Captopril and Hypertension (Topics in Cardiovascular Disease)

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Correlations between BMI and serum levels of the cytokines were evaluated using Spearman' rho correlation of coefficient r s. Also, comparison of drug usage frequencies across the four studied groups was performed using chi -square test. For the statistical analysis, the statistical software SPSS version With regard to oral medications before coronary angiography, although administration of Aspirin 80mg daily, Clopidogrel 75mg daily, Betablockers and Nitrates was similar between patients groups 1, 2 and 3 and control group 4 , Losartan, Captopril and Atorvastatin were administered more to patients in comparison to control group, and these differences were significant Table 1.

Doses of Losartan and Captopril were 50mg twice daily groups 1 and 2 and 25mg daily groups 3 and 4. Dose of Atorvastatine was 40mg daily groups 1, 2 and 3 and 10—20mg for group 4. Frequency of drug usage was compared using chi -square test or Fisher's exact test across the four studied groups.

Associated Data

As mentioned in the Fig 1 , the results demonstrated that the serum levels of IL-6 were significantly decreased in group 1 The fig illustrates that serum levels of the cytokines were not significantly different among males and females in the group 1. The fig illustrates that serum levels of the cytokines were not significantly different among males and females in the group 2.

The fig illustrates that serum levels of the cytokines were not significantly different among males and females in the group 3. Statistical analysis revealed that, although weight was similar among groups, age was significantly different among groups Table 2.

The table illustrates that age and BMI were significantly different between groups. CAD but not hypertension, Group 4: The correlation between age, weight and BMI with cytokines was too poor to affect their expression in the group. The correlation between age, weight and BMI with cytokines was too poor to affect their expression. Other correlations with cytokines were too poor to affect their expression. Other correlations with cytokines were too poor to affect their expression Table 5. Statistical analysis in the control group group 4 also demonstrated that there are poor positive correlations between age vs IL Other correlations were too poor with cytokines to affect their expression in the group Table 6.

The table illustrates that there are poor positive correlations between age vs IL It has been documented that most of the drugs which are used for treatment of hypertension and CAD play key roles as anti-inflammatory agents.

Previous investigations also confirmed the anti-inflammatory effects of the components. For example, it has been demonstrated that Atorvastatin modulates the innate immune responses by activation of endothelial [ 17 ], macrophage [ 18 ], monocyte [ 19 ], NK cell [ 19 ], and neutrophil function [ 20 ].

Accordingly, Blankier et al. Decreased expression of pro-inflammatory cytokines by immune cells under treatment of other drug components including Aspirin, Clopidogrel, Metoprolol, Nitrates, Losartan, Captopril and Carvedilol have also been reported previously [ 23 — 25 ]. Thus, it has been hypothesized that the drugs may downregulate pro-inflammatory cytokines in the patients suffering from hypertension and CAD.

Our results showed that all four groups have received all the mentioned drugs, but the control group has received lower doses of Atorvastatin, Losartan and Captopril when compared to other groups group 1, 2 and 3. Thus, although, we have not evaluated the cytokines serum levels before and after treatment with Atorvastatin, Losartan and Captopril, but based on the results it may be hypothesized that alterations in the cytokine serum levels in the groups suffering from hypertension and CAD in comparison to controls may be associated with the higher doses of the drugs.

Thus, more clinical trial investigations using Atorvastatin, Losartan and Captopril can shed light on the understanding of the main mechanisms played by the drugs. The cytokine is an angiogeneic factor which actively participates in the development of vessels [ 5 ]. It has also been reported that IL-6 is a potential inducer of addressing molecules on the inflamed vessels [ 21 ]. Increased expression of the cytokine in the patients suffering from hypertension and CAD has been reported in the previous investigations [ 26 ].

Our results revealed that Atorvastatin, Losartan and Captopril may have an indirect therapeutic manner via downregulation of IL Besides, cytokines play important roles in the cells proliferation and also fibrogenic features disorders like atherosclerosis [ 30 ]. It appears that the drugs show various features when they are used alone or in combination with other components.

