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Recent Longevity News for the seven days ending 12/7/11.  You should consult your doctor if you are taking any medications.

Low Vitamin D May Raise Diabetes Risk in Kids - WebMD, 12/5/11 - "The study included more than 400 obese kids and teens between the ages of 6 and 16, and 87 normal-weight children and teens ... Obese children were more than three times more likely than non-obese children to be vitamin D deficient, and both obesity and low vitamin D levels were associated with higher degrees of insulin resistance ... Obese children were also more likely than non-obese children to skip breakfast and drink more soda and juice, suggesting that these lifestyle factors may contribute to lower vitamin D levels ... current evidence suggests that vitamin D may help increase insulin production to help compensate for insulin resistance" - See vitamin D at Amazon.com.

Young women may reduce heart disease risk eating fish with omega 3 fatty acids, study finds - Science Daily, 12/5/11 - "In the first population-based study in women of childbearing age, those who rarely or never ate fish had 50 percent more cardiovascular problems over eight years than those who ate fish regularly. Compared to women who ate fish high in omega-3 weekly, the risk was 90 percent higher for those who rarely or never ate fish ... Fish oil contains long chain omega-3 polyunsaturated fatty acids, which are believed to protect against heart and vascular disease. Few women in the study took fish oil supplements, so these were excluded from the analyses and the results were based on the dietary intake of omega-3 fatty acids, not intake from supplements" - See Mega Twin EPA at Amazon.com and Jarrow Max DHA at Amazon.com.

MRI Highly Accurate in Guiding Prostate Biopsy - Medscape, 12/5/11 - "In the post-prostate-specific antigen era, the diagnosis of prostate cancer is made using the 10-12 core transrectal US-guided biopsy procedure. However, this initial biopsy procedure can have a miss rate of 71% ... This study evaluated whether multiparametric MRI provides a diagnostic advantage over the standard T2W MRI in this challenging clinical situation. Although combination of all 4 MRI techniques provided a perfect detection rate in this group of patients, excluding 1H-MRS from the combination was associated with a miss rate of only 6%"

Eating Fish Provides Immediate CVD Benefits for Young Women - Medscape, 12/5/11 - "The first large prospective study to examine fish consumption among young women has shown that even moderate intake of fish, just once a week, can be cardioprotective ... women who never or very rarely ate fish had an almost doubling of cardiovascular disease risk compared with those who ate fish every week ... in a subset of women who consistently reported the same frequency of fish intake on three different occasions during a period of 30 weeks, there was a threefold higher CVD risk for those women who never ate fish compared with those eating it every week ... However, she stresses that to obtain the greatest gain from fish, it should be consumed as a main meal at least twice a week. "There are other health benefits that are obtained only at high intakes," ... there have been studies that have shown that the gains from the particular nutrients found in fish, such as long-chain n-3 polyunsaturated fatty acids and selenium, outweigh the risks from contaminants such as mercury in pregnant women"

Increased Fitness, Not Weight Loss, Improves Mortality - Medscape, 12/5/11 - "Fitness appears to trump weight loss when it comes to reducing all-cause and cardiovascular mortality [1]. Data from a large longitudinal study show that maintaining and improving physical-fitness levels were associated with lower risks of all-cause and cardiovascular disease mortality, whereas changes in body-mass index (BMI) were not ... Cardiorespiratory fitness, expressed in metabolic equivalents (METs), is a strong independent predictor of mortality ... men who maintained their physical-fitness levels had a 30% and 27% lower risk of death and cardiovascular death, respectively, when compared with men who lost fitness. Those who got into better shape from baseline had a 39% and 42% lower risk of death and cardiovascular mortality, respectively, when compared with those who lost fitness over the years. Every 1-MET improvement resulted in a significant 15% reduction in the risk of death and a 19% reduction in the risk of cardiovascular disease mortality ... BMI changes, on the other hand, were not significantly associated with all-cause mortality"

Boost your 'good fats' to help fend off diabetes - MSNBC, 12/4/11 - Note:  I threw this in because I've been hammering "Prevention" for some time.  Note all the omega-6 oils in their recommendations when people get 10 to 20 times too much omega-6 as it is.  I'd be leery of their canola oil recommendation also:

