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Recent Longevity News for the seven days ending 10/10/12.  You should consult your doctor if you are taking any medications.

Oral Bisphosphonates and the Risk of Esophageal Cancer - Medscape, 10/9/12 - "Seven studies, with 19 700 oesophageal cancer cases, met our inclusion criteria. We found a positive relationship between exposure to bisphosphonates and oesophageal cancer, with an odds ratio (OR) of 1.74 with a 95% CI of 1.19–2.55. Heterogeneity was observed (I2 = 85%, P < 0.001). Publication bias was not present. An increased risk of oesophageal cancer was also found in the group exposed to bisphosphonates for a longer period of time, compared with the group who experienced a shorter period of exposure (OR 2.32; 95% CI 1.57–3.43 vs. OR 1.35; 95% CI 0.77–2.39). An increased risk was associated with exposure to Etidronate (OR 1.58; 95% CI 1.12–2.24), but not to Aledronate"

Are we throwing away 'expired' medications too soon? - CNN.com, 10/8/12 - "A new laboratory analysis of eight prescription drugs that expired between 28 and 40 years ago has found that most have remained just as potent as they were on the day they were made ... Overall, the eight drugs included 14 different active ingredients, including aspirin, codeine and hydrocodone"

Tomatoes May Lower Your Risk for Stroke - WebMD, 10/8/12 - "Men who had the highest levels of lycopene in their blood were 55% less likely to have a stroke, compared with men who had the lowest levels of the antioxidant in their blood ... The new study included slightly more than 1,000 men from Finland aged 46 to 65. Researchers measured the level of lycopene in their blood when the study began and followed the men for about 12 years" - See Jarrow Lyco-Sorb (contains Lyco-O-Mato) at Amazon.com.

Prenatal mercury exposure may be linked to risk of ADHD-related behaviors; Fish consumption may be linked to lower risk - Science Daily, 10/8/12 - "Nonoccupational methylmercury exposure comes primarily from eating fish, and the U.S. Environmental Protection Agency and the U.S. Food and Drug Administration have recommended pregnant women limit their total fish intake to no more than two, six-ounce servings per week. However, fish is also a source of nutrients, such as omega-3 fatty acids, which have been shown to benefit brain development, potentially confounding mercury-related risk estimates ... analyzed data from the New Bedford birth cohort, a group of infants born between 1993 and 1998, to investigate the association of peripartum maternal hair mercury levels (n=421) and prenatal fish intake (n=515) with ADHD-related behaviors at age 8 years ... In this population-based prospective cohort study, hair mercury levels were consistently associated with ADHD-related behaviors, including inattention and hyperactivity/impulsivity. We also found that higher prenatal fish consumption was protective for these behaviors"

BPA linked to thyroid hormone changes in pregnant women, newborns - Science Daily, 10/3/12 - "The researchers found that for each doubling of BPA levels, there was an associated decrease of 0.13 micrograms per deciliter of total thyroxine (T4) in mothers during pregnancy, which suggests a hypothyroid effect. For newborn boys, each doubling of BPA levels linked to a 9.9 percent decrease in thyroid stimulating hormone (TSH), indicating a hyperthyroid effect ... studies suggest that small changes in thyroid level, even if they're within normal limits, may still have a cognitive effect"

New study sheds light on cancer-protective properties of milk - Science Daily, 10/3/12 - "lactoferricin4-14 (Lfcin4-14), a milk protein with known health effects, significantly reduces the growth rate of colon cancer cells over time by prolonging the period of the cell cycle before chromosomes are replicated. In a new study, investigators report that treatment with Lfcin4-14 reduced DNA damage in colon cancer cells exposed to ultraviolet (UV) light ... Our data suggest that the effects of Lfcin4-14 in prolonging the cell cycle may contribute to the cancer preventive effect of milk"