Hypertension Management in the High Cardiovascular Risk Population

Thus, more clinical trials are needed to improve our knowledge regarding the in vivo effects of the drug components on human immune system. While no significant association between evaluated cytokines and gender was observed among other groups. Results revealed that age, BMI and weight have no or poor correlations with the cytokine production. Thus, although the groups differed regarding age and BMI, it seems that the interfered criteria have not affected expression of evaluated cytokines. The cytokines are the main cause of macrophage activator and induction of arthrosclerosis. The strengths of the our study is the fact that this study is conducted on human samples and simultaneous analysis of plasma levels of several important cytokines in different conditions in individuals treated with various ranges of drugs.

However, the potential limitations of our results were due to the fact that the study were recruited in one centre, which may limit the external validity of our findings, and also some data of the study was limited by questions and observation. Regarding to wide spread of hypertension and CAD in the world and various ranges of drugs accessible, it is suggested to perform similar study on the other populations to attain more evidences.

The authors wish to express their sincere thanks to all participants who helped us to perform the project. National Center for Biotechnology Information , U. Published online Dec Author information Article notes Copyright and License information Disclaimer. The authors have declared that no competing interests exist.

Received Feb 15; Accepted Nov This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This article has been corrected.

This article has been cited by other articles in PMC. Results With regard to the medications, Atorvastatin, Losartan and Captopril were administered more in patients groups 1, 2 and 3 than the patients without hypertension and CAD. Introduction Cytokines which are mostly produced by immune cells, are the main arm of immune system and play several roles from inflammation to tissue damage or regeneration [ 1 ]. Results With regard to oral medications before coronary angiography, although administration of Aspirin 80mg daily, Clopidogrel 75mg daily, Betablockers and Nitrates was similar between patients groups 1, 2 and 3 and control group 4 , Losartan, Captopril and Atorvastatin were administered more to patients in comparison to control group, and these differences were significant Table 1.

Table 1 Comparison of drug usage frequencies across the four studied groups. Open in a separate window. Table 2 Demographic information of participants. Beta-blockers have been shown to improve survival, decrease the risk of recurrent myocardial infarction MI , and decrease the incidence of sudden cardiac death among patients with CHD [ 9 — 12 ].

However, in patients with no CHD, there is no sufficient evidence for the cardioprotective effect of beta-blockers. ACE inhibitors are recommended for all patients after MI. Mean followup was 4. The benefit of treatment with perindopril was comparable for patients with or without hypertension [ 16 ]. Median followup was 4. There was a 4. The VALUE trial Valsartan Antihypertensive Long-Term Use Evaluation showed that there was no difference in cardiac mortality and morbidity in patients with hypertension and high risk of cardiovascular events who were treated with valsartan versus amlodipine, eventhough the BP-lowering effect of amlodipine was greater than that of valsartan [ 19 , 20 ].

However, the VALIANT trial also revealed that when valsartan and captopril were given in combination, they did not improve survival, but increased the rate of adverse events in these patients [ 21 ]. This trial showed that telmisartan is comparable with ramipril in patients with cardiovascular disease or diabetes, with fewer cough and angioedema events.

The combination of two drugs did not improve the outcomes and was associated with more adverse events [ 22 ]. The dihydropyridine calcium channel blockers CCBs , amlodipine and nifedipine, can be added to the beta-blocker regimen, if blood pressure remains uncontrolled in patients with CHD. The nondihydropyridine agents such as diltiazem and verapamil can be substituted for beta-blockers when side effects develop or there are contraindications. CCBs reduce blood pressure by causing vasodilation and decreasing peripheral vascular resistance, thus reducing the myocardial oxygen demand [ 24 ].

Primary prevention with verapamil-based therapy was shown to be similar to diuretic or beta-blocker-based therapy. CCBs are the alternatives to beta-blockers in the treatment of HTN in patients with CHD but are not recommended for secondary cardiac prevention because of their inability to prevent ventricular dilatation, especially when compared to ACE inhibitors or ARBs. The effectiveness of thiazide diuretics in controlling blood pressure and preventing cardiovascular events has been demonstrated in several studies. Nitrates are the preferred choice for the management of acute hypertension, acute relief of angina, or chronic angina that cannot be controlled with beta-blockers and calcium channel blockers.

