The prevalence and outcome of hypertension in patients with acute coronary syndrome in six Middle-Eastern countries

Abstract

Aims. The aim was to report the prevalence and significance of hypertension (HTN) in patients with acute coronary syndrome (ACS). Methods and major findings. Over a 6-month period in 2007, 8171 consecutive patients (49.4% hypertensive and 50.6% non-hypertensive) presenting with ACS were enrolled in a prospective, multicenter study from six Middle Eastern adjacent countries. Patients with HTN were older (59.2 vs 53.1 years, p<0.001), and more likely to be female (34% vs 14.4%, p<0.001) when compared with patients without HTN. Patients with HTN were also more likely to have diabetes mellitus, hyperlipidemia, cerebrovascular disease, prior history of coronary artery disease, peripheral artery disease but less likely to be cigarette smokers. At admission, HTN patients had higher Killip class, heart rate and GRACE risk scoring. In-hospital mortality was higher in hypertensive patients with ST-elevation myocardial infarction (STEMI) but not in patients with non-STEMI or unstable angina. The incidence of heart failure complications was significantly higher among patients with HTN in overall ACS type (OR = 1.2, 95% CI 1.001–1.338, p= 0.04). Main conclusion. In this large cohort of patients with ACS, HTN was an independent predictor of heart failure and was associated with an increased rate of in-hospital mortality in STEMI only.

Key Words::

• Acute coronary syndrome
• heart failure
• hypertension
• myocardial infarction

Introduction

Hypertension (HTN) is a well-known risk factor for the development of atherosclerosis (1) resulting in increased incidence of peripheral vascular disease (2), cerebrovascular disease (3), renal disease (4), heart failure (5,6) and coronary artery disease (7). The prevalence of antecedent HTN in patients with acute myocardial infarction (AMI) varies from 31% to 59% (8–10). Despite extensive epidemiological data regarding the prevalence of HTN and its sequelae in the general population, its relationship to prognosis among patients with acute coronary syndrome (ACS) is not well established; data are conflicting. In some clinical trials (11,12), HTN was an independent correlate of mortality, while another study of the ACS failed to identify a difference in long-term outcomes when comparing hypertensive and non-HTN patients (13). The purpose of the present analysis was to assess the prevalence and importance of HTN as a prognostic factor among large cohort of Middle-Eastern patients with ACS.

Patients and methods

The data was collected from a 6-month prospective, multicenter study of the Gulf Registry of Acute Coronary Events (Gulf RACE) that recruited 8169 consecutive ACS patients from six adjacent Middle Eastern Gulf countries (Bahrain, Kuwait, Qatar, Oman, United Arab Emirates and Yemen). Patients were recruited from 64 hospitals with the diagnosis of ACS including unstable angina (UA) and non-ST-and ST-elevation myocardial infarction (NSTEMI and STEMI). An on-site cardiac catheterization laboratory was available in 30% of hospitals, while 31% of hospitals had a laboratory available within a 60-min drive. The majority of hospital (73%) had a coronary care unit on-site. There were no exclusion criteria and thus all the prospective patients with ACS were actually enrolled. The study received ethical approval from the institutional ethical bodies in all participating countries. Full details of the methods have been published (14). Diagnosis of the different types of ACS and definitions of data variables were based on the American College of Cardiology clinical data standards (15).

All patients gave informed consent to process their anonymous data. Data were collected on record forms by the treating physicians. Completed data sheets were sent to the central data processing center, for uniform monitoring and registration.

Definition of hypertension

Systemic HTN was defined in the current registry as either (i) history of HTN diagnosed and treated with medication, diet, and/or exercise or (ii) blood pressure greater than 140 mmHg systolic and/or diastolic pressure greater than 90 mmHg on at least two occasions.

Statistical analysis

Patients’ characteristics data are presented as proportions, medians, or mean±SD as appropriate. Whenever possible, rates were used to describe patient populations. The frequencies of categorical variables in the two populations (hypertensive and non-hypertensive) were compared using the chi-square test. Continuous variables were compared using the two-tailed Student t-test. Variables influencing in-hospital heart failure were assessed with multiple logistic regressions after adjustment for all the confounders (i.e. age, sex, heart rate, blood pressure and diabetes mellitus). Odds ratios, 95% CI and p-values were reported for significant predictors. A p-value <0.05 was considered significant. All data analyses were carried out using the Statistical Package for Social Sciences version 14 (SPSS Inc., USA).

