Individual Coronary Heart Disease Risk Research Articles

Comparing the drug target effects of Cholesteryl ester transfer protein (CETP) on cardiovascular diseases in East Asian and European populations

Abstract Introduction Cholesteryl ester transfer protein (CETP) is a drug target originally evaluated for raising HDL-C, for efficacy against coronary heart disease (CHD). Previous attempts to develop a licensed drug compound inhibiting CETP have heterogeneous CHD effects, which are likely attributable to the developed compound rather than CETP itself. Currently, novel CETP inhibitors are being pursued for the treatment of CHD. Drug target Mendelian randomization studies, leveraging genetic evidence, have shown that on-target CETP inhibition reduces CHD risk in individuals of European ancestries. However, similar MR studies conducted in East Asian ancestries have failed to show a CHD effect, questioning the value of pharmacological inhibition of CETP in this population. Purpose In this study, we compared drug target MR effects of CETP inhibition in Europeans and East Asians, focusing on cardiovascular efficacy outcomes, and relevant safety outcomes. Methods We used ancestry-specific GWAS summary statistics for Europeans (n=1,320,016) and East Asians (n=146,492) from the Global Lipids Genetics Consortium, taking variants from within and around ±50 kbp of the CETP locus. Colocalization was employed to determine potential trans-ancestry signals between CETP variants for HDL-C and LDL-C. Subsequently, drug target MR was used to estimate ancestry-specific effects of on-target CETP inhibition on 11 plasma biomarkers and 15 clinical outcomes between East Asian and European populations. Differences between ancestries were evaluated using interaction tests. Results There was strong support (posterior probability: 99.8%) of a shared causal CETP variant affecting HDL-C in both populations. Given the absence of a LDL-C signal in East Asians, similar colocalization was not observed for LDL-C. Employing drug target MR scaled to a standard deviation increase in HDL-C, we found that lower CETP had more pronounced decreasing effects in Europeans on LDL-C, LP[a], systolic blood pressure and pulse pressure (interaction p-values >1.9×10-3). Nevertheless, lower CETP protected against CHD, angina, intracerebral haemorrhage, and heart failure in both ancestries, for example for CHD (OR, 0.89; 95%CI, 0.84-0.94) in East Asians, compared to Europeans (OR, 0.95; 95%CI, 0.92-0.99, interaction p-value: 0.05). Exploring potential safety outcomes, lower CETP was protective against pneumonia in Europeans and East Asians (interaction p-value=0.53) and had a potential harmful effect on asthma and chronic kidney disease in East Asians (interaction p-value > 1.9×10-3). Conclusion In conclusion, on-target and sufficiently potent CETP inhibition is anticipated to prevent cardiovascular diseases in both European and East Asian populations.

High-Density Lipoprotein Subfractions: Much Ado about Nothing or Clinically Important?

High-density lipoproteins (HDL) are a heterogenous group of plasma molecules with a large variety in composition. There is a wide specter in lipid content and the number of different proteins that has been associated with HDL is approaching 100. Given this heterogeneity and the fact that the total amount of HDL is inversely related to the risk of coronary heart disease (CHD), there has been increasing interest in the function of specific HDL subgroups and in what way measuring and quantifying these subgroups could be of clinical importance in determining individual CHD risk. If certain subgroups appear to be more protective than others, it may also in the future be possible to pharmacologically increase beneficial and decrease harmful subgroups in order to reduce CHD risk. In this review we give a short historical perspective, summarize some of the recent clinical findings regarding HDL subclassifications and discuss why such classification may or may not be of clinical relevance.

Spatially Weighted Coronary Artery Calcium Score and Coronary Heart Disease Events in the Multi-Ethnic Study of Atherosclerosis.

