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  1. Selvarajah S, Kaur G, Haniff J, Cheong KC, Hiong TG, van der Graaf Y, et al.
    Int J Cardiol, 2014 Sep;176(1):211-8.
    PMID: 25070380 DOI: 10.1016/j.ijcard.2014.07.066
    BACKGROUND:Cardiovascular risk-prediction models are used in clinical practice to identify and treat high-risk populations, and to communicate risk effectively. We assessed the validity and utility of four cardiovascular risk-prediction models in an Asian population of a middle-income country.
    METHODS:Data from a national population-based survey of 14,863 participants aged 40 to 65 years, with a follow-up duration of 73,277 person-years was used. The Framingham Risk Score (FRS), SCORE (Systematic COronary Risk Evaluation)-high and -low cardiovascular-risk regions and the World Health Organization/International Society of Hypertension (WHO/ISH) models were assessed. The outcome of interest was 5-year cardiovascular mortality. Discrimination was assessed for all models and calibration for the SCORE models.
    RESULTS:Cardiovascular risk factors were highly prevalent; smoking 20%, obesity 32%, hypertension 55%, diabetes mellitus 18% and hypercholesterolemia 34%. The FRS and SCORE models showed good agreement in risk stratification. The FRS, SCORE-high and -low models showed good discrimination for cardiovascular mortality, areas under the ROC curve (AUC) were 0.768, 0.774 and 0.775 respectively. The WHO/ISH model showed poor discrimination, AUC=0.613. Calibration of the SCORE-high model was graphically and statistically acceptable for men (χ(2) goodness-of-fit, p=0.097). The SCORE-low model was statistically acceptable for men (χ(2) goodness-of-fit, p=0.067). Both SCORE-models underestimated risk in women (p<0.001).
    CONCLUSIONS:The FRS and SCORE-high models, but not the WHO/ISH model can be used to identify high cardiovascular risk in the Malaysian population. The SCORE-high model predicts risk accurately in men but underestimated it in women.
    KEYWORDS:Cardiovascular disease prevention; Mortality; Risk prediction; Risk score; Validation
  2. Selvarajah S, Fong AY, Selvaraj G, Haniff J, Uiterwaal CS, Bots ML
    PLoS One, 2012;7(7):e40249.
    PMID: 22815733 DOI: 10.1371/journal.pone.0040249
    Risk stratification in ST-elevation myocardial infarction (STEMI) is important, such that the most resource intensive strategy is used to achieve the greatest clinical benefit. This is essential in developing countries with wide variation in health care facilities, scarce resources and increasing burden of cardiovascular diseases. This study sought to validate the Thrombolysis In Myocardial Infarction (TIMI) risk score for STEMI in a multi-ethnic developing country.
  3. Selvarajah S, Haniff J, Kaur G, Hiong TG, Cheong KC, Lim CM, et al.
    Eur J Prev Cardiol, 2013 Apr;20(2):368-75.
    PMID: 22345688 DOI: 10.1177/2047487312437327
    BACKGROUND: This study aimed to estimate the prevalence of cardiovascular risk factors and its clustering. The findings are to help shape the Malaysian future healthcare planning for cardiovascular disease prevention and management.
    METHODS: Data from a nationally representative cross-sectional survey was used. The survey was conducted via a face-to-face interview using a standardised questionnaire. A total of 37,906 eligible participants aged 18 years and older was identified, of whom 34,505 (91%) participated. Focus was on hypertension, hyperglycaemia (diabetes and impaired fasting glucose), hypercholesterolaemia and central obesity.
    RESULTS: Overall, 63% (95% confidence limits 62, 65%) of the participants had at least one cardiovascular risk factor, 33% (32, 35%) had two or more and 14% (12, 15%) had three risk factors or more. The prevalence of hypertension, hyperglycaemia, hypercholesterolaemia and central obesity were 38%, 15%, 24% and 37%, respectively. Women were more likely to have a higher number of cardiovascular risk factors for most age groups; adjusted odds ratios ranging from 1.1 (0.91, 1.32) to 1.26 (1.12, 1.43) for the presence of one risk factor and 1.07 (0.91, 1.32) to 2.00 (1.78, 2.25) for two or more risk factors.
    CONCLUSIONS: Cardiovascular risk-factor clustering provides a clear impression of the true burden of cardiovascular disease risk in the population. Women displayed higher prevalence and a younger age shift in clustering was seen. These findings signal the presence of a cardiovascular epidemic in an upcoming middle-income country and provide evidence that drastic measures have to be taken to safeguard the health of the nation.