Beta-blocker use not associated with lower risk of cardiovascular events - Science Daily, 10/2/12 - "The researchers found that in the prior MI group, the event rates were not significantly different among those with beta-blocker use (489 [16.93 percent]) vs. those without beta-blocker use (532 [18.60 percent]) for the primary outcome, or the secondary outcome (30.96 percent vs. 33.12 percent, respectively). In the CAD without MI cohort, the event rates were not different in those with beta-blocker use (391 [12.94 percent]) vs. those without p-blocker use (405 [13.55 percent]) for the primary outcome, for cardiovascular death, for stroke, and for MI. The event rates were higher in those with beta-blocker use (1,101 [30.59 percent] vs. those without beta-blocker use (1,002 [27.84 percent]) for the secondary outcome and for hospitalization in the propensity score-matched model ... In the risk factors alone group, the event rates were higher in those with beta-blocker use (467 [14.22 percent] vs. those without beta-blocker use (403 [12.11 percent]) for the primary outcome, for the secondary outcome (870 [22.01 percent] vs. 797 [20.17 percent], respectively) but not for MI or stroke. In the propensity score-matched model, there were similar event rates for cardiovascular death and for hospitalization" - Note:  Plus beta-blockers increase the chances of diabetes and their side effect profile is intolerable for many.  It seems like the only reason they are prescribed is their low cost or for dual drug hypertension therapy.  See my telmisartan as first line therapy page.  That said, I'm not a doctor.

  • Thiazide and Beta-Blocker Use Linked With Increased Risk for Incident Diabetes - Medscape, 5/8/07 - "the relative risk of incident diabetes for those taking a thiazide diuretic compared with those not taking a thiazide was 1.20 (95% confidence interval [CI], 1.08 - 1.33) in older women; 1.45 (95% CI, 1.17 - 1.79) in younger women; and 1.36 (95% CI, 1.17 - 1.58) in men ... the risk for incident diabetes was also increased in patients taking beta-blockers relative to those who were not: 1.32 (95% CI, 1.20 - 1.46) in older women and 1.20 (95% CI, 1.05 -1.38) in men. In younger women, a category of "other antihypertensives" was used that included beta-blockers, and their use was associated with an increased risk for 1.46"
  • Thiazide and Beta-Blocker Use Linked With Increased Risk for Incident Diabetes - Medscape, 5/8/06 - "The multivariate risk ratios of developing diabetes associated with taking beta-blocker medications were 1.25 and 1.21 in the NHS I and HPFS, respectively"
  • Strategies to Prevent Type 2 Diabetes - Medscape, 8/8/05 - "Valsartan reduced the incidence of new-onset diabetes by 23% ... Traditional beta-blockers worsen insulin sensitivity and increase the risk of developing new diabetes ... Some of the most widely used anti-hypertensives, particularly the traditional beta blockers such as propranolol, timolol, metoprolol and atenolol, and diuretics such as hydrochlorothiazide and chlorthalidone (in high doses), worsen insulin resistance and increase the risk of developing type 2 diabetes"
  • Antihypertensive persistence and drug class - Can J Cardiol. 2002 Jun;18(6):649-56 - "Angiotensin II antagonists had the highest persistence followed by angiotensin-converting enzyme inhibitors, calcium channel blockers, beta-blockers and diuretics" - Note: It doesn't prove that they have the most side effects but was was the reason people weren't taking them?  It wasn't highest persistence were the highest cost.

Low vitamin D levels linked to more severe multiple sclerosis symptoms - Science Daily, 10/2/12 - "For the study, Mowry and her colleagues used data from a five-year study of 469 people with MS. Each year, beginning in 2004, researchers drew blood from, and performed MRIs on, the brains of study participants, looking for both new lesions and active spots of disease, which lit up when a contrast dye was used. The investigators found that each 10-nanograms-per-milliliter increase in vitamin D levels was associated with a 15 percent lower risk of new lesions and a 32 percent lower risk of spots of active disease, which require treatment with medication to reduce likelihood of permanent nerve damage. Higher vitamin D levels were also associated with lower subsequent disability" - See vitamin D at Amazon.com.

Low levels of vitamin D are associated with mortality in older adults - Science Daily, 10/2/12 - "We observed vitamin D insufficiency (defined as blood levels <20 ng/ml), in one third of our study participants. This was associated with nearly a 50 percent increase in the mortality rate in older adults" - See vitamin D at Amazon.com.