Results

Study population characteristics

We enrolled 8171 patients who were admitted with ACS, 4039 (49.4%) patients had HTN and 4139 (50.6%) had no HTN. Among patients with HTN, NSTEMI was the commonest presentation followed by UA and STEMI. While in non-HTN patients, STEMI was the commonest presentation followed by NSTEMI and UA.

Presenting symptoms and baseline clinical characteristics

When compared with patients without HTN, patients with HTN were older, more likely to be female and were more likely to have diabetes mellitus, hyperlipidemia and cerebrovascular disease. Peripheral artery disease, chronic kidney disease, prior aspirin use, previous MI, previous angina, previous percutaneous coronary interventions (PCI) and previous coronary artery bypass grafting (CABG) were also more common among patients with HTN when compared with those without HTN. Cigarette smoking was less prevalent among HTN patients. On admission, systolic and diastolic blood pressures, heart rate, body mass index (BMI), Killip class and GRACE risk scoring were higher and left ventricular (LV) ejection fraction was lower in HTN patients.

Admission serum creatinine and glucose were higher in HTN than in non-HTN patients, but the level of total cholesterol, triglyceride and peak troponin were higher in non-HTN patients (Table I).

Table I. Clinical characteristics and risk factors for acute coronary syndrome.

	HTN (n = 4039)	Non-HTN (n = 4132)	p-value
Age (mean±SD)	59.2 ± 11.6	53.1 ± 12.4	<0.001
Females, %	34	14.4	<0.001
Prior angina pectoris, %	53	28	<0.001
Prior myocardial infarction, %	32.2	16.8	<0.001
Prior CABG, %	8.6	2.7	<0.001
Prior PCI, %	16.8	6.7	<0.001
Family history of CAD, %	13.6	13.5	0.87
Diabetes mellitus, %	55.8	25.4	<0.001
Smoking, %	23.5	38.6	<0.001
Dyslipidemia, %	48.6	15.5	<0.001
Stroke, %	7.8	1.5	<0.001
Chronic obstructive pulmonary disease, %	3.7	6.9	<0.001
Prior aspirin use, %	57.4	24.4	<0.001
Peripheral vascular disease, %	1	3.4	<0.001
Dialysis, %	1.8	0.2	<0.001
Heart rate (mean, beats/min)	87 ± 23	84 ± 22	<0.001
SBP (mean, mmHg)	147 ± 33	132 ± 26	<0.001
DBP (mean, mmHg)	86 ± 19	81.1 ± 17	<0.001
BMI (mean)	28 ± 6	26 ± 5	<0.001
Ischemic chest pain, %	74.2	84.4	<0.001
Atypical chest pain, %	6.7	6.4	<0.001
Dyspnea, %	14.2	5.5	<0.001
Killip class >I, %	28	15.8	<0.001
GRACE risk scoring
Low, n (%)	1012 (32.6)	1495 (45.7)	<0.001
Medium, n (%)	881 (28.4)	955 (29.2)
High, n (%)	1211 (39)	820 (25.1)
Lab. findings
First blood sugar (mg/dl)	11.1 ± 12.1	9.7 ± 10.8	<0.001
Fasting blood sugar (mg/dl)	8.2 ± 8.3	7.2 ± 7.1	<0.001
Peak troponin (ng/ml)	10.3 ± 40.6	22 ± 145	<0.001
First creatinine (μmol/l)	103.5 ± 112.6	82.3 ± 69.3	<0.001
Total cholesterol	4.5 ± 2.5	4.7 ± 2.9	<0.001
HDL(μmol/l)	1.3 ± 3.9	1.33 ± 3.6	0.715
LDL(μmol/l)	3.7 ± 9.6	4.0 ± 9	0.355
Fasting triglyceride (μmol/l)	2.4 ± 8.7	2.7 ± 8.9	0.03
First hemoglobin(mean,gm/l)	14.35 ± 11.8	14.99 ± 10.6	0.009
LV ejection fraction (%)
<40%, n (%)	891 (32.7)	816 (28.2)	<0.001

HTN, hypertension; CABG, coronary artery bypass graft; PCI; percutaneous coronary interventions, CAD; coronary artery disease, SBP; systolic blood pressure, DBP; diastolic blood pressure. GRACE; Global registry of acute coronary events; HDL, high-density lipoprotein; LDL, low-density lipoprotein; LV, left ventricular.