    Study name: National Health and Morbidity Survey (NHMS-2006)
  4. Selvarajah S, van der Graaf Y, Visseren FL, Bots ML, SMART study group
    PMID: 21729268 DOI: 10.1186/1471-2261-11-40
    To determine if recommended treatment targets, as specified in clinical practice guidelines for the management of cardiovascular disease, reduces the risk of renal complications in high risk patient populations.
  5. Selvarajah S, Haniff J, Kaur G, Guat Hiong T, Bujang A, Chee Cheong K, et al.
    PMID: 23442728 DOI: 10.1186/1471-2261-13-10
    Recent increases in cardiovascular risk-factor prevalences have led to new national policy recommendations of universal screening for primary prevention of cardiovascular disease in Malaysia. This study assessed whether the current national policy recommendation of universal screening was optimal, by comparing the effectiveness and impact of various cardiovascular screening strategies.
  6. Selvarajah S, Fong AY, Selvaraj G, Haniff J, Hairi NN, Bulgiba A, et al.
    Am J Cardiol, 2013 May 1;111(9):1270-6.
    PMID: 23415636 DOI: 10.1016/j.amjcard.2013.01.271
    Developing countries face challenges in providing the best reperfusion strategy for patients with ST-segment elevation myocardial infarction because of limited resources. This causes wide variation in the provision of cardiac care. The aim of this study was to assess the impact of variation in cardiac care provision and reperfusion strategies on patient outcomes in Malaysia. Data from a prospective national registry of acute coronary syndromes were used. Thirty-day all-cause mortality in 4,562 patients with ST-segment elevation myocardial infarctions was assessed by (1) cardiac care provision (specialist vs nonspecialist centers), and (2) primary reperfusion therapy (thrombolysis or primary percutaneous coronary intervention [P-PCI]). All patients were risk adjusted by Thrombolysis In Myocardial Infarction (TIMI) risk score. Thrombolytic therapy was administered to 75% of patients with ST-segment elevation myocardial infarctions (12% prehospital and 63% in-hospital fibrinolytics), 7.6% underwent P-PCI, and the remainder received conservative management. In-hospital acute reperfusion therapy was administered to 68% and 73% of patients at specialist and nonspecialist cardiac care facilities, respectively. Timely reperfusion was low, at 24% versus 31%, respectively, for in-hospital fibrinolysis and 28% for P-PCI. Specialist centers had statistically significantly higher use of evidence-based treatments. The adjusted 30-day mortality rates for in-hospital fibrinolytics and P-PCI were 7% (95% confidence interval 5% to 9%) and 7% (95% confidence interval 3% to 11%), respectively (p = 0.75). In conclusion, variation in cardiac care provision and reperfusion strategy did not adversely affect patient outcomes. However, to further improve cardiac care, increased use of evidence-based resources, improvement in the quality of P-PCI care, and reduction in door-to-reperfusion times should be achieved.
  7. Hwong WY, Bots ML, Selvarajah S, Kappelle LJ, Abdul Aziz Z, Sidek NN, et al.
    PLoS One, 2016;11(10):e0165330.
    PMID: 27768752 DOI: 10.1371/journal.pone.0165330
    A shortage of computed tomographic (CT) machines in low and middle income countries often results in delayed CT imaging for patients suspected of a stroke. Yet, time constraint is one of the most important aspects for patients with an ischemic stroke to benefit from thrombolytic therapy. We set out to assess whether application of the Siriraj Stroke Score is able to assist physicians in prioritizing patients with a high probability of having an ischemic stroke for urgent CT imaging.
  8. Selvarajah S, Uiterwaal CS, Haniff J, van der Graaf Y, Visseren FL, Bots ML, et al.
    Eur J Clin Invest, 2013 Feb;43(2):198-207.
    PMID: 23301500 DOI: 10.1111/eci.12035
    BACKGROUND:
    Renal impairment and type 2 diabetes mellitus (DM) are well-known independent risk factors for mortality. The evidence of their combined effects on mortality is unclear, but of importance because it may determine aggressiveness of treatment. This study sought to assess and quantify the effect modification of diabetes on renal impairment in its association with mortality.