A limitation of the Agatston coronary artery calcium (CAC) score is that it does not use all of the calcium density information in the computed tomography scan such that many individuals have a score of zero. We examined the predictive validity for incident coronary heart disease (CHD) events of the spatially weighted coronary calcium score (SWCS), an alternative scoring method for CAC that assigns scores to individuals with Agatston CAC=0. The MESA (Multi-Ethnic Study of Atherosclerosis) is a longitudinal study that conducted a baseline exam from 2000 to 2002 in 6814 participants including computed tomography scanning for CAC. Subsequent exams and systematic follow-up of the cohort for outcomes were performed. Statistical models were adjusted using the MESA risk score based on age, sex, race/ethnicity, systolic blood pressure, use of hypertension medications, diabetes, total and HDL (high-density lipoprotein) cholesterol, use of lipid-lowering medications, smoking status, and family history of heart attack. In the 3286 participants with Agatston CAC=0 at baseline and for whom SWCS was computed, 98 incident CHD events defined as definite or probably myocardial infarction or definite CHD death occurred during a median follow-up of 15.1 years. In this group, SWCS predicted incident CHD events after multivariable adjustment (hazard ratio=1.30 per SD of natural logarithm [SWCS] [95% CI, 1.04-1.60]; P=0.005); and progression from Agatston CAC=0 at baseline to CAC>0 at subsequent exams (multivariable-adjusted incidence rate difference per SD of natural logarithm [SWCS] per 100 person-years 1.68 [95% CI, 1.03-2.33]; P<0.0001). SWCS predicts incident CHD events in individuals with Agatston CAC score=0 as well as conversion to Agatston CAC>0 at repeat computed tomography scanning at later exams. SWCS has predictive validity as a subclinical phenotype and marker of CHD risk in individuals with Agatston CAC=0.

Abstract 15273: Estimating Coronary Heart Disease Risk and Treatment Benefit in Patients With Familial Hypercholesterolemia to Enable Shared Decision Making

Introduction: Current risk equations for coronary heart disease (CHD) do not take into account family history or cumulative exposure to LDL-C. We modified CHD risk equations for use in familial hypercholesterolemia (FH) patients and developed a decision aid (DA) for FH to facilitate shared decision making (SDM). Methods: Literature review, evidence synthesis and expert input were used to adapt the 30-year Framingham Risk Score (FRS) and 10-year ACC/AHA pooled cohort equations to calculate the CHD risk in individuals with FH aged 20-39 years and ≥40 years, respectively. Based on published data, estimated risk was multiplied by 2 for family history of early CHD or 3 in the presence of a pathogenic variant. Treatment benefit of lipid lowering was estimated based on the ‘cumulative exposure to LDL-C’ model ( JACC 2012; 60 ) using the following equations: Post-treatment 30-yr risk in those aged 20-39 years = Baseline Risk (FRS) x 0.54 delta LDL-C (mmol/L) Post-treatment 10-yr risk in those aged ≥40 years = Baseline Risk (ACC/AHA Pooled Cohort) x 0.72 delta LDL-C (mmol/L) To convey CHD risk and treatment benefit, we developed a DA using an iterative, patient-centered design process for use in FH encounters. Results: Using the DA, providers can discuss baseline CHD risk estimates, lipid lowering drug (LLD) options and the expected post-treatment risk reduction with FH patients. The estimated % LDL-C reduction for each LLD and the predicted risk reduction per mmol/L of LDL-C lowered were obtained from literature review. Lowering LDL-C by 1 mmol/L (39 mg/dL) was associated with a 28% CHD risk reduction over 10 years and a 46% reduction over 30 years ( Eur Heart J 2017; 38 ). We describe 2 examples of estimating CHD risk and treatment benefit in FH cases in Table 1 . Conclusion: We adapted CHD risk prediction equations to account for family history of CHD and presence of a pathogenic FH variant and designed a DA to convey personalized CHD risk estimates and treatment benefit to facilitate SDM with FH patients.

The association between bacterial infections and the risk of coronary heart disease in type 1 diabetes.