In-hospital treatment and outcome

In STEMI patients, 571 (54%) patients with HTN received thrombolytic therapy while 1287 (60%) non-HTN patients received thrombolytic therapy. The median door to needle time was shorter in patients with HTN. Primary PCI were low and comparable between the two groups.

Other evidence-based medications including aspirin, clopidogrel, heparin and low-molecular weight heparin were administered more frequently to patients without HTN while angiotensin-converting enzyme inhibitors (ACE) and angiotensin receptor blockers (ARB) were prescribed more frequently to patients with HTN (Table II). At discharge, diuretics and ACE were prescribed more frequently to patients with HTN, whereas beta-blockers were prescribed more frequently to non-HTN patients.

Table II. Management of patients with acute coronary syndrome (ACS) with and without hypertension (HTN).

	HTN	Non-HTN	p-value
On-admission medications
Door to needle (median, IQR), min	45.9 ± 142.5	63 ± 176.6	0.004
Thrombolysis, %	54	60.2	<0.001
Aspirin, %	97.4	98.3	0.008
Clopidogrel, %	52.2	54.5	0.03
Heparin, %	40.5	54.3	<0.001
LMW-heparin, %	52.7	40.9	<0.001
Gp IIb/IIIa inhibitor, %	10.4	11.1	0.3
Beta-blocker, %	64.9	65.3	0.7
ACE, %	67.7	59.6	<0.001
ARB, %	8.3	1.5	<0.001
Primary PCI, %	19.1	19.9	0.5
Facilitated PCI, %	2.6	3.4	0.01
Discharge medications
Aspirin, n (%)	93.6	94.1	0.3
Clopidogrel, n (%)	48.8	51.2	0.2
Statin, n (%)	82.0	79.5	0.004
ACE/ARB, n (%)	69.5	67.8	0.1
Beta-blocker, n (%)	73.8	76.2	0.01
Diuretics, n (%)	33.6	16	<0.001

LMW-heparin, low molecular weight heparin; Gp IIb/IIIa inhibitor, glycoprotein IIb/IIIa inhibitor; ACE, angiotensin-converting enzyme inhibitors; ARB, angiotensin receptor blockers; PCI, percutaneous coronary interventions.

Multivariate predictors of outcome

Overall, there were no significant differences between HTN and non-HTN patients in in-hospital death, recurrent myocardial infarction, cardiogenic shock, major bleeding or stroke, although patients with HTN had significantly higher heart failure complications. In patients with STEMI, the presence of HTN was significantly associated with increased risk of death (Figure 1), heart failure, recurrent myocardial ischemia and myocardial infarction, cardiogenic shock and a trend towards increased risk of bleeding complications. In NSTEMI and UA, HTN was associated with significantly higher incidence of heart failure complications only (Table III). To find clinical factors that could predict the occurrence of in-hospital heart failure, we used a logistic regression model in which in-hospital heart failure was the dependent variable. The following risk factors were entered as independent variables: sex, age, HTN and diabetes mellitus. After adjustment for age, sex and diabetes mellitus, HTN was independent predictor of in-hospital heart failure in overall ACS (OR = 1.2, 95% CI 1.001–1.338, p =0.04) and STEMI (OR =1.6, 95% CI 1.27–1.98, p<0.01) but not in NSTEACS (Figure 2).

Figure 1. In-hospital mortality in hypertension (HTN) versus non-HTN stratified according to acute coronary syndrome (ACS) diagnosis [ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI) or unstable angina].

Figure 2. Predictors of in-hospital heart failure in patients with acute coronary syndrome (ACS); STEMI, ST-segment elevation myocardial infarction; NSTEMI, non-ST-segment elevation ACS.

Table III. In-hospital clinical outcomes.