    MATERIALS AND METHODS:
    Patients with cardiovascular disease or at high risk, recruited in the Second Manifestations of ARTerial disease cohort study, were selected. A total of 7135 patients were enrolled with 33 198 person-years of follow-up. Renal impairment was defined by albuminuria status and estimated glomerular filtration rate (eGFR). Outcome was all-cause mortality.

    RESULTS:
    Mortality increased progressively with each stage of renal impairment, for both albuminuria status and eGFR, for diabetics and non-diabetics. There was no effect modification by diabetes on mortality risk due to renal impairment. The relative excess risk due to interaction (RERI) for DM and microalbuminuria was 0·21 (-0·11, 0·52), for overt proteinuria -1·12 (-2·83, 0·59) and for end-stage renal failure (ESRF) 0·32 (-3·65, 4·29). The RERI for DM with eGFR of 60-89 mL/min/1·73 m(2) was -0·31(-0·92, 0·32), for eGFR of 30-59 mL/min/1·73 m(2) -0·07 (-0·76, 0·62) and for eGFR of < 30 mL/min/1·73 m(2) 0·38 (-0·85, 1·61).

    CONCLUSIONS:
    Type 2 diabetes mellitus does not modify nor increase the risk relation between all-cause mortality and renal impairment. These findings suggest that the hallmark for survival is the prevention and delay in progression of renal impairment in patients with cardiovascular disease.
  9. Ang SH, Hwong WY, Bots ML, Sivasampu S, Abdul Aziz AF, Hoo FK, et al.
    PLoS One, 2021;16(1):e0245448.
    PMID: 33465103 DOI: 10.1371/journal.pone.0245448
    BACKGROUND AND OBJECTIVES: Risk of readmissions is an important quality indicator for stroke care. Such information is limited among low- and middle-income countries. We assessed the trends for 28-day readmissions after a stroke in Malaysia from 2008 to 2015 and evaluated the causes and factors associated with readmissions in 2015.

    METHODS: Using the national hospital admission records database, we included all stroke patients who were discharged alive between 2008 and 2015 for this secondary data analysis. The risk of readmissions was described in proportion and trends. Reasons were coded according to the International Classification of Diseases, 10th Edition. Multivariable logistic regression was performed to identify factors associated with readmissions.

    RESULTS: Among 151729 patients, 11 to 13% were readmitted within 28 days post-discharge from their stroke events each year. The trend was constant for ischemic stroke but decreasing for hemorrhagic stroke. The leading causes for readmissions were recurrent stroke (32.1%), pneumonia (13.0%) and sepsis (4.8%). The risk of 28-day readmission was higher among those with stroke of hemorrhagic (adjusted odds ratio (AOR): 1.52) and subarachnoid hemorrhage (AOR: 2.56) subtypes, and length of index admission >3 days (AOR: 1.48), but lower among younger age groups of 35-64 (AORs: 0.61-0.75), p values <0.001.

