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Recent Longevity News for the seven days ending 8/14/13.  You should consult your doctor if you are taking any medications.

Phytosterols, Red Yeast Rice, and Lifestyle Change vs Statin - Medscape, 8/13/13 - "All participants took RYR and had significant decreases in LDL-C, total cholesterol, triglycerides, high-sensitivity C-reactive protein, and an increase in high-density lipoprotein cholesterol for 1 year when compared with baseline" - See red yeast rice at Amazon.com.

The Effect of Coffee Consumption on the Development of HCC - Medscape, 8/12/13 - "a high lifetime coffee consumption (≥20 000 cups) was an independent protective factor against HCC, in each analyses using healthy and risky control groups respectively (HCE group, OR 0.56, 95% CI 0.33–0.95; CLD group, OR 0.55, 95% CI 0.36–0.85). However, the high coffee consumption did not affect the HCC risk in patients with HBV (OR 0.64, 95% CI 0.36–1.14) after adjustment for HBeAg status, serum HBV DNA level and antiviral therapy"

Dementia risk tied to blood sugar level, even with no diabetes - Science Daily, 8/7/13 - "more than 2,000 Group Health patients age 65 and older in the Adult Changes in Thought (ACT) study ... in people without diabetes, risk for dementia was 18 percent higher for people with an average glucose level of 115 milligrams per deciliter compared to those with an average glucose level of 100 mg/dl. And in people with diabetes, whose blood sugar levels are generally higher, dementia risk was 40 percent higher for people with an average glucose level of 190 mg/dl compared to those with an average glucose level of 160 mg/dl ... The most interesting finding was that every incrementally higher glucose level was associated with a higher risk of dementia in people who did not have diabetes" - [Abstract] - Note that the patients in this study were 65 years old or older which begs the question whether the risks might even be higher is the high blood sugar started at a much earlier age.  See my insulin and aging page.

Early BPA Exposure Linked to Depression, Inattention in Kids - Medscape, 8/7/13 - "A study of almost 292 participants showed that prenatal exposure to BPA, as measured in maternal urine tests, was associated with internalizing behaviors, such as anxiety and depression, in the boys at the age of 7 years — but not in the girls ... However, early childhood BPA concentrations were associated with increased externalizing behaviors, such as conduct problems, in the girls. Childhood urine measurements of BPA were also linked to the internalizing behaviors of inattention and hyperactivity in both sexes"

Eating a big breakfast fights obesity and disease - Science Daily, 8/5/13 - "Metabolism is impacted by the body's circadian rhythm -- the biological process that the body follows over a 24 hour cycle. So the time of day we eat can have a big impact on the way our bodies process food ... 93 obese women were randomly assigned to one of two isocaloric groups. Each consumed a moderate-carbohydrate, moderate-fat diet totaling 1,400 calories daily for a period of 12 weeks. The first group consumed 700 calories at breakfast, 500 at lunch, and 200 at dinner. The second group ate a 200 calorie breakfast, 500 calorie lunch, and 700 calorie dinner ... By the end of the study, participants in the "big breakfast" group had lost an average of 17.8 pounds each and three inches off their waist line, compared to a 7.3 pound and 1.4 inch loss for participants in the "big dinner" group ... those in the big breakfast group were found to have significantly lower levels of the hunger-regulating hormone ghrelin"

Scientists learn how soy foods protect against colon cancer - Science Daily, 8/5/13 - "lifelong exposure to genistein, a bioactive component in soy foods, protects against colon cancer by repressing a signal that leads to accelerated growth of cells, polyps, and eventually malignant tumors ... the scientists modeled lifetime exposure to soy by feeding pregnant rats and their offspring a diet containing soy protein isolate and a diet that contained genistein compound. At seven weeks of age, offspring rats were exposed to a carcinogen, and they continued eating either the soy protein or the genistein diet until they were 13 weeks old ... At that time, the researchers inspected the colons of rats in both soy groups and compared them to rats in a control group, noting the number and severity of tiny abnormal growths in each ... Genistein decreased the expression of three genes and repressed this signaling process that is associated with abnormal cell growth and cancer development" - See genistein at Amazon.com.

