Join Us | Latest Articles | Contact

Journal Home


Editorial Board


Recent Articles


Submit to this journal


Special Issues


Current issue

Journal of Hypertension and Management





DOI: 10.23937/2474-3690/1510015



Angiotensin-Converting Enzyme Inhibitor-Induced Cough Prevalence in Refractory Hypertensive Patients

André Nascimento Públio Pereira*, Roque Aras Júnior, Cristiano Ricardo Bastos Macedo, Ricardo Ribeiro do Nascimento Teixeira, Iuri Resedá Magalhães, Diego Sant'ana Sondré, Bianca de Almeida Nunes and Juliana Queiroz Vasconcelos Muniz


Medical School of Bahia, Federal University of Bahia, Brazil


*Corresponding author: André Nascimento Públio Pereira, Medical School of Bahia, Federal University of Bahia, Rua Clarival do Prado Valadares, 371, Caminho das Árvores, Condomínio Monte Trianon, Apt 502, Salvador, Bahia, Brazil, Tel: 71-3353-1925, 71-99691-6739, E-mail: andrepublio@gmail.com
J Hypertens Manag, JHM-2-015, (Volume 2, Issue 2), Original Article; ISSN: 2474-3690
Received: May 26, 2016 | Accepted: August 15, 2016 | Published: August 18, 2016
Citation: Pereira ANP, Júnior RA, Macedo CRB, Teixeira RRDN, Magalhães IR, et al. (2016) Angiotensin-Converting Enzyme Inhibitor-Induced Cough Prevalence in Refractory Hypertensive Patients. J Hypertens Manag 2:015. 10.23937/2474-3690/1510015
Copyright: © 2016 Pereira ANP, et al. 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.



Abstract

Refractory Arterial Hypertension (RAH) is characterized by persistently high blood pressure values. Angiotensin Converting Enzyme (ACE) inhibitors in combination with other antihypertensive drugs are effective for RAH and have good clinical tolerance. According to the literature, the adverse effect of cough in patients using ACE inhibitors occurs in 5 to 20% of them. However, in clinical practice, the incidence appears to be higher, making it difficult the therapeutic adherence. This study aimed to evaluate the prevalence of cough induced by ACE inhibitors in patients with RAH as well as their clinical and laboratory characteristics. Cross-sectional study in a referral hospital in severe hypertensive cardiovascular disease. To assess the adverse effect cough in the use of ACE inhibitors, patients answered a questionnaire and blood pressure (BP) was measured on the day of the interview. 111 patients were analyzed and 67.6% were female (75). The average age was 62.8 ± 12 years. 100% (111) of the patients use or had used ACE inhibitors. The prevalence of cough was 64.9% (72). 62.2% (69) of patients were switched to angiotensin II receptor blocker as an ACE inhibitor substitute. 9.9% (11) of patients reported that the cough continued even after the discontinuation of ACE inhibitor. Patients used an average of 4.7 ± 1.1 antihypertensive medications. The average systolic blood pressure was 152.5 ± 28.4 mmHg and the average diastolic pressure was 88.5 ± 17.1 mmHg. We observed a high prevalence of cough associated with the use of ACE inhibitors in this population, different from that described in the literature. Despite the large number of antihypertensive drugs in use, the blood pressure was not controlled in most patients. It is possible that the non-use of ACE inhibitors may contribute to the low hypertensive control.


Keywords

Hypertension, ACE inhibitors, Cough, Side effect


Introduction

Systemic arterial hypertension (SAH) is one of the most common diseases in the world and is considered one of the main risk factor for cardiovascular diseases [1-3].

Refractory arterial hypertension (RAH) is defined as persistent blood pressure (BP) elevations above the recommended targets (> 140/90 mmHg or > 130/80 mmHg in patients with diabetes mellitus or established clinical nephropathy) despite the use of three antihypertensive drugs, one being a diuretic, or when using four or more antihypertensive drugs even with controlled BP [4,5].

While the prevalence of RAH is unknown, several cross-sectional studies have shown that is not uncommon [6]. Some studies suggest that the prevalence is around 4.5 to 15% of all hypertensive population [7-11].