    CONCLUSION: The risk of 28-day readmission remained constant from 2008 to 2015, where one in eight stroke patients required readmission, mainly attributable to preventable causes. Age, ethnicity, stroke subtypes and duration of the index admission influenced the risk of readmission. Efforts should focus on minimizing potentially preventable admissions, especially among those at higher risk.

  10. Hwong WY, Bots ML, Selvarajah S, Abdul Aziz Z, Sidek NN, Spiering W, et al.
    PLoS One, 2016;11(11):e0166524.
    PMID: 27846309 DOI: 10.1371/journal.pone.0166524
    BACKGROUND: The increase in angiotensin II (Ang II) formation by selected antihypertensive drugs is said to exhibit neuroprotective properties, but this translation into improvement in clinical outcomes has been inconclusive. We undertook a study to investigate the relationship between types of antihypertensive drugs used prior to a stroke event and ischemic stroke severity. We hypothesized that use of antihypertensive drugs that increase Ang II formation (Ang II increasers) would reduce ischemic stroke severity when compared to antihypertensive drugs that suppress Ang II formation (Ang II suppressors).

    METHODS: From the Malaysian National Neurology Registry, we included hypertensive patients with first ischemic stroke who presented within 48 hours from ictus. Antihypertensive drugs were divided into Ang II increasers (angiotensin-I receptor blockers (ARBs), calcium channel blockers (CCBs) and diuretics) and Ang II suppressors (angiotensin-converting-enzyme inhibitors (ACEIs) and beta blockers). We evaluated stroke severity during admission with the National Institute of Health Stroke Scale (NIHSS). We performed a multivariable logistic regression with the score being dichotomized at 15. Scores of less than 15 were categorized as less severe stroke.

    RESULTS: A total of 710 patients were included. ACEIs was the most commonly prescribed antihypertensive drug in patients using Ang II suppressors (74%) and CCBs, in patients prescribed with Ang II increasers at 77%. There was no significant difference in the severity of ischemic stroke between patients who were using Ang II increasers in comparison to patients with Ang II suppressors (OR: 1.32, 95%CI: 0.83-2.10, p = 0.24).

    CONCLUSION: In our study, we found that use of antihypertensive drugs that increase Ang II formation was not associated with less severe ischemic stroke as compared to use of antihypertensive drugs that suppress Ang II formation.

  11. Hwong WY, Bots ML, Selvarajah S, Sivasampu S, Reidpath DD, Law WC, et al.
    Int J Stroke, 2019 10;14(8):826-834.
    PMID: 30843480 DOI: 10.1177/1747493019832995
    BACKGROUND: Sex differences in cardiovascular diseases generally disadvantage women, particularly within developing regions.

    AIMS: This study aims to examine sex-related differences in stroke metrics across Southeast Asia in 2015. Furthermore, relative changes between sexes are compared from 1990 to 2015.

    METHODS: Data were sourced from the Global Burden of Disease Study. Incidence and mortality from ischemic and hemorrhagic strokes were explored with the following statistics derived: (1) women-to-men incidence/mortality ratio and (2) relative percentage change in rate.

    RESULTS: Women had lower incidence and mortality from stroke compared to men. Notable findings include higher ischemic stroke incidence for women at 30-34 years in high-income countries (women-to-men ratio: 1.3, 95% CI: 0.1, 16.2 in Brunei and 1.3, 95% CI: 0.5, 3.2 in Singapore) and the largest difference between sexes for ischemic stroke mortality in Vietnam and Myanmar across most ages. Within the last 25 years, greater reductions for ischemic stroke metrics were observed among women compared to men. Nevertheless, women below 40 years in some countries showed an increase in ischemic stroke incidence between 0.5% and 11.4%, whereas in men, a decline from -4.2% to -44.2%. Indonesia reported the largest difference between sexes for ischemic stroke mortality; a reduction for women whereas an increase in men. For hemorrhagic stroke, findings were similar: higher incidence among young women in high-income countries and greater reductions for stroke metrics in women than men over the last 25 years.

