Improvement in Prediction of Coronary Heart Disease Risk over Conventional Risk Factors Using SNPs Identified in Genome-Wide Association Studies

Objective

We examined whether a panel of SNPs, systematically selected from genome-wide association studies (GWAS), could improve risk prediction of coronary heart disease (CHD), over-and-above conventional risk factors. These SNPs have already demonstrated reproducible associations with CHD; here we examined their use in long-term risk prediction.

Study Design and Setting

SNPs identified from meta-analyses of GWAS of CHD were tested in 840 men and women aged 55–75 from the Edinburgh Artery Study, a prospective, population-based study with 15 years of follow-up. Cox proportional hazards models were used to evaluate the addition of SNPs to conventional risk factors in prediction of CHD risk. CHD was classified as myocardial infarction (MI), coronary intervention (angioplasty, or coronary artery bypass surgery), angina and/or unspecified ischaemic heart disease as a cause of death; additional analyses were limited to MI or coronary intervention. Model performance was assessed by changes in discrimination and net reclassification improvement (NRI).

Results

There were significant improvements with addition of 27 SNPs to conventional risk factors for prediction of CHD (NRI of 54%, P<0.001; C-index 0.671 to 0.740, P = 0.001), as well as MI or coronary intervention, (NRI of 44%, P<0.001; C-index 0.717 to 0.750, P = 0.256). ROC curves showed that addition of SNPs better improved discrimination when the sensitivity of conventional risk factors was low for prediction of MI or coronary intervention.

Conclusion

There was significant improvement in risk prediction of CHD over 15 years when SNPs identified from GWAS were added to conventional risk factors. This effect may be particularly useful for identifying individuals with a low prognostic index who are in fact at increased risk of disease than indicated by conventional risk factors alone.     

Serum Levels of Monocyte Chemoattractant Protein-1 and All-Cause and Cardiovascular Mortality among Patients with Coronary Artery Disease

Background

Monocyte chemoattractant protein-1 (MCP-1) is an important chemokine at multiple phases of atherosclerosis in animals, but human studies are few and inconsistent. The aim of this study is to investigate the association of serum MCP-1with all-cause and cardiovascular disease (CVD) mortality among coronary artery disease (CAD) patients and determine whether this biomarker can add secondary prognostic value to standard risk predictors.

Methods

MCP-1 was measured at baseline in 1411 CAD patients who were 40–85 years of age. Cox proportional hazards regression models were used to estimate the association of MCP-1 levels with death risk.

Results

During a median follow-up of 3.3 years, 117 deaths were recorded, 88 of which were due to CVD. The multivariable-adjusted hazard ratios across tertiles of MCP-1 were 1.51 (95% confidence intervals [CI] 0.89–2.58), 1.00, and 2.11 (95% CI 1.31–3.40) for all-cause mortality, and 1.50 (95% CI 0.80–2.81), 1.00, and 2.21 (95% CI 1.27–3.87) for CVD mortality. The addition of serum MCP-1 to the fully adjusted model increased the C-index by 0.009 (p<0.0001) for all-cause mortality and 0.008 (p<0.0001) for CVD mortality and significantly improved the predictive ability by 12.1% (P = 0.006) on all-cause mortality and 12.6% (P = 0.003) on CVD mortality using the net reclassification improvement method.

Conclusions

Both lower and higher MCP-1 levels are associated with an increased risk of all-cause and CVD mortality among CAD patients. More research is needed to confirm its clinical relevance.     

Resting Heart Rate Is Not a Good Predictor of a Clustered Cardiovascular Risk Score in Adolescents: The HELENA Study

BackgroundResting heart rate (RHR) reflects sympathetic nerve activity a significant association between RHR and all-cause and cardiovascular mortality has been reported in some epidemiologic studies.MethodsTo analyze the predictive power and accuracy of RHR as a screening measure for individual and clustered cardiovascular risk in adolescents. The study comprised 769 European adolescents (376 boys) participating in the HELENA cross-sectional study (2006–2008) were included in this study. Measurements on systolic blood pressure, HOMA index, triglycerides, TC/HDL-c, VO₂máx and the sum of four skinfolds were obtained, and a clustered cardiovascular disease (CVD) risk index was computed. The receiver operating characteristics curve was applied to calculate the power and accuracy of RHR to predict individual and clustered CVD risk factors.ResultsRHR showed low accuracy for screening CVD risk factors in both sexes (range 38.5%–54.4% in boys and 45.5%–54.3% in girls). Low specificity’s (15.6%–19.7% in boys; 18.1%–20.0% in girls) were also found. Nevertheless, the sensitivities were moderate-to-high (61.4%–89.1% in boys; 72.9%–90.3% in girls).ConclusionRHR is a poor predictor of individual CVD risk factors and of clustered CVD and the estimates based on RHR are not accurate. The use of RHR as an indicator of CVD risk in adolescents may produce a biased screening of cardiovascular health in both sexes.     