Diabetes increases the risk of infections and coronary heart disease (CHD). Whether infections increase the risk of CHD and how this applies to individuals with diabetes is unclear. To investigate the association between bacterial infections and the risk of CHD in type 1 diabetes. Individuals with type 1 diabetes (n=3781) were recruited from the Finnish Diabetic Nephropathy Study (FinnDiane), a prospective follow-up study. CHD was defined as incident events: fatal or nonfatal myocardial infarction, coronary artery bypass surgery or percutaneous coronary intervention, identified through national hospital discharge register data. Infections were identified through national register data on all antibiotic purchases from outpatient care. Register data were available from 1 January 1995 to 31 December 2015. Bacterial lipopolysaccharide (LPS) activity was measured from serum samples at baseline. Data on traditional risk factors for CHD were collected during baseline and consecutive visits. Individuals with an incident CHD event (n=370) had a higher mean number of antibiotic purchases per follow-up year compared to those without incident CHD (1.34 [95% CI: 1.16-1.52], versus 0.79 [0.76-0.82], P<0.001), as well as higher levels of LPS activity (0.64 [0.60-0.67], versus 0.58EUmL-1 [0.57-0.59], P<0.001). In multivariable-adjusted Cox proportional hazards models, the mean number of antibiotic purchases per follow-up year was an independent risk factor for incident CHD (HR 1.21, 95% CI: 1.14-1.29, P<0.0001). High LPS activity was a risk factor for incident CHD (HR 1.93 [1.34-2.78], P<0.001) after adjusting for static confounders. Bacterial infections are associated with an increased risk of incident CHD in individuals with type 1 diabetes.

Polygenic risk for coronary heart disease acts through atherosclerosis in type 2 diabetes

BackgroundType 2 diabetes increases the risk of coronary heart disease (CHD), yet the mechanisms involved remain poorly described. Polygenic risk scores (PRS) provide an opportunity to understand risk factors since they reflect etiologic pathways from the entire genome. We therefore tested whether a PRS for CHD influenced risk of CHD in individuals with type 2 diabetes and which risk factors were associated with this PRS.MethodsWe tested the association of a CHD PRS with CHD and its traditional clinical risk factors amongst individuals with type 2 diabetes in UK Biobank (N = 21,102). We next tested the association of the CHD PRS with atherosclerotic burden in a cohort of 352 genome-wide genotyped participants with type 2 diabetes who had undergone coronary angiograms.ResultsIn the UK Biobank we found that the CHD PRS was strongly associated with CHD amongst individuals with type 2 diabetes (OR per standard deviation increase = 1.50; p = 1.5 × 10− 59). But this CHD PRS was, at best, only weakly associated with traditional clinical risk factors, such as hypertension, hyperlipidemia, glycemic control, obesity and smoking. Conversely, in the angiographic cohort, the CHD PRS was strongly associated with multivessel stenosis (OR = 1.65; p = 4.9 × 10− 4) and increased number of major stenotic lesions (OR = 1.35; p = 9.4 × 10− 3).ConclusionsPolygenic predisposition to CHD is strongly associated with atherosclerotic burden in individuals with type 2 diabetes and this effect is largely independent of traditional clinical risk factors. This suggests that genetic risk for CHD acts through atherosclerosis with little effect on most traditional risk factors, providing the opportunity to explore new biological pathways.

Examination of a Nurse-led Community-based Education and Coaching Intervention for Coronary Heart Disease High-risk Individuals in China

