Life Extension Magazine®

Man having blood pressure measurement for hypertension

Best Drug To Treat Hypertension

One in three adults has high blood pressure, yet only 45% have it controlled. Recently, the FDA approved the sale of generic telmisartan. This drug offers blood pressure control, improves insulin sensitivity, boosts mitochondrial activity, and enhances endothelial function.

Scientifically reviewed by Dr. Gary Gonzalez, MD, in August 2023. Written by: William Faloon.

William Faloon
William Faloon

As I was finishing this article, two people I personally know suffered strokes that were most likely caused by their high blood pressure. One of them is paralyzed on one side and will likely be confined to a nursing home for their remaining years. Both knew they had hypertension, but like so many individuals today, they dealt with this deadly disorder as if it were a trivial matter. No medical authority discounts the dangers posed by hypertension. Yet a stupendous number of aging people are failing to maintain their blood pressure in optimal ranges.

In the United States, 1 out of every 3 adults has high blood pressure.1

Only 45% have it controlled. To make matters worse, this 45% statistic is based on higher-than-optimal blood pressure ranges, meaning most adults today endure chronic hypertensive damage to their tissues.2

Conventional doctors diagnose hypertension when a patient’s readings exceed 140/90. The scientific literature, however, indicates that the ideal range should be around 115/75.3 When blood pressure exceeds 115/75, there is an increased risk of heart attack and stroke, which are the leading causes of disability and death in modern societies.4

The market for antihypertensive drugs is huge. Virtually every pharmaceutical company at one time or another has aggressively promoted their patented product to physicians. Once a doctor gets into the routine of prescribing an antihypertensive drug, they often continue prescribing the same drug even when newer and better ones are approved.

Best Drug To Treat Hypertension  

Insurance companies are increasingly refusing to pay for newer and better drugs because generics cost less.

For those with blood pressure readings significantly over 115/75, I have some great news. In 2014, the FDA approved a generic version of an antihypertensive drug that lowers blood pressure more consistently than other classes of medications and has ancillary longevity benefits.

The side benefits of this drug include improved insulin sensitivity, enhanced mitochondrial activity, and better endothelial function.5-12 Preclinical research indicates that it may also help control body weight.6,13,14

This article reviews conventional protocols that are failing to maintain optimal blood pressure levels throughout the day. The reader will then be enlightened to what we believe is the best drug for most people with elevated blood pressure that cannot be controlled with lifestyle changes.

Medicine often progresses at a dreadfully slow pace.

The first direct measurement of arterial pressure occurred in 1733 in a horse.15 It took almost 100 years before a primitive device was developed to measure blood pressure noninvasively in humans.

Around 1900, some physicians started testing their patients’ blood pressure. Skeptics criticized that reliance on a mechanical device would “weaken clinical acuity.”16

The impetus for widespread blood pressure testing did not emanate in the medical community. It was life insurance companies who spearheaded it because early mortality was so clearly evident in those with higher blood pressure readings. Credit the Northwestern Mutual Life Insurance Company for stating in 1911 that blood pressure testing devices are “indispensable in life-insurance examinations.”17

Conventional doctors were not persuaded by insurance company actuaries. In 1931, an article published in the British Medical Journal stated that, “The greatest danger to a man with high blood pressure lies in its discovery because then some fool is certain to try and reduce it .”15

This misguided thought process persisted for decades, despite a growing body of published studies linking hypertension with sharply higher rates of stroke, heart disease, and kidney failure.15,18-27

I relate this brief history to demonstrate how far behind medical authorities have been in recognizing this leading killer. The problem is that most conventional doctors still are not optimally diagnosing and treating hypertension.

Overworked Doctors And Under-Motivated Patients

Overworked Doctors And Under-Motivated Patients  

I am more sympathetic to practicing physicians than ever before. The volume of published medical studies has exponentially increased, record numbers of different antihypertensive drugs are available, and doctors face humongous patient loads.

So a typical person today will be diagnosed as having hypertension when readings exceed 140/90. They will usually be prescribed a drug that the physician has long used. Another appointment will be made to see if the drug is working. This is all wrong!

For example, a 2002 meta-analysis of 61 prospective studies showed that blood pressure readings over 115/75 increase mortality from stroke and heart attack.4 This means a huge number of people today are being told their blood pressure is “normal,” when it may be dangerously high, i.e. over 115/75.

No one should think “normal” connotes safety. There’s nothing “normal” when an aging person suffers a stroke, heart attack, or kidney failure. You don’t want to be “normal” when it comes to the diseases of aging…you must seek “optimization.”

Secondly, most drugs don’t keep blood pressure low over a 24-hour time period.28 One might wrongly assume that lowering blood pressure most of the day is sufficient. The reality is that damage to blood vessels occurs whenever blood pressure is elevated.

By relying solely on doctor’s visits to measure blood pressure, patients taking their antihypertensive drug in the morning may show perfect readings at the doctor’s office that day, but their blood pressure could spike dangerously high in the evening and throughout the night. Anyone with a hint of hypertension should have an at-home monitoring device to ensure that whatever drug they are prescribed is working 24 hours a day and that their blood pressure readings do not significantly exceed 115/75.

