High mortality risk in ischaemic stroke patients in Arab countries

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24 April 2017

Combined data from the OPTIC (Outcomes in Patients with TIA and Cerebrovascular disease) registry and PERFORM (Prevention of Cerebrovascular and Cardiovascular Events of Ischemic Origin with Terutroban in the Patients with a History of Ischemic Stroke or Transient Ischemic Attack) trial highlight a higher residual risk of recurrent events, notably mortality, in patients with ischaemic stroke living in Arab countries compared with those in non-Arab countries. Socioeconomic risk factors were a key difference between the two groups.

Abboud H, Sissani L, Labreuche J et al. Specificities of ischemic stroke risk factors in Arab-speaking countries. Cerebrovasc Dis 2017;43:169–77.

STUDY SUMMARY

Objective:

To compare risk factors and 2-year outcomes in ischaemic stroke patients living in Arab (Middle East and North Africa) and non-Arab countries.

Study design:

The OPTIC registry enrolled patients with cerebrovascular disease aged ≥45 years from 17 low- and middle-income countries. PERFORM was an international randomized controlled trial which compared terutroban with aspirin for prevention of cerebral and cardiovascular ischaemic events in patients aged ≥ 55 years with a noncardioembolic ischaemic stroke (≤ 3 months) or a transient ischaemic attack (≤ 8 days).

Study population:

The composition of Arab and non-Arab subgroups in OPTIC and PERFORM is summarized.

	Arab	Non-Arab
OPTIC (n=3,487)	1,669 (47.9%)	1,818
Mean age, yr	64.1±10.4	66.3±11.2
Male, %	62%	52%
Prevalence of risk factors, %
Dyslipidaemia	69.6	76.7
Hypertension	81.5	83.6
Diabetes	43.9	29.3
Smoking	28.1	15.3
PERFORM (n=19,100)	268 (1.4%)	18,832
Mean age, yr	66.2±7.2	64.1±10.4
Male, %	53%	63%
Prevalence of risk factors, %
Dyslipidaemia	34.3	60.4
Hypertension	72.0	83.7
Diabetes	50.0	27.4
Smoking	20.5	26.7

Key endpoints:

Primary: a composite of composite of nonfatal stroke, nonfatal myocardial infarction (MI), or cardiovascular death

Secondary: MI or stroke (separately and either fatal or nonfatal)

Methods:

Linear regression analysis was used to compare baseline characteristics (demographics, medical history, examination findings, socioeconomic factors, medication use) between the 2 groups after adjustment on age and gender. Data for triglycerides, creatinine, and glucose concentrations were log-transformed before analysis.

Cox proportional hazard modelling was used to compare 2-year event rates for the primary and secondary outcomes) between the 2 groups, adjusting for age and gender (model). A multivariable model was performed including hypertension, dyslipidaemia, and smoking (model 2); model 2 variables plus body mass index and diabetes (model 3); and model 3 variables plus socioeconomic data (model 4).

Results:

Patients from Arab countries had a higher prevalence of diabetes (OPTIC registry 43.9% vs. 29.3%, p < 0.0001; PERFORM trial 50.0% vs. 27.4%, p < 0.0001). In addition, data from the OPTIC registry highlighted significant (p<0.0001) socioeconomic differences between individuals in Arab and non-Arab countries; the former were more likely to be living in rural areas (19% vs. 7%), unemployed (36% vs. 27%), have no health insurance (32% vs. 15%) and have a low educational level (43% vs. 12%).

In both studies, the risk of a recurrent event was significantly higher in Arab than non-Arab countries over the 2-year follow-up. This difference was most notable for cardiovascular death, which was nearly 50% higher in OPTIC and nearly 4-fold higher in PERFORM in patients from Arab than non-Arab countries (Table).

In OPTIC, modelling incorporating socioeconomic cardiovascular risk factors resulted in no significant difference between the 2 groups (Table).

