Practice patterns and outcomes after stroke across countries at different economic levels (INTERSTROKE): an international observational study.

BACKGROUND: Stroke disproportionately affects people in low-income and middle-income countries. Although improvements in stroke care and outcomes have been reported in high-income countries, little is known about practice and outcomes in low and middle-income countries. We aimed to compare patterns of care available and their association with patient outcomes across countries at different economic levels. METHODS: We studied the patterns and effect of practice variations (ie, treatments used and access to services) among participants in the INTERSTROKE study, an international observational study that enrolled 13 447 stroke patients from 142 clinical sites in 32 countries between Jan 11, 2007, and Aug 8, 2015. We supplemented patient data with a questionnaire about health-care and stroke service facilities at all participating hospitals. Using univariate and multivariate regression analyses to account for patient casemix and service clustering, we estimated the association between services available, treatments given, and patient outcomes (death or dependency) at 1 month. FINDINGS: We obtained full information for 12 342 (92%) of 13 447 INTERSTROKE patients, from 108 hospitals in 28 countries; 2576 from 38 hospitals in ten high-income countries and 9766 from 70 hospitals in 18 low and middle-income countries. Patients in low-income and middle-income countries more often had severe strokes, intracerebral haemorrhage, poorer access to services, and used fewer investigations and treatments (p<0·0001) than those in high-income countries, although only differences in patient characteristics explained the poorer clinical outcomes in low and middle-income countries. However across all countries, irrespective of economic level, access to a stroke unit was associated with improved use of investigations and treatments, access to other rehabilitation services, and improved survival without severe dependency (odds ratio [OR] 1·29; 95% CI 1·14-1·44; all p<0·0001), which was independent of patient casemix characteristics and other measures of care. Use of acute antiplatelet treatment was associated with improved survival (1·39; 1·12-1·72) irrespective of other patient and service characteristics. INTERPRETATION: Evidence-based treatments, diagnostics, and stroke units were less commonly available or used in low and middle-income countries. Access to stroke units and appropriate use of antiplatelet treatment were associated with improved recovery. Improved care and facilities in low-income and middle-income countries are essential to improve outcomes. FUNDING: Chest, Heart and Stroke Scotland.

Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study.

BACKGROUND: Stroke is a leading cause of death and disability, especially in low-income and middle-income countries. We sought to quantify the importance of potentially modifiable risk factors for stroke in different regions of the world, and in key populations and primary pathological subtypes of stroke. METHODS: We completed a standardised international case-control study in 32 countries in Asia, America, Europe, Australia, the Middle East, and Africa. Cases were patients with acute first stroke (within 5 days of symptom onset and 72 h of hospital admission). Controls were hospital-based or community-based individuals with no history of stroke, and were matched with cases, recruited in a 1:1 ratio, for age and sex. All participants completed a clinical assessment and were requested to provide blood and urine samples. Odds ratios (OR) and their population attributable risks (PARs) were calculated, with 99% confidence intervals. FINDINGS: Between Jan 11, 2007, and Aug 8, 2015, 26 919 participants were recruited from 32 countries (13 447 cases [10 388 with ischaemic stroke and 3059 intracerebral haemorrhage] and 13 472 controls). Previous history of hypertension or blood pressure of 140/90 mm Hg or higher (OR 2·98, 99% CI 2·72-3·28; PAR 47·9%, 99% CI 45·1-50·6), regular physical activity (0·60, 0·52-0·70; 35·8%, 27·7-44·7), apolipoprotein (Apo)B/ApoA1 ratio (1·84, 1·65-2·06 for highest vs lowest tertile; 26·8%, 22·2-31·9 for top two tertiles vs lowest tertile), diet (0·60, 0·53-0·67 for highest vs lowest tertile of modified Alternative Healthy Eating Index [mAHEI]; 23·2%, 18·2-28·9 for lowest two tertiles vs highest tertile of mAHEI), waist-to-hip ratio (1·44, 1·27-1·64 for highest vs lowest tertile; 18·6%, 13·3-25·3 for top two tertiles vs lowest), psychosocial factors (2·20, 1·78-2·72; 17·4%, 13·1-22·6), current smoking (1·67, 1·49-1·87; 12·4%, 10·2-14·9), cardiac causes (3·17, 2·68-3·75; 9·1%, 8·0-10·2), alcohol consumption (2·09, 1·64-2·67 for high or heavy episodic intake vs never or former drinker; 5·8%, 3·4-9·7 for current alcohol drinker vs never or former drinker), and diabetes mellitus (1·16, 1·05-1·30; 3·9%, 1·9-7·6) were associated with all stroke. Collectively, these risk factors accounted for 90·7% of the PAR for all stroke worldwide (91·5% for ischaemic stroke, 87·1% for intracerebral haemorrhage), and were consistent across regions (ranging from 82·7% in Africa to 97·4% in southeast Asia), sex (90·6% in men and in women), and age groups (92·2% in patients aged ≤55 years, 90·0% in patients aged >55 years). We observed regional variations in the importance of individual risk factors, which were related to variations in the magnitude of ORs (rather than direction, which we observed for diet) and differences in prevalence of risk factors among regions. Hypertension was more associated with intracerebral haemorrhage than with ischaemic stroke, whereas current smoking, diabetes, apolipoproteins, and cardiac causes were more associated with ischaemic stroke (p<0·0001). INTERPRETATION: Ten potentially modifiable risk factors are collectively associated with about 90% of the PAR of stroke in each major region of the world, among ethnic groups, in men and women, and in all ages. However, we found important regional variations in the relative importance of most individual risk factors for stroke, which could contribute to worldwide variations in frequency and case-mix of stroke. Our findings support developing both global and region-specific programmes to prevent stroke. FUNDING: Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland (Sweden), AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network.