  • Differential effects of dietary canola and soybean oil intake on oxidative stress in stroke-prone spontaneously hypertensive rats - Lipids Health Dis. 2011 Jun 13;10(1):98 - "Canola oil shortens the life span of stroke-prone spontaneously hypertensive (SHRSP) rats compared with rats fed soybean oil when given as the sole dietary lipid source. One possible mechanism leading to the damage and deterioration of organs due to canola oil ingestion is oxidative stress ... Canola oil ingestion significantly decreased the life span of SHRSP rats compared with soybean oil, 85.8 +/- 1.1 and 98.3 +/- 3.4 days, respectively. Systolic blood pressure increased over time with a significant difference between the diets at the 6th week of feeding. Canola oil ingestion significantly reduced RBC superoxide dismutase, glutathione peroxidase and catalase activities, total cholesterol and low-density lipoprotein cholesterol compared with soybean oil. There were no significant differences in RBC MDA concentration between canola oil fed and soybean oil fed rats. In contrast, plasma MDA and 8-isoprostane concentration was significantly lower in the canola oil group compared to the soybean oil group"

Driving Stoned: Safer Than Driving Drunk? - ABC News, 12/2/11 - "traffic fatalities in those states fell nearly 9 percent after medical pot became legal" - Note:  First of all there is no way to tie the 9% drop in accidents to legalizing maryjane and second (just for beginners and just the tip of the iceberg, not counting many other issues) what about the retarded offspring do to DNA damage? So they might (and I emphasize “might”) have improved one problem but they’ve exasperated a multitude of other problems. Talk about warped logic.  It's way too far fetched.  There are way too many variables.

Vegetables, fruits, grains reduce stroke risk in women - Science Daily, 12/1/11 - "They used a standard database to determine participants' total antioxidant capacity (TAC), which measures the free radical reducing capacity of all antioxidants in the diet and considers synergistic effects between substances ... For women with no history of cardiovascular disease who had the highest TAC, fruits and vegetables contributed about 50 percent of TAC ... Other contributors were whole grains (18 percent), tea (16 percent) and chocolate (5 percent) ... Women without cardiovascular disease with the highest levels of dietary TAC had a statistically significant 17 percent lower risk of total stroke compared to those in the lowest quintile ... Women with history of cardiovascular disease in the highest three quartiles of dietary TAC had a statistically significant 46 percent to 57 percent lower risk of hemorrhagic stroke compared with those in the lowest quartile"

Probiotics reduce infections for patients in intensive care, study finds - Science Daily, 12/1/11 - "including probiotics with nutrients, supplied via the patient's feeding tube, increased interferon levels, reduced the number of infections, and even reduced the amount of time patients spent in intensive care ... by day 15 the patients who received the probiotics had significantly higher levels of both IL-12 and IFNy than the control patients. They also showed a decrease in the Th2-associated factors IL-4 and IL-10 ... probiotic therapy reduced the number of infections occurring after seven days, reduced the number of different antibiotics needed to treat infections, and shortened the length of time the patients were required to stay in ICU"

Apple juice's other health risk: It'll make you fat - MSNBC, 12/1/11 - "Apple juice has few natural nutrients, lots of calories and, in some cases, more sugar than soda has. It trains a child to like very sweet things, displaces better beverages and foods, and adds to the obesity problem, its critics say ... Only 17 percent of the apple juice sold in the U.S. is produced here. The rest comes from other countries, mostly China, Argentina, Chile and Brazil"

Lower antioxidant level might explain higher skin-cancer rate in males - Science Daily, 12/1/11 - "Men are three times more likely than women to develop a common form of skin cancer but medical science doesn't know why ... male mice had lower levels of an important skin antioxidant than female mice and higher levels of certain cancer-linked inflammatory cells ... The antioxidant, a protein called catalase, inhibits skin cancer by mopping up hydrogen peroxide and other DNA-damaging reactive-oxygen compounds that form during exposure to ultraviolet B light (UVB), a common source of sunburn and cancer-causing skin damage ... women may have more natural antioxidant protection in the skin than men"