	HTN (n = 4036)	Non-HTN (n = 4129)	p-value
In-hospital death, %	3.7	3.4	0.5
Heart failure, %	19.7	12.9	<0.001
Recurrent ischemia, %	10.2	8.9	0.05
Re-infarction, %	2.3	2.6	0.4
Cardiogenic shock, %	5.3	4.9	0.4
Major bleeding, %	0.8	0.6	0.2
Stroke, %	0.6	0.8	0.1
Hospital stay (mean) (days)	5.5 ± 5	5.57 ± 4.1	0.1
STEMI	(n = 1067)	(n = 2133)
In-hospital death, %	9.2	4.7	<0.001
Heart failure, %	23.8	13.8	<0.001
Recurrent ischemia, %	12.2	8.4	0.001
Re-infarction, %	4.1	2.5	0.014
Cardiogenic shock, %	13	7.3	<0.001
Major bleeding, %	1.6	0.8	0.055
Stroke, %	1.8	0.8	0.013
NSTEMI	(n = 1523)	(n = 1107)
In-hospital death, %	2.6	2.5	0.9
Heart failure, %	20.3	11.8	<0.001
Recurrent ischemia, %	10.4	10.5	0.9
Re-infarction, %	3.2	3.3	0.9
Cardiogenic shock, %	3.5	2.9	0.3
Major bleeding, %	0.7	0.5	0.4
Stroke, %	0.7	0.4	0.3
Unstable angina	(n = 1448)	(n = 892)
In-hospital death, %	0.9	1.5	0.2
Heart failure, %	15.9	12	0.009
Recurrent ischemia, %	8.5	8.1	0.7
Re-infarction, %	0.8	0.7	0.8
Cardiogenic shock, %	1.3	1.7	0.4
Major bleeding, %	0.5	0.2	0.3
Stroke, %	0.3	0.2	0.8

HTN, hypertension; STEMI, ST-segment elevation myocardial infarction; NSTEMI, non-ST-segment elevation myocardial infarction.

Discussion

This is the first systematic description of the characteristics and the prognostic impact of HTN on patients with ACS in the Arab Middle East. We assessed the importance of HTN in large group of patients with ACS recruited from six countries over a 6-month period. In this observational study of an ACS population, almost 50% of subjects had a history of systemic HTN. HTN was independent predictor of heart failure complications across the spectrum of ACS. In STEMI patients, the presence of HTN was associated with increased risk of in-hospital death and recurrent myocardial ischemia.

The proportion of hypertensive patients in our study was comparable with some (16,17) but not all reported studies (18,19), which reported lower prevalence of hypertensive patients: 23–37% among patients admitted with MI (Table IV). On the other hand, Majahalme et al. (13) reported higher frequency of hypertensive patients (64.4%) compared with the current study. Furthermore, Dumaine et al. (20) reported an even higher prevalence of HTN utilizing data of six randomized Thrombolysis in Myocardial Infarction (TIMI) trials, where the prevalence of patients with HTN was 71.3% but only patients with non-ST-segment elevation ACS were included in that analysis.

Table IV. Reported studies of hypertension (HTN) and acute coronary syndrome.

Author/year/origin (ref.)	Study design	No of patients	Prev. HTN (%)	Follow-up	Outcome
Majahalme et al./ 2003/USA (13)	Registry	890	64.4%	Long-term	• Adverse events were equivalent in HTN and non-HTN patients
Ivanuša et al./2008/Croatia (28)	Retrospective/registry	436	47.2%	In-hospital	• HTN patients with AMI had better in-hospital outcome than normotensive patient
Kang et al./2009/Korea (12)	Registry	8568	48.5%	Long-term	• HTN at the time of AMI is associated with ↑ in-hospital mortality
					• Antecedent HTN was not significantly associated with higher mortality
Thune et al./2008/USA (30)	Registry	14,703	53.8%	Long-term	• Antecedent HTN independently increased heart failure and death complications in high risk AMI
					• 6-months after a high-risk MI, elevated systolic blood pressure, a potentially modifiable risk factor, is associated with an increased risk of subsequent stroke and cardiovascular events
Dumaine et al./2006/USA (20)	Randomized trials (pos-hoc analysis)	15,414	71.3%	Long-term	• HTN was independent marker for major short- and long-term cardiac adverse outcomes after NST-ACS
Abrignani et al./ 2005/Italy (27)	Registry	4994	27.6%	In-hospital	• HTN patients with first AMI had better in-hospital outcome than age- and gender matched normotensive subjects
Gustafsson et al./ 1998/Denmark (18)	Retrospective/registry	6676	23%	Long-term	• HTN is a moderate risk factor for mortality after MI in patients aged ≤65 years
Irma et al./2004/Denmark (29)	Registry	3326	25%	In-hospital	• After an acute MI, survival rates for patients with and without a history of HTN are identical when contemporary medical therapy is employed
Bener et al./2005/Qatar (23)	Retrospective/registry	5390	37%	In-hospital	• Strong association between HTN and acute MI
Current study/2010	Registry	8171	49.4%	In-hospital	• In-hospital mortality ↑ in HTN with STEMI but not in NSTEMI or unstable angina
					• The incidence of heart failure complications was ↑ among patients with HTN regardless of the ACS type

ACS, acute coronary syndrome; STEMI, ST-elevation myocardial infarction; NSTEMI, Non-ST elevation myocardial infarction; AMI, acute myocardial infarction; ↑, increased.