I am often surprised when someone is prescribed an old-line antihypertensive drug (like a calcium channel blocker or beta blocker) when more effective medications with fewer side effects were long ago approved.

The good news is that a motivated patient today can work with their physician to achieve optimal blood pressure readings 24 hours a day, every day.

Is Lower Always Better In Terms Of Blood Pressure?
Is Lower Always Better In Terms Of Blood Pressure?

The concept that “lower is always better” can be a recipe for disaster in terms of blood pressure reduction, in particular for elderly, frail patients.

Often told is the story of the young intern fresh from medical school graduation starting ward duties. The intern aggressively treats his older patients to achieve rapid blood pressure reduction, yet is dismayed when their kidney function and cognitive abilities deteriorate rapidly.

Wiser, experienced physicians know that older patients with significant pre-existing vascular disease and other medical problems often require higher blood pressure than optimal levels to perfuse critical organs like the kidneys and brain. These patients require a higher perfusion pressure to allow blood to reach critical organs and tissues throughout the body.29

Some patients simply do not tolerate aggressive blood pressure reduction to a predefined value, and careful monitoring of kidney function with simple, cost-effective blood tests for BUN (blood urea nitrogen), creatinine, and electrolytes like potassium and sodium, as well as assessment of cognitive function, allows for appropriate titration of antihypertensive medication to a tolerated blood pressure best for these types of patients.

For those with systemic circulatory problems, blood pressure readings over 115/75 may be needed despite the increased damage this may inflict over the longer term. This adds to the critical importance of protecting one’s inner arterial lining (endothelium) throughout life.

Low-Cost Antihypertensive Drug With Side Benefits

In 1995,30 the first drug in the class of angiotensin II receptor blockers was approved.31,32 Two trade names for this class of drug are Cozaar® (losartan) and Hyzaar® (losartan plus a diuretic). This class of drug had many advantages over previously used drugs for hypertension, yet it never gained the widespread acceptance it deserved. One reason was an overwhelming amount of medical journal advertising for older-line antihypertensive drugs, and the aversion doctors have to “changing” their prescribing habits.

In 2002,33 the drug Benicar® was approved, and an advantage was that it required only once-a-day dosing.34 Losartan often failed to control blood pressure all day, but this information was not widely known. I recommended to members that they check their blood pressure 12 to 15 hours after taking losartan and many reported back that they needed to take it twice daily (and thanked me for possibly saving their lives).

Benicar® has recently and uncommonly been associated in some sensitive patients with chronic diarrhea, weight loss, and other digestive problems caused by shrinkage of the villi in their small intestine.35 It is the only blood pressure drug in this class linked to this condition. Fortunately, there is a superior antihypertensive drug called telmisartan, in the same drug class as Benicar®. A number of studies suggest that telmisartan provides multiple disease-preventing effects.

Telmisartan (trade name Micardis®) was first approved in 1998.36 In 2009, following the results of the ONTARGET trial, it was the first drug in its class that the FDA allowed a claim that it “reduces the risk of heart attack, stroke, or death from cardiovascular disease in patients at high cardiovascular risk who are unable to take ACE inhibitors.”37

What should pleasantly surprise members taking antihypertensive drugs now is that telmisartan has displayed longevity benefits above and beyond its ability to control blood pressure 24 hours a day—and it recently became available in generic form, making it more eligible for health insurance coverage.38,39

Insurance coverage is important for most people because even generic telmisartan can cost about $145 per month.

Who Should Keep Blood Pressure Levels Higher?
Who Should Keep Blood Pressure Levels Higher?

Elevated blood pressure at young ages inflicts damage to capillaries40 and small arteries41 that may result in stroke (ischemic and hemorrhagic), coronary artery disease, renal failure, and dementia later in life.42-53

In the March 2014 issue of this publication, we featured an article on a small artery disease (leukoaraiosis) in which tiny areas of the brain become oxygen deprived.54 The pathological result of this cerebral blood flow deficit is sharply higher risks of dementia,55 stroke, and cognitive impairment.56-68

Hypertension is a leading risk factor for leukoaraiosis,56,57,69 as is elevated homocysteine,70-74 endothelial dysfunction,75-77 inflammation,78 abnormal platelet aggregation,79 and other common vascular toxins.80-87

The problem with some elderly individuals who have had chronic high blood pressure is that they need to maintain a higher-than-optimal blood pressure to literally squeeze oxygenated blood through damaged capillaries in their brain and other organs. Until their endothelial damage can be reversed, these individuals need to maintain higher-than-optimal blood pressure readings to adequately perfuse certain organs.

This is regrettable since the short-term fix for diminished capillary blood flow, i.e. higher blood pressure levels, causes even more capillary and small artery damage. Validated ways to markedly reverse endothelial dysfunction are urgently needed.

Pomegranate is one of the better documented nutrients one can take today to help restore endothelial function.88-92

Longevity Benefits Of Telmisartan

Typical prescription drugs have unpleasant or lethal side effects that cause health-conscious people to want to avoid them wherever possible. There are exceptions, such as the antidiabetic drug metformin, which for most people provides far more benefits than risks.