Abstracts from this week's Doctor's Guide Nutrition/Dietetics plus abstracts from my RSS feeds (Click here for the journals, the PubMed ones at the top):

Metabolic Syndrome: A Potential and Independent Risk Factor for Erectile Dysfunction in the Chinese Male Population - Urology. 2012 Oct 4 - "our results showed that subjects with MetS had a significantly greater risk of ED (OR 1.34, 95% CI 1.04-1.72; P = .02), especially in middle-age (40-59 years) men (OR 2.43, 95% CI 1.71-3.47; P <.001). Of the MetS components, abnormal fasting blood glucose was the most significantly independent factor of MetS for ED (OR 1.31, 95% CI 1.11-1.55; P = .002)"

Effects of Serum n-3 to n-6 Polyunsaturated Fatty Acids Ratios on Coronary Atherosclerosis in Statin-Treated Patients With Coronary Artery Disease - Am J Cardiol. 2012 Oct 2 - "A low ratio of n-3 to n-6 polyunsaturated fatty acids has been associated with cardiovascular events ... Coronary atherosclerosis in nonculprit lesions in the percutaneous coronary intervention vessel was evaluated using virtual histology intravascular ultrasound in 101 patients at the time of percutaneous coronary intervention and 8 months after statin therapy ... decreases in serum n-3 to n-6 polyunsaturated fatty acid ratios are associated with progression in coronary atherosclerosis evaluated using virtual histology intravascular ultrasound in statin-treated patients with coronary artery disease" - See Mega Twin EPA at Amazon.com and Jarrow Max DHA at Amazon.com.

Approximate percent fatty acid composition

  Saturated Fat Omega-6 Omega-3 ** Omega-9
Canola oil 8% 20% 10% 62%
Sunola oil 10% 6% 0% 84%
Safflower oil 9% 77% 0% 14%
Sunflower oil 11% 63% trace 26%
Olive oil 14% 10% trace 76%
Corn oil 14% 52% 2% 32%
Soyabean oil 15% 54% 8% 23%
Peanut oil 19% 34% 2% 45%
Cottonseed oil 27% 55% 0% 18%
Palm oil 51% 10% trace 39%
Coconut oil 91% 2% 0% 7%
Tallow oil 50% 2% 1% 47%
Butterfat 64% 2% 1% 33%

** The omega-3 in vegetable oils is in the form of alpha linolenic acid (no EPA, DHA or DPA).

Dietary and Supplemental Folate and the Risk of Left- and Right-Sided Colorectal Cancer - Nutr Cancer. 2012 Oct 4 - "Epidemiological evidence suggests that folate may lower the risk of colorectal cancer (CRC) although studies have been inconsistent and some have indicated differences in the effects of naturally occurring dietary folate and the synthetic form of this vitamin, folic acid. Most studies to date have considered CRC as a single disease; however, cancers that develop on the left and right sides of the colorectum display important phenotypic differences, suggesting they may also have different risk factors. A population-based case-control study was conducted in Western Australia to examine the relationship between intake of both natural dietary folate and supplements containing folic acid and the risk of left- and right-sided CRC ... There was no association between natural dietary folate intake and risk of either left-or right-sided CRC. Supplement use similarly had no significant effect on right-sided CRC. However, long-term supplement users (4+ yr) were at lower risk of left-sided CRC than those who had not taken supplements (OR = 0.65, 95% CI, 0.50-0.86) and there was a significant trend in risk reduction as duration of use increased" - See folic acid products at Amazon.com.

Dietary phylloquinone intake and risk of type 2 diabetes in elderly subjects at high risk of cardiovascular disease - Am J Clin Nutr. 2012 Oct 3 - "Limited evidence from human and animal studies has suggested that vitamin K has a potentially beneficial role in glucose metabolism and insulin resistance ... Cross-sectional associations were tested in 1925 men and women in the Prevention with the Mediterranean Diet trial ... Dietary intake was collected during each annual visit by using a food-frequency questionnaire, and phylloquinone intake was estimated by using the USDA database ... Dietary phylloquinone at baseline was significantly lower in subjects who developed type 2 diabetes during the study. After adjustment for potential confounders, risk of incident diabetes was 17% lower for each additional intake of 100 μg phylloquinone/d. Moreover, subjects who increased their dietary intake of vitamin K during the follow-up had a 51% reduced risk of incident diabetes compared with subjects who decreased or did not change the amount of phylloquinone intake" - See vitamin K at Amazon.com.