According to the guidelines for pharmacological treatment of hypertension published by the World Health Organization and the International Society of Hypertension and the International Society of Hypertension, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), β-blockers, calcium channel blockers, and diuretics should be the first line treatment of hypertension. In adults, there is sufficient evidence to prove the effectiveness of ACE inhibitor in the treatment of SAH [12,13].

ACE inhibitors have fewer side effects in comparison to many β-blockers and diuretics [14]. However, among the side effects, dry cough is the most common and well known, making it difficult the medical adherence. ACE inhibitors promote an increase of the substance bradykinin and results in the side effect cough.

According to the literature, the incidence of ACE inhibitor-induced cough has been reported to be 5% - 20%. It is not dose dependent or related to the active ingredient of the drug. It is more common in women and in blacks, suggesting that the genotype is relevant [15-18]. Although this incidence is a literature's consensus, in medical practice what is observed is different. It is believed that, in hypertension clinics, over 20% of patients have their therapeutic plans modified (exchanging ACE inhibitor for other antihypertensive drug) complaining of constant coughing soon after the adoption of ACE inhibitors. With therapeutic change, patients generally report cough's improvement.

There is no article in the literature that studies the prevalence of cough due to ACE inhibitors in patients with RAH. The knowledge of the true prevalence will allow physicians better evaluate the adoption of this drug as first-line treatment of RAH. There will be then, with further studies, the possibility to suggest a better administration of ACE inhibitors during clinical performance.


Objectives

The primary aim of this study was to estimate and analyze the prevalence of dry cough due to ACE inhibitors in patients with refractory arterial hypertension. The secondary objectives were to evaluate clinical and laboratory characteristics of refractory arterial hypertensive patients and to assess the prevalence of patients who discontinued ACE inhibitor due to its side effects.


Methods

Study design

This study was a cross-sectional observational analysis of patients referred to the Federal University of Bahia (UFBA) Severe Hypertensive Cardiovascular Disease Service at José Maria de Magalhães Netto clinic, that belongs to the Professor Edgard Santos University Hospital Complex (Complexo-HUPES), from November, 2012 to June, 2015. All patients participating in the study were invited and informed about the objectives and all the stages of the study. Those who agreed to participate signed the Informed Consent. This study was approved by the research team's institutional review board.


Study population

Patients were included in the study if they had a BP above 140/90 mmHg using three or more antihypertensive drugs, one being a diuretic, or were using four or more antihypertensive drugs despite the value of the BP. Patients were excluded of the study if they did not sign the Informed Consent, were not able to perform the necessary laboratory exams, never used ACE inhibitor as an antihypertensive drug and had any respiratory disease with cough as one of its symptoms. The patients then underwent a complete clinical and laboratory evaluation.

Patients were determined to have refractory hypertension based on their number of medications, BP measurement at the day of the visit and medication adherence. Adherent was determined by patient self-report. Those who were adherent to medications and filled the criteria of inclusion above were determined to have refractory hypertension.

A questionnaire was applied for each patient, which obtained qualitative variables (gender, race, acute myocardial infarction history, stroke history, cigarette smoking, alcohol consumption , diabetes mellitus, metabolic syndrome, Framingham score, antihypertensive drugs in use and the presence of side effects of these medications) and quantitative variables (age, body weight, height, body mass index, waist circumference, heart rate, time of hypertension, systolic and diastolic BP and routine laboratory data). Body mass index was calculated dividing the weight in kilograms by the square of the height in meters. The waist circumference was measured in the standing position at the mid-point between the lower ribs and the iliac crest. BP was the average of 2 measurements taken after the patient had been resting for at least 5 minutes. Routine laboratory data were total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, triglycerides, glycemia, plasma sodium, plasma potassium, plasma creatinine and urea. After the first interview, the patients were instructed to return to the clinic with the laboratory test results. All antihypertensive medications from each patient were registered from the medical records and prescriptions.