Pioglitazone Back on Market in India - Medscape, 8/6/13 - "The decision to suspend the manufacture, sale, and distribution of pioglitazone in India, citing concerns over adverse effects, particularly bladder cancer, came out of the blue in June and was widely criticized by doctors and others there. In mid-July, however, a meeting of the drug technical advisory board (DTAB) recommended that pioglitazone be put back on the market ... Now, the Ministry of Health and Family Welfare has announced that all formulations containing pioglitazone for human use are allowed to be manufactured, sold, and distributed once again, albeit with warnings on the package insert" - Note:  Pioglitazone from India was one of the medications I was taking in low does for anti-aging.  See my insulin and aging page.

Metformin May Lower Risk of Prostate Cancer Death, Researchers Say - WebMD, 8/5/13 - "metformin is associated with improved survival among diabetic patients with prostate cancer ... whether metformin can prevent prostate cancer progression in people without diabetes remains to be seen ... those who took metformin had a 24 percent reduction in risk from prostate cancer death for every additional six months of use after their cancer diagnosis. The risk reduction of death from other causes was initially the same but declined over time ... No reduction in death risk was seen for patients taking any other diabetes drug ... other diabetes drugs work by increasing the body's insulin production, metformin is an "insulin sensitizer" that works by making the body more sensitive to the insulin already produced ... Some research suggests that high insulin levels can influence cancer growth. Metformin, by not increasing the body's insulin production, may decrease cancer cells' growth, some experts say" - Note:  Metformin is another one that I take in low dose for anti-aging.  I don't think that's true that [all] "other diabetes drugs work by increasing the body's insulin production".  Rosiglitazone and pioglitazone are also insulin sensitizers. - See metformin at IAS.

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):

Effects of the brown rice diet on visceral obesity and endothelial function: the BRAVO study - Br J Nutr. 2013 Aug 12:1-11 - "Brown rice (BR) and white rice (WR) produce different glycaemic responses and their consumption may affect the dietary management of obesity ... In study 1, acute postprandial metabolic parameters and flow- and nitroglycerine-mediated dilation (FMD and NMD) of the brachial artery were determined in male volunteers with or without the metabolic syndrome after ingestion of either BR or WR. The increases in glucose and insulin AUC were lower after ingestion of BR than after ingestion of WR (P= 0.041 and P= 0.045, respectively). FMD values were decreased 60 min after ingestion of WR (P= 0.037 v. baseline), but the decrease was protected after ingestion of BR. In study 2, a separate cohort of male volunteers (n 27) with the metabolic syndrome was randomised into two groups with different BR and WR consumption patterns. The values of weight-based parameters were decreased after consumption of BR for 8 weeks, but returned to baseline values after a WR consumption period. Insulin resistance and total cholesterol and LDL-cholesterol levels were reduced after consumption of BR" - See brown rice pasta at Amazon.com.

Raw garlic consumption as a protective factor for lung cancer, a population-based case-control study in a Chinese population - Cancer Prev Res (Phila). 2013 Jul;6(7):711-8 - "Epidemiologic data were collected by face-to-face interviews using a standard questionnaire among 1,424 lung cancer cases and 4,543 healthy controls ... raw garlic consumption of 2 times or more per week is inversely associated with lung cancer (OR = 0.56; 95% CI, 0.44-0.72) with a monotonic dose-response relationship" - See garlic supplements at Amazon.com.

