Luft, F. C. Twins in cardiovascular genetic research. Hypertension 37, 350–356 (2001).
Fagard, R. et al. Heritability of conventional and ambulatory blood pressures: a study in twins. Hypertension 26, 919–924 (1995).
Surendran, P. et al. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension. Nat. Genet. 48, 1151–1161 (2016).
Ehret, G. B. et al. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals. Nat. Genet. 48, 1171–1184 (2016).
Liu, C. et al. Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci. Nat. Genet. 48, 1162–1170 (2016). Together with references 3 and 4, these large-scale studies analysed the genomes of ∼1 million individuals, identifying new BP-associated loci, doubling the number of reported BP-associated genes and helping to identify potential new targets for BP treatment.
Dominiczak, A., Delles, C. & Padmanabhan, S. Genomics and precision medicine for clinicians and scientists in hypertension. Hypertension 69, e10–e13 (2017).
Lifton, R. P., Gharavi, A. G. & Geller, D. S. Molecular mechanisms of human hypertension. Cell 104, 545–556 (2001).
Ehret, G. B. & Caulfield, M. J. Genes for blood pressure: an opportunity to understand hypertension. Eur. Heart J. 34, 951–961 (2013).
Maass, P. G. et al. PDE3A mutations cause autosomal dominant hypertension with brachydactyly. Nat. Genet. 47, 647–653 (2015).
Forouzanfar, M. H. et al. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 388, 1659–1724 (2016). The Global Burden of Disease Study 2015 summarizes the evidence for risk factor exposure and the attributable burden of disease spanning 25 years and establishes hypertension as one of the top ten largest contributors to global disability-adjusted life years, highlighting a huge opportunity for intervention.
Blood Pressure Lowering Treatment Trialists’ Collaboration. Blood pressure-lowering treatment based on cardiovascular risk: a meta-analysis of individual patient data. Lancet 384, 591–598 (2014).
Page, L. B., Damon, A. & Moellering, R. C. Antecedents of cardiovascular disease in six Solomon Islands societies. Circulation 49, 1132–1146 (1974).
Poulter, N. R., Prabhakaran, D. & Caulfield, M. Hypertension. Lancet 386, 801–812 (2015).
Rose, G. & Day, S. The population mean predicts the number of deviant individuals. BMJ 301, 1031–1034 (1990).
Mills, K. T. et al. Global Disparities of hypertension prevalence and control: a systematic analysis of population-based studies from 90 countries. Circulation 134, 441–450 (2016). This study examines global disparities in hypertension prevalence, awareness, treatment and control in 2010 compared with trends from 2000 and shows that the incidence of hypertension increased in low-income and middle-income countries whereas BP control rates decreased. BP control rates in 2010 remained low worldwide: 28.4% in high-income countries and 7.7% in middle-income and low-income countries.
Forouzanfar, M. H. et al. Global burden of hypertension and systolic blood pressure of at least 110 to 115 mmHg, 1990–2015. JAMA 317, 165 (2017).
Lewington, S. et al. 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 360, 1903–1913 (2002). This landmark study shows that usual (that is, the estimated BP at the start of that decade) BP is strongly and directly related to vascular and overall mortality, down to a threshold of 115/75 mmHg, below which there is little evidence.
Rapsomaniki, E. et al. Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1.25 million people. Lancet 383, 1899–1911 (2014).
Stamler, J., Stamler, R. & Neaton, J. D. Blood pressure, systolic and diastolic, and cardiovascular risks. US population data. Arch. Intern. Med. 153, 598–615 (1993).
Klag, M. J. et al. Blood pressure and end-stage renal disease in men. N. Engl. J. Med. 334, 13–18 (1996).
Goff, D. C. et al. 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk. J. Am. Coll. Cardiol. 63, 2935–2959 (2014).
Hall, M. E. & Hall, J. E. in Hypertension: A Companion to Braunwald's Heart Disease 3rd edn (eds Bakris, G. L. & Sorrentino, M.) 33–51 (Elsevier, 2018). This comprehensive review of the pathogenesis of hypertension includes the mechanisms involved in both the short-term and long-term control of BP and the integration of cardiovascular, renal, neural, endocrine, local tissue, inflammatory, genetic and environmental effects on the genesis of hypertension.
Gangwisch, J. E. A review of evidence for the link between sleep duration and hypertension. Am. J. Hypertens. 27, 1235–1242 (2014).
Palagini, L. et al. Sleep loss and hypertension: a systematic review. Curr. Pharm. Des. 19, 2409–2419 (2013).
Mikael, L. de R. et al. Vascular aging and arterial stiffness. Arq. Bras. Cardiol. 109, 253–258 (2017).
Sindler, A. L. et al. Nitrite supplementation reverses vascular endothelial dysfunction and large elastic artery stiffness with aging. Aging Cell 10, 429–437 (2011).
Steppan, J., Barodka, V., Berkowitz, D. E. & Nyhan, D. Vascular stiffness and increased pulse pressure in the aging cardiovascular system. Cardiol. Res. Pract. 2011, 263585 (2011).