The metabolic syndrome evaluation was done according to the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III-ATPIII) [19]. The presence of 3 of the following 5 criteria closed the diagnosis: waist circumference > 102 cm for men and > 88 cm for women; triglycerides ≥ 150 mg/dL; HDL-cholesterol < 40 mg/dL for men and < 50 mg/dL for women; BP ≥ 130 × 85 mmHg and fasting glucose ≥ 100 mg/dL.

To evaluate the presence of side effects due to ACE inhibitors and qualify them a questionnaire was applied. In this questionnaire the patient is asked if captopril or enalapril (in this population there was no use of other ACE-inhibitors) has been used; if there is any complaint regard those medications; if dry cough, dry throat and throat clearing were a complaint and if those symptoms continued after the drug was discontinued. For patients who still use ACE inhibitor the last question was ignored. Finally, patients were divided in 2 groups for a better characteristics analysis. The criteria for the division was the presence or not of cough. In this division gender and cough as a side effect from ACE inhibitor was taken into account.


Statistical analysis

Collected data were compiled into databases through Microsoft Excel® and were analyzed using the Statistical Package for the Social Sciences (SPSS), version 21.0 for MAC. Values are expressed as absolute frequencies, means ± standard deviation (SD) and percentage of incidence rates of events and/or procedures. Quantitative variables were analyzed by two-sample Student's t test or Mann-Whitney test, where appropriate. Categorical variables were analyzed using chi-square test. In this statistical analysis a P value ≤ 0.05 was taken as statistical significance. For a normal distribution check the Kolmogorov-Smirnov test was performed.


Results

Initially, a total of 151 refractory hypertensive patients were studied. However, 111 met the inclusion criteria and were included in the analysis. 40 patients were excluded because they never used ACE inhibitor or did not go back to the clinic with the laboratory tests results.

The mean age was 62.8 years, 67.6% were women and 50.5% were black. Most of the population was overweight, had metabolic syndrome and had a high Framingham risk score. Most did not consume alcoholic beverages, did not have cigarettes smoking habits and did not have diabetes mellitus. Baseline characteristics of the analyzed patients are presented in table 1.



Table 1: Baseline characteristics. View Table 1


The average values of total cholesterol, triglycerides, LDL-c, plasma sodium, plasma potassium, plasma creatinine and urea are within normal values. The average blood glucose value is increased. Table 2 shows the laboratory results studied in those patients.



Table 2: Laboratory results. View Table 2


Most patients had a BP outside the control range (≥ 140 × 90 mmHg). However diastolic BP remained controlled in the majority of the population as shown in table 3.



Table 3: BP values (N = 111). View Table 3


When responding to the questionnaire about ACE inhibitors, 72 (64.9%) patients reported side effects at the beginning of the treatment with ACE inhibitor. Most of them reported dry cough, throat clearing and dry throat, 68 (61.3%), 61 (55%) and 59 (53.2%) patients, respectively. 38 (34.2%) patients continued using ACE inhibitors and 69 (62.2%) patients were switched to angiotensin receptor blocker (ARB). 11 (9.9%) patients still reported those symptoms even after discontinuation of ACE inhibitor (Table 4).



Table 4: ACE inhibitor questionnaire. View Table 4


In table 5, patients were divided into 2 groups: those who had dry cough and those who did not have dry cough. The female population represented the majority in both groups, with a greater percentage in the group who reported cough (p = 0.66). Age was similar in both groups.



Table 5: Baseline characteristics comparing patients who reported cough and patients who did not reported. View Table 5


The prevalence of alcoholism was 9% in the general population, being similar between the 2 groups (p = 0.93). The presence of diabetes mellitus was higher in patients who had no cough (p = 0.11). The average body mass index in both groups was high, however there was no difference in values between the groups (p = 0.64). The mean systolic blood pressure and diastolic blood pressure did not differ between the groups, with p values of 0.33 and 0.36 respectively. The number of antihypertensive drugs used in both groups was similar (p = 0.27). In the group that reported cough, 58.8% had metabolic syndrome compared to 51.2% in the group that did not reported cough (p = 0.43). There were more current smokers in the group of patients with cough (p = 0.16).