It should be noted that the prevalence of HTN also depends on the study circumstances; in a cross-sectional study in primary health care centers in Qatar, we have previously reported an overall 32.1% prevalence of HTN (32.6% in men and 31.7% in women) among 1500 Qatari patients studied, which is lower than the prevalence in the current study supporting the association between HTN and ACS (21). On the other hand, on a 10-year retrospective analysis of all patients admitted with acute cardiac conditions in Qatar between 1991 and 2001, we reported a 46.9% prevalence of HTN among patients admitted with congestive heart failure (22) and 37% prevalence of HTN among patients admitted with acute myocardial infarction (23). The current study extends these observations in the entire spectrum of ACS and involves patients enrolled from six Middle-eastern countries in the current era.

There was a greater frequency of co-morbidity in our hypertensive ACS population. Our hypertensive population was also older and than non-HTN patients and this consistent with other studies (16,18), HTN patients were also more often women when compared with non-HTN patients. It is well known that HTN is often associated with the metabolic syndrome, and our data showed an excess prevalence of obesity and diabetes mellitus among hypertensives, thus supporting that theory. Our hypertensive patients also had greater frequency of a history of cardiac and cardiovascular events compared with normotensives.

Our finding of fewer numbers of STEMI in hypertensives resonates also with the report of Aursnes & Landmark (19) on a relatively small population of hypertensives with acute myocardial infarctions. They found more NSTEMI but similar infarct sizes in patients with HTN compared with normotensives. They speculated that hypertensives had hypertrophied myocardium and that a smaller proportion of patients with hypertrophy developed necrosis. Because HTN induces structural changes within the left ventricle, it was expected that the patients with HTN would develop clinical signs of heart failure more often than non-HTN patients. When we compared admission Killip class, as a measure of hemodynamic compromise, we found significant differences between two groups of patients; ACS patients with HTN were more likely to develop heart failure. The current findings are consistent with our previous report of HTN as a predictor of congestive heart failure (22).

The adverse effect of ventricular remodeling and greater activation of neurohormonal systems after AMI in a group of hypertensive patients described by Richards et al. (24), obviously, have influence in the early post-infarction period in our patients. The impact of HTN on prognosis during hospitalization for AMI was evaluated in several studies. The results of Kang et al.'s (12), Herlitz et al.'s (25) and Dumaine et al.'s (20) studies showed that a history of HTN was associated with more adverse outcomes in patients with AMI or non ST-segment elevation ACS. Studies by Boden (26), Majahalme et al. (13) and Irma et al. (29) did not show worse in-hospital outcome in hypertensive patients with AMI. On the other hand, some studies found that patients with AMI and HTN, treated in a county hospital, had better in hospital outcome than normotensive patients (27,28). In the current study though, the hypertensive patients’ mortality was higher in STEMI only and not in NSTEMI and UA. HTN, however, was an independent risk factor for heart failure in overall ACS, which is similar to previous observations (24,25,30).

Study limitations

Our data was collected from an observational study, which is a limitation. The fundamental limitations of observational studies cannot be eliminated because of the non-randomized nature and unmeasured confounding factors. However, well-designed observational studies provide valid results and do not systematically overestimate the results compared with the results of randomized controlled trials. Long-term follow-up is needed in both groups to consolidate our findings.

Conclusion

HTN is highly prevalent among patients presenting with ACS in six Middle-eastern countries. HTN is associated with higher risk profile characteristics and increased risk of development of heart failure. In STEMI patients, HTN is associated with increased risk of death and recurrent myocardial ischemia.

Funding

The Gulf RACE is a Gulf Heart Association project and was financially supported by Sanofi Aventis, Paris, France and Qatar Telecommunications Company, Doha, Qatar. The sponsors had no role in study design, data collection or data analysis. The sponsors had no role in the writing of the report and submission of the manuscript.

Conflict of interest:

The authors have no conflict of interest.