The effect of coffee consumption on blood pressure and the development of hypertension: a systematic review and meta-analysis - J Hypertens. 2012 Oct 1 - "Ovid, MEDLINE (from 1948), EMBASE (from 1988), and all of Web of Science and Scopus ... Low-quality evidence did not show any statistically significant effect of coffee consumption on BP or the risk of hypertension. Given the quality of the currently available evidence, no recommendation can be made for or against coffee consumption as it relates to BP and hypertension"

Losartan improves erectile dysfunction in diabetic patients: a clinical trial - Int J Impot Res. 2012 Aug 30 - "Erectile function was assessed by International Index of Erectile Function (IIEF-5) questionnaire, the percentage of positive responses to sexual encounter profile questions 2 (SEP2), 3 (SEP3) and the global assessment question (GAQ). Losartan or tadalafil or losartan plus tadalafil significantly improved the mean IIEF-5 scores, the percentage of successful penetrations (SEP2), the successful intercourse completions (SEP3) and GAQ (P<0.05). The combination of losartan and tadalafil is more effective than the single-use of losartan or tadalafil (P<0.05). The patients with moderate and mild ED had better response rates to losartan than patients with severe ED" - Note:  It seems like the benefit would extend to the entire ARB class of anti-hypertensives but I haven't seen studies on it.

Moderate-Intensity Physical Activity Ameliorates the Breast Cancer Risk in Diabetic Women - Diabetes Care. 2012 Oct 1 - "A population-based case-control study was conducted using 1,000 incident case subjects and 1,074 control subjects ... The association between diabetes and BC risk decreased with increasing tertiles of moderate-intensity physical activity (odds ratio [OR] = 4.9 [95% CI 2.3-10.8]; 3.0 [1.3-6.9]; and 1.0 [0.1-9.2] respectively, for each tertile) (test for interaction = 0.04). Compared with the women in the lowest tertiles, increased risk was observed in those premenopausal women with the highest serum C-peptide, IGF-1, and IGF-1 binding protein 3 levels"

Fish consumption and risk of stroke and its subtypes: accumulative evidence from a meta-analysis of prospective cohort studies - Eur J Clin Nutr. 2012 Oct 3 - "A database was derived from 16 eligible studies (19 cohorts), including 402 127 individuals (10 568 incident cases) with an average 12.8 years of follow-up ... Accumulated evidence generated from this meta-analysis suggests that fish intake may have a protective effect against the risk of stroke, particularly ischemic stroke" - See Mega Twin EPA at Amazon.com and Jarrow Max DHA at Amazon.com.

Magnesium intake and risk of colorectal cancer: a meta-analysis of prospective studies - Eur J Clin Nutr. 2012 Oct 3 - "We performed a literature search on PubMed database through July 2012 to identify prospective studies of magnesium intake in relation to CRC risk ... On the basis of the findings of this meta-analysis, a higher magnesium intake seems to be associated with a modest reduction in the risk of CRC, in particular, colon cancer" - See magnesium supplements at Amazon.com.

The relationship of breakfast skipping and type of breakfast consumed with overweight/obesity, abdominal obesity, other cardiometabolic risk factors and the metabolic syndrome in young adults. The National Health and Nutrition Examination Survey (NHANES): 1999-2006 - Public Health Nutr. 2012 Oct 3:1-10 - "metabolic syndrome (MetS) ... Three breakfast groups were identified, breakfast skippers (BS), ready-to-eat-cereal (RTEC) consumers and other breakfast (OB) consumers, using a 24 h dietary recall ... Relative to the BS, the RTEC consumers were 31%, 39%, 37%, 28%, 23%, 40 % and 4 % less likely to be overweight/obese or have abdominal obesity, elevated blood pressure, elevated serum total cholesterol, elevated serum LDL-cholesterol, reduced serum HDL-cholesterol or elevated serum insulin, respectively. Relative to the OB consumers, the BS were 1.24, 1.26 and 1.44 times more likely to have elevated serum total cholesterol, elevated serum LDL-cholesterol or reduced serum HDL-cholesterol, respectively. Relative to the OB consumers, the RTEC consumers were 22%, 31% and 24% less likely to be overweight/obese or have abdominal obesity or elevated blood pressure, respectively. No difference was seen in the prevalence of the MetS by breakfast skipping or type of breakfast consumed"