Table. Risk of primary and secondary outcomes (Arab vs. non-Arab countries)

Study/outcome	HR (95% CI) Model 3	p-value	HR (95% CI) Model 4	p-value
OPTIC
Primary	1.32 (1.07-1.63)	0.009	1.24 (0.98-1.55)	0.07
MI	1.12 (0.72-1.75)	NS	1.25 (0.78-2.02)	NS
Stroke	1.36 (1.05-1.76)	0.02	1.22 (0.92-1.62)	NS
CVD death	1.67 (1.16-2.43)	0.007	1.48 (0.98-2.24)	0.06
PERFORM
Primary	1.85 (1.36-2.50)	<0.0001	1.84 (1.35-2.51)	0.0001
MI	1.99 (0.88-4.53)	0.10	2.33 (1.00-5.42)	0.05
Stroke	1.13 (0.74-1.73)	0.57	1.12 (0.73-1.73)	0.59
CVD death	4.89 (3.09-7.76)	<0.0001	3.81 (2.34-6.21)	<0.0001

Model 3 included hypertension, dyslipidaemia, smoking, body mass index and diabetes as risk factors; Model 4 also incorporated socioeconomic cardiovascular risk factors.

Conclusion:

Patients with ischaemic stroke living in Arab countries had a lower mean socioeconomic status, a much higher prevalence of diabetes mellitus, and a higher rate of major adverse cardiovascular events compared with patients from non-Arab countries. This finding is partly explained by a higher prevalence of risk factors and also by a high prevalence of poverty and low educational level.

COMMENT

Stroke is important contributor to cardiovascular morbidity and mortality. In developing regions, such as the Middle East and North Africa, projected rates of death due to stroke are anticipated to double by 2030 (1). The current report also shows that among individuals with a history of cerebrovascular disease, there is a high risk of recurrent events in Arab countries, which is at least 50% higher than in non-Arab regions.

Consistent with other reports, it is clear that a high prevalence of cardiovascular risk factors is a driver for this high risk for both first and recurrent events. While high blood pressure has been reported to be a factor in over half of all strokes in the Middle East and North Africa (2), the current report indicated no difference in hypertension prevalence between Arab and non-Arab countries, implying that other risk factors are more relevant for the risk of recurrent stroke. Key among these are diabetes and smoking, both of which are common in Arab regions. For example, in the Centralized Pan-Middle East Survey on the undertreatment of hypercholesterolaemia (CEPHEUS) in the Arabian Gulf, 13% of the cohort’s patients were smokers, 76% had diabetes and 71% had metabolic syndrome (3). Adoption of a Western diet and lifestyle explains the high prevalence of diabetes in this region (4). Moreover, as shown by the OPTIC data, there is a high persistence of cardiovascular risk factors in patients with pre-existing cardiovascular disease in Arab countries, as nearly half have diabetes, and over one-quarter smoke.

Low socioeconomic status is also relevant to the high stroke risk in Arab countries, as previously shown by the Gulf Cooperation Council stroke awareness study (5). OPTIC highlighted the importance of socioeconomic cardiovascular risk factors, such as unemployment, lack of health insurance, and limited education as contributors to the risk of a recurrent cardiovascular event. The fact that adjustment for socioeconomic risk factors attenuated the significance of differences between patients living in Arab and non-Arab countries implies that disparity in economic status is a key driver of risk in Arab countries.

Taken together, these data underline an urgent need for education to prevent stroke, and improve the prognosis of patients with a history of ischaemic stroke in Arab countries. Stroke education has to focus on the high-risk groups, particularly the younger population, as OPTIC has shown that stroke occurred at an earlier age for individuals living in Arab countries. Strategies should focus on improving lifestyle, smoking cessation, as well as overcoming poverty to reduce the residual risk of recurrent cardiovascular events in ischaemic stroke patients in Arab countries.

References

1. Tran J, Mirzaei M, Anderson L, Leeder SR. The epidemiology of stroke in the Middle East and North Africa. J Neurol Sci 2010;295(1-2):38-40.

2. Tran J, Mirzaei M. The population attributable fraction of stroke associated with high blood pressure in the Middle East and North Africa. J Neurol Sci 2011;308:135-8.

3. Al-Zakwani I, Al-Mahmeed W, Arafah M et al. Control of risk factors for cardiovascular disease among multinational patient population in the Arabian Gulf. Curr Vasc Pharmacol 2016;14:374-81.

4. Aljefree N, Ahmed F. Association between dietary pattern and risk of cardiovascular disease among adults in the Middle East and North Africa region: a systematic review. Food Nutr Res 2015;59:27486.

5. Kamran S, Bener AB, Deleu D et al. The level of awareness of stroke risk factors and symptoms in the Gulf Cooperation Council countries: Gulf Cooperation Council stroke awareness study. Neuroepidemiol 2007;29:235-42.

Key words

residual cardiovascular risk; ischaemic stroke; Arab countries; diabetes; socioeconomic risk factors