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Aims: To develop and externally validate the LIFE‐T1D model for the estimation of lifetime and 10‐year risk of cardiovascular disease (CVD) in individuals with type 1 diabetes. Materials and Methods: A sex‐specific competing risk‐adjusted Cox proportional hazards model was derived in individuals with type 1 diabetes without prior CVD from the Swedish National Diabetes Register (NDR), using age as the time axis. Predictors included age at diabetes onset, smoking status, body mass index, systolic blood pressure, glycated haemoglobin level, estimated glomerular filtration rate, non‐high‐density lipoprotein cholesterol, albuminuria and retinopathy. The model was externally validated in the Danish Funen Diabetes Database (FDDB) and the UK Biobank. Results: During a median follow‐up of 11.8 years (interquartile interval 6.1–17.1 years), 4608 CVD events and 1316 non‐CVD deaths were observed in the NDR (n = 39 756). The internal validation c‐statistic was 0.85 (95% confidence interval [CI] 0.84–0.85) and the external validation c‐statistics were 0.77 (95% CI 0.74–0.81) for the FDDB (n = 2709) and 0.73 (95% CI 0.70–0.77) for the UK Biobank (n = 1022). Predicted risks were consistent with the observed incidence in the derivation and both validation cohorts. Conclusions: The LIFE‐T1D model can estimate lifetime risk of CVD and CVD‐free life expectancy in individuals with type 1 diabetes without previous CVD. This model can facilitate individualized CVD prevention among individuals with type 1 diabetes. Validation in additional cohorts will improve future clinical implementation. [ABSTRACT FROM AUTHOR]

Objectives: There is conflicting evidence around the role of sex hormones with cardiovascular outcomes. The aim of this study was to examine the association of sex hormones with the risk of myocardial infarction (MI) in pre- and post-menopausal women, and men in the UK Biobank. Methods: The UK Biobank is a prospective population-based cohort study, that recruited over 500,000 (aged 40–69 years) women and men between 2006 and 2010. Sex specific cox regression models, estimating hazard ratios (HRs) and women to men ratio of HRs (RHR) with respective 95% confidence intervals (CI), were used to model the association of sex hormones [oestrogen, testosterone, oestrogen: testosterone (O/T) ratio, sex hormone–binding globulin (SHBG) and the free androgen index (FAI)], measured at study baseline, with incident MI for women and men. Results: Data were from 479,797 participants [264,282 (55.1%) women] without a history of MI at study baseline. Over 12.5 years of follow-up, there were 4,908 MI events in women and 10,517 in men. Neither oestrogen nor testosterone were associated with MI in women and men after multiple adjustment. For men, but not women, a unit higher log-transformed O/T ratio was associated with a lower risk of MI 0.79 (0.65, 0.95) after adjustment for traditional CVD risk factors. The corresponding women to men RHR (95% CI) was 1.24 (0.99, 1.56). Higher SHBG (per unit) was also associated with a lower risk of MI in men 0.94 (0.89, 0.99), and not in women 1.02 (0.95, 1.09) after multiple adjustment, the corresponding women to men RHR (95% CI) was 1.09 (1.00, 1.18). Higher FAI was associated with a higher risk of MI in men 1.09 (1.02, 1.15), though not in women 0.97 (0.92, 1.02), the corresponding women to men RHR was 0.89 (0.82, 0.97). Finally, there were differential effects in the association of SHBG and FAI between pre- and post-menopausal women. Conclusions: A higher O/T ratio was associated with a lower risk of MI, and a higher FAI with a higher risk of MI after adjustment for CVD risk factors in men, but not in women. Thus, hormone ratios, rather than each alone, may play an important role in modulating the effect of MI. Plain Language Summary: There are conflicting findings surrounding the association of sex hormones and myocardial infarction (MI) (heart disease). In particular, high oestradiol levels in women are often thought to be protective and explain why the rates of heart disease are lower in women than men. For men, those with low levels of testosterone are often thought to be more prone to develop heart disease in their lifetimes. Our study presents a comprehensive analysis of the association of sex hormones (in isolation and also together via their ratios), in women and men using the large-scale UK Biobank. We found that neither oestrogen nor testosterone alone were associated with heart disease in women and men after accounting for cardiovascular risk factors, but the ratio of testosterone and oestrogen was associated with a lower risk of heart disease in men, though not in women. We also saw the association of sex hormone–binding globulin (SHBG), and free androgen index (FAI) (calculated by the ratio of total testosterone level to SHBG) with heart disease was different between women and men, and between pre- and post-menopausal women. This paper highlights the complex interplay between sex hormones with heart disease in the presence of age and cardiovascular risk factors. In particular the balance (ratio) of sex hormones maybe more important, rather than each in isolation, when exploring their association with heart disease. Highlights: Neither oestrogen nor testosterone were associated with MI in women and men after multiple adjustment. For men, but not women, higher oestrogen/testosterone ratio was associated with a lower risk of MI after adjustment for traditional CVD risk factors. Higher SHBG was associated with a lower risk of MI in men, but not women overall. Higher FAI was associated with a higher risk of MI in men but not women overall. There were differential effects in SHBG and FAI between pre- and post-menopausal women. [ABSTRACT FROM AUTHOR]