Neat Tech Stuff / "How To's":

Health Focus (Combining ACEI's and ARBs, Pros and Cons):

Arguments for/against combining ARBs and ACE inhibitors:

  • Are ACE Inhibitor/ARB Combinations Beneficial? - Medscape, 5/16/12 - "several trials comparing ACE inhibitor monotherapy vs combined treatment with an ARB used suboptimal doses of ACE inhibitors, were relatively short in duration, and had small sample sizes. Combination therapy may have a benefit in reducing proteinuria in patients with hypertensive nephropathy. Whether the long-term BP effects of ACE inhibitors and ARBs are additive or synergistic is still not completely confirmed. Nonetheless, the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) study demonstrated that reductions in BP, as seen with combination ACE inhibitor and ARB treatment, does not necessarily correlate to improved morbidity and mortality, even in high-risk patients"
  • Telmisartan, ramipril and their combination improve endothelial function in different tissues in a murine model of cholesterol-induced atherosclerosis - Br J Pharmacol. 2011 Feb 16 - "Erectile dysfunction correlates with cardiovascular disease and its common risk factors due to the development of endothelial dysfunction. Positive effects on endothelial and erectile function have been described for substances inhibiting the renin-angiotensin-system ... Wildtype (WT, C57/B6) and ApoE(-/-) mice were treated with a cholesterol-rich diet for 8 weeks. ApoE(-/-) mice were supplemented with either telmisartan (20mg/kg/day), ramipril (2.5mg/kg/day) or the combination thereof. Key results: Systolic blood pressure significantly decreased in treatment groups (p < 0.001), with significantly smaller reduction under ramipril monotherapy (p < 0.05). Endothelial function (assessed by pharmacological stimulation of aortic rings and CC in organ bath chambers) was impaired in ApoE(-/-) mice compared to WT animals, which was improved by all three treatments to a comparable extent (p < 0.05). Atherosclerotic lesion size in the ascending aorta and aortic sinus (p < 0.001), the amount of lipid peroxides in cavernosal and aortic tissue (p < 0.05) and free radical load (DHE-stain) (p < 0.05) were enhanced in untreated ApoE(-/-) mice in comparison to WT animals and were significantly reduced by either treatment. In penile tissue, expression of eNOS could be restored by RAAS-blockade. Conclusions and implications: Telmisartan and ramipril significantly improved endothelial function of aortic and cavernosal tissues in ApoE(-/-) via reduction of oxidative stress. Combination of both agents does not enhance beneficial effects significantly"
  • Effects of telmisartan added to Angiotensin-converting enzyme inhibitors on mortality and morbidity in hemodialysis patients with chronic heart failure a double-blind, placebo-controlled trial - J Am Coll Cardiol. 2010 Nov 16;56(21):1701-8 - "In hemodialysis patients, CHF is responsible for a high mortality rate ... At 3 years, telmisartan significantly reduced all-cause mortality (35.1% vs. 54.4%; p < 0.001), cardiovascular death (30.3% vs. 43.7%; p < 0.001), and hospital admission for CHF (33.9% vs. 55.1%; p < 0.0001). With Cox proportional hazards analysis, telmisartan was an independent determinant of all-cause mortality (hazard ratio [HR]: 0.51; 95% confidence interval [CI]: 0.32 to 0.82; p < 0.01), cardiovascular mortality (HR: 0.42; 95% CI: 0.38 to 0.61; p < 0.0001), and hospital stay for deterioration of heart failure (HR: 0.38; 95% CI: 0.19 to 0.51; p < 0.0001). Adverse effects, mainly hypotension, occurred in 16.3% of the telmisartan group versus 10.7% in the placebo group" - Note:  It makes me wonder if similar effects on mortality might be seen in people without kidney disease.
  • ARB Plus ACE Not for Heart Failure - Medscape, 9/10/09
  • Combining ACE Inhibitors With Angiotensin Receptor Blockers May Not Be Optimal for Treating Hypertension - Doctor's Guide, 5/11/09