The Prognostic Value of Family History for the Estimation of Cardiovascular Mortality Risk in Men: Results from a Long-Term Cohort Study in Lithuania

Aim

To evaluate the additional prognostic value of family history for the estimation of cardiovascular (CVD) mortality risk in middle-aged urban Lithuanian men.

Methods

The association between family history of CVD and the risk of CVD mortality was examined in a population-based cohort of 6,098 men enrolled during 1972–1974 and 1976–1980 in Kaunas, Lithuania. After up to 40 years of follow-up, 2,272 deaths from CVD and 1,482 deaths from coronary heart disease (CHD) were identified. Multivariate Cox proportional hazards models were used to estimate hazard ratios (HR) for CVD and CHD mortality.

Results

After adjustment for traditional CVD risk factors, the HR for CVD mortality was 1.24 (95% CI 1.09–1.42) and for CHD mortality 1.20 (1.02–1.42) in men with first-degree relatives having a history of myocardial infarction (MI), compared to men without positive family history. A significant effect on the risk of CVD and CHD mortality was also observed for the family history of sudden cardiac death and any CVD. Addition of family history of MI, sudden death, and any CVD to traditional CVD risk factors demonstrated modest improvement in the performance of Cox models for CVD and CHD mortality.

Conclusions

Family history of CVD is associated with a risk of CVD and CHD mortality significantly and independently of other risk factors in a middle-aged male population. Addition of family history to traditional CVD risk factors improves the prediction of CVD mortality and could be used for identification of high-risk individuals.     

Cardiovascular disease risk profile and management practices in 45 low-income and middle-income countries: A cross-sectional study of nationally representative individual-level survey data

BackgroundGlobal cardiovascular disease (CVD) burden is high and rising, especially in low-income and middle-income countries (LMICs). Focussing on 45 LMICs, we aimed to determine (1) the adult population’s median 10-year predicted CVD risk, including its variation within countries by socio-demographic characteristics, and (2) the prevalence of self-reported blood pressure (BP) medication use among those with and without an indication for such medication as per World Health Organization (WHO) guidelines.Methods and findingsWe conducted a cross-sectional analysis of nationally representative household surveys from 45 LMICs carried out between 2005 and 2017, with 32 surveys being WHO Stepwise Approach to Surveillance (STEPS) surveys. Country-specific median 10-year CVD risk was calculated using the 2019 WHO CVD Risk Chart Working Group non-laboratory-based equations. BP medication indications were based on the WHO Package of Essential Noncommunicable Disease Interventions guidelines. Regression models examined associations between CVD risk, BP medication use, and socio-demographic characteristics. Our complete case analysis included 600,484 adults from 45 countries. Median 10-year CVD risk (interquartile range [IQR]) for males and females was 2.7% (2.3%–4.2%) and 1.6% (1.3%–2.1%), respectively, with estimates indicating the lowest risk in sub-Saharan Africa and highest in Europe and the Eastern Mediterranean. Higher educational attainment and current employment were associated with lower CVD risk in most countries. Of those indicated for BP medication, the median (IQR) percentage taking medication was 24.2% (15.4%–37.2%) for males and 41.6% (23.9%–53.8%) for females. Conversely, a median (IQR) 47.1% (36.1%–58.6%) of all people taking a BP medication were not indicated for such based on CVD risk status. There was no association between BP medication use and socio-demographic characteristics in most of the 45 study countries. Study limitations include variation in country survey methods, most notably the sample age range and year of data collection, insufficient data to use the laboratory-based CVD risk equations, and an inability to determine past history of a CVD diagnosis.ConclusionsThis study found underuse of guideline-indicated BP medication in people with elevated CVD risk and overuse by people with lower CVD risk. Country-specific targeted policies are needed to help improve the identification and management of those at highest CVD risk.     

Maternal weight change from prepregnancy to 18 months postpartum and subsequent risk of hypertension and cardiovascular disease in Danish women: A cohort study