Background: It is commonly assumed that high oestradiol levels in women are cardioprotective. We assessed the association between oestradiol and the risk of incident myocardial infarction (MI) in women.Methods: We used data from 263 295 female UK Biobank participants [mean age 56.2; standard deviation (SD) 8.0 years] without previous cardiovascular disease (CVD). Associations of oestradiol with age and other cardiovascular risk factors were assessed. Cox proportional hazards models estimated crude, ag- and multiple-adjusted hazard ratios (HR) for MI associated with oestradiol levels.Results: After a mean follow-up of 9 years, 2206 incident cases of MI had been recorded, including 230 events among the 57 204 women (mean age 48) with detectable oestradiol levels. In the unadjusted analyses, a unit higher in log-transformed oestradiol was associated with an HR [95% confidence interval (CI) for MI of 0.73 (0.58; 0.92)]. After adjusting for age, this HR became 0.94 (0.75; 1.17), and after further adjusting for classical CVD risk factors, it was 1.05 (0.83; 1.31. Results were similar in subgroup analyses defined by age, menopausal status, socioeconomic status, contraceptive pill use and the use of hormone replacement therapy. The multivariable-adjusted HR for the 171 431 women (mean age 59) with undetectable levels of oestradiol, compared with those with detectable levels, was 0.97 (0.92; 1.02).Conclusions: Higher levels of oestradiol were not associated with a decreased risk of MI. The presumed cardioprotective effects of oestradiol seem to be largely confounded by age and further confounded by other cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Background: Sex differences in major cardiovascular risk factors for incident (fatal or non-fatal) all-cause dementia were assessed in the UK Biobank. The effects of these risk factors on all-cause dementia were explored by age and socioeconomic status (SES).Methods: Cox proportional hazards models were used to estimate hazard ratios (HRs) and women-to-men ratio of HRs (RHR) with 95% confidence intervals (CIs) for systolic blood pressure (SBP) and diastolic blood pressure (DBP), smoking, diabetes, adiposity, stroke, SES and lipids with dementia. Poisson regression was used to estimate the sex-specific incidence rate of dementia for these risk factors.Results: 502,226 individuals in midlife (54.4% women, mean age 56.5 years) with no prevalent dementia were included in the analyses. Over 11.8 years (median), 4068 participants (45.9% women) developed dementia. The crude incidence rates were 5.88 [95% CI 5.62-6.16] for women and 8.42 [8.07-8.78] for men, per 10,000 person-years. Sex was associated with the risk of dementia, where the risk was lower in women than men (HR = 0.83 [0.77-0.89]). Current smoking, diabetes, high adiposity, prior stroke and low SES were associated with a greater risk of dementia, similarly in women and men. The relationship between blood pressure (BP) and dementia was U-shaped in men but had a dose-response relationship in women: the HR for SBP per 20 mmHg was 1.08 [1.02-1.13] in women and 0.98 [0.93-1.03] in men. This sex difference was not affected by the use of antihypertensive medication at baseline. The sex difference in the effect of raised BP was consistent for dementia subtypes (vascular dementia and Alzheimer's disease).Conclusions: Several mid-life cardiovascular risk factors were associated with dementia similarly in women and men, but not raised BP. Future bespoke BP-lowering trials are necessary to understand its role in restricting cognitive decline and to clarify any sex difference. [ABSTRACT FROM AUTHOR]