A little known side benefit to the class of antihypertensive drugs known as angiotensin II receptor blockers is that they enhance insulin sensitivity, increase utilization of fat as energy, and improve mitochondrial function.5,7,13,38,39,100 Of all the drugs in this class, telmisartan stands out as superior for potential longevity enhancement.101-103

As humans age, mitochondrial dysfunction becomes a deadly factor in the development of obesity, insulin resistance, endothelial breakdown, and type II diabetes.104-109 Telmisartan helps correct these underlying mechanisms of aging and death (as do many of the nutrients Life Extension® members already take).

Telmisartan activates a regulator of cellular energy called PPAR-gamma coactivator 1 alpha (PGC-1a), which stimulates the burning of excess calories.110,111 This can be a crucial factor in weight management.

Studies indicate that telmisartan directly stimulates PPAR-gamma (peroxisome proliferator-activated receptor gamma), a key inducer of beneficial metabolic effects.112-114 PPAR-gamma activating properties have also been reported for other angiotensin II receptor blocker drugs, but telmisartan is at least 10 times more powerful.112

Telmisartan has been shown in preclinical models to reduce weight gain, increase total energy expenditure, and increase expression of key mitochondrial enzymes in skeletal muscle better than a more popular drug in this class (Diovan®).7,13,39,115-117

Atherosclerosis remains a leading killer of Americans.118 Telmisartan functions by multiple mechanisms to protect against arterial occlusion,119-121 including increasing beneficial endothelial nitric oxide.39,122,123

Lastly, telmisartan appears to promote biochemical, biological, and metabolic effects that some researchers have suggested could boost athletic performance.112

A Lung Cancer Controversy For Telmisartan… Or A Statistical Fluke?
A Lung Cancer Controversy For Telmisartan… Or A Statistical Fluke?

A highly controversial 2010 meta-analysis suggested that patients taking angiotensin-receptor blockers (ARBs) for hypertension, including telmisartan, experienced an increased risk for lung cancer, but no link to breast or prostate cancer.93

This finding is quite strange, and inconsistent with other research, since telmisartan has been shown to exert antitumor effects in human lung cancer (adeonocarcinoma) cells.94

In 2010, the manufacturer of telmisartan (Boehringer Ingelheim) conducted a rigorous assessment involving 50,000 patients treated with telmisartan, which including data from the ONTARGET, PROFESS, and TRANSCEND studies. The results showed no increased risk of cancer in the telmisartan treatment groups. “In preclinical trials, clinical trials, and day-to-day patient exposure with telmisartan, we have not seen any significant finding related to malignancies,” said Senior Vice President of Medicine, Dr. Klaus Dugi at Boehringer Ingelheim, in a company statement.95

Subsequent peer-reviewed publications have failed to show a cancer increase in patients using telmisartan.

For example, a subsequent 2011 analysis using data from 31 trials and 156,000 patients compared patients randomized to an ARB or “non-ARB treatment.” Overall incidence of cancer events in the ARB group were 1.82 per 100 patient-years, compared with 1.84 per 100 patient-years in the non-ARB group. This meta-analysis found no evidence of an increased risk of cancer-related death, breast cancer, lung cancer, or prostate cancer in patients receiving ARBs, and no difference between the two groups was found regardless of statistical method or comparator group (placebo or another drug).96

As another example, in 2013, published research from the US Department of Veterans Affairs of over 1,000,000 veterans did not show any evidence of risk for either lung cancer or prostate cancer.97,98 In fact, using a double-robust statistical regression, the researchers found a 26% reduced risk of lung cancer with ARB use. These researchers indicated: “In this large nationwide cohort of US Veterans, we found no evidence to support any concern of increased risk of lung cancer among new users of ARBs compared with non-users. Our findings were consistent with a protective effect of ARBs.”

At the present time, the weight of the evidence does not suggest ARBs, or telmisartan in particular, increase lung cancer risk.99

How To Take Telmisartan

Those with elevated blood pressure (levels exceeding 115/75 based on our findings) can be prescribed telmisartan in one-a-day doses of 20 mg, 40 mg, or 80 mg.

Even in generic form, the cost is currently around $145 for a 30-day supply of any dose. Drug companies for years have charged the same price for “any dose” of their drugs, which reveals that the active ingredient costs virtually nothing.

As more generic competitors emerge, prices may come down, but as we’ve exposed in past issues of this magazine, many generic prices remain stubbornly high.

Consumers of higher-priced branded antihypertensive drugs may save considerable dollars by switching to telmisartan, and derive potentially lifesaving side benefits. Some insurers virtually give away generic drugs, but charge patients a fortune for name brand versions.

Our Mission Is To Keep Our Members Alive!

We offer a number of dietary supplements that have been shown to lower blood pressure. If these supplements fail to keep blood readings consistently around 115/75, and other lifestyle modifications like weight loss are unsuccessful, we suggest that you ask your doctor to consider prescribing telmisartan.

We have no financial interest in telmisartan or other prescription drugs we have recommended for their ancillary disease-preventing benefits (such as metformin). Our interests lie purely in keeping our members alive and healthy for as long as possible.

If one needs to take an antihypertensive drug, it makes sense to take one that provides the best longevity side benefits, which telmisartan appears to do.

I am grateful to report that the cost of quality at-home blood pressure monitors keeps dropping. A new model has features that enable precise data about one’s blood pressure fluctuations to be stored and calculated over an extended time. You can read about this new at-home monitor on the next page.