Out of the data presented only race and a high Framingham score showed a relationship with the appearance of dry cough with a p value of 0.03 and 0.05 respectively. Finally, laboratory parameters examined in this study are described in table 6. It can be observed that fasting blood glucose was higher in the group that did not report cough (p = 0.78). Triglycerides also showed higher values in this group (p = 0.33).



Table 6: Laboratory results compared on both groups (dry cough and no dry cough). View Table 6


Discussion

Because ACE inhibitors are first-line treatment for refractory hypertension, lack of therapeutic adhesion due to the side effect dry cough can greatly impair the treatment. Therefore, relationship between dry and ACE inhibitor has been extensively studied. This present work was a cross-sectional study and aimed to estimate and analyze the prevalence of dry cough due ACE inhibitor in patients with RAH.

In this study it was found, through the ACE inhibitors questionnaire, that 61.3% of patients reported dry cough as a side effect of the drug. This value was higher than the ones found in the literature. In the study by Sato A, et al. (2015) [18], conducted in a prospective way to verify cough's frequency and characteristics during treatment with ACE inhibitor, it was found an incidence of 20%. In the study by Ng L, et al. (2014) [20], held in Singapore, with the aim to analyze the impact discontinuation of ACE inhibitor due to cough, the incidence was 30.4%. However, the relationship between race and drug tolerance must not be underestimated [20]. The difference in the incidence of cough found in our study may suggest a lower tolerance to ACE inhibitor in patients with RAH contributing to greater difficulty in controlling BP. However, more studies are needed to elucidate these issues.

In relation to the other side effects studied, more than half of the population reported throat clearing and dry throat. In the study by Ye WW on the prevalence of persistent cough during long-term treatment with enalapril, the prevalence for voice changes was 14% and for sore throat was 10% [21]. The difference of incidence may also be attributed to a lower tolerance to ACE inhibitor in patients with RAH.

Studies have shown that the discontinuation of ACE inhibitor due to cough ranged between 2.4% and 30.4% [17,18,20]. However, in this study it was found that the substitution of ACE inhibitor for ARB occurred in 62.2% of patients. This large difference can be explained by the higher incidence of cough I this study. One should take into consideration that it was not asked or studied the cause of ACE inhibitor discontinuation.

When analyzing the number of antihypertensive drugs and BP control, it can be noticed that BP of the vast majority of the population is not controlled but the systolic blood pressure is controlled even with the average use of 4.7 antihypertensive drugs. This result is similar with what has been described by Lloyd-Jones, et al. (2000) [22] and Cushman, et al. (2002) [23], which also showed a significant control of DBP and a weak control of SBP and BP. Historically, a correlation was made between SBP with arteriosclerosis process, with consequent loss of elasticity in the arterial system, common in the human being's natural aging process [2], and recommended that a more drastic therapeutic actions should be taken only if there is an elevation of DBP. However, it has been shown that a high SBP is much more common in the population [23] and may be a better predictor for cardiovascular disease than a high DBP [22]. This acknowledges is important to know especially in our population that presents with additional risk factor for isolated systolic hypertension, such as obesity and advanced age.

Patients with cough were mostly of black race, compared with the group of patients who did not have cough (p = 0.04). In the literature there is clear evidence of a higher incidence and severity of hypertension in blacks compared with the white population. The studies of Rivero-Becerra J, et al. (2004) [24], Lackland DT (2014) [25] and Saunders E (1991) [26] are examples of some of these evidences [24-26]. Bicket DP (2002) [15] found that the side effect cough due to ACE inhibitors is more common in blacks than in whites. The study by Elliott WJ (1996) [17] found that the prevalence of the side effect cough that required discontinuation of ACE inhibitors was 9.6% among blacks compared with 2.4% among other ethnicities.

When comparing the average age and hypertension time between the 2 groups of patients with and without cough it can be seen that there was no statistical significance between them (p = 0.82 and 0.62 respectively). Similarly, the comparison of laboratory date, such as total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, serum glucose, serum sodium, serum potassium, serum creatinine and serum urea, between these 2 groups of patients shows that there was no statistical significance between them (p = 0.31; 0.51; 0.39; 0.33; 0.78; 0.12; 0.37; 0.11; 0.11, respectively). These results seem to show that none of these factors has a direct influence on the incidence of side effect cough.