    CONCLUSIONS: Distinct sex-specific differences observed across Southeast Asia should be accounted in future stroke preventive guidelines.

  12. Hwong WY, Ang SH, Bots ML, Sivasampu S, Selvarajah S, Law WC, et al.
    Glob Heart, 2021 05 26;16(1):39.
    PMID: 34211825 DOI: 10.5334/gh.791
    Background: Data on nationwide trends for stroke metrics are crucial to understand the extent of the disease burden to a country's health system. Yet, this information remains scarce in low- and middle-income countries.

    Objectives: This study investigated trends of stroke incidence and 28-day all-cause mortality after a stroke from 2008 to 2016 in Malaysia, through linkage across national data sources.

    Methods: Hospital admissions with a principal diagnosis of stroke or transient ischemic attack were included. Cases with first stroke were identified through linkage of hospital admission registers where age and sex-standardized trends of stroke incidence and its subtypes were calculated. By linking hospital registers to the National Death Register, the 28-day all-cause mortality rates after a stroke were estimated. Mann-Kendall's test was used for trend evaluation.

    Results: From 243,765 records, the trend of stroke incidence showed an increase of 4.9% in men and a drop of 3.8% among women. Incidences were higher in men, at 99.1 per 100,000 population in 2008 and 103.9 per 100,000 in 2016 than women (80.3 per 100,000 in 2008 and 77.2 per 100,000 in 2016). There was a substantial increase in stroke incidence among those below 65 years old, with the largest increase of 53.3% in men aged between 35-39 years and 50.4% in women of similar age group. The trend for 28-day all-cause mortality showed a decline for men at -13.1% and women, -10.6%. Women had higher mortality from stroke (22.0% in 2008 and 19.7% in 2016) than men (19.4% in 2008 to 17.2% in 2016).

    Conclusion: This first empirical study on stroke trends in Malaysia revealed a worrying increase in stroke incidence among the younger population. Despite a declining trend, mortality rates remained moderately high especially in women. Comprehensive strategies to strengthen the prevention and management of stroke care are warranted.

  13. Hwong WY, Abdul Aziz Z, Sidek NN, Bots ML, Selvarajah S, Kappelle LJ, et al.
    BMC Neurol, 2017 Nov 23;17(1):203.
    PMID: 29169331 DOI: 10.1186/s12883-017-0984-1
    BACKGROUND: Evaluation of secondary stroke prevention in low and middle-income countries remains limited. This study assessed the prescription of secondary preventive drugs among ischemic stroke patients upon hospital discharge in Malaysia and identified factors related to the prescribing decisions.

    METHODS: From Malaysian National Stroke Registry, we included patients with non-fatal ischemic stroke. Prescriptions of antiplatelet, anticoagulants, antihypertensive drugs and lipid-lowering drugs were assessed. Multi-level logistic regressions were performed to determine the relation between potential factors and drug prescriptions.

    RESULTS: Of 5292 patients, 48% received antihypertensive drugs, 88.9% antiplatelet and 88.7% lipid-lowering drugs upon discharge. Thirty-three percent of patients with an indication for anticoagulants (n = 391) received it. Compared to patients <=50 years, patients above 70 years were less likely to receive antiplatelet (OR: 0.72, 95% CI: 0.50-1.03), lipid-lowering drugs (OR: 0.66, 95% CI: 0.45-0.95) and anticoagulants (OR: 0.27, 95% CI: 0.09-0.83). Patients with moderate to severe disability upon discharge had less odds of receiving secondary preventive drugs; an odds ratio of 0.57 (95% CI: 0.45-0.71) for antiplatelet, 0.86 (95% CI: 0.75-0.98) for antihypertensive drugs and 0.78 (95% CI: 0.63-0.97) for lipid-lowering drugs in comparison to those with minor disability. Having prior specific comorbidities and drug prescriptions significantly increased the odds of receiving these drugs. No differences were found between sexes and ethnicities.