Deep breathing: A simple test for white coat effect detection in primary care.

AIM: White coat hypertension (WCH) is hard to differentiate from sustained hypertension without the use of 24-h ambulatory blood pressure monitoring (ABPM). This invaluable procedure is nevertheless cumbersome and expensive. A simple test of deep breathing over 30 s (DBT) was proposed as a method to unveil WCH. METHODS: Two hundred and fourteen outpatients referred for the evaluation of uncontrolled hypertension (blood pressure, BP > 140/90 mmHg despite therapy) were enrolled in a controlled clinical trial. The examinees were randomly divided in two groups: control (n = 108; sequential standard BP measurement only) and intervention (n = 106; the same+DBT), using ABPM as the reference standard. RESULTS: The relative decrease in BP was significantly larger in the intervention group than in the control group, by 15/4 mmHg (p = 0.005). The best detection of WCH was obtained at ≥ 15% systolic BP reduction following DBT, with a positive predictive value of 94.0% (95% CI 72.0-100.0). BP reduction of ≤ 8% may rule WCH out with a negative predictive value of 78.4% (95% CI 64.0 - 85.9). CONCLUSION: DBT is a reliable, inexpensive and fast test for the detection of WCH in primary care.

Variations in the prevalence of atrial fibrillation, and in the strength of its association with ischemic stroke, in countries with different income levels: INTERSTROKE case-control study.