  • Beneficial Effects of Combination Therapy with Angiotensin II Receptor Blocker and Angiotensin-Converting Enzyme Inhibitor on Vascular Endothelial Function - Hypertens Res. 2008 Aug;31(8):1603-10 - "these results suggest that the angiotensin I-converting enzyme inhibitor perindopril is superior to the calcium channel blocker amlodipine for reducing vascular endothelial dysfunction when co-administered with angiotensin receptor blockers in patients with essential hypertension"
  • Use of Combination ACE Inhibitors and ARB Therapy in Patients With CKD - Medscape, 9/29/08
  • Effects of Angiotensin Converting Enzyme Inhibitor and Angiotensin II Receptor Antagonist Combination on Nitric Oxide Bioavailability and Atherosclerotic Change in Watanabe Heritable Hyperlipidemic Rabbits - Hypertens Res. 2008 Mar;31(3):575-84 - "1) vehicle (control), 2) the ACEI enalapril (E: 3 mg/kg/day), 3) the ARB losartan (L: 30 mg/kg/day) and 4) enalapril (1.5 mg/kg/day) + losartan (15 mg/kg/day) (E+L). Intra-aortic infusion of ACh produced an increase in plasma NO concentration, which was significantly greater with all the drug treatments than with the control. E increased ACh-induced NO significantly more than L (by 6.9 nmol/L, and 4.7 nmol/L, respectively). E+L increased ACh-induced NO by 9.5 nmol/L, significantly more than either E or L ... the combined treatment with an ACEI and an ARB may have additive protective effects on endothelial function as well as atherosclerotic change"
  • Angiotensin-Converting Enzyme Inhibitors, Angiotensin Receptor Blockers, or Both for Patients With Proteinuria? A Best Evidence Review - Medscape, 5/20/08 - "Most significantly, the addition of ACEIs to ARBs reduced proteinuria to a greater degree than ARBs alone (ratio of means 0.76 at 1 to 4 months and 0.75 at 5 to 12 months). Combination therapy was also superior to treatment with ACEIs alone ... The 2 important conclusions that can be drawn from this meta-analysis are that ARBs are not superior to ACEIs in improving proteinuria, and that the combination of these 2 treatments appears superior in this outcome compared with either treatment alone ... Two of the biggest safety concerns regarding the combination therapy include the risks for hyperkalemia and acute worsening of renal function. A review of the literature, however, suggests that these risks may not be significantly worse with combination treatment vs monotherapy"
  • ACE Inhibitors Plus ARBs Reduce Proteinuria But Increase Kidney Damage - Doctor's Guide, 8/15/08 - "in people at high vascular risk, telmisartan's effects on major renal outcomes are similar to [those of] ramipril. Although combination therapy reduces proteinuria to a greater extent than monotherapy, overall it worsens major renal outcomes"
  • Telmisartan, Ramipril, or Both in Patients at High Risk for Vascular Events - N Engl J Med. 2008 Mar 31 - "Telmisartan was equivalent to ramipril in patients with vascular disease or high-risk diabetes and was associated with less angioedema. The combination of the two drugs was associated with more adverse events without an increase in benefit" - Yeah but if you have to go with two drugs it sure seems like it's the least of all the evils regarding side effects.
  • ACE Inhibitors May Protect Diabetics From Cancer, Peptic Ulcer - Medscape, 12/19/08 - "There was a significant association between ACE inhibitor use and the risk for cancer, with an adjusted odds ratio of 0.59 ... The rate of cancer among users of ACE inhibitors was 10% vs 15% for nonusers ... There was also a significant association between ACE inhibitor use and peptic ulcer disease, with an odds ratio of 0.68 ... The rate of peptic ulcer disease among ACE inhibitor users was 12% vs 16% among nonusers"
  • Establishing A New Option for Target-organ Protection: Rationale for ARB Plus ACE Inhibitor Combination Therapy - Am J Hypertens. 2008 Jan 24 - "Combination therapy targeting RAS activation may reduce target-organ damage and provide superior blood pressure (BP) control; combining angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) represents one possible approach"