    CONCLUSIONS: Prescription of antihypertensive drugs and anticoagulants among ischemic stroke patients in Malaysia were suboptimal. Efforts to initiate regular clinical audits to evaluate the uptake and effectiveness of secondary preventive strategies are timely in low and middle-income settings.

  14. Poorthuis MHF, Morris DR, de Borst GJ, Bots ML, Greving JP, Visseren FLJ, et al.
    Br J Surg, 2021 Aug 19;108(8):960-967.
    PMID: 33876207 DOI: 10.1093/bjs/znab040
    BACKGROUND: Recommendations for screening patients with lower-extremity arterial disease (LEAD) to detect asymptomatic carotid stenosis (ACS) are conflicting. Prediction models might identify patients at high risk of ACS, possibly allowing targeted screening to improve preventive therapy and compliance.

    METHODS: A systematic search for prediction models for at least 50 per cent ACS in patients with LEAD was conducted. A prediction model in screened patients from the USA with an ankle : brachial pressure index of 0.9 or less was subsequently developed, and assessed for discrimination and calibration. External validation was performed in two independent cohorts, from the UK and the Netherlands.

    RESULTS: After screening 4907 studies, no previously published prediction models were found. For development of a new model, data for 112 117 patients were used, of whom 6354 (5.7 per cent) had at least 50 per cent ACS and 2801 (2.5 per cent) had at least 70 per cent ACS. Age, sex, smoking status, history of hypercholesterolaemia, stroke/transient ischaemic attack, coronary heart disease and measured systolic BP were predictors of ACS. The model discrimination had an area under the receiver operating characteristic (AUROC) curve of 0.71 (95 per cent c.i. 0.71 to 0.72) for at least 50 per cent ACS and 0.73 (0.72 to 0.73) for at least 70 per cent ACS. Screening the 20 per cent of patients at greatest risk detected 12.4 per cent with at least 50 per cent ACS (number needed to screen (NNS) 8] and 5.8 per cent with at least 70 per cent ACS (NNS 17). This yielded 44.2 and 46.9 per cent of patients with at least 50 and 70 per cent ACS respectively. External validation showed reliable discrimination and adequate calibration.

    CONCLUSION: The present risk score can predict significant ACS in patients with LEAD. This approach may inform targeted screening of high-risk individuals to enhance the detection of ACS.

  15. Gijsberts CM, Groenewegen KA, Hoefer IE, Eijkemans MJ, Asselbergs FW, Anderson TJ, et al.
    PLoS One, 2015;10(7):e0132321.
    PMID: 26134404 DOI: 10.1371/journal.pone.0132321
    BACKGROUND: Clinical manifestations and outcomes of atherosclerotic disease differ between ethnic groups. In addition, the prevalence of risk factors is substantially different. Primary prevention programs are based on data derived from almost exclusively White people. We investigated how race/ethnic differences modify the associations of established risk factors with atherosclerosis and cardiovascular events.

    METHODS: We used data from an ongoing individual participant meta-analysis involving 17 population-based cohorts worldwide. We selected 60,211 participants without cardiovascular disease at baseline with available data on ethnicity (White, Black, Asian or Hispanic). We generated a multivariable linear regression model containing risk factors and ethnicity predicting mean common carotid intima-media thickness (CIMT) and a multivariable Cox regression model predicting myocardial infarction or stroke. For each risk factor we assessed how the association with the preclinical and clinical measures of cardiovascular atherosclerotic disease was affected by ethnicity.

    RESULTS: Ethnicity appeared to significantly modify the associations between risk factors and CIMT and cardiovascular events. The association between age and CIMT was weaker in Blacks and Hispanics. Systolic blood pressure associated more strongly with CIMT in Asians. HDL cholesterol and smoking associated less with CIMT in Blacks. Furthermore, the association of age and total cholesterol levels with the occurrence of cardiovascular events differed between Blacks and Whites.