BACKGROUND: The contribution of atrial fibrillation (AF) to the etiology and burden of stroke may vary by country income level. AIMS: We examined differences in the prevalence of AF and described variations in the magnitude of the association between AF and ischemic stroke by country income level. METHODS: In the INTERSTROKE case-control study, participants with acute first ischemic stroke were recruited across 32 countries. We included 10,363 ischemic stroke cases and 10,333 community or hospital controls who were matched for age, sex, and center. Participants were grouped into high-income (HIC), upper-middle-income (subdivided into two groups-UMIC-1 and UMIC-2), and lower-middle-income (LMIC) countries, based on gross national income. We evaluated the risk factors for AF overall and by country income level, and evaluated the association of AF with ischemic stroke. RESULTS: AF was documented in 11.9% (n = 1235) of cases and 3.2% (n = 328) of controls. Compared to HIC, the prevalence of AF was significantly lower in UMIC-2 (aOR 0.35, 95% CI 0.29-0.41) and LMIC (aOR 0.50, 95% CI 0.41-0.60) on multivariable analysis. Hypertension, female sex, valvular heart disease, and alcohol intake were stronger risk factors for AF in lower-income countries, and obesity a stronger risk factor in higher-income countries. The magnitude of association between AF and ischemic stroke was significantly higher in lower-income countries compared to higher-income countries. The population attributable fraction for AF and stroke varied by region and was 15.7% (95% CI 13.7-17.8) in HIC, 14.6% (95% CI 12.3-17.1) in UMIC-1, 5.7% (95% CI 4.9-6.7) in UMIC-2, and 6.3% (95% CI 5.3-7.3) in LMIC. CONCLUSION: Risk factors for AF vary by country income level. AF contributes to stroke burden to a greater extent in higher-income countries than in lower-income countries, due to a higher prevalence and despite a lower magnitude of odds ratio.

Tobacco use and risk of acute stroke in 32 countries in the INTERSTROKE study: a case-control study.

Background: Smoking is a major risk factor for the global burden of stroke. We have previously reported a global population attributable risk (PAR) of stroke of 12.4% associated with current smoking. In this study we aimed to explore the association of current tobacco use with different types of tobacco exposure and environmental tobacco smoke (ETS) exposure on the risk of stroke and stroke subtypes, and by regions and country income levels. Methods: The INTERSTROKE study is a case-control study of acute first stroke and was undertaken with 13,462 stroke cases and 13,488 controls recruited between January 11, 2007 and August 8, 2015 in 32 countries worldwide. Association of risk of tobacco use and ETS exposure were analysed with overall stroke, ischemic and intracerebral hemorrhage (ICH), and with TOAST etiological stroke subtypes (large vessel, small vessel, cardioembolism, and undetermined). Findings: Current smoking was associated with an increased risk of all stroke (odds ratio [OR] 1.64, 95% CI 1.46-1.84), and had a stronger association with ischemic stroke (OR 1.85, 95% CI 1.61-2.11) than ICH (OR 1.19 95% CI 1.00-1.41). The OR and PAR of stroke among current smokers varied significantly between regions and income levels with high income countries (HIC) having the highest odds (OR 3.02 95% CI 2.24-4.10) and PAR (18.6%, 15.1-22.8%). Among etiological subtypes of ischemic stroke, the strongest association of current smoking was seen for large vessel stroke (OR 2.16, 95% CI 1.63-2.87) and undetermined cause (OR 1.97, 95% CI 1.55-2.50). Both filtered (OR 1.73, 95% CI 1.50-1.99) and non-filtered (OR 2.59, 95% CI 1.79-3.77) cigarettes were associated with stroke risk. ETS exposure increased the risk of stroke in a dose-dependent manner, exposure for more than 10 h per week increased risk for all stroke (OR 1.95, 95% CI 1.69-2.27), ischemic stroke (OR 1.89, 95% CI 1.59-2.24) and ICH (OR 2.00, 95% CI 1.60-2.50). Interpretation: There are significant variations in the magnitude of risk and PAR of stroke according to the types of tobacco used, active and ETS exposure, and countries with different income levels. Specific strategies to discourage tobacco use by any form and to build a smoke free environment should be implemented to ease the global burden of stroke. Funding: The Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from Astra Zeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MERCK, Sharp and Dohme, Swedish Heart and Lung Foundation, UK Chest, and UK Heart and Stroke.

Estimating modifiable coronary heart disease risk in multiple regions of the world: the INTERHEART Modifiable Risk Score.