PurposeEarly detection and management of coronary heart disease (CHD) are embedded into many community health service and primary care practices in western countries. The Framingham CHD risk score has been used to predict CHD and mortality for nearly 20 years, and it has predicted CHD event risk accurately in multiethnic populations. The aim of this study was to access the effect of a 6-month community-based intervention on CHD risk in individuals at high risk. MethodsA randomized controlled trial of individuals with a high 10-year CHD risk were recruited from two communities in China. Individuals in the intervention group (n = 53) received a 3-month group education and a 3-month coaching session. Physical examination and self-report questionnaires were used to collect both pre- and postintervention data on blood pressure, glucose, cholesterol, body mass index, smoking, depression, and health-related quality of life (HRQoL). ResultsA total of 102 participants (85.0%) completed the 6-month study. Compared with the usual care group, the intervention group had a 5 mmHg greater reduction in systolic blood pressure (t = 2.01, p = .047), larger declines in glucose (t = −2.49, p = .015), cholesterol (t = −2.44, p = .017), body mass index (t = −2.58, p = .011), and depression (t = −2.05, p = .043), and better reports of HRQoL (t = 3.36, p = .001). No significant group differences in smoking behaviors were reported. ConclusionA 6-month community-based intervention in a CHD high-risk population improved disease-related risk factors, depression, and HRQoL. Results provide preliminary evidence for primary prevention of cardiovascular disease risk in a community high-risk population.

Modulation of coronary heart disease risk by insulin resistance in subjects with normal glucose tolerance or prediabetes.

This study was based on the hypothesis that: (1) coronary heart disease (CHD) risk is accentuated in the insulin-resistant subset of persons with normal glucose tolerance (NGT) or prediabetes (PreDM); (2) the prevalence of insulin resistance, and associated abnormalities, is greater in subjects with PreDM; and (3) insulin resistance is the major contributor to increased CHD risk in these individuals. A 75 g oral glucose challenge was used to classify volunteers as having NGT or PreDM. Steady-state plasma glucose (SSPG) concentrations during the insulin suppression test subdivided both groups into insulin sensitive (IS = SSPG < 8.4 mmol/L) or resistant (IR = SSPG ≥ 8.4 mmol/L). Measurements were made of demographic characteristics, blood pressure, and lipid and lipoprotein concentrations, and comparisons made between the subgroups. Subjects with PreDM (n = 127) were somewhat older, more likely to be non-Hispanic men, with increased adiposity than those with NGT (n = 315). In addition, they had higher FPG concentrations, were insulin resistant (SSPG concentration; 11.4 vs. 7.2 mmol/L), with higher blood pressures, and a significantly more adverse CHD risk lipid profile (p < 0.001). Twice as many subjects with PreDM were IR (72 vs. 35 %), and the CHD risk profile was significantly worse in the IR subgroups in those with either NGT or PreDM. Coronary heart disease risk profile is significantly more adverse in subjects with PreDM as compared to individuals with NGT. However, glucose tolerance status is not the only determinant of CHD risk in nondiabetic individuals, and differences in degree of insulin resistance significantly modulate CHD risk in subjects with NGT or PreDM.

Risk of coronary heart disease in patients with HIV infection.

The lives of individuals infected with HIV who have access to combination antiretroviral therapy (cART) are substantially prolonged, which increases the risk of developing non-AIDS comorbidities, including coronary heart disease (CHD). In Europe and the USA, individuals with HIV infection have a ∼1.5-fold increased risk of myocardial infarction relative to uninfected individuals. In Africa, the relative risk of myocardial infarction is unknown, but broadened access to life-extending cART suggests that rates of CHD will rise in this and other resource-constrained regions. Atherogenesis in HIV is affected by complex interactions between traditional and immune risk factors. cART has varied, regimen-specific effects on metabolic risk factors. Overall, cART seems to lessen proatherogenic immune activation, but does not eliminate it even in patients in whom viraemia is suppressed. Current strategies to decrease the risk of CHD in individuals infected with HIV include early initiation of cART regimens with the fewest metabolic adverse effects, and careful management of traditional CHD risk factors throughout treatment. Future strategies to prevent CHD in patients with HIV infection might involve the use of HIV-tailored CHD risk-prediction paradigms and the administration of therapies alongside cART that will further decrease proatherogenic HIV-specific immune activation.

GW24-e3664 Study of quantitative evaluation of individual risk of coronary heart disease

ObjectivesTo explore the quantitative evaluation methods of individual risk of coronary heart disease (CHD).MethodsRisk factors and OR values were sifted out based on the case-control study and logistic regression analysis,...