The presence of alcoholics, smokers and history of acute myocardial infarction and stroke was low in the general population and no statistical significance was found between the 2 groups, demonstrating a homogeneity pattern analyzing these factors and probably, individually, are not risk factors for the occurrence of cough due to ACE inhibitors.

In both groups the number of antihypertensive drugs and the average DBP were similar. The average SBP in the group of patients without cough was higher. Despite these results, there was no statistically significant difference between the 2 groups in any of the mentioned factors. It is worth noting that most of the patients were using 4 to 5 antihypertensive drugs. As this is a population with severe hypertension, mostly with long-time diagnosis, possible the pressure values and the number of medications in use did not influence the incidence of cough.

When the BMI in compared, it is clear there is a similarity between the 2 groups and there was no statistical significance (p = 0.64). In the group with cough the average BMI was 28.7 and in the group without cough the average BMI was 27.4. Mancia G, et al. (2014) [27] conducted a randomized, double-blind, placebo-controlled study that was conducted in 100 centers in 7 European countries. 1039 patients were studied. The study showed that the group taking 20 mg of enalapril had a BMI of 30.12 × 5.2 and the incidence of cough was 3.6%. The BMI value is close to the value found in our work and, despite the absence of dosage of the drugs, the incidence of cough was much higher than in the study of Mancia G, et al. (2014) [27]. The BMI values should not have contributed to the onset of coughing.

Despite the higher incidence of Diabetes Mellitus in the group without cough and a higher incidence of Metabolic Syndrome in the group of patients with cough, there was no statistical significance in the comparison of any of these factor (p = 0.11 and 0.43 respectively).

There are many potential limitations of this study inherent in its format. Because it is a cross-sectional study, it may have some biases and cannot evaluate causal and temporal relationships between the studied factors. In addition, there was some difficulty performing Ambulatory Blood Pressure Monitoring in all patients. Therefore, we cannot verify if the patients have truly refractory hypertension or have white-coat hypertension, characterizing pseudo hypertension. It was found, in the study performed by la Sierra, et al. (2011) [28], that 37.5% of patients considered having refractory hypertension may be under the white-coat effect, with normal BP levels after Ambulatory Blood Pressure Monitoring. However, because this study has a population treated at a referral center for severe hypertensive cardiovascular disease, and mostly accompanied by a long period already, it is expected that much of the sample actually fill the criteria for refractory hypertension.

In summary, the present study found that the prevalence of the side effect cough due to ACE inhibitors in the studied population was higher than the ones found in the literature for hypertensive patients. Also, refractory hypertensive patients who had cough showed a higher incidence of high Framingham score than the patients who did not have cough as well as in the first group there was more black patients than the second. Finally, a large number of patients switched the ACE inhibitor for an ARB.

Based on this discussion, physicians should better evaluate the adoption of ACE inhibitors as first-line treatment of RAH. There is a possibility that the use of other first line drugs for hypertension would result in a better medical adherence and BP control.


Perspectives

There are no studies addressing the relationship between RAH and side effect cough due to ACE inhibitor, justifying the importance of this work. The characterization of the population with refractory hypertension and the knowledge of cough's incidence is important to avoid non adherence, which may contribute to the worsening of the overall picture of these patients. For these reason reasons, further clinical research is needed to better understand this relationship, as this study showed a high prevalence of cough due to ACE inhibitors, higher than the ones found in the literature for patients with SAH.


Acknowledgement

We wish to thank Mr. Adilson Machado Gomes Junior, Ms. Priscila Neri Lacerda, Ms. Liliane Goes Bastos, Mr. Thiago Matos e Silva, Ms. Louise Medeiros Porto, Mr. André Oliveira Barbosa, Ms. Camila Barbosa Pereira and Mr. Paulo Chenaud Neto for assisting in the acquisition of data for this manuscript.


Conflicts of Interest

There are no conflicts of interest.