AIMS: Summating risk factor burden is a useful approach in the assessment of cardiovascular risk among apparently healthy individuals. We aimed to derive and validate a new score for myocardial infarction (MI) risk using modifiable risk factors, derived from the INTERHEART case-control study (n = 19 470). METHODS AND RESULTS: Multiple logistic regression was used to create the INTERHEART Modifiable Risk Score (IHMRS). Internal validation was performed using split-sample methods. External validation was performed in an international prospective cohort study. A risk model including apolipoproteins, smoking, second-hand smoke exposure, hypertension, and diabetes was developed. Addition of further modifiable risk factors did not improve score discrimination in an external cohort. Split-sample validation studies showed an area under the receiver-operating characteristic (ROC) curve c-statistic of 0.71 [95% confidence interval (CI): 0.70, 0.72]. The IHMRS was positively associated with incident MI in a large cohort of people at low risk for cardiovascular disease [12% increase in MI risk (95% CI: 8, 16%) with a 1-point increase in score] and showed appropriate discrimination in this cohort (ROC c-statistic 0.69, 95% CI: 0.64, 0.74). Results were consistent across ethnic groups and geographic regions. A non-laboratory-based score is also supplied. CONCLUSIONS: Using multiple modifiable risk factors from the INTERHEART case-control study, we have developed and validated a simple score for MI risk which is applicable to an international population.

[Why do treated hypertensives disregard our advice? A contribution to the "crash" initiative]. / Zasto lijeceni hipertonicari ne postuju nase savjete? Doprinos inicijativi "crash".

Salt intake contributes to the rise in blood pressure and prevalence of hypertension. In this interventional trial on 110 treated hypertensives over three months a permanently elevated sodium excretion was found, averaging 187.9 +/- 81.5 mmol/day (range 103-297), because of inappropriate salt intake. The treated hypertensives, despite opposite claims, consume large amounts of salt, which, in addition to noncompliance, is the leading cause of poor hypertension control. Dietary education is an important part of preventive care in family medicine, and legal measures to enforce salt labeling on alimentary products are mandatory.

Association of Lipids, Lipoproteins, and Apolipoproteins with Stroke Subtypes in an International Case Control Study (INTERSTROKE).

BACKGROUND AND PURPOSE: The association of dyslipidemia with stroke has been inconsistent, which may be due to differing associations within etiological stroke subtypes. We sought to determine the association of lipoproteins and apolipoproteins within stroke subtypes. METHODS: Standardized incident case-control STROKE study in 32 countries. Cases were patients with acute hospitalized first stroke, and matched by age, sex and site to controls. Concentrations of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (apoA1), and apoB were measured. Non-HDL-C was calculated. We estimated multivariable odds ratio (OR) and population attributable risk percentage (PAR%). Outcome measures were all stroke, ischemic stroke (and subtypes), and intracerebral hemorrhage (ICH). RESULTS: Our analysis included 11,898 matched case-control pairs; 77.3% with ischemic stroke and 22.7% with ICH. Increasing apoB (OR, 1.10; 95% confidence interval [CI], 1.06 to 1.14 per standard deviation [SD]) and LDL-C (OR, 1.06; 95% CI, 1.02 to 1.10 per SD) were associated with an increase in risk of ischemic stroke, but a reduced risk of ICH. Increased apoB was significantly associated with large vessel stroke (PAR 13.4%; 95% CI, 5.6 to 28.4) and stroke of undetermined cause. Higher HDL-C (OR, 0.75; 95% CI, 0.72 to 0.78 per SD) and apoA1 (OR, 0.63; 95% CI, 0.61 to 0.66 per SD) were associated with ischemic stroke (and subtypes). While increasing HDL-C was associated with an increased risk of ICH (OR, 1.20; 95% CI, 1.14 to 1.27 per SD), apoA1 was associated with a reduced risk (OR, 0.80; 95% CI, 0.75 to 0.85 per SD). ApoB/A1 (OR, 1.38; 95% CI, 1.32 to 1.44 per SD) had a stronger magnitude of association than the ratio of LDL-C/HDL-C (OR, 1.26; 95% CI, 1.21 to 1.31 per SD) with ischemic stroke (P<0.0001). CONCLUSIONS: The pattern and magnitude of association of lipoproteins and apolipoproteins with stroke varies by etiological stroke subtype. While the directions of association for LDL, HDL, and apoB were opposing for ischemic stroke and ICH, apoA1 was associated with a reduction in both ischemic stroke and ICH. The ratio of apoB/A1 was the best lipid predictor of ischemic stroke risk.

