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Arterial Disease

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  • Hypertension Perspective

    We might wish that all the effort in hypertension research over several decades had determined an optimal approach for the treatment of hypertension. Instead, the proliferation of often-conflicting study results creates confusion and less certainly about an optimal approach. MDs are willing to prescribe several drugs to achieve “normal” blood pressure. In contrast, the US, the National Heart, Lung and Blood Institute the sponsor of the ALLHAT study, launched a High Blood Pressure Education Program in 2006. They hoped to encourage patients to adopt healthier lifestyles and to influence physicians’ drug prescribing habits. They stated that the basis for the program is the ALLHAT conclusion that "overall, diuretics are more beneficial than calcium channel blockers (CCBs), angiotensin converting enzyme (ACE) inhibitors, or alpha-blockers as initial treatment to lower blood pressure and to protect against adverse effects of high blood pressure."

    While "lifestyle Changes" get attention from academic researchers, the lifestyle of citizens in most affluent countries tolerates and causes more disease.

    Two major problems in the medical view of vascular disease remain unchanged:

    1. The drug bias

    2. Body Divided

    Hypertension & Diabetes Guidelines

    American Society of Hypertension (ASH) called for patient-centered management and early, aggressive treatment of hypertension in diabetics. Their advice might apply to everyone. The ASH urged physicians to adopt a more integrated, individualized approach to treating hypertension by treating the intricacies of each patient rather than focusing on the disease in isolation. Goal blood pressure in hypertensive diabetic patients remained 130/80 mm Hg. All patients should reduce weight reduction, improve diet, increase physical activity, limit alcohol consumption, never smoke and limit salt intake to less than 2.4 g/day. The report stressed a reduction to glycated hemoglobin [HbA1c] to less than 7% maintaining finger test fasting glucose levels in the range of 70-130 mg/d. Low-dose ASA (aspirin) 80 mg/day was recommended. Lipid levels in the blood should be: low-density lipoprotein cholesterol < 70 mg/dL, triglycerides < 150 mg/dL, and high-density lipoprotein cholesterol > 40 mg/dL in men and > 45 mg/dL in women. Potassium levels should be kept to < 5 mEq/L.

    Treating to New Targets

    An analysis of the Treating to New Targets (TNT) study was presented at the American Society of Hypertension 2009 Scientific Meeting. Messerli et al published did an analysis of the INVEST study, a trial comparing two antihypertensive regimens in 22 576 patients with hypertension and coronary artery disease, and found that excessively lowering diastolic blood pressure was harmful. Messerli stated: "It stands to reason that when you lower blood pressure too much, you can do harm," After all, if blood pressure is zero, mortality is 100%. So somewhere there must be a nadir, below which the lowering of blood pressure becomes counterproductive." Compared with the reference blood pressures, systolic >130 to 140 mm Hg and diastolic >70 to 80 mm Hg, patients with systolic blood pressure <110 mm Hg had a threefold increased risk of cardiovascular events, whereas those with diastolic blood pressure <60 mm Hg had a 3.3-fold increased risk of events. Messerli suggested that lowest point of inflection on the morbidity and mortality curves was 140.6 mm Hg for systolic blood pressure and 79.8 mm Hg for diastolic blood pressure. By 2017 new lower levels of BP have been suggested as targets for medical therapy. As with most medical topics studies that contradict old truths are often fallowed in motivation and methodology. When drug companies fund these studies, new and older drugs are promoted and proposed cost of management is increased.

    Calcium channel blockers

    Among the most widely prescribed drugs in the United States, CCBs are used to treat angina, hypertension, and dysrhythmias and to prevent migraines. They are marketed under many brand names, in a range of doses and formulations. Their popularity is not a measure of their therapeutic efficacy and there are many negative effects. The L-type calcium channel blockers decrease the flow of calcium into the cells of the cardiac conduction pathway, which leads to an inhibition of the phase 0 in cardiac pacemaker cells and slows the phase 2 plateau in Purkinje cells, cardiac myocytes, and vascular smooth muscle cells.

    ACE Inhibitors

    In a best evidence review Vega stated: ”Angiotensin-converting enzyme (ACE) inhibitors are some of the most commonly prescribed medications for hypertension. This enthusiasm for ACE inhibitors is somewhat inconsistent with current recommendations, which prefer thiazide diuretics as first-line medication for uncomplicated cases of hypertension. With the popularity of ACE inhibitors in mind, investigators conducted a systematic review of published studies to determine how effective the drugs actually are in reducing blood pressure.”