For longer life,

For Longer Life

William Faloon


  1. Available at: Accessed October 27, 2014.
  2. Available at: October 27, 2014.
  3. Freitag MH, Vasan RS. What is normal blood pressure? Curr Opin Nephrol Hypertens. 2003 May;12(3):285-92.
  4. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R, 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 Dec 14;360(9349):1903-13.
  5. Shiota A, Shimabukuro M, Fukuda D, et al. Telmisartan ameliorates insulin sensitivity by activating the AMPK/SIRT1 pathway in skeletal muscle of obese db/db mice. Cardiovasc Diabetol. 2012 Nov 8;11:139.
  6. Sharma AM. Telmisartan: the ACE of ARBs? Hypertension. 2006 May;47(5):822-3.Epub 2006 Mar 27.
  7. Takeuchi K1, Yamamoto K, Ohishi M, et al. Telmisartan modulates mitochondrial function in vascular smooth muscle cells. Hypertens Res. 2013 May;36(5):433-9.
  8. Schlimmer N, Kratz M, Böhm M, Baumhäkel M. Telmisartan, ramipril and their combination improve endothelial function in different tissues in a murine model of cholesterol-induced atherosclerosis. Br J Pharmacol. 2011 Jun;163(4):804-14.
  9. Zankl AR, Ivandic B, Andrassy M, et al. Telmisartan improves absolute walking distance and endothelial function in patients with peripheral artery disease. Clin Res Cardiol. 2010 Dec;99(12):787-94.
  10. Hu ZP, Fang XL, Qian HY, Fang N, Wang BN, Wang Y. Telmisartan prevents angiotensin II-induced endothelial dysfunction in rabbit aorta via activating HGF/Met system and PPARγ pathway. Fundam Clin Pharmacol. 2014 Oct;28(5):501-11.
  11. Terashima M, Kaneda H, Nasu K, et al. Protective effect of telmisartan against endothelial dysfunction after coronary drug-eluting stent implantation in hypertensive patients. JACC Cardiovasc Interv. 2012 Feb;5(2):182-90.
  12. Takagi H, Umemoto T. A meta-analysis of randomized controlled trials of telmisartan for flow-mediated dilatation. Hypertens Res. 2014 Sep;37(9):845-51.
  13. He H, Yang D, Ma L, et al. Telmisartan prevents weight gain and obesity through activation of peroxisome proliferator-activated receptor-delta-dependent pathways. Hypertension. 2010 Apr;55(4):869-79.
  14. Sugimoto K, Qi NR, Kazdová L, Pravenec M, Ogihara T, Kurtz TW. Telmisartan but not valsartan increases caloric expenditure and protects against weight gain and hepatic steatosis. Hypertension. 2006 May;47(5):1003-9.
  15. Kotchen TA. Historical trends and milestones in hypertension research: a model of the process of translational research. Hypertension. 2011 58:522-538.
  16. Booth J. A short history of blood pressure measurement. Proc Royal Soc Med. 1977 70:793-9.
  17. Fisher JW. The diagnostic value of the sphygmomanometer in examinations for life insurance. JAMA. 1914; 63:1752-4.
  18. Effects of treatment on morbidity in hypertension. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg. JAMA. 1967 Dec 11;202(11):1028-34.
  19. Effects of treatment on morbidity in hypertension. II. Results in patients with diastolic blood pressure averaging 90 through 114 mm Hg. JAMA. 1970 Aug 17;213(7):1143-52.
  20. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. JAMA. 1991 Jun 26;265(24):3255-64.
  21. Staessen JA, Fagard R, Thijs L, et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. Lancet. 1997 Sep 13;350(9080):757-64.
  22. Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet. 1998 Jun 13;351(9118):1755-62.
  23. Kotchen TA. The search for strategies to control hypertension. Circulation. 2010 Sep 21;122(12):1141-3.
  24. Stamler J, Stamler R, Neaton JD. Blood pressure, systolic and diastolic, and cardiovascular risks. US population data. Arch Intern Med. 1993 Mar 8;153(5):598-615.
  25. Vasan RS, Larson MG, Leip EP, et al. Impact of high-normal blood pressure on the risk of cardiovascular disease. N Engl J Med. 2001 Nov 1;345(18):1291-7.
  26. Klag MJ, Whelton PK, Randall BL, et al. Blood pressure and end-stage renal disease in men. N Engl J Med. 1996 Jan 4;334(1):13-8.
  27. Whitworth JA. Progression of renal failure -- the role of hypertension. Ann Acad Med Singapore. 2005 Jan;34(1):8-15.
  28. Available at: Accessed December 19, 2014.
  29. Stocchetti N, Chieregato A, De Marchi M, Croci M, Benti R, Grimoldi N. High cerebral perfusion pressure improves low values of local brain tissue O2 tension (PtiO2) in focal lesions. Acta Neurochir Suppl. 1998;71:162-5.