Female Renal Transplant Recipients Potentially at Increased Risk of Fatal Coronary Heart Disease Associated with Ambient Air Pollutants

Background: There is increasing evidence that specific ambient air pollutants are associated with coronary heart disease (CHD) morbidity and mortality and risks may differ by gender. Renal transplant recipients have previously been identified as a potentially sensitive subgroup. The purpose of this study was to evaluate the possible effect of long-term ambient pollutant ozone (O3) and particulate matter (PM10) on risk of coronary heart disease (CHD) mortality and determine if gender differences exist among renal transplant recipients. Methods: This retrospective cohort study included 38,101 (22,276 males and 15,825 females) subjects identified through the US Renal Data System (USRDS), which included adult, renal transplant recipients, transplanted between 1997-2003, and living in the continental U.S.A. Air pollution statistics collected over the national ambient monitoring network, were extracted from US Environmental Protection Agency (EPA) Air Quality System (AQS). Mean monthly concentrations of O3, and PM10 calculated from ambient monitoring data and interpolated to ZIP code centroids according to residence of the subjects. Cox proportional hazard models used to estimate effect of air pollutants on mortality (CHD) risks, while adjusting for potential confounders. All analyses conducted were gender-specific. Results: In both the age-and multivariable adjusted models, there was a significant association between risk of fatal CHD and O3 for females (HR=1.56, 95%CI: 1.06-2.30), no significant association found for males. O3 displayed the strongest association with CHD mortality among females with a HR=1.57 (95%CI: 1.07-2.30) after adjustment for PM10 in the two pollutant multivariable model. For both pollutants and across all models, females consistently experienced greater risk than males. No significant association identified for PM10 for either gender. Conclusions: The findings from our study have potential implications for policies and regulations of air pollution. Gender, as a higher risk category, may be relevant in developing individual CHD risk reduction strategies for renal transplant recipients to ultimately improve long-term survival.

An analysis of the metabolic syndrome phenotype in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is associated with an increased risk of coronary heart disease (CHD) not fully explained by classic risk factors. Metabolic syndrome (MetS) is associated with an increased risk of CHD in the general population and whilst its prevalence is increased in SLE, its phenotypic expression may differ. We studied 200 women with SLE and 100 controls and compared the prevalence of MetS and its individual components. We examined whether any SLE features were associated with MetS and whether MetS in SLE patients was associated with carotid plaque. Patients with SLE were more likely to meet the MetS criteria (age-adjusted OR 2.1 (1.1-3.8)). However, this was not due to increased central obesity (median waist circumference 84 cm vs. 82 cm, p = 0.65) but rather increased prevalence of hypertension (p <0.01) and low HDL-cholesterol (p = 0.01). In a multivariable analysis, age, disease duration, low complement C3 and corticosteroid use ever, were associated with the presence of MetS in SLE. Overall MetS was not associated with the presence of carotid plaque in either SLE or controls. We have shown that MetS is more prevalent in SLE, but the lupus-MetS phenotype reflects risk factor changes driven by disease activity and steroid exposure, rather than obesity. Reliance on clinical measures of central obesity to consider MetS in SLE is not reliable and continued attention to individual CHD risk factors is recommended.

Gender differences in the accuracy of time-dependent blood pressure indices for predicting coronary heart disease: A random-effects modeling approach