Page, I. H. Pathogenesis of arterial hypertension. JAMA 140, 451–458 (1949).
Harrison, D. G. The Mosaic Theory revisited: common molecular mechanisms coordinating diverse organ and cellular events in hypertension. J. Am. Soc. Hypertens. 7, 68–74 (2013). This update of the mosaic theory of hypertension, proposed by Irvine Page in 1949, reviews the genetic, environmental, neural, mechanical and hormonal perturbations that interdigitate to raise BP, particularly the interactions that occur at the cellular and molecular level.
Feng, W., Dell’Italia, L. J. & Sanders, P. W. Novel paradigms of salt and hypertension. J. Am. Soc. Nephrol. 28, 1362–1369 (2017).
Wilck, N. et al. Salt-responsive gut commensal modulates TH17 axis and disease. Nature 551, 585 (2017).
Singh, A. & Williams, G. H. Textbook of Nephro-Endocrinology 2nd edn (Academic Press, 2017).
Varagic, J., Ahmad, S., Nagata, S. & Ferrario, C. M. ACE2: angiotensin II/angiotensin-(1–7) balance in cardiac and renal injury. Curr. Hypertens. Rep. 16, 420 (2014).
Ferrario, C. M. ACE2: more of Ang-(1–7) or less Ang II? Curr. Opin. Nephrol. Hypertens. 20, 1–6 (2011).
Zimmerman, D. & Burns, K. D. Angiotensin-(1–7) in kidney disease: a review of the controversies. Clin. Sci. 123, 333–346 (2012).
Zhou, Z. H. & Bubien, J. K. Nongenomic regulation of EnaC by aldosterone. Am. J. Physiol. Cell Physiol. 281, C1118–C1130 (2001).
McCurley, A. & Jaffe, I. Z. Mineralocorticoid receptors in vascular function and disease. Mol. Cell. Endocrinol. 350, 256–265 (2012).
Kerkelä, R., Ulvila, J. & Magga, J. Natriuretic peptides in the regulation of cardiovascular physiology and metabolic events. J. Am. Heart Assoc. 4, e002423 (2015).
Woodard, G. E. & Rosado, J. A. Chapter 3 Natriuretic peptides in vascular physiology and pathology. Int. Rev. Cell. Mol. Biol. 268, 59–93 (2008).
Curry, F.-R. E. Atrial natriuretic peptide: an essential physiological regulator of transvascular fluid, protein transport, and plasma volume. J. Clin. Invest. 115, 1458–1461 (2005).
Armaly, Z., Assady, S. & Abassi, Z. Corin: a new player in the regulation of salt-water balance and blood pressure. Curr. Opin. Nephrol. Hypertens. 22, 713–722 (2013).
Schlueter, N. et al. Metabolic actions of natriuretic peptides and therapeutic potential in the metabolic syndrome. Pharmacol. Ther. 144, 12–27 (2014).
Khaddaj Mallat, R., Mathew John, C., Kendrick, D. J. & Braun, A. P. The vascular endothelium: a regulator of arterial tone and interface for the immune system. Crit. Rev. Clin. Lab. Sci. 54, 458–470 (2017).
Sandoo, A., van Zanten, J. J. C. S. V., Metsios, G. S., Carroll, D. & Kitas, G. D. The endothelium and its role in regulating vascular tone. Open Cardiovasc. Med. J. 4, 302–312 (2010).
Spieker, L. E., Flammer, A. J. & Lüscher, T. F. in The Vascular Endothelium II (Moncada, S. & Higgs, A.) 249–283 (Springer, Berlin, Heidelberg, 2006).
Ayub, T., Khan, S. N., Ayub, S. G., Dar, R. & Andrabi, K. I. Reduced nitrate level in individuals with hypertension and diabetes. J. Cardiovasc. Dis. Res. 2, 172–176 (2011).
Panza, J. A., Casino, P. R., Badar, D. M. & Quyyumi, A. A. Effect of increased availability of endothelium-derived nitric oxide precursor on endothelium-dependent vascular relaxation in normal subjects and in patients with essential hypertension. Circulation 87, 1475–1481 (1993).
Kohan, D. E. & Barton, M. Endothelin and endothelin antagonists in chronic kidney disease. Kidney Int. 86, 896–904 (2014).
Serrano-Ponz, M. et al. Temporal profiles of blood pressure, circulating nitric oxide, and adrenomedullin as predictors of clinical outcome in acute ischemic stroke patients. Mol. Med. Rep. 13, 3724–3734 (2016).
Vendégh, Z. et al. Calcitonin gene-related peptide, substance P, nitric oxide and epinephrine modulate bone marrow micro circulation of the rabbit tibia and femur. Clin. Hemorheol. Microcirc. 45, 9–17 (2010).
Yu, M. et al. Antihypertensive effect of glucagon-like peptide 1 in Dahl salt-sensitive rats. J. Hypertens. 21, 1125–1135 (2003).
Popolo, A., Autore, G., Pinto, A. & Marzocco, S. Oxidative stress in patients with cardiovascular disease and chronic renal failure. Free Radic. Res. 47, 346–356 (2013).