  30. Ripley E, Hirsch A. Fifteen years of losartan: what have we learned about losartan that can benefit chronic kidney disease patients? Int J Nephrol Renovasc Dis. 2010;3:93-8.
  31. Aulakh GK, Sodhi RK, Singh M. An update on non-peptide angiotensin receptor antagonists and related RAAS modulators. Life Sci. 2007 Aug 2;81(8):615-39.
  32. Schaefer KL, Porter JA. Angiotensin II receptor antagonists: the prototype losartan. Ann Pharmacother. 1996 Jun;30(6):625-36.
  33. Goldenberg MM. Pharmaceutical approval update. P T. 2010 Apr;35(4):216-8.
  34. Smith DH. Strategies to meet lower blood pressure goals with a new standard in angiotensin II receptor blockade. Am J Hypertens. 2002 Oct;15(10 Pt 2):108S-14S.
  35. Tran TH, Li H. Olmesartan and drug-induced enteropathy. P T. 2014;39(1):47-50.
  36. Akhrass PR, McFarlane SI. Telmisartan and cardioprotection. Vasc Health Risk Manag. 2011;7:677-83.
  37. Yusuf S, Teo K, Anderson C,Pogue J, Dyal L, Copland I, Schumacher H, Dagenais G, Sleight P. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomized controlled trial. Lancet. 2008 Sep 27;372(9644):1174-83.
  38. Cassis P, Conti S, Remuzzi G, Benigni A. Angiotensin receptors as determinants of life span. Pflugers Arch. 2010 Jan;459(2):325-32.
  39. Scalera F, Martens-Lobenhoffer J, Bukowska A, Lendeckel U, Tager M, Bode-Boger SM. Effect of telmisartan on nitric oxide--asymmetrical dimethylarginine system: role of angiotensin II type 1 receptor gamma and peroxisome proliferator activated receptor gamma signaling during endothelial aging. Hypertension. Mar 2008;51(3):696-703.
  40. Cheng C, Daskalakis C, Falkner B. Alterations in capillary morphology are found in mild blood pressure elevation. J Hypertens. 2010 Nov;28(11):2258-66.
  41. Schiffrin EL, Hayoz D. How to assess vascular remodelling in small and medium-sized muscular arteries in humans. J Hypertens. 1997 Jun;15(6):571-84.
  42. Wilson BJ, Watson MS, Prescott GJ, Sunderland S, Campbell DM, Hannaford P, Smith WC. Hypertensive diseases of pregnancy and risk of hypertension and stroke in later life: results from cohort study. BMJ. 2003 Apr 19;326(7394):845.
  43. Jónsdóttir LS, Arngrímsson R, Geirsson RT, Sigvaldason H, Sigfússon N. Death rates from ischemic heart disease in women with a history of hypertension in pregnancy. Acta Obstet Gynecol Scand. 1995 Nov;74(10):772-6.
  44. Dandapani BK, Suzuki S, Kelley RE, Reyes-Iglesias Y, Duncan RC. Relation between blood pressure and outcome in intracerebral hemorrhage. Stroke. 1995 Jan;26(1):21-4.
  45. Arakawa S, Saku Y, Ibayashi S, Nagao T, Fujishima M. Blood pressure control and recurrence of hypertensive brain hemorrhage. Stroke. 1998 Sep;29(9):1806-9.
  46. Allen N, Berry JD, Ning H, Van Horn L, Dyer A, Lloyd-Jones DM. Impact of blood pressure and blood pressure change during middle age on the remaining lifetime risk for cardiovascular disease: the cardiovascular lifetime risk pooling project. Circulation. 2012 Jan 3;125(1):37-44.
  47. Allen NB, Siddique J, Wilkins JT, et al. Blood pressure trajectories in early adulthood and subclinical atherosclerosis in middle age. JAMA. 2014 Feb 5;311(5):490-7.
  48. Sundin PO, Udumyan R, Sjöström P, Montgomery S. Predictors in adolescence of ESRD in middle-aged men. Am J Kidney Dis. 2014 Nov;64(5):723-9.
  49. Männistö T, Mendola P, Vääräsmäki M, et al. Elevated blood pressure in pregnancy and subsequent chronic disease risk.Circulation . 2013 Feb 12;127(6):681-90.
  50. Ecder T, Schrier RW. Hypertension in autosomal-dominant polycystic kidney disease: early occurrence and unique aspects. J Am Soc Nephrol. 2001 Jan;12(1):194-200.
  51. Yaffe K, Vittinghoff E, Pletcher MJ, et al. Early adult to midlife cardiovascular risk factors and cognitive function. Circulation. 2014 Apr 15;129(15):1560-7.
  52. Gottesman RF, Schneider AL, Albert M, et al. Midlife hypertension and 20-year cognitive change: the atherosclerosis risk in communities neurocognitive study. JAMA Neurol. 2014 Oct 1;71(10):1218-27.
  53. Muller M, Sigurdsson S, Kjartansson O, et al. Age, gene/environment susceptibility-Reykjavik Study Investigators. Joint effect of mid- and late-life blood pressure on the brain: the AGES-Reykjavik study. Neurology. 2014 Jun 17;82(24):2187-95.
  54. Available at: Accessed October 29, 2014.
  55. Chutinet A, Rost NS. White matter disease as a biomarker for long-term cerebrovascular disease and dementia. Curr Treat Options Cardiovasc Med. 2014 Mar;16(3):292.