BackgroundOne-fourth of women experience substantially higher weight years after childbirth. We examined weight change from prepregnancy to 18 months postpartum according to subsequent maternal risk of hypertension and cardiovascular disease (CVD).Methods and findingsWe conducted a cohort study of 47,966 women with a live-born singleton within the Danish National Birth Cohort (DNBC; 1997–2002). Interviews during pregnancy and 6 and 18 months postpartum provided information on height, gestational weight gain (GWG), postpartum weights, and maternal characteristics. Information on pregnancy complications, incident hypertension, and CVD was obtained from the National Patient Register. Using Cox regression, we estimated adjusted hazard ratios (HRs; 95% confidence interval [CI]) for hypertension and CVD through 16 years of follow-up. During this period, 2,011 women were diagnosed at the hospital with hypertension and 1,321 with CVD. The women were on average 32.3 years old (range 18.0–49.2) at start of follow-up, 73% had a prepregnancy BMI <25, and 27% a prepregnancy BMI ≥25. Compared with a stable weight (±1 BMI unit), weight gains from prepregnancy to 18 months postpartum of >1–2 and >2 BMI units were associated with 25% (10%–42%), P = 0.001 and 31% (14%–52%), P < 0.001 higher risks of hypertension, respectively. These risks were similar whether weight gain presented postpartum weight retention or a new gain from 6 months to 18 months postpartum and whether GWG was below, within, or above the recommendations. For CVD, findings differed according to prepregnancy BMI. In women with normal-/underweight, weight gain >2 BMI units and weight loss >1 BMI unit were associated with 48% (17%–87%), P = 0.001 and 28% (6%–55%), P = 0.01 higher risks of CVD, respectively. Further, weight loss >1 BMI unit combined with a GWG below recommended was associated with a 70% (24%–135%), P = 0.001 higher risk of CVD. No such increased risks were observed among women with overweight/obesity (interaction by prepregnancy BMI, P = 0.01, 0.03, and 0.03, respectively). The limitations of this observational study include potential confounding by prepregnancy metabolic health and self-reported maternal weights, which may lead to some misclassification.ConclusionsPostpartum weight retention/new gain in all mothers and postpartum weight loss in mothers with normal-/underweight may be associated with later adverse cardiovascular health.

Helene Kirkegaard and co-workers study maternal weight changes and cardiovascular risk over 16 years of follow-up.     

Ethnic differences in guideline-indicated statin initiation for people with type 2 diabetes in UK primary care, 2006–2019: A cohort study

BackgroundType 2 diabetes is 2–3 times more prevalent in people of South Asian and African/African Caribbean ethnicity than people of European ethnicity living in the UK. The former 2 groups also experience excess atherosclerotic cardiovascular disease (ASCVD) complications of diabetes. We aimed to study ethnic differences in statin initiation, a cornerstone of ASCVD primary prevention, for people with type 2 diabetes.Methods and findingsObservational cohort study of UK primary care records, from 1 January 2006 to 30 June 2019. Data were studied from 27,511 (88%) people of European ethnicity, 2,386 (8%) people of South Asian ethnicity, and 1,142 (4%) people of African/African Caribbean ethnicity with incident type 2 diabetes, no previous ASCVD, and statin use indicated by guidelines. Statin initiation rates were contrasted by ethnicity, and the number of ASCVD events that could be prevented by equalising prescribing rates across ethnic groups was estimated. Median time to statin initiation was 79, 109, and 84 days for people of European, South Asian, and African/African Caribbean ethnicity, respectively. People of African/African Caribbean ethnicity were a third less likely to receive guideline-indicated statins than European people (n/N [%]: 605/1,142 [53%] and 18,803/27,511 [68%], respectively; age- and gender-adjusted HR 0.67 [95% CI 0.60 to 0.76], p < 0.001). The HR attenuated marginally in a model adjusting for total cholesterol/high-density lipoprotein cholesterol ratio (0.77 [95% CI 0.69 to 0.85], p < 0.001), with no further diminution when deprivation, ASCVD risk factors, comorbidity, polypharmacy, and healthcare usage were accounted for (fully adjusted HR 0.76 [95% CI 0.68, 0.85], p < 0.001). People of South Asian ethnicity were 10% less likely to receive a statin than European people (1,489/2,386 [62%] and 18,803/27,511 [68%], respectively; fully adjusted HR 0.91 [95% CI 0.85 to 0.98], p = 0.008, adjusting for all covariates). We estimated that up to 12,600 ASCVD events could be prevented over the lifetimes of people currently affected by type 2 diabetes in the UK by equalising statin prescribing across ethnic groups. Limitations included incompleteness of recording of routinely collected data.ConclusionsIn this study we observed that people of African/African Caribbean ethnicity with type 2 diabetes were substantially less likely, and people of South Asian ethnicity marginally less likely, to receive guideline-indicated statins than people of European ethnicity, even after accounting for sociodemographics, healthcare usage, ASCVD risk factors, and comorbidity. Underuse of statins in people of African/African Caribbean or South Asian ethnicity with type 2 diabetes is a missed opportunity to prevent cardiovascular events.

In a retrospective cohort study, Sophie Eastwood and colleagues investigate the association between ethnicity and statin initiation for people with type 2 diabetes in UK.     

Dose-Response Association of Uncontrolled Blood Pressure and Cardiovascular Disease Risk Factors with Hyperuricemia and Gout

Background

First-line therapy of hypertension includes diuretics, known to exert a multiplicative increase on the risk of gout. Detailed insight into the underlying prevalence of hyperuricemia and gout in persons with uncontrolled blood pressure (BP) and common comorbidities is informative to practitioners initiating antihypertensive agents. We quantify the prevalence of hyperuricemia and gout in persons with uncontrolled BP and additional cardiovascular disease (CVD) risk factors.