Previous studies on blood pressure (BP) indices as a predictor of coronary heart disease (CHD) have provided equivocal results and generally relied on Cox proportional hazards regression methodology, with age and sex accounting for most of the predictive capability of the model. The aim of the present study was to use serially collected BP measurements to examine age-and gender-related differences in BP indices for predicting CHD. The predictive accuracy of time-dependent BP indices for CHD was investigated using a method of risk prediction based on posterior probabilities calculated from mixed-effects regression to utilize intraindividual differences in serial BP measurements according to age changes within gender groups. Data were collected prospectively from 2 community-dwelling cohort studies in the United States (Baltimore Longitudinal Study of Aging [BLSA]) and Europe (Vorarlberg Health Monitoring and Promotion Program [VHM&PP]). The study comprised 152,633 participants (aged 30-74 years) and 610,061 BP measurements. During mean follow-up of 7.5 years, 2457 nonfatal and fatal CHD events were observed. In both study populations, pulse pressure (PP) and systolic blood pressure (SBP) performed best as individual predictors of CHD in women (area under the receiver operating characteristic curve [AUC(ROC)] was between 0.83 and 0.85 for PP, and between 0.77 and 0.81 for SBP). Mean arterial pressure (MAP) and diastolic blood pressure (DBP) performed better for men (AUC(ROC) = 0.67 and 0.65 for MAP and DBP, respectively, in the BLSA; AUC(ROC) = 0.77 and 0.75 in the VHM&PP) than for women (AUC(ROC) = 0.60 for both MAP and DBP in the BLSA; AUC(ROC) = 0.75 and 0.52, respectively, in the VHM&PP). The degree of discrimination in both populations was overall greater but more varied for all BP indices for women (AUC(ROC) estimates between 0.85 [PP in the VHM&PP] and 0.52 [DBP in the VHM&PP]) than for men (AUC(ROC) estimates between 0.78 [MAP + PP in the VHM&PP] and 0.63 [PP in the BLSA]). Our findings indicate differences in discrimination between women and men in the accuracy of longitudinally collected BP measurements for predicting CHD, implicating the usefulness of gender-specific BP indices to assess individual CHD risk.

Prediabetes: The Importance of Early Identification and Intervention

Prediabetes is a state of abnormal glucose homeostasis characterized by the presence of impaired fasting glucose, impaired glucose tolerance, or both. Individuals with prediabetes are at increased risk for type 2 diabetes, compared with individuals with normal glucose values (normal fasting plasma glucose, < 100 mg/dL [5.6 mmol/L]). The increased risk for cardiovascular disease in prediabetes is multifactorial, with etiologies including insulin resistance, hyperglycemia, dyslipidemia, hypertension, systemic inflammation, and oxidative stress. The preferred treatment is intensive lifestyle management and aggressive pharmacologic therapies directed toward individual coronary heart disease risk factors. The use of antihyperglycemic agents in this setting is a topic of intense debate. This review discusses the pathophysiology of prediabetes and its clinical implications, highlighting the importance of early identification and intervention.

National Cholesterol Education Panel ΙΙΙ Guidelines Performance Role in Preventing Myocardial Infarction in a Large Cohort Without a History of Coronary Artery Disease: Korea Acute Myocardial Infarction Registry Study

The Third Report of the Adult Treatment Panel National Cholesterol Education Program (NCEP-ATP III) guidelines are widely used for the primary prevention of a coronary event. These guidelines were developed using experimental data from studies that enrolled mostly Caucasian patients. The pathogenesis of atherosclerosis varies with ethnicity. Given these two circumstances, the authors sought to investigate the performance of the guidelines in a large Asian cohort. The Korea Acute Myocardial Infarction Registry (KAMIR) includes data collected between November 2005 and December 2006 from 41 referral centers in South Korea. A retrospective review of the clinical data was performed. After patients with a history of coronary heart disease (CHD), CHD equivalent, and those taking lipid-lowering medications were excluded, 2969 individuals (76% men; 61+/-12 years) were enrolled. The recommendations for lipid-lowering treatments according to the NCEP-ATP III were examined in the context of the cohort. A total of 38%, 66%, and 8% of the study participants had hypertension, were smokers, and had a family history of premature CHD, respectively. When patients were stratified by the number of risk factors present and their 10-year CHD risk, 69% diagnosed with an acute myocardial infarction did not qualify for drug therapy. Irrespective of the age group examined (young, intermediate, and old), the percentage of patients who did not qualify for a lipid-lowering pharmacologic intervention was higher than 60%. NCEP-ATP III underestimates CHD risk in individuals of Asian descent. Further studies are needed to improve primary CHD prevention in this patient population.