  • Rationale for double renin-angiotensin-aldosterone system blockade - Am J Cardiol. 2007 Aug 6;100(3A):25J-31J - "The clinical benefits of both angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) extend beyond blood pressure reduction to encompass tissue-protective effects in target organs, such as the heart, vasculature, and kidneys, that underlie the reductions in cardiovascular mortality and morbidity seen in large outcome trials. However, these effects are achieved by different mechanisms. ACE inhibitors reduce circulating and tissue angiotensin II levels and potentiate the beneficial effects of bradykinin, including generation of nitric oxide (NO). By contrast, the protective effects of ARBs are owing to the blockade of the angiotensin II type 1 (AT(1)) receptors and possibly also to the stimulation of angiotensin II type 2 (AT(2)) receptors, again resulting in NO release. In addition, some ARBs, such as telmisartan, are selective activators of peroxisome proliferator-activated receptor-gamma (PPAR-gamma), thereby increasing insulin sensitivity. In contrast to other PPAR-gamma ligands, such as the thiazolidinediones, activation of this receptor by telmisartan does not result in weight gain. The complementary mechanisms of action of ACE inhibitors and ARBs create a rationale for combination therapy in high-risk patients"
  • New opportunities in cardiovascular patient management: a survey of clinical data on the combination of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers - Am J Cardiol. 2007 Aug 6;100(3A):45J-52J - "Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) differ in their actions on the renin-angiotensin-aldosterone system (RAAS). ACE inhibitors prevent the formation of angiotensin II, although angiotensin II may still be generated by alternative pathways. However, ACE inhibitors interrupt bradykinin breakdown, which in turn potentially enhances nitric oxide and prostacyclin mechanisms. In contrast, ARBs selectively prevent the binding of angiotensin II to the angiotensin type 1 (AT(1)) receptor while leaving the potentially beneficial effects of the AT(2) receptor unaffected. The supposition is that dual blockade of the RAAS effectively overcomes the harmful effects of angiotensin II mediated by the AT(1) receptor while offering the additional effects of the ACE inhibitor"
  • Do we use an ACE, an ARB, or both? What clinical trials tell us - Patient Care, 4/1/05 - "Combining ACEs and ARBs can improve outcomes, particularly for patients with heart failure and those who have hypertension with diabetes"
  • Impact of Telmisartan Versus Ramipril on Renal Endothelial Function in Patients with Hypertension and Type 2 Diabetes - Diabetes Care. 2007 Mar 2 - "In patients with type 2 diabetes telmisartan and ramipril both increased NO activity of the renal endothelium significantly that in turn may support the preservation of cardiovascular and renal function"
  • Addition of an angiotensin receptor blocker to full-dose ACE-inhibition: controversial or common sense? - Eur Heart J. 2005 Nov;26(22):2361-7 - "combination of a full-dose ACE-inhibitor and an ARB can be a rational choice in selected patients" - [full article]
  • Combination ACE inhibitor and angiotensin receptor blocker therapy - future considerations - J Clin Hypertens (Greenwich). 2007 Jan;9(1):78-86. - "The individual gains seen with each of these drug classes have led to speculation that their combination might offer additive if not synergistic outcome benefits. The foundation of this hypothesis, although biologically possible, has thus far not been sufficiently well proven to support the everyday use of these 2 drug classes in combination. Additional outcomes trials, which are currently proceeding to their conclusion, may provide the necessary proof to support an expanded use of these 2 drug classes in combination"
  • Do ACE inhibitors and ARBs mix well? Analysis urges caution - theheart.org, 10/10/07 - "patients receiving both an ACE inhibitor and an ARB were more likely not to comply with therapy due to side effects, which included hypotension, cough, angioedema, worsening renal function as defined by a change in serum creatinine >0.5 mg/dL, hyperkalemia as defined by serum potassium level changes >5.5 mEq/L, and symptomatic hypotension"
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