Methods and Findings

We performed a cross-sectional study of non-institutionalized US adults, 18 years and older, using the National Health and Nutrition Examination Surveys in 1988–1994 and 1999–2010. Hyperuricemia was defined as serum uric acid >6.0 mg/dL in women; >7.0 mg/dL in men. Gout was ascertained by self-report of physician-diagnosed gout. Uncontrolled BP was based on measured systolic BP≥140 mmHg and diastolic BP≥90 mmHg. Additional CVD risk factors included obesity, reduced glomerular filtration rate, and dyslipidemia. The prevalence of hyperuricemia was 6–8% among healthy US adults, 10–15% among adults with uncontrolled BP, 22–25% with uncontrolled BP and one additional CVD risk factor, and 34–37% with uncontrolled BP and two additional CVD risk factors. Similarly, the prevalence of gout was successively greater, at 1–2%, 4–5%, 6–8%, and 8–12%, respectively, across these same health status categories. In 2007–2010, those with uncontrolled BP and 2 additional CVD risk factors compared to those without CVD risk factors had prevalence ratios of 4.5 (95% CI 3.5–5.6) and 4.5 (95% CI: 3.1–6.3) for hyperuricemia and gout respectively (P<0.01).

Conclusions

Health care providers should be cognizant of the incrementally higher prevalence of hyperuricemia and gout among patients with uncontrolled BP and additional CVD risk factors. With one in three people affected by hyperuricemia among those with several CVD risk factors, physicians should consider their anti-hypertensive regimens carefully and potentially screen for hyperuricemia or gout.     

Assessment of the causal relevance of ECG parameters for risk of atrial fibrillation: A mendelian randomisation study

BackgroundAtrial electrical and structural remodelling in older individuals with cardiovascular risk factors has been associated with changes in surface electrocardiographic (ECG) parameters (e.g., prolongation of the PR interval) and higher risks of atrial fibrillation (AF). However, it has been difficult to establish whether altered ECG parameters are the cause or a consequence of the myocardial substrate leading to AF. This study aimed to examine the potential causal relevance of ECG parameters on risk of AF using mendelian randomisation (MR).Methods and findingsWeighted genetic scores explaining lifelong differences in P-wave duration, PR interval, and QT interval were constructed, and associations between these ECG scores and risk of AF were estimated among 278,792 UK Biobank participants (mean age: 57 years at recruitment; 19,132 AF cases). The independent genetic variants contributing to each of the separate ECG scores, and their corresponding weights, were based on published genome-wide association studies. In UK Biobank, genetic scores representing a 5 ms longer P-wave duration or PR interval were significantly associated with lower risks of AF (odds ratio [OR] 0.91; 95% confidence interval [CI]: 0.87–0.96, P = 2 × 10⁻⁴ and OR 0.94; 95% CI: 0.93–0.96, P = 2 × 10⁻¹⁹, respectively), while longer QT interval was not significantly associated with AF. These effects were independently replicated among a further 17,931 AF cases from the AFGen Consortium. Investigation of potential mechanistic pathways showed that differences in ECG parameters associated with specific ion channel genes had effects on risk of AF consistent with the overall scores, while the overall scores were not associated with changes in left atrial size. Limitations of the study included the inherent assumptions of MR, restriction to individuals of European ancestry, and possible restriction of results to the normal ECG ranges represented in UK Biobank.ConclusionsIn UK Biobank, we observed evidence suggesting a causal relationship between lifelong differences in ECG parameters (particularly PR interval) that reflect longer atrial conduction times and a lower risk of AF. These findings, which appear to be independent of atrial size and concomitant cardiovascular comorbidity, support the relevance of varying mechanisms underpinning AF and indicate that more individualised treatment strategies warrant consideration.

In a Mendelian randomization analysis, Parag Gajendragadkar and colleagues investigate associations between genetically-predicted EEG parameters and risk of atrial fibrillation among UK Biobank participants.     

Repeat Cardiovascular Risk Assessment after Four Years: Is There Improvement in Risk Prediction?

Background

Framingham risk equations are widely used to predict cardiovascular disease based on health information from a single time point. Little is known regarding use of information from repeat risk assessments and temporal change in estimated cardiovascular risk for prediction of future cardiovascular events. This study was aimed to compare the discrimination and risk reclassification of approaches using estimated cardiovascular risk at single and repeat risk assessments

Methods

Using data on 12,197 individuals enrolled in EPIC-Norfolk cohort, with 12 years of follow-up, we examined rates of cardiovascular events by levels of estimated absolute risk (Framingham risk score) at the first and second health examination four years later. We calculated the area under the receiver operating characteristic curve (aROC) and risk reclassification, comparing approaches using information from single and repeat risk assessments (i.e., estimated risk at different time points).