Ethical Statement

This study in an addition of the "Clinical and Metabolic Assessment in Refractory Arterial Hypertension" and was already planned within their specific objectives. The project was approved by the Research Ethics Committee of Hospital Ana Nery under number 138371, on 05/11/2012. All patients signed the Informed Consent.


References
  1. Sociedade Brasileira de Cardiologia/Sociedade Brasileira de Hipertensão/Sociedade Brasileira de Nefrologia (2010) VI Diretrizes Brasileiras de Hipertensão. Arq Bras Cardiol 95: 1-51.

  2. Kannel WB, Dawber TR, McGee DL (1980) Perspectives on systolic hypertension. The Framingham study. Circulation 61: 1179-1182.

  3. Mancia G, Laurent S, Rosei-Agabiti E, Ambrosioni E, Burnier M, et al. (2009) European Society of Hypertension. Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document. J Hypertens 27: 2121-2158.

  4. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, et al. (2003) Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 42: 1206-1252.

  5. Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, et al. (2007) 2007 Guidelines for the Management of Arterial Hypertension The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 25: 1105-1187.

  6. DA Calhoun, D Jones, S Textor, Goff DC, Murphy TP, et al. (2008) Resistant Hypertension: Diagnosis, Evaluation, and Treatment: a Scientific Statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Hypertension 117: e510-e526.

  7. Pimenta E, Calhoun DA (2012) Resistant hypertension: incidence, prevalence and prognosis. Circulation 125: 1594-1596.

  8. Kaplan NM (2005) Resistant hypertension. J Hypertens 23: 1441-1444.

  9. Brown MA, Buddle ML, Martin A (2001) Is resistant hypertension really resistant? Am J Hypertens 14: 1263-1269.

  10. Massierer D, Oliveira ACT, Steinhorst AM, Gus M, Ascoli AM, et al. (2012) Prevalência de Hipertensão Resistente em Adultos não Idosos: Estudo Prospectivo em Contexto Ambulatorial. Arq Bras Cardiol 99: 630-635.

  11. McAdam-Marx C, Ye X, Sung JC, Brixner DI, Khaler KH (2009) Results of a retrospective, observational pilot study using electronic medical records to assess the prevalence and characteristics of patients with resistant hypertension in an ambulatory care setting. ClinTher 31: 1116-1123.

  12. Case DB, Atlas SA, Laragh JH, Sealey JE, Sullivan PA, et al. (1978) Clinical experience with blockade of renin-angiotensin-aldosterone system by an oral converting enzyme inhibitor (SQ 14,225, captopril) in hypertensive patients. Prog Cardiovasc Dis 21: 195-206.

  13. Gavras H, Brunner HR, Turini GA, Kershaw GR, Tifft CP, et al. (1978) Antihypertensive effect of the oral converting-enzyme inhibitor SQ 14225 in man. N Engl J Med 298: 991-995.

  14. Gifford RW Jr (1997) Antihypertensive therapy. Angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, and calcium antagonists. Med Clin North Am 81: 1319-1333.

  15. Bicket DP (2002) Using ACE inhibitors appropriately. Am Fam Physician 66: 461-468.

  16. Visser LE, Stricker BH, van der Velden J, Paes AH, Bakker A (1995) Angiotensin converting enzyme inhibitor associated cough: a population-based case-control study. J Clin Epidemiol 48: 851-857.

  17. Elliott WJ (1996) Higher incidence of discontinuation of angiotensin converting enzyme inhibitors due to cough in black subjects. Clin Pharmacol Ther 60: 582-588.

  18. Sato A, Fukuda S (2015) A prospective study of frequency and characteristics of cough during ACE inhibitor treatment. Clin Exp Hypertens 20: 1-6.

  19. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (2002) Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 106: 3143-3421.

  20. Ng LP, Goh PS (2014) Incidence of discontinuation of angiotensin-converting enzyme inhibitors due to cough, in a primary healthcare centre in Singapore. Singapore Med J 55: 146-149.

  21. Yeo WW, Foster G, Ramsay LE (1991) Prevalence of persistent cough during long-term enalapril treatment: controlled study versus nifedipine. Q J Med 80: 763-770.