    The conclusions: ACE inhibitors (benazepril, moexipril, ramipril captopril) were associated with an average reduction in systolic blood pressure between 6 mm Hg and 9 mm Hg and in diastolic blood pressure of 4-5 mm Hg; all drugs in this class are similar and achieved most of their power in reducing blood pressure at half of the maximum recommended dose, or less.

    Angiotensin receptor blockers

    Related drugs, angiotensin receptor blockers (losartan, valsartan, candesartan,irbesartan ) provide modest reductions in blood pressure; 46 randomized controlled trials examining 9 ARBs, and found that average reductions in systolic and diastolic blood pressure were 8 mm Hg and-5 mm Hg, similar to ACE inhibitors. ARBs were effective at one eighth to one half of the manufacturers' recommended doses. There is no strong evidence that ACE inhibitors can prevent diabetes or heart failure. Telmisartan, an angiotensin II receptor antagonist has activities that may benefit diabetics with the metabolic syndrome. According to Benson et al: “The metabolic syndrome is characterized by the clustering of insulin resistance, dyslipidemia, and increased blood pressure. In humans, mutations in the peroxisome proliferator activated receptor-gamma (PPARgamma) have been reported to cause the full-blown metabolic syndrome, and drugs that activate PPARgamma have proven to be effective agents for the prevention and treatment of insulin resistance and type 2 diabetes. Telmisartan can influence the expression of PPARgamma target genes involved in carbohydrate and lipid metabolism, reducing levels of glucose, insulin, and triglyceride in rats fed a high-fat, high-carbohydrate diet.” (Benson SC; Pershadsingh HA; Ho CI; Chittiboyina A; Desai P; Pravenec M; Qi N; Wang J; Avery MA; Kurtz TW. Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPARgamma-modulating activity. Hypertension 2004 May;43(5):993-1002)

    In a best evidence review, Vega stated: ”Angiotensin-converting enzyme (ACE) inhibitors are some of the most commonly prescribed medications for hypertension. This enthusiasm for ACE inhibitors is somewhat inconsistent with current recommendations, which prefer thiazide diuretics as a first-line medication for uncomplicated cases of hypertension. With the popularity of ACE inhibitors in mind, investigators conducted a systematic review of published studies to determine how effective the drugs actually are in reducing blood pressure.” The conclusions: ACE inhibitors (benazepril, moexipril, ramipril captopril) were associated with an average reduction in systolic blood pressure between 6 mm Hg and 9 mm Hg and in diastolic blood pressure of 4-5 mm Hg; all drugs in this class are similar and achieved most of their power in reducing blood pressure at half of the maximum recommended dose, or less. Related drugs, angiotensin receptor blockers (ARB), provide similar modest reductions in blood pressure; 46 randomized controlled trials examining 9 ARBs, and found that average reductions in systolic and diastolic blood pressure were 8 mm Hg and-5 mm Hg, similar to ACE inhibitors. ARBs were effective at one-eighth to one-half of the manufacturers' recommended doses. There is no strong evidence that ACE inhibitors can prevent diabetes mellitus or heart failure.
    References

    Bakris GL, Sowers JR; on behalf of the American Society of Hypertension Writing Group. ASH Position Paper: Treatment of hypertension in patients with diabetes -- an update. J Clin Hypertens (Greenwich). 2008;10:707-713.

    Charles P. Vega .How Effective Are ACE Inhibitors for Hypertension? A Best Evidence Review. Posted Medscape Online 03/13/2009

    Heran BS, Wong MM, Heran IK, Wright JM. Blood pressure lowering efficacy of angiotensin converting enzyme (ACE) inhibitors for primary hypertension. Cochrane Database Syst Rev. 2008;(4):CD003823.

    Bangalore S, Messerli FH, Wun CC, et al. J-curve revisited: An analysis of blood pressure and cardiovascular events in the Treating to New Targets (TNT) trial. American Society of Hypertension; May 7, 2009; San Francisco, CA.


  • Topics from the book Heart & Arterial Disease The author is Stephen Gislason MD 2018 Edition: 190 Pages

    Major diseases originate from eating too much of the wrong food and damage is done to many organs simultaneously. The evidence does suggest that some interventions are beneficial in terms of preventing heart attacks and strokes and that disease progression can be halted by important changes in diet and increased exercise. The occurrence of a heart attack or stroke confirms that atherosclerosis is advanced, damage has been done and that the rules of intervention have changed. We suggest that a prudent person suffering early vascular dysfunction symptoms would be wise to pursue vigorous, thorough diet revision at the earliest opportunity.

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    ECG MD


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