Results

The mean Framingham risk score increased from 15.5% to 17.5% over a mean of 3.7 years from the first to second health examination. Individuals with high estimated risk (≥20%) at both health examinations had considerably higher rates of cardiovascular events than those who remained in the lowest risk category (<10%) in both health examinations (34.0 [95%CI 31.7–36.6] and 2.7 [2.2–3.3] per 1,000 person-years respectively). Using information from the most up-to-date risk assessment resulted in a small non-significant change in risk classification over the previous risk assessment (net reclassification improvement of -4.8%, p>0.05). Using information from both risk assessments slightly improved discrimination compared to information from a single risk assessment (aROC 0.76 and 0.75 respectively, p<0.001).

Conclusions

Using information from repeat risk assessments over a period of four years modestly improved prediction, compared to using data from a single risk assessment. However, this approach did not improve risk classification.     

Genetic information improves the prediction of major adverse cardiovascular events in the GENEMACOR population

The inclusion of a genetic risk score (GRS) can modify the risk prediction of coronary artery disease (CAD), providing an advantage over the use of traditional models. The predictive value of the genetic information on the recurrence of major adverse cardiovascular events (MACE) remains controversial. A total of 33 genetic variants previously associated with CAD were genotyped in 1587 CAD patients from the GENEMACOR study. Of these, 18 variants presented an hazard ratio >1, so they were selected to construct a weighted GRS (wGRS). MACE discrimination and reclassification were evaluated by C-Statistic, Net Reclassification Index and Integrated Discrimination Improvement methodologies. After the addition of wGRS to traditional predictors, the C-index increased from 0.566 to 0.572 (p=0.0003). Subsequently, adding wGRS to traditional plus clinical risk factors, this model slightly improved from 0.620 to 0.622 but with statistical significance (p=0.004). NRI showed that 17.9% of the cohort was better reclassified when the primary model was associated with wGRS. The Kaplan-Meier estimator showed that, at 15-year follow-up, the group with a higher number of risk alleles had a significantly higher MACE occurrence (p=0.011). In CAD patients, wGRS improved MACE risk prediction, discrimination and reclassification over the conventional factors, providing better cost-effective therapeutic strategies.     

Direct comparison of predictive performance of PRECISE-DAPT versus PARIS versus CREDO-Kyoto: a subanalysis of the ReCre8 trial

BackgroundMultiple scores have been proposed to guide risk stratification after percutaneous coronary intervention. This study assessed the performance of the PRECISE-DAPT, PARIS and CREDO-Kyoto risk scores to predict post-discharge ischaemic or bleeding events.MethodsA total of 1491 patients treated with latest-generation drug-eluting stent implantation were evaluated. Risk scores for post-discharge ischaemic or bleeding events were calculated and directly compared. Prognostic performance of both risk scores was assessed with calibration, Harrell’s c‑statistics net reclassification index and decision curve analyses.ResultsPost-discharge ischaemic events occurred in 56 patients (3.8%) and post-discharge bleeding events in 34 patients (2.3%) within the first year after the invasive procedure. C‑statistics for the PARIS ischaemic risk score was marginal (0.59, 95% confidence interval (CI) 0.51–0.68), whereas the CREDO-Kyoto ischaemic risk score was moderate (0.68, 95% CI 0.60–0.75). With regard to post-discharge bleeding events, CREDO-Kyoto displayed moderate discrimination (c-statistic 0.67, 95% CI 0.56–0.77), whereas PRECISE-DAPT (0.59, 95% CI 0.48–0.69) and PARIS (0.55, 95% CI 0.44–0.65) had a marginal discriminative capacity. Net reclassification index and decision curve analysis favoured CREDO-Kyoto-derived bleeding risk assessment.ConclusionIn this contemporary all-comer population, PARIS and PRECISE-DAPT risk scores were not resilient to independent testing for post-discharge bleeding events. CREDO-Kyoto-derived risk stratification was associated with a moderate predictive capability for post-discharge ischaemic or bleeding events. Future studies are warranted to improve risk stratification with more focus on robustness and rigorous testing.Electronic supplementary materialThe online version of this article (10.1007/s12471-020-01486-y) contains supplementary material, which is available to authorized users.     

Cardiovascular Disease Risk Factor Profiles of 263,356 Older Australians According to Region of Birth and Acculturation,with a Focus on Migrants Born in Asia