Prohypertensive effects of non-steroidal anti-inflammatory drugs are mostly due to vasoconstriction.

Non-steroidal anti-inflammatory drugs (NSAIDs) have prohypertensive effects and blunt the effects of many antihypertensives. The mechanism of this interaction is still not understood enough. The objective of this investigation was to determine the level of prohypertensive effects of two NSAIDs (ibuprofen, piroxicam) and paracetamol, co-prescribed with two antihypertensive drugs (lisinopril + hydrochlorothiazide, amlodipine), and to improve the understanding of this interaction. A prospective clinical trial, conducted in a Croatian family practice, included 110 already treated hypertensive patients, aged 56-85 years; 50 control patients and 60 patients who were also taking NSAIDs for osteoarthritis treatment. The antihypertensive regimens remained the same during this study, while NSAIDs and paracetamol were crossed-over in three monthly periods. Blood pressure, body weight, serum creatinine, potassium, sodium, diuresis and 24 h urinary sodium excretion were followed-up. In the lisinopril/hydrochlorothiazide subgroup, both ibuprofen and piroxicam elevated mean arterial pressure by 8.9-9.5% (p < 0.001). Body weight increased significantly in the lisinopril/ hydrochlorothiazide + piroxicam subgroup only, while creatinine, urinary output and electrolyte values did not change appreciably in any of the subgroups. NSAID's prohypertensive effects seem to be mostly due to vasoconstriction and, to a minor degree, to volume expansion, since no marked changes in body weight, urinary output, serum creatinine or serum/urinary electrolyte profile were observed.

[Merits of paracetamol in osteoarthritic hypertensive patients]. / Prednosti paracetamola u lijecenju osoba s hipertonijom i artrozom.

BACKGROUND: Nonsteroidal anti-inflammatory drug (NSAID) side effects can impair quality of life in patients with osteoarthritis. Due to its particular mechanism of action, paracetamol might bypass these negative effects. OBJECTIVES: To determine both the role of paracetamol in the treatment of osteoarthritis patients and optimal combination of antihypertensives and antirheumatics for these patients. METHODS: A prospective clinical trial in a family practice included 110 treated hypertensives aged over 55 years: 50 controls and 60 also taking NSAIDs for osteoarthritis. This 3-month study compared two antihypertensives, lisinopril/hydrochlorothiazide fixed combination and amlodipine, with two NSAIDs, ibuprofen and piroxicam, and with paracetamol. Following clinical work-up and NSAID discontinuation for at least 3 days (run-in period of only 3-7 days), osteoarthritis subjects were randomized to 1-month periods of ibuprofen (400-600 mg t.i.d.) or piroxicam (10-20 mg o.d.) with one month of paracetamol (1000 mg t.i.d.) in the middle as a "wash-out" interval, continuing the prescribed amlodipine (5-10 mg o.d.) or lisinopril/hydrochlorothiazide fixed drug combination (10/6.25-20/12.5 mg o.d.), while control subjects (hypertensives with no osteoarthritis) were just keeping their antihypertensive therapy. Blood pressure was measured with standard mercury sphygmomanometer and with an automatic device, in standing, sitting and supine position. The intensity of arthritic pain (on a visual analogue scale from 1 to 10, where 0 means "no pain" and 10 "the worst pain you may imagine") and the patient's quality of life estimate (on a visual analogue scale from 1 to 10, where 0 means "general condition excellent" and 10 "the worst possible") were recorded. RESULTS: Blood pressure control was unchanged in the amiodipine group across the study periods and impaired in the lisinopril/ hydrochlorothiazide group during either ibuprofen or piroxicam, but not during paracetamol. In the amlodipine +/- ibuprofen subgroup, the reduction of the average pain intensity score throughout the study was significant (chi2 = 8.250; df 3; P = 0.037). In the lisinopril/hydrochlorothiazide +/- piroxicam subgroup, the assessed quality of life differed significantly (chi2 = 9.716; df 3; P = 0.018), while in the amlodipine +/- ibuprofen and amlodipine +/- piroxicam subgroups the changes were marginal (chi2 = 6.936; df 3; P = 0.072 and chi2 = 7146; df 3; P = 0.065, respectively).