    CONCLUSION: The magnitude of associations between risk factors and the presence of atherosclerotic disease differs between race/ethnic groups. These subtle, yet significant differences provide insight in the etiology of cardiovascular disease among race/ethnic groups. These insights aid the race/ethnic-specific implementation of primary prevention.

  16. Eikendal AL, Groenewegen KA, Anderson TJ, Britton AR, Engström G, Evans GW, et al.
    Hypertension, 2015 Apr;65(4):707-13.
    PMID: 25624341 DOI: 10.1161/HYPERTENSIONAHA.114.04658
    Although atherosclerosis starts in early life, evidence on risk factors and atherosclerosis in individuals aged <45 years is scarce. Therefore, we studied the relationship between risk factors, common carotid intima-media thickness (CIMT), and first-time cardiovascular events in adults aged <45 years. Our study population consisted of 3067 adults aged <45 years free from symptomatic cardiovascular disease at baseline, derived from 6 cohorts that are part of the USE-IMT initiative, an individual participant data meta-analysis of general-population-based cohort studies evaluating CIMT measurements. Information on risk factors, CIMT measurements, and follow-up of the combined end point (first-time myocardial infarction or stroke) was obtained. We assessed the relationship between risk factors and CIMT and the relationship between CIMT and first-time myocardial infarction or stroke using a multivariable linear mixed-effects model and a Cox proportional-hazards model, respectively. During a follow-up of 16.3 years, 55 first-time myocardial infarctions or strokes occurred. Median CIMT was 0.63 mm. Of the risk factors under study, age, sex, diastolic blood pressure, body mass index, total cholesterol, and high-density lipoprotein cholesterol related to CIMT. Furthermore, CIMT related to first-time myocardial infarction or stroke with a hazard ratio of 1.40 per SD increase in CIMT, independent of risk factors (95% confidence interval, 1.11-1.76). CIMT may be a valuable marker for cardiovascular risk in adults aged <45 years who are not yet eligible for standard cardiovascular risk screening. This is especially relevant in those with an increased, unfavorable risk factor burden.
  17. Wang X, Dalmeijer GW, den Ruijter HM, Anderson TJ, Britton AR, Dekker J, et al.
    PLoS One, 2017;12(3):e0173393.
    PMID: 28323823 DOI: 10.1371/journal.pone.0173393
    BACKGROUND: The relation of a single risk factor with atherosclerosis is established. Clinically we know of risk factor clustering within individuals. Yet, studies into the magnitude of the relation of risk factor clusters with atherosclerosis are limited. Here, we assessed that relation.

    METHODS: Individual participant data from 14 cohorts, involving 59,025 individuals were used in this cross-sectional analysis. We made 15 clusters of four risk factors (current smoking, overweight, elevated blood pressure, elevated total cholesterol). Multilevel age and sex adjusted linear regression models were applied to estimate mean differences in common carotid intima-media thickness (CIMT) between clusters using those without any of the four risk factors as reference group.

    RESULTS: Compared to the reference, those with 1, 2, 3 or 4 risk factors had a significantly higher common CIMT: mean difference of 0.026 mm, 0.052 mm, 0.074 mm and 0.114 mm, respectively. These findings were the same in men and in women, and across ethnic groups. Within each risk factor cluster (1, 2, 3 risk factors), groups with elevated blood pressure had the largest CIMT and those with elevated cholesterol the lowest CIMT, a pattern similar for men and women.

    CONCLUSION: Clusters of risk factors relate to increased common CIMT in a graded manner, similar in men, women and across race-ethnic groups. Some clusters seemed more atherogenic than others. Our findings support the notion that cardiovascular prevention should focus on sets of risk factors rather than individual levels alone, but may prioritize within clusters.

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