Risk factors for cardiovascular disease (CVD), such as obesity, diabetes, hypertension and physical inactivity, are common in Australia, but the prevalence varies according to cultural background. We examined the relationship between region of birth, measures of acculturation, and CVD risk profiles in immigrant, compared to Australian-born, older Australians. Cross-sectional data from 263,356 participants aged 45 and over joining the population-based 45 and Up Study cohort from 2006–2008 were used. Prevalence ratios for CVD risk factors in Australian- versus overseas-born participants were calculated using modified Poisson regression, adjusting for age, sex and socioeconomic factors and focusing on Asian migrants. The association between time resident in Australia and age at migration and CVD risk factors in Asian migrants was also examined. Migrants from Northeast (n = 3,213) and Southeast Asia (n = 3,942) had lower levels of overweight/obesity, physical activity and female smoking than Australian-born participants (n = 199,356), although differences in prevalence of overweight/obesity were sensitive to body-mass-index cut-offs used. Compared to Australian-born participants, migrants from Northeast Asia were 20–30% less likely, and from Southeast Asia 10–20% more likely, to report being treated for hypertension and/or hypercholesterolaemia; Southeast Asian migrants were 40–60% more likely to report diabetes. Northeast Asian-born individuals were less likely than Australian-born to have 3 or more CVD risk factors. Diabetes, treated hypertension and hypercholesterolaemia occurred at relatively low average body-mass-index in Southeast Asian migrants. The CVD risk factor profiles of migrants tended to approximate those of Australian-born with increasing acculturation, in both favourable (e.g., increased physical activity) and unfavourable directions (e.g., increased female smoking). Minimizing CVD risk in migrant populations may be achieved through efforts to retain the healthy facets of the traditional lifestyle, such as a normal body mass index and low prevalence of smoking in women, in addition to adopting healthy aspects of the host country lifestyle, such as increased physical activity.     

Burden of Hospital Admission and Repeat Angiography in Angina Pectoris Patients with and without Coronary Artery Disease: A Registry-Based Cohort Study

Aims

To evaluate risk of hospitalization due to cardiovascular disease (CVD) and repeat coronary angiography (CAG) in stable angina pectoris (SAP) with no obstructive coronary artery disease (CAD) versus obstructive CAD, and asymptomatic reference individuals.

Methods and Results

We followed 11,223 patients with no prior CVD having a first-time CAG in 1998–2009 due to SAP symptoms and 5,695 asymptomatic reference individuals from the Copenhagen City Heart Study through registry linkage for 7.8 years (median). In recurrent event survival analysis, patients with SAP had 3–4-fold higher risk of hospitalization for CVD irrespective of CAG findings and cardiovascular comorbidity. Multivariable adjusted hazard ratios(95%CI) for patients with angiographically normal coronary arteries was 3.0(2.5–3.5), for angiographically diffuse non-obstructive CAD 3.9(3.3–4.6) and for 1–3-vessel disease 3.6–4.1(range)(all P<0.001). Mean accumulated hospitalization time was 3.5(3.0–4.0)(days/10 years follow-up) in reference individuals and 4.5(3.8–5.2)/7.0(5.4–8.6)/6.7(5.2–8.1)/6.1(5.2–7.4)/8.6(6.6–10.7) in patients with angiographically normal coronary arteries/angiographically diffuse non-obstructive CAD/1-, 2-, and 3-vessel disease, respectively (all P<0.05, age-adjusted). SAP symptoms predicted repeat CAG with multivariable adjusted hazard ratios for patients with angiographically normal coronary arteries being 2.3(1.9–2.9), for angiographically diffuse non-obstructive CAD 5.5(4.4–6.8) and for obstructive CAD 6.6–9.4(range)(all P<0.001).

Conclusions

Patients with SAP symptoms and angiographically normal coronary arteries or angiographically diffuse non-obstructive CAD suffer from considerably greater CVD burdens in terms of hospitalization for CVD and repeat CAG compared with asymptomatic reference individuals even after adjustment for cardiac risk factors and exclusion of cardiovascular comorbidity as cause. Contrary to common perception, excluding obstructive CAD by CAG in such patients does not ensure a benign cardiovascular prognosis.     

Mortality and major disease risk among migrants of the 1991–2001 Balkan wars to Sweden: A register-based cohort study

BackgroundIn recent decades, millions of refugees and migrants have fled wars and sought asylum in Europe. The aim of this study was to quantify the risk of mortality and major diseases among migrants during the 1991–2001 Balkan wars to Sweden in comparison to other European migrants to Sweden during the same period.Methods and findingsWe conducted a register-based cohort study of 104,770 migrants to Sweden from the former Yugoslavia during the Balkan wars and 147,430 migrants to Sweden from 24 other European countries during the same period (1991–2001). Inpatient and specialized outpatient diagnoses of cardiovascular disease (CVD), cancer, and psychiatric disorders were obtained from the Swedish National Patient Register and the Swedish Cancer Register, and mortality data from the Swedish Cause of Death Register. Adjusting for individual-level data on sociodemographic characteristics and emigration country smoking prevalence, we used Cox regressions to contrast risks of health outcomes for migrants of the Balkan wars and other European migrants. During an average of 12.26 years of follow-up, being a migrant of the Balkan wars was associated with an elevated risk of being diagnosed with CVD (HR 1.39, 95% CI 1.34–1.43, p < 0.001) and dying from CVD (HR 1.45, 95% CI 1.29–1.62, p < 0.001), as well as being diagnosed with cancer (HR 1.16, 95% CI 1.08–1.24, p < 0.001) and dying from cancer (HR 1.27, 95% CI 1.15–1.41, p < 0.001), compared to other European migrants. Being a migrant of the Balkan wars was also associated with a greater overall risk of being diagnosed with a psychiatric disorder (HR 1.19, 95% CI 1.14–1.23, p < 0.001), particularly post-traumatic stress disorder (HR 9.33, 95% CI 7.96–10.94, p < 0.001), while being associated with a reduced risk of suicide (HR 0.68, 95% CI 0.48–0.96, p = 0.030) and suicide attempt (HR 0.57, 95% CI 0.51–0.65, p < 0.001). Later time period of migration and not having any first-degree relatives in Sweden at the time of immigration were associated with greater increases in risk of CVD and psychiatric disorders. Limitations of the study included lack of individual-level information on health status and behaviors of migrants at the time of immigration.ConclusionsOur findings indicate that migrants of the Balkan wars faced considerably elevated risks of major diseases and mortality in their first decade in Sweden compared to other European migrants. War migrants without family members in Sweden or with more recent immigration may be particularly vulnerable to adverse health outcomes. Results underscore that persons displaced by war are a vulnerable group in need of long-term health surveillance for psychiatric disorders and somatic disease.