  22. Lloyd-Jones DM, Evans JC, Larson MG, O'Donnell CJ, Rocella EJ, et al. (2000) Differential control of systolic and diastolic blood pressure: factors associated with lack of blood pressure control in the community. Hypertension 36: 594-599.

  23. Cushman WC, Ford CE, Cutler JA, Margolis KL, Davis BR, et al. (2002) Success and predictors of blood pressure control in diverse North American settings: the Antihypertensive and Lipid-Lowering and Treatment to Prevent Heart Attack Trial (ALLHAT). J Clin Hypertens 4: 393-404.

  24. Rivero-Becerra J, Rodriguez CJ (2004) Effects of Race and Socioeconomic Status in the Incidence of Hypertension and Increased Left Ventricular Mass: a Review. Rev Bras Hipertens 11: 147-150.

  25. Lackland DT (2014) Racial differences in hypertension: implications for high blood pressure management. Am J Med Sci 348: 135-138.

  26. Saunders E (1991) Hypertension in African-Americans. Circulation 83: 1465-1467.

  27. Mancia G, Coca A, Chazova I, Girerd X, Haller H, et al. (2014) Effects on office and home blood pressure of the lercanidipine-enalapril combination in patients with Stage 2 hypertension: a European randomized, controlled clinical trial. J Hypertens 32: 1700-1707.

  28. de La Sierra A, Segura J, Banegas JR, Gorostidi M, de la Cruz JJ, et al. (2011) Clinical features of 8295 patients with resistant hypertension classified on the basis of ambulatory blood pressure monitoring. Hypertension 57: 898-902.

International Journal of Anesthetics and Anesthesiology (ISSN: 2377-4630)
International Journal of Blood Research and Disorders   (ISSN: 2469-5696)
International Journal of Brain Disorders and Treatment (ISSN: 2469-5866)
International Journal of Cancer and Clinical Research (ISSN: 2378-3419)
International Journal of Clinical Cardiology (ISSN: 2469-5696)
Journal of Clinical Gastroenterology and Treatment (ISSN: 2469-584X)
Clinical Medical Reviews and Case Reports (ISSN: 2378-3656)
Journal of Dermatology Research and Therapy (ISSN: 2469-5750)
International Journal of Diabetes and Clinical Research (ISSN: 2377-3634)
Journal of Family Medicine and Disease Prevention (ISSN: 2469-5793)
Journal of Genetics and Genome Research (ISSN: 2378-3648)
Journal of Geriatric Medicine and Gerontology (ISSN: 2469-5858)
International Journal of Immunology and Immunotherapy (ISSN: 2378-3672)
International Journal of Medical Nano Research (ISSN: 2378-3664)
International Journal of Neurology and Neurotherapy (ISSN: 2378-3001)
International Archives of Nursing and Health Care (ISSN: 2469-5823)
International Journal of Ophthalmology and Clinical Research (ISSN: 2378-346X)
International Journal of Oral and Dental Health (ISSN: 2469-5734)
International Journal of Pathology and Clinical Research (ISSN: 2469-5807)
International Journal of Pediatric Research (ISSN: 2469-5769)
International Journal of Respiratory and Pulmonary Medicine (ISSN: 2378-3516)
Journal of Rheumatic Diseases and Treatment (ISSN: 2469-5726)
International Journal of Sports and Exercise Medicine (ISSN: 2469-5718)
International Journal of Stem Cell Research & Therapy (ISSN: 2469-570X)
International Journal of Surgery Research and Practice (ISSN: 2378-3397)
Trauma Cases and Reviews (ISSN: 2469-5777)
International Archives of Urology and Complications (ISSN: 2469-5742)
International Journal of Virology and AIDS (ISSN: 2469-567X)
More Journals

Contact Us

ClinMed International Library | Science Resource Online LLC
3511 Silverside Road, Suite 105, Wilmington, DE 19810, USA
Email: contact@clinmedlib.org
 

Feedback

Get Email alerts
 
Creative Commons License
Open Access
by ClinMed International Library is licensed under a Creative Commons Attribution 4.0 International License based on a work at https://clinmedjournals.org/.
Copyright © 2017 ClinMed International Library. All Rights Reserved.