Background: Insight in sex disparities in the detection of cardiovascular risk factors and diabetes-related complications may improve diabetes care. The aim of this systematic review is to study whether sex disparities exist in the assessment of cardiovascular risk factors and screening for diabetes-related complications. Methods: PubMed was systematically searched up to April 2020, followed by manual reference screening and citations checks (snowballing) using Google Scholar. Observational studies were included if they reported on the assessment of cardiovascular risk factors (HbA1c, lipids, blood pressure, smoking status, or BMI) and/or screening for nephropathy, retinopathy, or performance of feet examinations, in men and women with diabetes separately. Studies adjusting their analyses for at least age, or when age was considered as a covariable but left out from the final analyses for various reasons (i.e. backward selection), were included for qualitative analyses. No meta-analyses were planned because substantial heterogeneity between studies was expected. A modified Newcastle-Ottawa Quality Assessment Scale for cohort studies was used to assess risk of bias. Results: Overall, 81 studies were included. The majority of the included studies were from Europe or North America (84%).The number of individuals per study ranged from 200 to 3,135,019 and data were extracted from various data sources in a variety of settings. Screening rates varied considerably across studies. For example, screening rates for retinopathy ranged from 13% to 90%, with half the studies reporting screening rates less than 50%. Mixed findings were found regarding the presence, magnitude, and direction of sex disparities with regard to the assessment of cardiovascular risk factors and screening for diabetes-related complications, with some evidence suggesting that women, compared with men, may be more likely to receive retinopathy screening and less likely to receive foot exams. Conclusion: Overall, no consistent pattern favoring men or women was found with regard to the assessment of cardiovascular risk factors and screening for diabetes-related complications, and screening rates can be improved for both sexes. [ABSTRACT FROM AUTHOR]

Objective: To investigate sex differences in prevalence, treatment and control of major cardiovascular risk factors in England.Methods: Data from the Health Survey for England 2012-2017 on non-institutionalised English adults (aged ≥16 years) were used to investigate sex differences in prevalence, treatment and control of major cardiovascular risk factors: body mass index, smoking, systolic blood pressure and hypertension, diabetes, and cholesterol and dyslipidaemia. Physical activity and diet were not assessed in this study.Results: Overall, 49 415 adults (51% women) were included. Sex differences persisted in prevalence of cardiovascular risk factors, with smoking, hypertension, overweight and dyslipidaemia remaining more common in men than in women in 2017. The proportion of individuals with neither hypertension, dyslipidaemia, diabetes nor smoking increased from 32% to 36% in women and from 28% to 29% in men between 2012 and 2017. Treatment and control of hypertension and diabetes improved over time and were comparable in both sexes in 2017 (66% and 51% for treatment and control of hypertension and 73% and 20% for treatment and control of diabetes). However, women were less likely than men to have treated and controlled dyslipidaemia (21% vs 28% for treatment and 15% vs 24% for control, for women versus men in 2017).Conclusions: Important sex differences persist in cardiovascular risk factors in England, with an overall higher number of risk factors in men than in women. A combination of public health policy and individually tailored interventions is required to further reduce the burden of cardiovascular disease in England. [ABSTRACT FROM AUTHOR]

Obesity is associated with severe COVID‐19 outcomes, yet, it is unclear whether the risk of COVID‐19 mortality associated with obesity is similar between the sexes. We used data from the UK Biobank to assess the risk of COVID‐19 mortality associated with various anthropometric measures in women and men. To put these results in context, we also compared these estimates with those for mortality from influenza/pneumonia and coronary heart disease (CHD). The analyses included 502 493 individuals (54% women), of whom 410 (36% women) died from COVID‐19, 549 (36% women) died from influenza/pneumonia and 3355 (19% women) died from CHD. A higher body mass index (BMI), waist circumference, waist‐to‐hip ratio and waist‐to‐height ratio were each associated with a greater risk of death from COVID‐19, influenza/pneumonia and CHD in both sexes, with the exception of the association between higher BMI and the risk of influenza/pneumonia death in men. A higher BMI was associated with a stronger risk of COVID‐19 mortality in women than men; the women‐to‐men ratio of hazard ratios was 1.20 (95% confidence interval 1.00; 1.43). This study demonstrates the role of obesity in COVID‐19 mortality and shows that the relative effects of a higher BMI on COVID‐19 mortality may be stronger in women than men. [ABSTRACT FROM AUTHOR]