  56. Grueter BE, Schulz UG. Age-related cerebral white matter disease (leukoaraiosis): a review. Postgrad Med J. 2012 Feb;88(1036):79-87.
  57. Choi JH, Bae HJ, Cha JK. Leukoaraiosis on magnetic resonance imaging is related to long-term poor functional outcome after thrombolysis in acute ischemic stroke. J Korean Neurosurg Soc. 2011 Aug;50(2):75-80.
  58. Arsava EM, Bayrlee A, Vangel M, et al. Severity of leukoaraiosis determines clinical phenotype after brain infarction. Neurology. 2011 Jul 5;77(1):55-61.
  59. Inzitari D. Leukoaraiosis: an independent risk factor for stroke? Stroke. 2003 Aug;34(8):2067-71.
  60. Jeerakathil T, Wolf PA, Beiser A, et al. Stroke risk profile predicts white matter hyperintensity volume: the Framingham Study. Stroke. 2004 Aug;35(8):1857-61.
  61. Fu JH, Lu CZ, Hong Z, Dong Q, Luo Y, Wong KS. Extent of white matter lesions is related to acute subcortical infarcts and predicts further stroke risk in patients with first ever ischaemic stroke. J Neurol Neurosurg Psychiatry. 2005 Jun;76(6):793-6.
  62. Streifler JY, Eliasziw M, Benavente OR, et al. Prognostic importance of leukoaraiosis in patients with symptomatic internal carotid artery stenosis. Stroke. 2002 Jun;33(6):1651-5.
  63. Kuller LH, Longstreth WT Jr, Arnold AM, Bernick C, Bryan RN, Beauchamp NJ Jr. White matter hyperintensity on cranial magnetic resonance imaging: a predictor of stroke. Stroke. 2004 Aug;35(8):1821-5.
  64. Naka H, Nomura E, Wakabayashi S, et al. Frequency of asymptomatic microbleeds on T2*-weighted MR images of patients with recurrent stroke: association with combination of stroke subtypes and leukoaraiosis. AJNR Am J Neuroradiol. 2004 May;25(5):714-9.
  65. Neumann-Haefelin T, Hoelig S, Berkefeld J, et al. Leukoaraiosis is a risk factor for symptomatic intracerebral hemorrhage after thrombolysis for acute stroke. Stroke. 2006 Oct;37(10):2463-6.
  66. Macfarlane MD, Looi JC, Walterfang M, et al. Executive dysfunction correlates with caudate nucleus atrophy in patients with white matter changes on MRI: a subset of LADIS. Psychiatry Res. 2013 Oct 30;214(1):16-23.
  67. Schmidt R, Berghold A, Jokinen H, et al. White matter lesion progression in LADIS: frequency, clinical effects, and sample size calculations. Stroke. 2012 Oct;43(10):2643-7.
  68. Welker KM, De Jesus RO, Watson RE, Machulda MM, Jack CR. Altered functional MR imaging language activation in elderly individuals with cerebral leukoaraiosis. Radiology. 2012 Oct;265(1):222-32.
  69. Schwartz GL, Bailey KR, Mosley T, et al. Association of ambulatory blood pressure with ischemic brain injury. Hypertension. 2007 Jun;49(6):1228-34.
  70. Khan U, Crossley C, Kalra L, et al. Homocysteine and its relationship to stroke subtypes in a UK black population: the south London ethnicity and stroke study. Stroke. 2008 Nov;39(11):2943-9.
  71. Hassan A, Hunt BJ, O’Sullivan M, et al. Homocysteine is a risk factor for cerebral small vessel disease, acting via endothelial dysfunction. Brain . 2004 Jan;127(Pt 1):212-9.
  72. Censori B, Partziguian T, Manara O, Poloni M. Plasma homocysteine and severe white matter disease. Neurol Sci. 2007 Oct;28(5):259-63.
  73. Sachdev P, Parslow R, Salonikas C, et al. Homocysteine and the brain in midadult life: evidence for an increased risk of leukoaraiosis in men. Arch Neurol. 2004 Sep;61(9):1369-76.
  74. Naka H, Nomura E, Takahashi T, et al. Plasma total homocysteine levels are associated with advanced leukoaraiosis but not with asymptomatic microbleeds on T2*-weighted MRI in patients with stroke. Eur J Neurol. 2006 Mar;13(3):261-5.
  75. Calabro RS, Gervasi G, Baglieri A, Furnari A, Marino S, Bramanti P. Is high oral dose L-arginine intake effective in leukoaraiosis? Preliminary data, study protocol and expert’s opinion. Curr Aging Sci. 2013 Jul;6(2):170-7.
  76. Deplanque D, Lavallee PC, Labreuche J, et al. Cerebral and extracerebral vasoreactivity in symptomatic lacunar stroke patients: a case-control study. Int J Stroke. 2013 Aug;8(6):413-21.
  77. Szolnoki Z. Genetic variant-associated endothelial dysfunction behind small-vessel cerebral circulatory disorders: a new pathomechanism behind common cerebral phenotypes. Mini Rev Med Chem. 2007 May;7(5):527-30.