Lazich, I. & Bakris, G. L. Endothelin antagonism in patients with resistant hypertension and hypertension nephropathy. Contrib. Nephrol. 172, 223–234 (2011).
Dharmashankar, K. & Widlansky, M. E. Vascular endothelial function and hypertension: insights and directions. Curr. Hypertens. Rep. 12, 448–455 (2010).
Heymans, C. & Delaunois, A. L. Fundamental role of the tone and resistance to stretch of the carotid sinus arteries in the reflex regulation of blood pressure. Science 114, 546–547 (1951).
Pijacka, W. et al. Carotid sinus denervation ameliorates renovascular hypertension in adult Wistar rats. J. Physiol. 594, 6255–6266 (2016).
de Leeuw, P. W. et al. Sustained reduction of blood pressure with baroreceptor activation therapy. Results of the 6-year open follow-up. Hypertension 69, 836–843 (2017).
Grassi, G. et al. Excessive sympathetic activation in heart failure with obesity and metabolic syndrome: characteristics and mechanisms. Hypertension 49, 535–541 (2007).
Mancia, G. & Grassi, G. The autonomic nervous system and hypertension. Circ. Res. 114, 1804–1814 (2014). This review of the adrenergic and vagal abnormalities that occur in hypertension emphasizes the role of the autonomic nervous system as a promoter and amplifier of the elevated BP state.
Augustyniak, R. A. et al. Sympathetic nerves and the progression of chronic kidney disease during 5/6 nephrectomy: studies in sympathectomized rats. Clin. Exp. Pharmacol. Physiol. 37, 12–18 (2010).
Augustyniak, R. A., Tuncel, M., Zhang, W., Toto, R. D. & Victor, R. G. Sympathetic overactivity as a cause of hypertension in chronic renal failure. J. Hypertens. 20, 3–9 (2002).
DiBona, G. F. Sympathetic nervous system and hypertension. Hypertension 61, 556–560 (2013).
Grassi, G., Mark, A. & Esler, M. The sympathetic nervous system alterations in human hypertension. Circ. Res. 116, 976–990 (2015).
Grassi, G., Cattaneo, B. M., Seravalle, G., Lanfranchi, A. & Mancia, G. Baroreflex control of sympathetic nerve activity in essential and secondary hypertension. Hypertension 31, 68–72 (1998).
Smith, P. A., Graham, L. N., Mackintosh, A. F., Stoker, J. B. & Mary, D. Relationship between central sympathetic activity and stages of human hypertension. Am. J. Hypertens. 17, 217–222 (2004).
Fujita, T. Mechanism of salt-sensitive hypertension: focus on adrenal and sympathetic nervous systems. J. Am. Soc. Nephrol. 25, 1148–1155 (2014).
Mu, S. et al. Epigenetic modulation of the renal β-adrenergic–WNK4 pathway in salt-sensitive hypertension. Nat. Med. 17, 573–580 (2011).
Harrison, D. G. & Bernstein, K. E. in in Hypertension: A Companion to Braunwald's Heart Disease 3rd edn (eds Bakris, G. L. & Sorrentino, M.) 60–69 (Elsevier, 2018). This is an up-to-date summary of the role of inflammation and the immune system in the pathogenesis of hypertension.
Devallière, J. & Charreau, B. The adaptor Lnk (SH2B3): an emerging regulator in vascular cells and a link between immune and inflammatory signaling. Biochem. Pharmacol. 82, 1391–1402 (2011).
Rodriguez-Iturbe, B. Autoimmunity in the pathogenesis of hypertension. Hypertension 67, 477–483 (2016).
Mattson, D. L. et al. Genetic mutation of recombination activating gene 1 in Dahl salt-sensitive rats attenuates hypertension and renal damage. AJP Regul. Integr. Comp. Physiol. 304, R407–R414 (2013).
Roush, G. C. et al. Prognostic impact from clinic, daytime, and night-time systolic blood pressure in nine cohorts of 13 844 patients with hypertension. J. Hypertens. 32, 2332–2340 (2014). This systematic review of nine cohorts (n = 13,844) from Europe, Brazil and Japan shows that night-time systolic BP predicts cardiovascular events independently of office BP, providing support for the use of ABPM in the evaluation of patients with hypertension.
Stergiou, G. S. et al. Methodology and technology for peripheral and central blood pressure and blood pressure variability measurement. J. Hypertens. 34, 1665–1677 (2016).
Parati, G. et al. European Society of Hypertension Practice Guidelines for home blood pressure monitoring. J. Hum. Hypertens. 24, 779–785 (2010).
O’Brien, E. et al. European Society of Hypertension Position Paper on ambulatory blood pressure monitoring. J. Hypertens. 31, 1731–1768 (2013).
Muntner, P. & Whelton, P. K. Using predicted cardiovascular disease risk in conjunction with blood pressure to guide antihypertensive medication treatment. J. Am. Coll. Cardiol. 69, 2446–2456 (2017). This analysis of data from randomized trials that assessed relative and absolute CVD risk reduction that can occur when antihypertensive treatment is guided by CVD risk concludes that both CVD risk and BP levels should be considered in making treatment decisions.