Eating fish reduces risk of Alzheimer's disease - Science Daily, 11/30/11 - "This is the first study to establish a direct relationship between fish consumption, brain structure and Alzheimer's risk ... people who consumed baked or broiled fish at least one time per week had better preservation of gray matter volume on MRI in brain areas at risk for Alzheimer's disease ... Each patient underwent 3-D volumetric MRI of the brain. Voxel-based morphometry, a brain mapping technique that measures gray matter volume, was used to model the relationship between weekly fish consumption at baseline and brain structure 10 years later ... consumption of baked or broiled fish on a weekly basis was positively associated with gray matter volumes in several areas of the brain. Greater hippocampal, posterior cingulate and orbital frontal cortex volumes in relation to fish consumption reduced the risk for five-year decline to MCI or Alzheimer's by almost five-fold ... Consuming baked or broiled fish promotes stronger neurons in the brain's gray matter by making them larger and health"

High blood sugar levels in older women linked to colorectal cancer - Science Daily, 11/29/11 - "The Einstein study involved women who were enrolled in the National Institutes of Health''''s landmark Women''''s Health Initiative study ... By the end of the 12-year period, 81 of the women had developed colorectal cancer. The researchers found that elevated baseline glucose levels were associated with increased colorectal cancer risk -- and that women in the highest third of baseline glucose levels were nearly twice as likely to have developed colorectal cancer as women in the lowest third of blood glucose levels ... obesity''''s impact on this cancer may be due to elevated glucose levels, or to some factor associated with elevated glucose levels"

Lipitor Goes Generic: What Consumers Can Expect - ABC News, 11/29/11 - "On Wednesday, the drug's patent expires, opening the market for cheaper, generic versions of Lipitor, which should lower costs for consumers by about 50 percent"

  • Pfizer Plans to Protect Lipitor From Generic Competitors - ABC News, 11/29/11 - "Pfizer has devised discounts and incentives for patients, insurers and companies that process prescriptions that will, at least for the next six months, make the brand name drug about as cheap as or cheaper than the generics"

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):

Long-term effects of nutraceuticals (berberine, red yeast rice, policosanol) in elderly hypercholesterolemic patients - Adv Ther. 2011 Nov 21 - "containing berberine 500 mg, policosanol 10 mg, red yeast rice 200 mg, folic acid 0.2 mg, coenzyme Q10 2.0 mg, and astaxanthin 0.5 mg) or placebo ... There was a statistically significant reduction in total cholesterolemia (-20%), LDL-C (-31%), and insulin resistance (-10%) with nutraceutical treatment. No significant changes were detected for plasma high-density lipoprotein cholesterol (HDL-C). Furthermore, no statistical differences were found between baseline and end-study safety parameters. Medication compliance and tolerability were high" - Note: I’m been promoting synergy and talking lower doses of everything proven in specific areas like this for some time.  My combo for cholesterol reduction would be 10 mg policosanol, 600 mg red yeast rice and 150 my Sytrinol.  See policosanol products at iHerb, red yeast rice at Amazon.com and Sytrinol products at iHerb.

Fish oil attenuates surgery-induced immunosuppression, limits post-operative metastatic dissemination and increases long-term recurrence-free survival in rodents inoculated with cancer cells - Clin Nutr. 2011 Nov 26 - "ω-3FA feeding attenuates or even overcomes postoperative NK cell suppression, increases resistance to experimental and spontaneous metastasis, and enhances recurrence-free survival following excision of metastasizing primary tumors" - See Mega Twin EPA at Amazon.com and Jarrow Max DHA at Amazon.com.