Aim: To examine possible sex differences in the excess risk of myocardial infarction (MI) consequent to a range of conventional risk factors in a large‐scale international cohort of patients with diabetes, and to quantify these potential differences both on the relative and absolute scales. Materials and methods: Eleven thousand and sixty‐five participants (42% women) with type 2 diabetes in the ADVANCE trial and its post‐trial follow‐up study, ADVANCE‐ON, were included. Cox regression models were used to estimate hazard ratios (HRs) for associations between risk factors and MI (fatal and non‐fatal) by sex, and the women‐to‐men ratio of HRs (RHR). Results: Over a median of 9.6 years of follow‐up, 719 patients experienced MI. Smoking status, smoking intensity, higher systolic blood pressure (SBP), HbA1c, total and LDL cholesterol, duration of diabetes, triglycerides, body mass index (BMI) and lower HDL cholesterol were associated with an increased risk of MI in both sexes. Furthermore, some variables were associated with a greater relative risk of MI in women than men: RHRs were 1.75 (95% CI: 1.05‐2.91) for current smoking, 1.53 (1.00‐2.32) for former smoking, 1.18 (1.02‐1.37) for SBP, and 1.13 (95% CI, 1.003‐1.26) for duration of diabetes. Although incidence rates of MI were higher in men (9.3 per 1000 person‐years) compared with women (5.8 per 1000 person‐years), rate differences associated with risk factors were greater in women than men, except for HDL cholesterol and BMI. Conclusions: In patients with type 2 diabetes, smoking, higher SBP and longer duration of diabetes had a greater relative and absolute effect in women than men, highlighting the importance of routine sex‐specific approaches and early interventions in women with diabetes. [ABSTRACT FROM AUTHOR]

Background: Earlier age at menopause has been associated with increased risk of coronary heart disease (CHD), but the shape of association and role of established cardiovascular risk factors remain unclear. Therefore, we examined the associations between menopausal characteristics and CHD risk; the shape of the association between age at menopause and CHD risk; and the extent to which these associations are explained by established cardiovascular risk factors.Methods: We used data from EPIC-CVD, a case-cohort study, which includes data from 23 centres from 10 European countries. We included only women, of whom 10 880 comprise the randomly selected sub-cohort, supplemented with 4522 cases outside the sub-cohort. We conducted Prentice-weighted Cox proportional hazards regressions with age as the underlying time scale, stratified by country and adjusted for relevant confounders.Results: After confounder and intermediate adjustment, post-menopausal women were not at higher CHD risk compared with pre-menopausal women. Among post-menopausal women, earlier menopause was linearly associated with higher CHD risk [HRconfounder and intermediate adjusted per-year decrease = 1.02, 95% confidence interval (CI) = 1.01-1.03, p = 0.001]. Women with a surgical menopause were at higher risk of CHD compared with those with natural menopause (HRconfounder-adjusted = 1.25, 95% CI = 1.10-1.42, p < 0.001), but this attenuated after additional adjustment for age at menopause and intermediates (HR = 1.12, 95% CI = 0.96-1.29, p = 0.15). A proportion of the association was explained by cardiovascular risk factors.Conclusions: Earlier and surgical menopause were associated with higher CHD risk. These associations could partially be explained by differences in conventional cardiovascular risk factors. These women might benefit from close monitoring of cardiovascular risk factors and disease. [ABSTRACT FROM AUTHOR]

Background: Diabetes is a stronger risk factor for cardiovascular complications in women than men. Aim: To evaluate whether there are sex differences in cardiovascular risk management in patients with diabetes in primary care. Design & setting: A cross-sectional study was undertaken using data from 12 512 individuals with diabetes within the Dutch Julius General Practitioners Network (JGPN) from 2013. Method: Linear and Poisson regression analyses were used to assess sex differences in risk factor levels, assessment, treatment, and control. Results: No sex differences were found in HbA1c levels and control, while small differences were found for cardiovascular risk management. Blood pressure levels were higher (mean difference [MD] 1.09 mmHg; 95% confidence intervals [CI] = 0.41 to 1.77), while cholesterol levels (MD -0.38 mmol/l; 95% CI = -0.42 to -0.34) and body mass index ([BMI] MD -1.79 kg/m2; 95% CI = -2.03 to 1.56) were lower in men than women. Risk factor assessment was similar between sexes, apart from high-density lipoprotein cholesterol (HDL-c), which was more commonly assessed in women (risk ratio [RR] 1.16; 95% CI = 1.13 to 1.20). Among those with a treatment indication for prevention, women with cardiovascular disease (CVD) were less likely to receive lipid-lowering drugs (RR 0.84; 95% CI = 0.76 to 0.93) than men, while women without CVD were more likely to receive lipid-lowering drugs (RR 1.16; 95% CI = 1.04 to 1.2). Among those treated, women were more likely to achieve systolic blood pressure (SBP) control (RR 1.06; 95% CI = 1.02 to 1.10) and less likely to achieve low-density lipoprotein cholesterol (LDL-c) control (RR 0.88; 95% CI = 0.85 to 0.91) than men. Conclusion: In this Dutch primary care setting, sex differences in risk factor assessment and treatment of people with diabetes were small. However, women with diabetes were less likely to achieve control for LDL-c and more likely to achieve blood pressure control than men with diabetes. [ABSTRACT FROM AUTHOR]