Mancia, G. et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension. J. Hypertens. 31, 1281–1357 (2013).
Pickering, T. G. Recommendations for blood pressure measurement in humans and experimental animals. Part 1: Blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Circulation 111, 697–716 (2005).
Whelton, P. K. The elusiveness of population-wide high blood pressure control. Annu. Rev. Publ. Health 36, 109–130 (2015).
Primatesta, P. & Poulter, N. R. Improvement in hypertension management in England: results from the Health Survey for England 2003. J. Hypertens. 24, 1187–1192 (2006).
Ashworth, M., Medina, J. & Morgan, M. Effect of social deprivation on blood pressure monitoring and control in England: a survey of data from the quality and outcomes framework. BMJ 337, a2030 (2008).
Serumaga, B. et al. Effect of pay for performance on the management and outcomes of hypertension in the United Kingdom: interrupted time series study. BMJ 342, d108 (2011).
Poulter, N. R. & Lackland, D. T. May Measurement Month: a global blood pressure screening campaign. Lancet 389, 1678–1680 (2017).
He, J. et al. Migration, blood pressure pattern, and hypertension: the Yi Migrant Study. Am. J. Epidemiol. 134, 1085–1101 (1991).
Poulter, N. R. et al. The Kenyan Luo migration study: observations on the initiation of a rise in blood pressure. BMJ 300, 967–972 (1990).
Rosenthal, T. The effect of migration on hypertension and other cardiovascular risk factors: a review. J. Am. Soc. Hypertens. 8, 171–191 (2014).
Klag, M. J. et al. The contribution of urinary cations to the blood pressure differences associated with migration. Am. J. Epidemiol. 142, 295–303 (1995).
Whelton, P. K. et al. The effects of nonpharmacologic interventions on blood pressure of persons with high normal levels. Results of the Trials of Hypertension Prevention, Phase I. JAMA 267, 1213–1220 (1992).
Whelton, P. K. et al. Efficacy of nonpharmacologic interventions in adults with high-normal blood pressure: results from phase 1 of the Trials of Hypertension Prevention. Trials Hypertension Prevention Collaborative Res. Group. Am. J. Clin. Nutr. 65, 652S–660S (1997).
[No authors listed.] Effects of weight loss and sodium reduction intervention on blood pressure and hypertension incidence in overweight people with high-normal blood pressure. The Trials of Hypertension Prevention, phase II. Arch. Intern. Med. 157, 657–667 (1997).
Sacks, F. M. et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. N. Engl. J. Med. 344, 3–10 (2001). This study shows that combining the DASH diet with a low sodium (50 mmol per day) intake led to significant reductions in systolic BP both in persons with hypertension and in those without hypertension compared with persons who consumed a high sodium diet (150 mmol per day).
Whelton, P. K. et al. Effects of oral potassium on blood pressure. Meta-analysis of randomized controlled clinical trials. JAMA 277, 1624–1632 (1997).
Aburto, N. J. et al. Effect of increased potassium intake on cardiovascular risk factors and disease: systematic review and meta-analyses. BMJ 346, f1378 (2013).
Whelton, S. P., Chin, A., Xin, X. & He, J. Effect of aerobic exercise on blood pressure: a meta-analysis of randomized, controlled trials. Ann. Intern. Med. 136, 493–503 (2002).
Xin, X. et al. Effects of alcohol reduction on blood pressure: a meta-analysis of randomized controlled trials. Hypertension 38, 1112–1117 (2001).
Roerecke, M. et al. The effect of a reduction in alcohol consumption on blood pressure: a systematic review and meta-analysis. Lancet Public Health 2 e108–e120 (2017).
Appel, L. J. et al. A clinical trial of the effects of dietary patterns on blood pressure. N. Engl. J. Med. 336, 1117–1124 (1997).
Whelton, P. K. Hypertension curriculum review: epidemiology and the prevention of hypertension. J. Clin. Hypertens. 6, 636–642 (2004).
Whelton, P. K. et al. Primary prevention of hypertension: clinical and public health advisory from The National High Blood Pressure Education Program. JAMA 288, 1882–1888 (2002).
Whelton, P. K. et al. Sodium reduction and weight loss in the treatment of hypertension in older persons. JAMA 279, 839 (1998).
[No authors listed.] National High Blood Pressure Education Program Working Group report on primary prevention of hypertension. Arch. Intern. Med. 153, 186–208 (1993).
Cook, N. R., Cohen, J., Hebert, P. R., Taylor, J. O. & Hennekens, C. H. Implications of small reductions in diastolic blood pressure for primary prevention. Arch. Intern. Med. 155, 701–709 (1995).
Julius, S. et al. Feasibility of treating prehypertension with an angiotensin-receptor blocker. N. Engl. J. Med. 354, 1685–1697 (2006).
Lüders, S. et al. The PHARAO study: prevention of hypertension with the angiotensin-converting enzyme inhibitor _abellin in patients with high-normal blood pressure: a prospective, randomized, controlled prevention trial of the German Hypertension League. J. Hypertens. 26, 1487–1496 (2008).