Effect of Magnolia officinalis and Phellodendron amurense (Relora(R)) on cortisol and psychological mood state in moderately stressed subjects - J Int Soc Sports Nutr. 2013 Aug 7;10(1):37 - "Magnolia (Magnolia officinalis) and Phellodendron (Phellodendron amurense) barks are medicinal plants commonly used as traditional remedies for reducing stress and anxiety ... assessed salivary cortisol exposure and psychological mood state in 56 subjects (35 men and 21 women) screened for moderate stress and supplemented with a standardized/patented MP combination (Relora(R), Next Pharmaceuticals) or Placebo for 4 weeks ... After 4 weeks of supplementation, salivary cortisol exposure was significantly (p<0.05) lower (-18%) in the Relora group compared to Placebo. Compared to Placebo, the Relora group had significantly better (p<0.05) mood state parameters, including lower indices of Overall Stress (-11%), Tension (-13%), Depression (-20%), Anger (-42%), Fatigue (-31%), and Confusion (-27%), and higher indices of Global Mood State (+11%) and Vigor (+18%)" - Note: The biggest affect was on anger (-42%).  - See Relora at Amazon.com.

Long-term orange juice consumption is associated with low LDL-cholesterol and apolipoprotein B in normal and moderately hypercholesterolemic subjects - Lipids Health Dis. 2013 Aug 6;12(1):119 - "The sample consisted of 103 men (18--66 y) and 26 women (18--65 y); all were employees of an orange juice factory with daily access to free orange juice. The results showed that 41% of the individuals consumed 2 cups (480 mL) of orange juice per day for at least twelve months, while 59% of the volunteers are non-consumers of orange juice ... Orange juice consumers with normal serum lipid levels had significantly lower total cholesterol (-11%, p <0.001), LDL-cholesterol (-18%, p < 0.001), apolipoprotein B (apo B) (-12%, p < 0.01) and LDL/HDL ratio (-12%, p < 0.04) in comparison to non-consumers, as did the consumers with moderate hypercholesterolemia: lower total cholesterol (-5%, p <0.02), LDL-cholesterol (-12%, p <0.03), apolipoprotein B (-12%, p <0.01) and LDL/HDL ratio (-16%, p <0.05) in comparison the non-consumers counterparts"

Are Curcuminoids Effective C-Reactive Protein-Lowering Agents in Clinical Practice? Evidence from a Meta-Analysis - Phytother Res. 2013 Aug 7 - "Inflammation plays a pivotal role in the pathogenesis of atherosclerosis and cardiovascular disease (CVD). In this context, C-reactive protein (CRP) has been identified as a strong predictor and independent risk factor of CVD. Curcuminoids are multifunctional natural product with promising cardioprotective and anti-inflammatory properties ... PubMed/MEDLINE and SCOPUS databases were searched ... Compared with placebo, supplementation with curcuminoids was associated with a significant reduction in circulating CRP levels (weighed mean difference: -6.44 mg/L; 95% CI: -10.77 - -2.11; p = 0.004). This significant effect was maintained in subgroups of trials that used bioavailability-improved preparations of curcuminoids and had supplementation duration of ≥4 weeks, but not in the subgroups without these characteristics ... effect appears to depend on the bioavailability of curcuminoids preparations and also duration of supplementation" - See curcumin products at Amazon.com.

Neat Tech Stuff / "How To's":

Health Focus (First line medications for hypertension):

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:

  • Ambulatory Blood Pressure Values in the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) - Hypertension. 2012 Oct 15 - "Twenty-four-hour systolic BP was similarly reduced by R (-2.0 mm Hg) and T (-2.1 mm Hg), whereas the reduction was more than twice as large in the T+R group (-5.3 mm Hg), which showed a lower on-treatment 24-hour BP also in additional patients (n=408) in whom ambulatory BP was performed only on-treatment. Twenty-four-hour systolic BP was ≈14 mm Hg lower than clinic systolic BP at baseline, whereas during treatment the 2 values became progressively closer as clinic systolic BP was more tightly controlled and superimposable when clinic systolic BP was <120 mm Hg. Similar results were obtained for diastolic BP. These findings provide evidence on the relationship of clinic and ambulatory BP target drug treatment. They also show that in the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial, failure of the R+T combination to enhance cardiovascular and renal protection was not because of inability to more effectively control daily life BP"
  • 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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