Edda Bjork Thordardottir and co-workers study health outcomes among migrants from the former Yugoslavia to Sweden.     

Prediction of Cardiovascular Risk Using Framingham,ASSIGN and QRISK2: How Well Do They Predict Individual Rather than Population Risk?

Background

The objective of this study was to evaluate the performance of risk scores (Framingham, Assign and QRISK2) in predicting high cardiovascular disease (CVD) risk in individuals rather than populations.

Methods and findings

This study included 1.8 million persons without CVD and prior statin prescribing using the Clinical Practice Research Datalink. This contains electronic medical records of the general population registered with a UK general practice. Individual CVD risks were estimated using competing risk regression models. Individual differences in the 10-year CVD risks as predicted by risk scores and competing risk models were estimated; the population was divided into 20 subgroups based on predicted risk. CVD outcomes occurred in 69,870 persons. In the subgroup with lowest risks, risk predictions by QRISK2 were similar to individual risks predicted using our competing risk model (99.9% of people had differences of less than 2%); in the subgroup with highest risks, risk predictions varied greatly (only 13.3% of people had differences of less than 2%). Larger deviations between QRISK2 and our individual predicted risks occurred with calendar year, different ethnicities, diabetes mellitus and number of records for medical events in the electronic health records in the year before the index date. A QRISK2 estimate of low 10-year CVD risk (<15%) was confirmed by Framingham, ASSIGN and our individual predicted risks in 89.8% while an estimate of high 10-year CVD risk (≥20%) was confirmed in only 48.6% of people. The majority of cases occurred in people who had predicted 10-year CVD risk of less than 20%.

Conclusions

Application of existing CVD risk scores may result in considerable misclassification of high risk status. Current practice to use a constant threshold level for intervention for all patients, together with the use of different scoring methods, may inadvertently create an arbitrary classification of high CVD risk.     

Racial differences in the burden of coronary artery calcium and carotid intima media thickness between Blacks and Whites

Background

Identification of racial differences in the burden and correlates of carotid intima media thickness (CIMT) and coronary artery calcium (CAC) may provide the basis for the development of race-specific cardiovascular disease (CVD) risk prediction algorithms.

Methods

In the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study, CIMT was measured by carotid ultrasonography in 792 individuals (35 % Black). CIMT >1 mm was considered significant. CAC was quantified by electron beam computed tomography in 776 individuals (46 % Black). CAC was considered significant if the Agatston score was >100. Cross-sectional associations between race, CIMT and CAC were assessed using logistic regression models.

Results

Blacks had greater CIMT (mean difference 0.033 mm, 95 % CI 0.005–0.06 mm; p = 0.02) and 1.5-fold (95 % CI 1.0–2.3) higher odds of having significant CIMT than Whites. Blacks had less CAC than Whites (mean Agatston score difference 66, [11–122]; p = 0.02) and 50 % lower odds of a significant CAC score compared with Whites (0.5 [0.3–0.7]). These associations were virtually unchanged after adjustment for CVD risk factors. Of the novel CVD risk markers assessed, small-dense low-density lipoprotein was independently associated with increased odds of significant CIMT, with the association being similar among Blacks and Whites (odds ratio [95 % CI]: 1.7 [1.2–2.5] and 1.4 [1.0–1.8] per 1-SD higher level, respectively). Interleukin-6 was significantly associated with CAC among Blacks (1.4 [1.0–2.0]).

Conclusion

Black race is independently associated with greater CIMT but less CAC than White race. CVD risk stratification strategies that incorporate these measures of subclinical atherosclerosis should consider race-specific algorithms.

Electronic supplementary material

The online version of this article (doi:10.1007/s12471-014-0610-4) contains supplementary material, which is available to authorized users.     