  78. Wright CB, Moon Y, Paik MC, et al. Inflammatory biomarkers of vascular risk as correlates of leukoariosis. Stroke. 2009 Nov;40(11):3466-71.
  79. Kang SJ, Park BJ, Shim JY, Lee HR, Hong JM, Lee YJ. Mean platelet volume (MPV) is associated with leukoaraiosis in the apparently healthy elderly. Arch Gerontol Geriatr. 2012 Mar-Apr;54(2):e118-21.
  80. Park JH, Ryoo S, Kim SJ, et al. Differential risk factors for lacunar stroke depending on the MRI (white and red) subtypes of microangiopathy. PLoS One. 2012 7(9):e44865.
  81. Putaala J, Kurkinen M, Tarvos V, Salonen O, Kaste M, Tatlisumak T. Silent brain infarcts and leukoaraiosis in young adults with first-ever ischemic stroke. Neurology. 2009 May 26;72(21):1823-9.
  82. Zeevi N, Pachter J, McCullough LD, Wolfson L, Kuchel GA. The blood-brain barrier: geriatric relevance of a critical brain-body interface. J Am Geriatr Soc. 2010 Sep;58(9):1749-57.
  83. Bokura H, Yamaguchi S, Iijima K, Nagai A, Oguro H. Metabolic syndrome is associated with silent ischemic brain lesions. Stroke. 2008 May;39(5):1607-9.
  84. Park K, Yasuda N, Toyonaga S, et al. Significant association between leukoaraiosis and metabolic syndrome in healthy subjects. Neurology. 2007 Sep 4;69(10):974-8.
  85. Seo SK, Jung I, Lee SM, et al. Relationship between leukoaraiosis and menopause in healthy middle-aged women. Fertil Steril. 2013 Aug;100(2):500-4.
  86. Szolnoki Z. Pathomechanism of leukoaraiosis: a molecular bridge between the genetic, biochemical, and clinical processes (a mitochondrial hypothesis). Neuromolecular Med. 2007 9(1):21-33.
  87. Pu Y, Liu L, Zou X, et al. Relationship between leukoaraiosis and cerebral large artery stenosis. Neurol Res. 2009 May;31(4):376-80.
  88. De Nigris F, Williams-Ignarro S, Botti C, Sica V, Ignarro LJ, Napoli C. Pomegranate juice reduces oxidized low-density lipoprotein downregulation of endothelial nitric oxide synthase in human coronary endothelial cells. Nitric Oxide. 2006 Nov;15(3):259-63.
  89. Aviram M, Rosenblat M, Gaitini D, et al. Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation. Clin Nutr. 2004 Jun;23(3):423-33.
  90. Sumner MD, Elliott-Eller M, Weidner G, et al. Effects of pomegranate juice consumption on myocardial perfusion in patients with coronary heart disease. Am J Cardiol. 2005 Sep 15;96(6):810-4.
  91. Ignarro LJ, Byrns RE, Sumi D, de Nigris F, Napoli C. Pomegranate juice protects nitric oxide against oxidative destruction and enhances the biological actions of nitric oxide. Nitric Oxide. 2006 Sep;15(2):93-102.
  92. De Nigris F, Williams-Ignarro S, Sica V, et al. Effects of a pomegranate fruit extract rich in punicalagin on oxidation-sensitive genes and eNOS activity at sites of perturbed shear stress and atherogenesis. Cardiovasc Res. 2007 Jan 15;73(2):414-23.
  93. Sipahi I, Debanne SM, Rowland DY, Simon DI, Fang JC. Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials. Lancet Oncol. 2010 Jul;11(7):627-36.
  94. Li J, Chen L, Yu P, Liu B, Zhu J, Yang Y. Telmisartan exerts antitumor effects by activating peroxisome proliferator-activated receptor-γ in human lung adenocarcinoma A549 cells. Molecules. 2014 Mar 5;19(3):2862-76.
  95. Available at: Accessed November 18, 2014.
  96. Available at: Accessed December 22, 2014.
  97. Rao GA, Mann JR, Shoaibi A, Pai SG, Bottai M, Sutton SS, Haddock KS, Bennett CL, Hebert JR. Angiotensin receptor blockers: are they related to lung cancer? J Hypertens. 2013 Aug;31(8):1669-75.
  98. Rao GA, Mann JR, Bottai M, et al. Angiotensin receptor blockers and risk of prostate cancer among United States veterans. J Clin Pharmacol. 2013 Jul;53(7):773-8.
  99. ARB Trialists Collaboration. Effects of telmisartan, irbesartan, valsartan, candesartan, and losartan on cancers in 15 trials enrolling 138,769 individuals. J Hypertens. 2011 Apr;29(4):623-35.
  100. Shiuchi T, Iwai M, Li HS, et al. Angiotensin II type-1 receptor blocker valsartan enhances insulin sensitivity in skeletal muscles of diabetic mice. Hypertension. 2004 May;43(5):1003-10.
  101. Lacourcière Y, Krzesinski JM, White WB, Davidai G, Schumacher H. Sustained antihypertensive activity of telmisartan compared with valsartan. Blood Press Monit. 2004 Aug;9(4):203-10.
  102. Littlejohn T, Mroczek W, Marbury T, VanderMaelen CP, Dubiel RF. A prospective, randomized, open-label trial comparing telmisartan 80 mg with valsartan 80 mg in patients with mild to moderate hypertension using ambulatory blood pressure monitoring. Can J Cardiol. 2000 Sep;16(9):1123-32.