Graphs and tables are indispensable aids to quantitative research. When developing a clinical prediction rule that is based on a cardiovascular risk score, there are many visual displays that can assist in developing the underlying statistical model, testing the assumptions made in this model, evaluating and presenting the resultant score. All too often, researchers in this field follow formulaic recipes without exploring the issues of model selection and data presentation in a meaningful and thoughtful way. Some ideas on how to use visual displays to make wise decisions and present results that will both inform and attract the reader are given. Ideas are developed, and results tested, using subsets of the data that were used to develop the ASSIGN cardiovascular risk score, as used in Scotland. [ABSTRACT FROM AUTHOR]

Background: Women's parity has been associated with risk of cardiovascular disease (CVD). It is unclear, however, whether it reflects biological effects of childbearing or uncontrolled socio-economic and lifestyle factors associated with childrearing. We assessed the association between number of children and incident CVD outcomes separately in women and men.Methods: In 2004-08, the nationwide China Kadoorie Biobank recruited 0.5 million individuals aged 30-79 years from 10 diverse regions. During 7 years of follow-up, 24 432 incident cases of coronary heart disease (CHD) and 35 736 of stroke were recorded among 489 762 individuals without prior CVD. Multivariable Cox regression models were used to estimate sex-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for CHD and stroke associated with number of children.Results: Overall, 98% of all participants had children and the mean number of children declined progressively from four in older participants to one or two in younger participants. Compared with childless women, women with children had an increased risk of CHD, but not of stroke [HR (95% CI): 1.14 (1.00; 1.30) and 1.03 (0.92; 1.16)]. Corresponding results for men were 1.20 (1.06; 1.35) and 1.13 (1.03; 1.24), respectively. In individuals with children, there was a log-linear association between number of children and CVD outcomes; in women, each additional child was associated with adjusted HRs of 1.02 (1.01; 1.04) for CHD and 1.02 (1.01; 1.03) for stroke, similar in magnitude to that in men [1.03 (1.01; 1.04) for CHD and 1.02 (1.01; 1.03) for stroke].Conclusion: In Chinese adults, the association between the number of children and risk of CHD and stroke was similar between men and women, suggesting that factors associated with parenthood and childrearing are more likely to affect the risk of CVD outcomes than factors associated with childbearing. [ABSTRACT FROM AUTHOR]

The article focuses on a study to see the applicability of thickness of common carotid in measuring the risk of cardiovascular disease. It mentions that atherosclerosis proceeds with the cardiovascular processes and remains asymptomatic over longer period which can be used for the identification of disease. The meta analysis method was used to collect the data from several cohorts and was also used in the formation of several risk prediction model. According to the result presented, inclusion of common carotid thickness measurement in the risk analysis process was not highly useful.