Antipsychotic effects on estimated 10-year coronary heart disease risk in the CATIE schizophrenia study

Objective Persons with schizophrenia die earlier than the general population, in large part due to cardiovascular disease. The study objective was to examine effects of different antipsychotic treatments on estimates of 10-year coronary heart disease (CHD) risk calculated by the Framingham Heart Study formula. Method Change in 10-year risk for CHD was compared between treatment groups in 1125 patients followed for 18 months or until treatment discontinuation in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia Trial. Results The covariate-adjusted mean change in 10-year CHD risk differed significantly between treatments. Olanzapine was associated with a 0.5% (SE 0.3) increase and quetiapine, a 0.3% (SE 0.3) increase; whereas risk decreased in patients treated with perphenazine, − 0.5% (SE 0.3), risperidone, − 0.6% (SE 0.3), and ziprasidone − 0.6% (SE 0.4). The difference in 10-year CHD risk between olanzapine and risperidone was statistically significant ( p = 0.004). Differences in estimated 10-year CHD risk between drugs were most marked in the tertile of subjects with a baseline CHD risk of at least 10%. Among individual CHD risk factors used in the Framingham formula, only total and HDL cholesterol levels differed between treatments. Conclusions These results indicate that the impact on 10-year CHD risk differs significantly between antipsychotic agents, with olanzapine producing the largest elevation in CHD risk of the agents studied in CATIE.

Risk Assessment for Coronary Heart Disease in a Veteran Population with Spinal Cord Injury

Persons with spinal cord injury (SCI) have premature coronary heart disease (CHD). Because of adverse changes in body composition and level of activity, there is an increased prevalence of abnormalities in carbohydrate and lipid metabolism. Hypertension appears to occur more frequently in persons with paraplegia. Knowledge of the relative risk of CHD in individuals with SCI would be important in determining appropriate intervention strategies. As such, the conventional risk factors for CHD, as defined by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), were determined in a population of 224 veterans with SCI to assign risk to be able to determine target low-density lipoprotein cholesterol levels for therapeutic intervention. The average age of the patients was 49 ± 15 years, with a mean duration of injury of 17 ± 13 years. Diabetes mellitus (DM), a risk equivalent for CHD, wa...

LDL and HDL subclasses and their relationship with Framingham risk score in middle-aged Serbian population

Objectives: Small, dense LDL particles are associated with an increased risk of coronary heart disease (CHD), and there is growing evidence that small HDL subclasses are less protective than the larger ones. Very limited information is available about the lipoprotein subclasses among populations living in South-East European region, and none for Serbia. Design and methods: We analyzed the distributions of LDL and HDL subclasses and their relationships with Framingham risk scores (FRS) in 229 Serbian middle-aged asymptomatic individuals. By use of non-denaturing gradient gel electrophoresis, we determined the diameters of LDL and HDL subfractions in a single run. Results: Comparing to women, men had smaller LDL and HDL particles ( P < 0.001, and P < 0.05, respectively), higher frequency of LDL B phenotype ( P < 0.005), and significant reduction of HDL 2b in favor of HDL 2a subclasses ( P < 0.05). The observed gender-related differences disappeared after the age of 60. We found a significant association of the small LDL particles with high FRS values ( P < 0.005). A notable incidence of risk lipoprotein phenotypes (LDL B-9.2%; small-sized HDL-9.9%) was found among subjects that were categorized as “low-risk”, requiring no further intervention, according to FRS. Conclusion: Measurement of LDL, and possibly HDL particle size could provide further insight into individual CHD risk, and enable them to benefit from targeted preventive measures.

