. 3, pp. 672–677, 2002.
[28]  A. M. Kuklinska, B. Mroczko, W. J. Musial et al., “Influence of atorvastatin on blood pressure control in treated hypertensive, normolipemic patients—an open, pilot study,” Blood Pressure, vol. 19, no. 4, pp. 260–266, 2010.
[29]  M. A. Zimmerman and J. C. Sullivan, “Hypertension: what's sex got to do with it?” Physiology, vol. 28, no. 4, pp. 234–244, 2013.
[30]  M. M. Wenner and N. S. Stachenfeld, “Blood pressure and water regulation: understanding sex hormone effects within and between men and women,” The Journal of Physiology, vol. 590, part 23, pp. 5949–5961, 2012.
[31]  E. C. Hart and M. J. Joyner, “The curse of the sympathetic nervous system: are men or women more unfortunate?” The Journal of Physiology, vol. 588, no. 22, pp. 4345–4346, 2010.
[32]  E. C. Hart, M. J. Joyner, B. G. Wallin, and N. Charkoudian, “Sex, ageing and resting blood pressure: gaining insights from the integrated balance of neural and haemodynamic factors,” The Journal of Physiology, vol. 590, part 9, pp. 2069–2079, 2012.
[33]  T. Nwankwo, S. S. Yoon, V. Burt, and Q. Gu, “Hypertension among adults in the united states: national health and nutrition examination survey 2011-2012,” NCHS Data Brief, vol. 133, pp. 1–8, 2013.
[34]  P. Muntner, J. He, E. J. Roccella, and P. K. Whelton, “The impact of JNC-VI guidelines on treatment recommendations in the US population,” Hypertension, vol. 39, no. 4, pp. 897–902, 2002.
[35]  S. Thom, N. Poulter, J. Field et al., “Effects of a fixed-dose combination strategy on adherence and risk factors in patients with or at high risk of CVD: the UMPIRE randomized clinical trial,” Journal of the American Medical Association, vol. 310, no. 9, pp. 918–929, 2013.
[36]  B. M. Egan, J. Li, F. N. Hutchison, and K. C. Ferdinand, “Hypertension in the United States 1999–2012: progress toward healthy people 2020 goals,” Circulation, vol. 130, no. 19, pp. 1692–1699, 2014.


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