α-Lipoic acid prevents mild portal endotoxaemia-induced hepatic inflammation and β cell dysfunction - Eur J Clin Invest. 2011 Nov 16 - "Male Sprague-Dawley rats were randomly assigned into four groups: those with intraportal vehicle (saline) or low-dose lipopolysaccharide (LPS) (0.42 ng/kg/min) infusion, combined with oral administration of vehicle or LA, a potent antioxidant (60 mg/kg/day) for 4 weeks ... The histopathological examination showed that inflammatory changes were clearly visible in liver and pancreatic islets of LPS-infused rats and rarely observed in those cotreated with LA. In addition, low-dose intraportal LPS infusion also significantly impaired glucose-stimulated insulin secretion but not affect the systemic insulin sensitivity and metabolic clearance rate of insulin. LA administration markedly reversed LPS-induced β cell dysfunction. Conclusions  α-Lipoic acid cotreatment could significantly prevent mild portal endotoxaemia-induced chronic hepatic inflammation and impaired pancreatic insulin secretion in absence of changing systemic insulin resistance" - See alpha lipoic acid at Amazon.com.

Plasma retinol: A novel marker for cardiovascular disease mortality in Australian adults - Nutr Metab Cardiovasc Dis. 2011 Nov 25 - "Vitamin A affects inflammation and immune function and is thus a factor of interest in relation to cardiovascular disease (CVD). As vitamin A circulates in the plasma in the form of retinol, this study aims to describe the relationship between plasma retinol and the 5-year incidence of CVD mortality ... Community-dwelling adults (n = 441, 45% with type 2 diabetes) were recruited in Melbourne, assessed at baseline and followed for 5 years. At baseline, CVD risk factors were assessed by clinical evaluation, by personal lifestyle questionnaire and from biochemistry (plasma fasting glucose, lipids, total homocysteine, C-reactive protein, retinol and carotenoids plus the urinary albumin excretion rate over 24 h.). Dietary intake was assessed by a validated food frequency questionnaire. CVD mortality over 5-years was determined by consulting state or national registries. The majority of participants had adequate plasma retinol concentrations (≥30 μg/dL). The final Cox regression model indicated that those in the highest tertile of plasma retinol (mean +/- SD) 76 +/- 14 μg/dL) had a significantly lower risk of 5-year CVD mortality (hazard ratio 0.27 [95% confidence interval 0.11, 0.68], P = 0.005), an effect that was not readily explained in terms of traditional CVD risk factors or dietary intake"

Neat Tech Stuff / "How To's":

Health Focus (First line medications for hypertension):

See telmisartan or ramipril at OffshoreRx1.com.

I feel that Micardis (telmisartan) (ARBs) with Altace (ramipril) (an ACE inhibitor, if two drugs are required), are the way to go for the least side effects.  I'm not a doctor, just someone that's done a lot of reading and experimenting with different blood pressure medications.  Consult your doctor before taking any supplement or medication.  See:

Arguments for Ramipril:

  • Combination ACE inhibitor therapy increases risk of kidney failure and death, study finds - Science Daily, 3/21/11 - "The researchers looked at 32,312 seniors in Alberta, Canada, aged 65 and older who were prescribed an ACE inhibitor and/or an ARB. They compared patients receiving both drugs together with patients who received only one of the drugs. They found a higher risk of adverse events such as high creatinine levels, end-stage renal disease and death in people taking combination therapy"
  • Effects of Ramipril on Endothelial Function and the Expression of Proinflammatory Cytokines and Adhesion Molecules in Young Normotensive Subjects With Successfully Repaired Coarctation of Aorta A Randomized Cross-Over Study - J Am Coll Cardiol. 2008 Feb 19;51(7):742-749 - "Ramipril reversed the impaired endothelial function and decreased the expression of proinflammatory cytokine IL-6, sCD40L, and adhesion molecules in normotensive subjects with SCR. These findings imply that ramipril treatment may have antiatherogenic effects in subjects with SCR, even in the absence of arterial hypertension"
  • Keeping Seniors Independent - WebMD, 3/14/02 - "the average three-year decline in walking speed among those women who used ACE inhibitors was 10 times lower than it was in the other groups ... Researchers think several factors may explain these drugs' beneficial effect on delaying disability: ACE inhibitors increase blood flow to the muscles, reduce inflammation, and promote healthy eating habits and better nutrition by inhibiting a substance known to reduce appetite"
  • Blood Pressure Drugs May Help People Avoid 'Type 2' Disease, but Healthy Habits Still Best - WebMD, 10/16/01 - "people at high risk for developing diabetes who take the drug Altace [ramipril] were 34% less likely to develop diabetes than those who did not get the drug"
  • Not All ACE Inhibitors Have the Same Effect on Mortality - Medscape, 7/28/04 - "enalapril, fosinopril, captopril, quinapril, and lisinopril were associated with higher mortality than was ramipril"
  • Angiotensin-converting Enzyme Inhibitors, Beta Blockers May Postpone Kidney Failure - Doctor's Guide, 10/13/00 - "The ACE inhibitor ramipril (Altace®) or the beta-blocker metoprolol (Toprol®) significantly reduced the risk of kidney failure compared to the CCB amlodipine (Norvasc®) in a group of patients who had at least one gram of protein in a 24-hour sample of urine when they joined the African American Study of Kidney Disease and Hypertension (AASK). Blood pressures were comparable."
  • Ramipril Reduces Advanced Glycation End Products In Non-Diabetic Nephropathy - Doctor's Guide, 4/21/03 - "Ramipril also mildly decreased levels of advanced glycation end products"
  • Some Hypertension Drugs May Help Reduce Dementia Risk - Science Daily, 5507 - "Centrally acting drugs include captropril (Capoten®), fosinopril (Monopril®), lisinopril (Prinivil® or Zestri®), perindopril (Aceon®), ramipril (Altace®) and trandolapril (Mavik®) ... The study found a link between taking centrally active ACE inhibitors and lower rates of mental decline as measured by the Modified Mini-Mental State Exam, a test that evaluates memory, language, abstract reasoning and other cognitive functions"
  • Effect of antihypertensive agents on plasma adiponectin levels in hypertensive patients with metabolic syndrome - Nephrology (Carlton). 2007 Apr;12(2):147-53 - "Ramipril and valsartan increased the plasma adiponectin levels significantly higher than the other regimens"
  • BP Reduction in the Metabolic Syndrome and Type 2 Diabetes - Medscape, 2/13/06 - "Beta blockers are now widely regarded as having worse outcomes than other major classes of antihypertensive agents, though this view is heavily influenced by a single drug, atenolol.[29] Furthermore, the thiazide/beta blocker combination has been associated with an increased risk of the emergence of new-onset diabetes.[30] This has been strongly reinforced by the ASCOT trial, where the likelihood of new diabetes was 30% greater in the thiazide/beta blocker patients as compared to those taking calcium channel blockers with an ACE inhibitor.[31] Conversely, a very recent meta-analysis has shown that overall ACE inhibitors and ARBs reduce the risk of diabetes by about 25%"
  • Blood Pressure Drugs Counter Cancer? - WebMD, 5/23/06 - "After crunching the numbers, the risk reduction in veterans taking ACE inhibitors was 53% for colon cancer, 52% for pancreatic cancer, and 46% for esophageal cancer"
  • Prevention of Type 2 diabetes: fact or fiction? - Expert Opin Pharmacother. 2007 Dec;8(18):3147-58 - "the DREAM (Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication) study (n = 5269) demonstrated that rosiglitazone at 8 mg once/day in subjects with prediabetes (IGT and/or impaired fasting glucose) was effective in reducing the risk of diabetes by 60%"
  • Keeping Seniors Independent - WebMD, 3/14/02 - "the average three-year decline in walking speed among those women who used ACE inhibitors was 10 times lower than it was in the other groups ... Researchers think several factors may explain these drugs' beneficial effect on delaying disability: ACE inhibitors increase blood flow to the muscles, reduce inflammation, and promote healthy eating habits and better nutrition by inhibiting a substance known to reduce appetite"
  • ACE Inhibitors May Protect Against Mental Decline - Clinical Psychiatry News, 8/07 - "The group of patients on an antihypertensive other than an ACE inhibitor had a mean decline in exam scores of 0.64 points per year. Those on an ACE inhibitor had a mean decline of 0.38 points per year ... It is thought that some ACE inhibitors protect from dementia and mental decline by decreasing oxidative stress and inflammation in the brain"

Arguments for/against combining ARBs and ACE inhibitors:

  • 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"
  • See telmisartan and ramipril at OffshoreRx1.com.


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