Matrix Gla Protein Is Associated With Risk Factors for Atherosclerosis but not With Coronary Artery Calcification

Atherosclerotic coronary artery calcification (CAC) is associated with increased coronary heart disease (CHD) risk. Matrix Gla protein (MGP) is an inhibitor of calcification in vivo. However, little is known regarding the distribution of circulating MGP and its associations with CHD risk factors or with CAC in humans. Serum MGP concentrations were determined in 2 independent populations of men and women free of clinically apparent cardiovascular disease: study A, n=316, mean age 58 years, and study B, n=452, mean age 68 years. CAC was determined by computed tomography. Mean MGP concentrations were 98.4 and 198 ng/mL in men, and 97.4 and 201 ng/mL in women, in study A and study B, respectively. In both cohorts, MGP levels were higher with increasing age. In age-adjusted analyses, there was an association of circulating MGP with increasing Framingham CHD risk score (in study A, P=0.003 in men and P=0.016 in women, respectively; in study B, a nonsignificant increase in men and P=0.05 in women, respectively). Significant associations of circulating MGP with high-density lipoprotein and other individual CHD risk factors were also noted in both cohorts. There were no consistent associations between MGP and CAC after adjustment for CHD risk score in the 2 cohorts. MGP is associated with individual CHD risk factors and the Framingham CHD risk score in men and women free of clinically apparent CHD. The relation of MGP with CAC deserves further study in larger populations.

The contrOL of dYslipideMia in outPatIent clinics in GreeCe (Olympic) Study

The objective of this study was to determine the proportion of Greek patients referred to outpatient clinics for dyslipidemia who achieved the low-density lipoprotein cholesterol (LDL-C) goal defined by the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) guidelines, using lifestyle changes, lipid-lowering drug treatment (LLDT), or both. Adult patients with dyslipidemia, who had been receiving a hypolipidemic diet and/or LLDT for at least 3 months were assessed in a multicenter study performed at 66 sites across Greece. Patients were followed up for an additional 3-month treatment period. Lipid levels were recorded at baseline and at the end of the study. The primary endpoint was the proportion of patients achieving their individual LDL-C target at the end of the study, according to their coronary heart disease (CHD) risk status or its equivalents, as defined by the NCEP-ATP III guidelines. Multivariate logistic models were used to identify determinants of undertreatment. The study included 2,660 adults (20-75 years) from 7 regions of Greece. Of the evaluable sample (n = 2,211; men 51%; mean age 62 +/-9 years) 81% were receiving LLDT (96% with statins and 3% with fibrates), 44% had a history of CHD, 61% arterial hypertension, 36% diabetes, and 26% a family history of premature CHD. Overall, 6% were at low CHD risk, 30% at medium CHD risk, and 63% at high CHD risk. At the end of the study, 26% of all patients and 30% of those receiving LLDT achieved the NCEP-specified LDL-C target levels. The percentage of patients at LDL-C goal according to CHD risk status was: low risk 67% (95% CI = 59-75), medium risk 29% (95% CI = 26-33), and high risk 20% (95% CI = 18-22). Statins proved to be more effective than fibrates (p <0.0001). Atorvastatin-treated subjects (n = 1,222, mean dose 19 mg/day) attained the LDL-C target (31% of the cases) at a higher rate than those receiving other LLDT (n = 574, 26% at target, p <0.01) or not receiving drug treatment (n = 415, 8%, p <0.001). This outcome was more evident in the high-CHD risk group (n = 1,402, 26% with atorvastatin vs 16% with other LLDT and 3% not receiving LLDT attained the LDL-C goal, ANOVA, p <0.001). The majority of dyslipidemic patients receiving LLDT, mainly those with high-CHD risk, are not achieving the NCEP LDL-C target. This is mainly explained by inadequate dose titration to ensure target goals are met. Promoting healthy lifestyle and appropriate LLDT (potent statins with sufficient dose titration) must be implemented to ensure that patients attain LDL-C treatment goals and thus benefit from the reduction in individual CHD risk.