The goal of therapy in hypertensive patients with heart failure and systolic dysfunction is to decrease preload and afterload. Beta-blockers are considered the standard therapy in managing hypertensive patients with heart failure, who have no contraindications to the use of these agents and who are not in acute decompensated HF.

Most commonly used beta-blockers in patients with heart failure include bisoprolol, metoprolol, and carvedilol. Bisoprolol and metoprolol are beta1-selective blockers without significant intrinsic sympathetic activity or vasodilating properties. Carvedilol has antagonist activity against alpha1, beta1, and beta2 receptors, as well as some antioxidant activity.

A number of large randomized trials showed a mortality benefit in using beta-blockers in patients with heart failure. The improvement in mortality was statistically significant [ 30 ]. MERIT-HF was a larger trial, which used metoprolol succinate and was stopped prematurely as the absolute mortality rate was 7. This difference was statistically significant [ 31 , 32 ]. This trial was terminated early as carvedilol showed a large mortality benefit in the treatment group [ 33 ]. ACE inhibitors are one of the main therapies in managing hypertensive patients with HF.

ACE inhibitors increase cardiac output, decrease congestion due to their vasodilator venodilatation activity, reduce the rate of progressive cardiac dysfunction, and improve cardiovascular mortality. In this trial, patients were assigned to receive either placebo or enalapril. Conventional treatment for heart failure, including the use of other vasodilators, was continued in both groups. This study concluded that the addition of enalapril to the conventional therapy in patients with HF reduces mortality and improves symptoms and it was also associated with significant reductions in the NYHA class [ 34 ].

They are mostly used in patients intolerant to ACE inhibitors. The combination of hydralazine and isosorbide dinitrate prolongs survival and is found to be effective in African-American patients with heart failure already being treated with the standard therapy. The African-American Heart Failure Trial A-HeFT involved a total of black patients who had the New York Heart Association's class III or IV heart failure with dilated ventricles, which were randomly assigned to receive a fixed dose of isosorbide dinitrate plus hydralazine or placebo in addition to the standard therapy for heart failure.

The primary endpoint was a composite score made up of weighted values for death from any cause, a first hospitalization for heart failure, and change in quality of life. The group treated with hydralazine plus isosorbide dinitrate versus placebo showed decreased mortality [ 36 ]. Spironolactone and eplerenone improve survival in patients with advanced HF. Two large trials have evaluated the use of an aldosterone receptor antagonist in patients with heart failure in addition to an ACE inhibitor: The RALES trial showed that a blockade of aldosterone receptors by spironolactone, in addition to the standard therapy, reduces significantly the risk of morbidity and mortality among patients with severe heart failure and a left ventricular ejection fraction of no more than 35 percent [ 37 ].

In the EPHESUS trial, the addition of eplerenone to the optimal medical therapy was shown to reduce morbidity and mortality among patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure [ 38 ]. Diuretic therapy loop diuretics-furosemide is used mostly for signs of fluid overload and improvement in symptoms. There is no evidence that loop diuretics improve survival in patients with HF.

CCBs also showed no mortality benefit in the treatment of hypertensive patients with HF. While the focus of therapy for HF patients has been on systolic dysfunction, hypertensive patients with diastolic dysfunction should be managed with beta-blockers, ARBs, and verapamil. These agents have been shown to improve left ventricular compliance, regress left ventricular hypertrophy, and decrease myocardial oxygen demand [ 39 ]. More than 10 million adults in the US have diabetes.

Hypertension is twice as common in patients with diabetes compared to the general population. Many studies have shown clear benefit of ACE inhibitors and ARBs in reducing microvascular and macrovascular complications in hypertensive patients with type I and II diabetes. Many trials have also shown ACE inhibitors to be of significantly greater benefit when compared with other antihypertensive agents in the reduction of acute MI, cardiovascular events, and all-cause mortality in diabetic patients. The UKPDS the United Kingdom Prospective Diabetes Study trial on the other hand showed no difference in terms of reduction in microvascular and macrovascular complications when it compared captopril with atenolol [ 42 ].

The CALM Candesartan and Lisinopril Microalbuminuria study showed that candesartan was as effective as lisinopril in blood pressure reduction and minimization of microalbuminuria [ 43 ]. To help detect the presence of undiagnosed bilateral renal artery stenosis, the serum creatinine level should be monitored at baseline and one week after the initiation of therapy with any of these agents. The RAAS blockade also may play a role in the prevention of diabetes.