Fuchs, S. C. et al. Effectiveness of chlorthalidone plus amiloride for the prevention of hypertension: the PREVER-Prevention randomized clinical trial. J. Am. Heart Assoc. 5, e004248 (2016).
James, P. A. et al. 2014 evidence-based guideline for the management of high blood pressure in adults. JAMA 311, 507 (2014).
SPRINT Research Group et al. A randomized trial of intensive versus standard blood-pressure control. N. Engl. J. Med. 373, 2103–2116 (2015). SPRINT shows that treating to a target systolic BP of <120 mmHg resulted in significantly lower rates of fatal and nonfatal cardiovascular events and all-cause mortality than treating to a target systolic BP of <140 mmHg in people with hypertension and increased CVD risk but without diabetes mellitus.
Johnson, K. C. et al. Blood pressure measurement in the Systolic Blood Pressure Intervention Trial (SPRINT). Hypertension (in the press).
Filipovský, J. et al. Automated compared to manual office blood pressure and to home blood pressure in hypertensive patients. Blood Press. 25, 228–234 (2016).
Kjeldsen, S. E., Lund-Johansen, P., Nilsson, P. M. & Mancia, G. Unattended blood pressure measurements in the systolic blood pressure intervention trial. Hypertension 67, 808–812 (2016).
Whelton, P. K. et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/AphA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension https://doi.org/10.1161/HYP.0000000000000066 (2017).
Aburto, N. J. et al. Effect of lower sodium intake on health: systematic review and meta-analyses. BMJ 346 f1326 (2013).
He, F. J., Li, J. & Macgregor, G. A. Effect of longer term modest salt reduction on blood pressure: Cochrane systematic review and meta-analysis of randomised trials. BMJ 346, f1325 (2013).
World Health Organization. Guideline: Sodium intake for adults and children (WHO, Geneva, 2012).
Van Horn, L. et al. Recommended dietary pattern to achieve adherence to the American Heart Association/American College of Cardiology (AHA/ACC) guidelines: a scientific statement from the American Heart Association. Circulation 134, e505–e529 (2016).
He, F. J. & MacGregor, G. A. Effect of modest salt reduction on blood pressure: a meta-analysis of randomized trials. Implications for public health. J. Hum. Hypertens. 16, 761–770 (2002).
Langford, H. G. Dietary therapy slows the return of hypertension after stopping prolonged medication. JAMA 253, 657–664 (1985).
Intersalt: an international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and potassium excretion. Intersalt Cooperative Research Group. BMJ 297, 319–328 (1988).
Bibbins-Domingo, K. et al. Projected effect of dietary salt reductions on future cardiovascular disease. N. Engl. J. Med. 362, 590–599 (2010).
Graudal, N. A., Hubeck-Graudal, T. & Jurgens, G. Effects of low-sodium diet versus high-sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride (Cochrane review). Am. J. Hypertens. 25, 1–15 (2012).
He, F. J. & MacGregor, G. A. Reducing population salt intake-time for global action. J. Clin. Hypertens. 17, 10–13 (2014).
Cappuccio, F. P. & MacGregor, G. A. Does potassium supplementation lower blood pressure? A meta-analysis of published trials. J. Hypertens. 9, 465–473 (1991).
Chalmers, J. et al. Australian National Health and Medical Research Council dietary salt study in mild hypertension. J. Hypertens. Suppl. 4, S629–S637 (1986).
Kidney Disease Outcomes Quality Initiative (K/DOQI). K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am. J. Kidney Dis. 43, S1–S290 (2004).
Börjesson, M., Onerup, A., Lundqvist, S. & Dahlöf, B. Physical activity and exercise lower blood pressure in individuals with hypertension: narrative review of 27 RCTs. Br. J. Sports Med. 50, 356–361 (2016).
MacDonald, H. V. et al. Dynamic resistance training as stand-alone antihypertensive lifestyle therapy: a meta-analysis. J. Am. Heart Assoc. 5, e003231 (2016).
Egan, B. M., Zhao, Y., Axon, R. N., Brzezinski, W. A. & Ferdinand, K. C. Uncontrolled and Apparent Treatment Resistant Hypertension in the United States, 1988 to 2008. Circulation 124, 1046–1058 (2011).
Zomer, E. et al. Interventions that cause weight loss and the impact on cardiovascular risk factors: a systematic review and meta-analysis. Obes. Rev. 17, 1001–1011 (2016).
Stevens, V. J. Long-term weight loss and changes in blood pressure: results of the Trials of Hypertension Prevention, phase II. Ann. Intern. Med. 134, 1 (2001).
Ettehad, D. et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet 387, 957–967 (2016).
Garjón, J. et al. First-line combination therapy versus first-line monotherapy for primary hypertension. Cochrane Database Syst. Rev. 1,CD010316 (2017).
[No authors listed.] Hypertension in adults: diagnosis and management (CG127). National Institute for Health and Care Excellence https://www.nice.org.uk/guidance/cg127 (2011).