Cancer risk in individuals with intellectual disability in Sweden: A population-based cohort study

BackgroundA knowledge gap exists about the risk of cancer in individuals with intellectual disability (ID). The primary aim of this study was to estimate the cancer risk among individuals with ID compared to individuals without ID.Methods and findingsWe conducted a population-based cohort study of all children live-born in Sweden between 1974 and 2013 and whose mothers were born in a Nordic country. All individuals were followed from birth until cancer diagnosis, emigration, death, or 31 December 2016 (up to age 43 years), whichever came first. Incident cancers were identified from the Swedish Cancer Register. We fitted Cox regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) as measures of cancer risk in relation to ID after adjusting for several potential confounders. We analyzed ID by severity, as well as idiopathic ID and syndromic ID separately. We performed a sibling comparison to investigate familial confounding. The study cohort included a total of 3,531,305 individuals, including 27,956 (0.8%) individuals diagnosed with ID. Compared with the reference group (individuals without ID and without a full sibling with ID), individuals with ID were in general more likely to be male. The median follow-up time was 8.9 and 23.0 years for individuals with ID and individuals without ID, respectively. A total of 188 cancer cases were identified among individuals with ID (incidence rate [IR], 62 per 1,000 person-years), and 24,960 among individuals in the reference group (IR, 31 per 1,000 person-years). A statistically significantly increased risk was observed for any cancer (HR 1.57, 95% CI 1.35–1.82; P < 0.001), as well as for several cancer types, including cancers of the esophagus (HR 28.4, 95% CI 6.2–130.6; P < 0.001), stomach (HR 6.1, 95% CI 1.5–24.9; P = 0.013), small intestine (HR 12.0, 95% CI 2.9–50.1; P < 0.001), colon (HR 2.0, 95% CI 1.0–4.1; P = 0.045), pancreas (HR 6.0, 95% CI 1.5–24.8; P = 0.013), uterus (HR 11.7, 95% CI 1.5–90.7; P = 0.019), kidney (HR 4.4, 95% CI 2.0–9.8; P < 0.001), central nervous system (HR 2.7, 95% CI 2.0–3.7; P < 0.001), and other or unspecified sites (HR 4.8, 95% CI 1.8–12.9; P = 0.002), as well as acute lymphoid leukemia (HR 2.4, 95% CI 1.3–4.4; P = 0.003) and acute myeloid leukemia (HR 3.0, 95% CI 1.4–6.4; P = 0.004). Cancer risk was not modified by ID severity or sex but was higher for syndromic ID. The sibling comparison showed little support for familial confounding. The main study limitations were the limited statistical power for the analyses of specific cancer types, and the potential for underestimation of the studied associations (e.g., due to potential underdetection or delayed diagnosis of cancer among individuals with ID).ConclusionsIn this study, we found that individuals with ID showed an increased risk of any cancer, as well as of several specific cancer types. These findings suggest that extended surveillance and early intervention for cancer among individuals with ID are warranted.

In a nationwide cohort study in Sweden, Qianwei Liu and co-workers report on cancer risk in people with intellectual disability.     

Health Factors and Risk of All-Cause,Cardiovascular, and Coronary Heart Disease Mortality: Findings from the MONICA and HAPIEE Studies in Lithuania

Aims

This study investigated the trends and levels of the prevalence of health factors, and the association of all-cause and cardiovascular (CVD) mortality with healthy levels of combined risk factors among Lithuanian urban population.

Methods

Data from five general population surveys in Kaunas, Lithuania, conducted between 1983 and 2008 were used. Healthy factors measured at baseline include non-smoking, normal weight, normal arterial blood pressure, normal level of total serum cholesterol, normal physical activity and normal level of fasting glucose. Among 9,209 men and women aged 45–64 (7,648 were free from coronary heart disease (CHD) and stroke at baseline), 1,219 death cases from any cause, 589 deaths from CVD, and 342 deaths from CHD occurred during follow up. Cox proportional hazards regression was used to estimate the association between health factors and mortality from all causes, CVD and CHD.

Results

Between 1983 and 2008, the proportion of subjects with 6 healthy levels of risk factors was higher in 2006–2008 than in 1983–1984 (0.6% vs. 0.2%; p = 0.09), although there was a significant increase in fasting glucose and a decline in intermediate physical activity. Men and women with normal or intermediate levels of risk factors had significantly lower all-cause, CVD and CHD mortality risk than persons with high levels of risk factors. Subjects with 5–6 healthy factors had hazard ratio (HR) of CVD mortality 0.35 (95% confidence interval (CI) 0.15–0.83) compared to average risk in the whole population. The hazard ratio for CVD mortality risk was significant in men (HR 0.34, 95% CI 0.12–0.97) but not in women (HR 0.38, 95% CI 0.09–1.67).

Conclusions

An inverse association of most healthy levels of cardiovascular risk factors with risk of all-cause and CVD mortality was observed in this urban population-based cohort. A greater number of cardiovascular health factors were related with significantly lower risk of CVD mortality, particularly among men.