[Why chlorthalidone, the thiazide antihypertensive of choice, is neglected?]. / Zasto se zanemaruje klortalidon, tijazidski antihipertenziv izbora?

Diuretics, particularly thiazides and thiazide-like drugs, are antihypertensives of first choice. A prominent role in this group is reserved to chlorthalidone because of several pharmacological (e.g. longer biological half-life) and clinical advantages (e.g. superior reduction in cardiovascular events). Nevertheless, favored is hydrochlorothiazide, especially in fixed drug combinations, revealing a poor policy.

How Are We Managing Patients with Hyperuricemia and Gout: A Cross Sectional Study Assessing Knowledge and Attitudes of Primary Care Physicians?

BACKGROUND: Studies show that hyperuricemia is an element of the pathophysiology of many conditions. Therefore, the aim of this study was to assess primary care physicians' knowledge and attitudes toward asymptomatic hyperuricemia and gout management. METHODS: A survey-based cross-sectional study was conducted to assess the primary physicians' attitudes, knowledge, and patient management regarding hyperuricemia and gout. RESULTS: A total of 336 primary care physicians were included. Physicians who read at least one scientific paper covering the topic of hyperuricemia in the past year scored significantly higher in knowledge questions (N = 152, 6.5 ± 2.05 vs. N = 183, 7.04 ± 2.14, p = 0.019). Only around half of physicians correctly identified drugs that can lower or elevate serum uric acid levels. Furthermore, the analysis of correct answers to specific questions showed poor understanding of the pathophysiology of hyperuricemia and possible risk factors. CONCLUSIONS: This study identified gaps in primary care physicians' knowledge essential for the adequate management of patients with asymptomatic hyperuricemia and gout. As hyperuricemia and gout are among the fastest rising non-communicable diseases, greater awareness of the available guidelines and more education about the causes and risks of hyperuricemia among primary care physicians may reduce the development of diseases that have hyperuricemia as risk factors.

Urinary Sodium and Potassium, and Risk of Ischemic and Hemorrhagic Stroke (INTERSTROKE): A Case-Control Study.

BACKGROUND: Although low sodium intake (<2 g/day) and high potassium intake (>3.5 g/day) are proposed as public health interventions to reduce stroke risk, there is uncertainty about the benefit and feasibility of this combined recommendation on prevention of stroke. METHODS: We obtained random urine samples from 9,275 cases of acute first stroke and 9,726 matched controls from 27 countries and estimated the 24-hour sodium and potassium excretion, a surrogate for intake, using the Tanaka formula. Using multivariable conditional logistic regression, we determined the associations of estimated 24-hour urinary sodium and potassium excretion with stroke and its subtypes. RESULTS: Compared with an estimated urinary sodium excretion of 2.8-3.5 g/day (reference), higher (>4.26 g/day) (odds ratio [OR] 1.81; 95% confidence interval [CI], 1.65-2.00) and lower (<2.8 g/day) sodium excretion (OR 1.39; 95% CI, 1.26-1.53) were significantly associated with increased risk of stroke. The stroke risk associated with the highest quartile of sodium intake (sodium excretion >4.26 g/day) was significantly greater (P < 0.001) for intracerebral hemorrhage (ICH) (OR 2.38; 95% CI, 1.93-2.92) than for ischemic stroke (OR 1.67; 95% CI, 1.50-1.87). Urinary potassium was inversely and linearly associated with risk of stroke, and stronger for ischemic stroke than ICH (P = 0.026). In an analysis of combined sodium and potassium excretion, the combination of high potassium intake (>1.58 g/day) and moderate sodium intake (2.8-3.5 g/day) was associated with the lowest risk of stroke. CONCLUSIONS: The association of sodium intake and stroke is J-shaped, with high sodium intake a stronger risk factor for ICH than ischemic stroke. Our data suggest that moderate sodium intake-rather than low sodium intake-combined with high potassium intake may be associated with the lowest risk of stroke and expected to be a more feasible combined dietary target.