Flack, J. M. et al. Management of high blood pressure in blacks: an update of the International Society on Hypertension in Blacks Consensus Statement. Hypertension 56, 780–800 (2010).
Iskedjian, M. et al. Relationship between daily dose frequency and adherence to antihypertensive pharmacotherapy: evidence from a meta-analysis. Clin. Ther. 24, 302–316 (2002).
Blood Pressure Lowering Treatment Trialists’ Collaboration. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet 362, 1527–1535 (2003).
Yusuf, S. et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N. Engl. J. Med. 358, 1547–1559 (2008).
Bosch, J. et al. Effect of ramipril on the incidence of diabetes. N. Engl. J. Med. 355, 1551–1562 (2006).
Brown, N. J., Ray, W. A., Snowden, M. & Griffin, M. R. Black Americans have an increased rate of angiotensin converting enzyme inhibitor-associated angioedema*. Clin. Pharmacol. Ther. 60, 8–13 (1996).
Brown, N. J., Byiers, S., Carr, D., Maldonado, M. & Warner, B. A. Dipeptidyl peptidase-IV inhibitor use associated with increased risk of ACE inhibitor-associated angioedema. Hypertension 54, 516–523 (2009).
Guazzi, M. D. et al. Disparate unloading efficacy of the calcium channel blockers, verapamil and nifedipine, on the failing hypertensive left ventricle. Am. Heart J. 108, 116–123 (1984).
Harari, D., Gurwitz, J. H., Avorn, J., Choodnovskiy, I. & Minaker, K. L. Correlates of regular laxative use by frail elderly persons. Am. J. Med. 99, 513–518 (1995).
Bernard, E., Goutelle, S., Bertrand, Y. & Bleyzac, N. Pharmacokinetic drug-drug interaction of calcium channel blockers with cyclosporine in hematopoietic stem cell transplant children. Ann. Pharmacother. 48, 1580–1584 (2014).
[No authors listed.] Effects of treatment on morbidity in hypertension. Results in patients with diastolic blood pressures averaging 115 through 129 mmHg. JAMA 202, 1028–1034 (1967).
Barzilay, J. I. et al. Long-term effects of incident diabetes mellitus on cardiovascular outcomes in people treated for hypertension: the ALLHAT Diabetes Extension Study. Circ. Cardiovasc. Qual. Outcomes 5, 153–162 (2012).
Roush, G. C., Holford, T. R. & Guddati, A. K. Chlorthalidone compared with hydrochlorothiazide in reducing cardiovascular events: systematic review and network meta-analyses. Hypertension 59, 1110–1117 (2012).
Roush, G. C., Ernst, M. E., Kostis, J. B., Tandon, S. & Sica, D. A. Head-to-head comparisons of hydrochlorothiazide with indapamide and chlorthalidone: antihypertensive and metabolic effects. Hypertension 65, 1041–1046 (2015). This systematic review shows that indapamide and chlorthalidone were more effective in lowering BP than hydrochlorothiazide at commonly prescribed doses without increasing the risk of adverse metabolic effects, including hypokalaemia, hyponatraemia and elevated creatinine.
Antman, E. M. Cardiovascular Therapeutics: A Companion to Braunwald's Heart Disease 4th edn (Saunders, 2013).
Wiysonge, C. S., Bradley, H. A., Volmink, J., Mayosi, B. M. & Opie, L. H. Beta-blockers for hypertension. Cochrane Database Syst. Rev. https://doi.org/10.1002/14651858.CD002003.pub5 (2017).
Boutouyrie, P., Achouba, A., Trunet, P. & Laurent, S. Amlodipine-valsartan combination decreases central systolic blood pressure more effectively than the amlodipine-atenolol combination: the EXPLOR Study. Hypertension 55, 1314–1322 (2010).
Sharma, A. M., Pischon, T., Hardt, S., Kunz, I. & Luft, F. C. Hypothesis: beta-adrenergic receptor blockers and weight gain: a systematic analysis. Hypertension 37, 250–254 (2001).
Bakris, G. L. et al. Metabolic effects of carvedilol versus metoprolol in patients with type 2 diabetes mellitus and hypertension. JAMA 292, 2227 (2004).
Ruilope, L. M. et al. Blood-pressure reduction with LCZ696, a novel dual-acting inhibitor of the angiotensin II receptor and neprilysin: a randomised, double-blind, placebo-controlled, active comparator study. Lancet 375, 1255–1266 (2010).
Ghofrani, H.-A. et al. Riociguat for the treatment of pulmonary arterial hypertension. N. Engl. J. Med. 369, 330–340 (2013).
Zinman, B. et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N. Engl. J. Med. 373, 2117–2128 (2015).
Oparil, S. & Schmieder, R. E. New approaches in the treatment of hypertension. Circ. Res. 116, 1074–1095 (2015). This is a review of new drugs and device-based treatments that are undergoing preclinical or clinical testing for hypertension treatment.
Jordan, J. et al. Improved insulin sensitivity with angiotensin receptor neprilysin inhibition in individuals with obesity and hypertension. Clin. Pharmacol. Ther. 101, 254–263 (2016).