A meta-analysis of 13 studies involving approximately 67, patients showed that ACEi and ARBs significantly reduced new-onset diabetes in patients with hypertension or other cardiovascular risk factors [ 44 , 45 ]. Diuretics are effective in the treatment of hypertension in patients with diabetes. They enhance the efficacy of other antihypertensives.

Lower doses of thiazide diuretics are well tolerated. In addition, chlorthalidone was found to be superior to amlodipine and lisinopril in preventing new-onset heart failure. Chlorthalidone was associated with a mild rise in plasma glucose [ 16 ]. However, thiazide diuretics are not as effective in patients with chronic kidney disease. Loop diuretics are preferred in those cases. In contrast, the HOT Hypertension Optimal Treatment trial concluded that the use of dihydropyridine CCBs as monotherapy or in combination with another agent was associated with a reduction in the cardiovascular risk in these patients [ 48 ].

Beta-blockers are effective means of therapy in controlling blood pressure in diabetic patients.

The UKPDS41 study showed that, in patients with DM type II, atenolol was as effective as captopril regarding blood pressure control and protection against microvascular complications. The LIFE trial demonstrated that losartan provides significantly more cardiovascular protection compared to atenolol [ 49 ].

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Cardioselective beta-blockers are associated with less blunting of hypoglycemic awareness and less elevation of lipid and glucose levels. Carvedilol that is a nonselective beta-blocker and alpha-1 adrenergic antagonist may have some advantages compared to other beta-blockers when used in diabetes patients. It has been shown to cause fewer alterations in lipid and glucose levels compared with the traditional beta-blockers [ 50 ]. Most patients require more than one blood pressure agent to achieve adequate blood pressure control. The choice of the antihypertensive therapy in diabetic patients is based upon their ability to prevent cardiovascular events and to slow progression of nephropathy if present.

The primary endpoint was a composite death from cardiovascular causes, nonfatal MI, nonfatal stroke, hospitalization for angina, resuscitation after sudden cardiac arrest, and coronary revascularization. The trial was terminated early, after a mean followup of 36 months, as it showed overwhelming efficacy in favor of the benazepril-amlodipine combination [ 51 ].

Treatment modalities should be individualized based on co-morbidities and tolerability. CCBs should be used as an alternative or added to the basic regimen. Nitrates should be used to relieve the ischemic pain. Hypertensive patients with systolic heart failure are treated mostly with ACEi, ARBs, beta-blockers, diuretics, and aldosterone antagonists. Appropriate agents also include hydralazine and isosorbide dinitrate as a supplement to the basic therapy.

The optimal therapy for hypertensive patients with diastolic dysfunction includes beta-blockers, ARBs, and verapamil. These agents have been shown to improve left ventricular compliance, regress left ventricular hypertrophy, and decrease myocardial oxygen demand. The choice of an antihypertensive agent used in patients with diabetes mellitus depends on their ability to decrease cardiovascular events, improve mortality, and to slow progression of nephropathy. ACEi or ARBs should be the initial therapy in hypertensive patients with diabetes mellitus and microalbuminuria.

If beta-blockers are to be given, carvedilol is shown to be superior compared to traditional selective beta-blockers.

Hypertension Management in the High Cardiovascular Risk Population

As can be seen by the review of prior trials and recommendations, appropriate management of these patients through targeted pharmacologic and nonpharmacologic therapies to improve mortality and reduce cardiovascular events is the optimal approach to treatment. National Center for Biotechnology Information , U.

Journal List Int J Hypertens v. Published online Feb 6. Ilir Maraj , 1 John N. Makaryus , 2 Anthony Ashkar , 1 Samy I. McFarlane , 1 and Amgad N. Author information Article notes Copyright and License information Disclaimer.

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Received Sep 27; Accepted Dec This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract The incidence of hypertension is increasing every year. Introduction Over 65 million adult Americans or approximately one-fourth of the US population has hypertension. Table 1 Traditional risk factors for cardiovascular disease. Open in a separate window.

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