Context Imaging for subclinical atherosclerosis on top of conventional risk factor assessment may improve risk prediction for the occurrence of cardiovascular disease events in asymptomatic individuals. Objective To systematically review the available evidence on this issue. Data Sources PubMed MEDLINE was systematically searched on 7 September 2011. Study selection Studies were included that evaluated the added value of flow mediated dilation (FMD), carotid intima-media thickness (CIMT), carotid plaques and/or coronary artery calcification (CAC) scoring in the prediction of risk for developing fatal or non-fatal cardiovascular events. Data extraction Data on general study characteristics and the added predictive performance of imaging markers in terms of discrimination, calibration and (re)classification were extracted. Results 25 studies were selected that provided information on added predictive value of FMD (n=2), CIMT (n=12), carotid plaques (n=6) and/or CAC (n=9). Heterogeneity existed across studies in the conventional risk models that were used and in the measurements of the imaging marker. The added predictive value, quantified by the difference in c-index, of FMD, CIMT, carotid plaques or CAC ranged from 0.00 to 0.01 for FMD, from 0.00 to 0.03 for CIMT, from 0.01 to 0.05 for carotid plaque and from 0.05 to 0.13 for CAC. The reported net reclassification improvement (NRI) by the imaging markers ranged from -1.4% to 12% for CIMT, 8% to 11% for carotid plaques, 14% to 25% for CAC and 29% for FMD). Although the definition of intermediate cardiovascular risk varied across studies, the NRI was the highest in those at intermediate cardiovascular risk. Conclusions Published evidence on the added value of atherosclerosis imaging varies across the different markers, with limited evidence for FMD and considerable evidence for CIMT, carotid plaque and CAC. The added predictive value of additional screening may be primarily found in asymptomatic individuals at intermediate cardiovascular risk. Additional research in asymptomatic individuals is needed to quantify the cost effectiveness and impact of imaging for subclinical atherosclerosis on cardiovascular risk factor management and patient outcomes. [ABSTRACT FROM AUTHOR]

Eur J Clin Invest 2012; 42 (1): 110-116 Abstract Background Identification of individuals at high risk for cardiovascular disease (CVD) is important to initiate adequate treatment and to prevent future events. Moreover, identification of low-risk individuals is important to refrain from unneeded therapy. Current risk prediction models do not accurately predict the risk of CVD in individuals, and new markers have been sought to improve the risk assessment in individuals. Coronary artery calcification (CAC) is a marker of atherosclerosis that might improve current risk assessment when added to traditional risk factors. Materials and methods We performed a systematic review on PubMed search (1 February 2011) on studies reporting on the added value of CAC in risk prediction in asymptomatic individuals. Results Of 39 publications on CAC and CVD, nine studies were carried out in asymptomatic individuals. All studies showed an increase in area under the curve ranging from 0·05 to 0·20 when CAC was added to the risk model. Four studies reported on improvements of individuals in low-, intermediate-, and high-risk categories. Addition of CAC to the risk model resulted in a net reclassification improvement ranging from 14% to 30%, meaning that CAC measurement reclassified a substantial proportion of individuals into correct risk categories. This improvement was most pronounced in those at intermediate Framingham risk. Conclusions The available studies consistently showed that CAC scoring improves risk stratification in CVD risk categories when added to traditional risk factors only, especially among individuals at intermediate risk for CVD. Cost-effectiveness analyses together with a randomized controlled trial are needed before widespread introduction of CAC in clinical care. [ABSTRACT FROM AUTHOR]

Measurements of carotid intima-media thickness (CIMT) are widely used in clinical research as a measure of atherosclerosis. Many randomized controlled trials (RCTs) have been performed using the rate of change in CIMT as the primary endpoint to study the efficacy of lipid-modifying therapies. The main advantage of using CIMT over the use of cardiovascular events as a primary endpoint is the greater efficiency and feasibility. The underlying assumption for the use of CIMTin trials is that the rate of change in CIMT achieved by a therapy reflects a change in the risk for cardiovascular events. We therefore set out to assess the evidence showing whether the rate of change in CIMT induced by lipid-lowering therapies has an impact on clinical outcomes, by reviewing the available evidence based on a search of the PubMed database. Solid evidence from observational studies shows that increased CIMT relates to an increase in cardiovascular risk. RCTs consistently demonstrate that the annual rate of change in CIMT is favourably affected by lipid-modifying therapies. One study investigating the relationship between the rate of change in CIMT and clinical events has been published and showed a positive relationship between these two outcomes. A published meta-analysis based on pooled CIMT data from statin trials has shown a positive relationship between attenuated rate of change in CIMT after statin therapy and clinical outcomes. However, methodological issues question the validity of the meta-analytical approach. The consistent agreement between results from CIMT trials and event trials on the effects of lipid-modifying therapies, however, clearly supports the presence of a relationship between changes in CIMT and clinical endpoints. Therefore, although direct evidence is scarce, the data overall on whether the attenuation of rate of change in CIMT by lipid-lowering therapies impact on clinical outcomes are supportive. [ABSTRACT FROM AUTHOR]