Seferovic, J. P. et al. Effect of sacubitril/valsartan versus enalapril on glycaemic control in patients with heart failure and diabetes: a post-hoc analysis from the PARADIGM-HF trial. Lancet Diabetes Endocrinol. 5, 333–340 (2017).
Calhoun, D. A. et al. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Hypertension 51, 1403–1419 (2008).
Sim, J. J. et al. Characteristics of resistant hypertension in a large, ethnically diverse hypertension population of an integrated health system. Mayo Clin. Proc. 88, 1099–1107 (2013).
Williams, B. et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet 386, 2059–2068 (2015). This trial shows that spironolactone was the most effective add-on drug for the treatment of resistant hypertension, regardless of the baseline renin levels.
Bobrie, G. et al. Sequential nephron blockade versus sequential renin–angiotensin system blockade in resistant hypertension. J. Hypertens. 30, 1656–1664 (2012).
Juurlink, D. N. et al. Rates of hyperkalemia after publication of the randomized aldactone evaluation study. N. Engl. J. Med. 351, 543–551 (2004).
Krum, H. et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet 373, 1275–1281 (2009).
Bhatt, D. L. et al. A controlled trial of renal denervation for resistant hypertension. N. Engl. J. Med. 370, 1393–1401 (2014).
Heusser, K. et al. Carotid baroreceptor stimulation, sympathetic activity, baroreflex function, and blood pressure in hypertensive patients. Hypertension 55, 619–626 (2010).
Bisognano, J. D. et al. Baroreflex activation therapy lowers blood pressure in patients with resistant hypertension. J. Am. Coll. Cardiol. 58, 765–773 (2011).
Spiering, W. et al. LB02.05: Controlling and lowering blood pressure with the Mobiushd device: first in-man results (CALM-FIM study). J. Hypertens. 33, e86 (2015).
Narkiewicz, K. et al. Unilateral carotid body resection in resistant hypertension. JACC Bas. Transl Sci. 1, 313–324 (2016).
O’Callaghan, E. L. et al. Chronic deep brain stimulation decreases blood pressure and sympathetic nerve activity in a drug- and device-resistant hypertensive patient. Hypertension 69, 522–528 (2017).
Lobo, M. D. et al. Central arteriovenous anastomosis for the treatment of patients with uncontrolled hypertension (the ROX CONTROL HTN study): a randomised controlled trial. Lancet 385, 1634–1641 (2015).
Testa, M. A. & Simonson, D. C. Assessment of quality-of-life outcomes. N. Engl. J. Med. 334, 835–840 (1996).
Trevisol, D. J., Moreira, L. B., Kerkhoff, A., Fuchs, S. C. & Fuchs, F. D. Health-related quality of life and hypertension: a systematic review and meta-analysis of observational studies. J. Hypertens. 29, 179–188 (2011). This meta-analysis of 20 cross-sectional studies shows that HRQOL was lower in persons with hypertension than in those with normal BP in the domains of physical and functional functioning, bodily pain, general health, vitality and mental health but that the magnitude of difference was small.
Bardage, C. & Isacson, D. G. Hypertension and health-related quality of life. An. Epidemiol. Study Sweden. J. Clin. Epidemiol. 54, 172–181 (2001).
Pickering, T. G. Now we are sick: labeling and hypertension. J. Clin. Hypertens. 8, 57–60 (2006).
Haynes, R. B., Sackett, D. L., Taylor, D. W., Gibson, E. S. & Johnson, A. L. Increased absenteeism from work after detection and labeling of hypertensive patients. N. Engl. J. Med. 299, 741–744 (1978).
Fogari, R. & Zoppi, A. Effect of antihypertensive agents on quality of life in the elderly. Drugs Aging 21, 377–393 (2004).
Carris, N. W. & Smith, S. M. Quality of life in treatment-resistant hypertension. Curr. Hypertens. Rep. 17, 61 (2015).
Croog, S. H. et al. The effects of antihypertensive therapy on the quality of life. N. Engl. J. Med. 314, 1657–1664 (1986).
Testa, M. A., Anderson, R. B., Nackley, J. F. & Hollenberg, N. K. Quality of life and antihypertensive therapy in men — a comparison of captopril with enalapril. N. Engl. J. Med. 328, 907–913 (1993).
Grimm, R. H. et al. Relationships of quality-of-life measures to long-term lifestyle and drug treatment in the Treatment of Mild Hypertension Study. Arch. Intern. Med. 157, 638–648 (1997).
Applegate, W. B. Quality of life during antihypertensive treatment. Lessons From Systol. Hypertension Elderly Program. Am. J. Hypertens. 11, 57S–61S (1998).
Fletcher, A. E. et al. Quality of life on randomized treatment for isolated systolic hypertension: results from the Syst-Eur Trial. J. Hypertens. 20, 2069–2079 (2002).
Saper, C. B. How low can you go? Ann. Neurol. 78, 665–666 (2015).
O’Connor, P. J. et al. Effect of intensive versus standard blood pressure control on depression and health-related quality of life in type 2 diabetes: the ACCORD trial. Diabetes Care 35, 1479–1481 (2012).