  103. Lacourcière Y, Lenis J, Orchard R, et al. A comparison of the efficacies and duration of action of the angiotensin II receptor blockers telmisartan and amlodipine. Blood Press Monit. 1998 Oct;3(5):295-302.
  104. Patti ME, Butte AJ, Crunkhorn S, et al. Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: potential role of PGC1 and NRF1. Proc Natl Acad Sci USA. 2003 100:8466-71.
  105. Bach D, Pich S, Soriano FX, et al. Mitofusin-2 determines mitochondrial network architecture and mitochondrial metabolism. A novel regulatory mechanism altered in obesity. J Biol Chem. 2003 May 9; 278(19):17190-7.
  106. Coletta DK, Mandarino LJ. Mitochondrial dysfunction and insulin resistance from the outside in: extracellular matrix, the cytoskeleton, and mitochondria. Am J Physiol Endocrinol Metab. 2011 Nov;301(5):E749-55.
  107. Conley KE, Marcinek DJ, Villarin J. Mitochondrial dysfunction and age. Curr Opin Clin Nutr Metab Care. 2007 Nov;10(6):688-92.
  108. Lesnefsky EJ, Moghaddas S, Tandler B, Kerner J, Hoppel CL. Mitochondrial dysfunction in cardiac disease: ischemia—reperfusion, aging, and heart failure. J Mol Cell Cardiol. 2001 Jun;33(6):1065-89.
  109. Hernandez-Mijares A, Rocha M, Rovira-Llopis S, et al. Human leukocyte/endothelial cell interactions and mitochondrial dysfunction in type 2 diabetic patients and their association with silent myocardial ischemia. Diabetes Care. 2013 Jun;36(6):1695-702.
  110. Terashima M, Kaneda H, Nasu K, et al. Protective effect of telmisartan against endothelial dysfunction after coronary drug-eluting stent implantation in hypertensive patients. JACC Cardiovasc Interv. 2012 Feb;5(2):182-90.
  111. Amano Y, Yamaguchi T, Ohno K, et al. Structural basis for telmisartan-mediated partial activation of PPAR gamma. Hypertens Res. 2012 Jul;35(7):715-9.
  112. Benson SC, Pershadsingh HA, Ho CI, et al. Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPARgamma-modulating activity. Hypertension. 2004 May;43(5):993-1002.
  113. Schupp M, Janke J, Clasen R, Unger T, Kintscher U. Angiotensin type 1 receptor blockers induce peroxisome proliferator-activated receptor-gamma activity. Circulation. 2004 May 4;109(17):2054-7.
  114. Berger JP, Petro AE, Macnaul KL, et al. Distinct properties and advantages of a novel peroxisome proliferator-activated protein [gamma] selective modulator. Mol Endocrinol. 2003 Apr;17(4):662-76.
  115. Feng X1, Luo Z, Ma L, et al. Angiotensin II receptor blocker telmisartan enhances running endurance of skeletal muscle through activation of the PPAR-δ/AMPK pathway. J Cell Mol Med. 2011 Jul;15(7):1572-81.
  116. Sanchis-Gomar F1, Lippi G. Telmisartan as metabolic modulator: a new perspective in sports doping? J Strength Cond Res. 2012 Mar;26(3):608-10.
  117. Sugimoto K, Qi NR, Kazdová L, Pravenec M, Ogihara T, Kurtz TW. Telmisartan but not valsartan increases caloric expenditure and protects against weight gain and hepatic steatosis. Hypertension. 2006 May;47(5):1003-9.
  118. Verma DR, Brinton EA. Management of hypercholesterolemia for prevention of atherosclerotic cardiovascular disease: focus on the potential role of recombinant antiPCSK9 monoclonal antibodies. Rev Cardiovasc Med. 2014;15(2):86-101; quiz 101.
  119. Goyal SN, Bharti S, Bhatia J, Nag TC, Ray R, Arya DS. Telmisartan, a dual ARB/partial PPAR-γ agonist, protects myocardium from ischaemic reperfusion injury in experimental diabetes. Diabetes Obes Metab. 2011 Jun;13(6):533-41.
  120. Iwai M, Inaba S, Tomono Y, et al. Attenuation of focal brain ischemia by telmisartan, an angiotensin II type 1 receptor blocker, in atherosclerotic apolipoprotein E-deficient mice. Hypertens Res. 2008 Jan;31(1):161-8.
  121. Iwanami J, Mogi M, Tsukuda K, et al. Low dose of telmisartan prevents ischemic brain damage with peroxisome proliferator-activated receptor-gamma activation in diabetic mice. J Hypertens. 2010 Aug;28(8):1730-7.
  122. Yuen CY, Wong WT, Tian XY, et al. Telmisartan inhibits vasoconstriction via PPARγ-dependent expression and activation of endothelial nitric oxide synthase. Cardiovasc Res. 2011 Apr 1;90(1):122-9.
  123. Myojo M, Nagata D, Fujita D, et al. Telmisartan activates endothelial nitric oxide synthase via Ser1177 phosphorylation in vascular endothelial cells. PLoS One. 2014 May 14;9(5):e96948.