Predictive impact of coronary risk factors in southern Croatia: a case control study.

The aim of study was to compare the impact of coronary risk factors on the incidence of acute myocardial infarction (MI) between Croatia, Central and Eastern Europe, and the rest of the world. As a part of the large international INTERHEART case-control study of acute MI in 52 countries (15,152 cases and 14,820 controls) we have investigated the relationship between several known risk factors (smoking, history of hypertension or diabetes, waist/hip ratio, dietary patterns, physical activity, consumption of alcohol, blood apolipoproteins, and psychosocial factors) and MI among patients without previously known coronary heart disease in Southern Croatia. The main identified MI risk factors in Southern Croatia were heavy smoking (>20 cig/day; OR 3.86; 95% CI 2.31-6.46), diabetes mellitus (OR 2.83; 95% CI 1.58-5.23), abnormal ratio of B-100 and A-1 apolipoproteins (OR 2.23; 95% CI 1.28-3.89), elevated waist to hip ratio (OR 1.96; 95% CI 1.21-3.18), and arterial hypertension (OR 1.68; 95% CI 1.15-2.45). Protective was moderate alcohol consumption (OR 0.63; 95% CI 0.40-0.99). The prevalence of major MI risk factors in Croatia is similar to that in the surrounding countries and in the world, accounting for over 90% of the population attributable risk. However, physical activity, dietary and psychosocial factors are seemingly less important in this country, while moderate alcohol consumption is more protective than regionally or globally.

Variations in knowledge, awareness and treatment of hypertension and stroke risk by country income level.

OBJECTIVE: Hypertension is the most important modifiable risk factor for stroke globally. We hypothesised that country-income level variations in knowledge, detection and treatment of hypertension may contribute to variations in the association of blood pressure with stroke. METHODS: We undertook a standardised case-control study in 32 countries (INTERSTROKE). Cases were patients with acute first stroke (n=13 462) who were matched by age, sex and site to controls (n=13 483). We evaluated the associations of knowledge, awareness and treatment of hypertension with risk of stroke and its subtypes and whether this varied by gross national income (GNI) of country. We estimated OR and population attributable risk (PAR) associated with treated and untreated hypertension. RESULTS: Hypertension was associated with a graded increase in OR by reducing GNI, ranging from OR 1.92 (99% CI 1.48 to 2.49) to OR 3.27 (2.72 to 3.93) for highest to lowest country-level GNI (p-heterogeneity<0.0001). Untreated hypertension was associated with a higher OR for stroke (OR 5.25; 4.53 to 6.10) than treated hypertension (OR 2.60; 2.32 to 2.91) and younger age of first stroke (61.4 vs 65.4 years; p<0.01). Untreated hypertension was associated with a greater risk of intracerebral haemorrhage (OR 6.95; 5.61 to 8.60) than ischaemic stroke (OR 4.76; 3.99 to 5.68). The PAR associated with untreated hypertension was higher in lower-income regions, PAR 36.3%, 26.3%, 19.8% to 10.4% by increasing GNI of countries. Lifetime non-measurement of blood pressure was associated with stroke (OR 1.80; 1.32 to 2.46). CONCLUSIONS: Deficits in knowledge, detection and treatment of hypertension contribute to higher risk of stroke, younger age of onset and larger proportion of intracerebral haemorrhage in lower-income countries.

[Some hints about the reviewers' ethical dilemmas]. / Neke natuknice o etickim dilemama recenziranja.

Some prevalent, important ethical issues concerning the manuscript reviewing process are discussed, with special reference to the referees' irresponsibility, bias, conflict of interest, conflict of opinion, clash between rapidity of publication and careful revision, and anonymity, suggesting possible amendments.