Berlowitz, D. et al. Effect of Intensive Blood-Pressure Treatment on Patient-Reported Outcomes. N. Engl. J. Med. 377, 733–744 (2017).
NCD Risk Factor Collaboration. Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19·1 million participants. Lancet 389, 37–55 (2017).
Kearney, P. M. et al. Global burden of hypertension: analysis of worldwide data. Lancet 365, 217–223 (2005).
O’Donnell, M. J., Mente, A., Smyth, A. & Yusuf, S. Salt intake and cardiovascular disease: why are the data inconsistent? Eur. Heart J. 34, 1034–1040 (2012).
Chow, C. K. et al. Prevalence, awareness, treatment, and control of hypertension in rural and urban communities in high-, middle-, and low-income countries. JAMA 310, 959 (2013).
Adler, A. J. et al. Reducing cardiovascular mortality through prevention and management of raised blood pressure. Glob. Heart 10, 111–122 (2015).
Olsen, M. H. et al. A call to action and a lifecourse strategy to address the global burden of raised blood pressure on current and future generations: the Lancet Commission on hypertension. Lancet 388, 2665–2712 (2016).
Mendis, S. et al. The availability and affordability of selected essential medicines for chronic diseases in six low- and middle-income countries. Bull. World Health Organ. 85, 279–288 (2007).
Park, I. U. & Taylor, A. L. Race and ethnicity in trials of antihypertensive therapy to prevent cardiovascular outcomes: a systematic review. Ann. Fam. Med. 5, 444–452 (2007).
Anchala, R. et al. The role of decision support system (DSS) in prevention of cardiovascular disease: a systematic review and meta-analysis. PLoS ONE 7, e47064 (2012).
World Health Organization. Task Shifting Global Recommendations and Guidelines (WHO, Geneva, 2008).
Ehret, G. B. et al. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature 478, 103–109 (2011).
Potter, L. R., Yoder, A. R., Flora, D. R., Antos, L. K. & Dickey, D. M. cGMP: in Generators, Effectors and Therapeutic Implications (eds Schmidt, H. H. H. W., Hofmann, F. & Stasch, J.-P.) 341–366 (Springer, Berlin, Heidelberg, 2009).
Dries, D. L. Corin gene minor allele defined by 2 missense mutations is common in blacks and associated with high blood pressure and hypertension. Circulation 112, 2403–2410 (2005).
Siebenhofer, A. et al. Long-term effects of weight-reducing drugs in people with hypertension. Cochrane Database Syst. Rev. https://doi.org/10.1002/14651858.cd007654.pub4 (2016).
James, W. P. T. et al. Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N. Engl. J. Med. 363, 905–917 (2010).
Ricci, C. et al. Long-term effects of bariatric surgery on type II diabetes, hypertension and hyperlipidemia: a meta-analysis and meta-regression study with 5-year follow-up. Obes. Surg. 25, 397–405 (2014).
Sjöström, C. D., Lystig, T. & Lindroos, A. K. Impact of weight change, secular trends and ageing on cardiovascular risk factors: 10-year experiences from the SOS study. Int. J. Obes. 35, 1413–1420 (2011).
Whelton, P. K. Epidemiology and the Prevention of Hypertension. J. Clin. Hypertens. 6, 636–642 (2004).
Crowley, S. D. et al. Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney. Proc. Natl Acad. Sci. USA 103, 17985–17990 (2006).
Crowley, S. D. et al. Distinct roles for the kidney and systemic tissues in blood pressure regulation by the renin-angiotensin system. J. Clin. Invest. 115, 1092–1099 (2005).
Reich, H. N., Oudit, G. Y., Penninger, J. M., Scholey, J. W. & Herzenberg, A. M. Decreased glomerular and tubular expression of ACE2 in patients with type 2 diabetes and kidney disease. Kidney Int. 74, 1610–1616 (2008).
Liu, L.-S. & Writing Group of 2010 Chinese Guidelines for the Management of Hypertension. 2010 Chinese guidelines for the management of hypertension [Chinese]. Zhonghua Xin Xue Guan Bing Za Zhi 39, 579–615 (2011).
Weber, M. A. et al. Clinical practice guidelines for the management of hypertension in the community. J. Clin. Hypertens. 16, 14–26 (2014).
Seedat, Y. K., Rayner, B. L. & Veriava, Y. South African hypertension practice guideline 2014: review article. Cardiovasc. J. Afr. 25, 288–294 (2014).
Shimamoto, K. et al. The Japanese Society of Hypertension guidelines for the management of hypertension (JSH 2014) Hypertens. Res. 37, 253–392 (2014).
Leung, A. A. et al. Hypertension Canada's 2016 Canadian hypertension education program guidelines for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension. Can. J. Cardiol. 32, 569–588 (2016).
National Heart Foundation of Australia. Guideline for the Diagnosis and Management of Hypertension in Adults (National Heart Foundation of Australia, 2016).
American Diabetes Association. Standards of medical care in diabetes — 2017. Diabetes Care 40 (Suppl. 1), S1–S142 (2017).