Distribution of LDL Particle Size in a Population-Based Sample of Children and Adolescents and Relationship with Other Cardiovascular Risk Factors

Abstract Background: Smaller, denser LDL particles are associated with an increased risk for cardiovascular diseases (CVD). In youths, data on the distribution of LDL particle size and on its association with other CVD risk factors are limited. Methods: We determined LDL peak particle size by nondenaturing 2%–16% gradient gel electrophoresis in a representative sample of 2249 youths 9, 13, and 16 years of age who participated in a school-based survey conducted in 1999 in the province of Quebec, Canada. Standardized clinical measurements and fasting plasma lipid, glucose, and insulin concentrations were available. Results: The LDL peak particle size distribution was gaussian. The 5th, 50th (median), and 95th percentiles by age and sex were 255.5–258.6, 262.1–263.2, and 268.1–269.5 Å, respectively. The prevalence of the small, dense LDL phenotype (LDL peak particle size ≤255 Å) was 10% in participants with insulin resistance syndrome (IRS), in contrast to 1% in those without IRS. In a multiple regression analysis, the association of LDL size with other CVD risk factors [apolipoprotein B, HDL-cholesterol (HDL-C), triglyceride (TG), and insulin concentrations, and body mass index] was strongest with TG and HDL-C concentrations: a 1 SD increase in loge-transformed TG concentration was associated with a 1.2 Å reduction in LDL size, and a 1 SD increase in HDL-C was associated with a 1.1 Å increase in LDL size. Conclusions: Although the small, dense LDL phenotype is less prevalent in youths than adults, its prevalence is clearly increased in childhood IRS. Metabolic correlates of LDL size are similar in youths and adults.

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Abstract 16055: Lipoprotein Subclasses, Size, and Statin-Associated Incident Diabetes: An Analysis From the JUPITER Trial

Circulation ◽

10.1161/circ.130.suppl_2.16055 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Sagar Dugani ◽

Akintunde O Akinkuolie ◽

Robert J Glynn ◽

Paul M Ridker ◽

Samia Mora

Keyword(s):

Risk Factors ◽

Cox Regression ◽

Incident Diabetes ◽

P Value ◽

Random Allocation ◽

Lipoprotein Subclass ◽

Lipoprotein Subclasses ◽

Ldl Particles ◽

Ldl Size ◽

Increased Risk

Statins reduce CVD events, LDL cholesterol (LDL-C) and triglycerides, with an increased risk of diabetes. The underlying predictors of statin-associated diabetes are unclear. We evaluated lipoprotein subclass and size changes in response to rosuvastatin to identify predictors of diabetes on statin therapy Among 11,918 non-diabetic participants in JUPITER (NCT00239681), lipoprotein subclasses and size were quantified by NMR spectroscopy (LipoScience, NC) prior to and 1 year after randomization to placebo or rosuvastatin (total 370 incident diabetes). Cox regression models were adjusted for diabetes risk factors Compared to baseline, rosuvastatin lowered LDL-C and particles by lowering cholesterol-enriched large LDL (58%) and IDL (46%), with less relative lowering of cholesterol-poor small LDL (22%), resulting in smaller LDL size (1.5%). Rosuvastatin lowered (15%-20%) triglycerides, VLDL triglycerides, and VLDL particles by lowering large (15%), medium (7%), and small (27%) particles, and increasing VLDL size (3%) (all p<0.0001). Among statin-allocated individuals, after adjusting for typical risk factors, incident diabetes was inversely associated with baseline levels of LDL-C, HDL-C, large LDL particles, and LDL size, and positively associated with baseline triglycerides, non-HDL-C, ApoB, LDL particles, VLDL particles, VLDL triglycerides and size (Table). Similar associations were seen in on-treatment rosuvastatin and placebo groups In JUPITER, random allocation to rosuvastatin altered the lipoprotein subclass profile in a manner associated with the development of diabetes Adjusted Hazard Ratios (95% CI) and Risk of Incident Diabetes with Rosuvastatin Baseline parameters HR per 1-SD p value LDL-C .86 (0.76-0.98) .02 HDL-C .69 (0.54-0.87) .002 Triglycerides 1.62 (1.41-1.86) <.0001 Non-HDL-C 1.20 (1.04-1.39) .01 ApoB 1.35 (1.18-1.55) <.0001 Total LDL* 1.32 (1.15-1.51) <.0001 Large LDL* .79 (0.71-0.87) <.0001 Small LDL* 1.71 (1.40-2.08) <.0001 IDL* .97 (0.85-1.11) .69 LDL size .66 (0.58-0.75) <.0001 Total VLDL* 1.16 (1.00-1.34) .046 Large VLDL* 1.78 (1.51-2.10) <.0001 Medium VLDL* 1.35 (1.15-1.58) .0002 Small VLDL* .93 (0.82-1.06) .30 VLDL size 1.58 (1.39-1.80) <.0001 VLDL triglycerides 1.51 (1.31-1.73) <.0001 *particles

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The Use of Sex-Specific Factors in the Assessment of Women’s Cardiovascular Risk

Circulation ◽

10.1161/circulationaha.119.043429 ◽

2020 ◽

Vol 141 (7) ◽

pp. 592-599 ◽

Cited By ~ 9

Author(s):

Anandita Agarwala ◽

Erin D. Michos ◽

Zainab Samad ◽

Christie M. Ballantyne ◽

Salim S. Virani

Keyword(s):

Risk Factors ◽

Cardiovascular Risk ◽

Primary Prevention ◽

American Heart Association ◽

American Heart ◽

Heart Association ◽

The United States ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Increased Risk

Cardiovascular disease (CVD) is the leading cause of death among women in the United States. As compared with men, women are less likely to be diagnosed appropriately, receive preventive care, or be treated aggressively for CVD. Sex differences between men and women have allowed for the identification of CVD risk factors and risk markers that are unique to women. The 2018 American Heart Association/American College of Cardiology Multi-Society cholesterol guideline and 2019 American College of Cardiology/American Heart Association guideline on the primary prevention of CVD introduced the concept of risk-enhancing factors that are specific to women and are associated with an increased risk of incident atherosclerotic CVD in women. These factors, if present, would favor more intensified lifestyle interventions and consideration of initiation or intensification of statin therapy for primary prevention to mitigate the increased risk. In this primer, we highlight sex-specific CVD risk factors in women, stress the importance of eliciting a thorough obstetrical and gynecological history during cardiovascular risk assessment, and provide a framework for how to initiate appropriate preventive measures when sex-specific risk factors are present.

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Progression of retinopathy and incidence of cardiovascular disease: findings from the Chronic Renal Insufficiency Cohort Study

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2019-315333 ◽

2020 ◽

pp. bjophthalmol-2019-315333

Author(s):

Juan E Grunwald ◽

Maxwell Pistilli ◽

Gui-Shuang Ying ◽

Maureen G Maguire ◽

Ebenezer Daniel ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Cohort Study ◽

Renal Insufficiency ◽

Chronic Renal Insufficiency ◽

Kidney Diseases ◽

Vascular Pathology ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Increased Risk

PurposeChronic kidney disease (CKD) patients often develop cardiovascular disease (CVD) and retinopathy. The purpose of this study was to assess the association between progression of retinopathy and concurrent incidence of CVD events in participants with CKD.DesignWe assessed 1051 out of 1936 participants in the Chronic Renal Insufficiency Cohort Study that were invited to have fundus photographs obtained at two timepoints separated by 3.5 years, on average.MethodsUsing standard protocols, presence and severity of retinopathy (diabetic, hypertensive or other) and vessel diameter calibre were assessed at a retinal image reading centre by trained graders masked to study participants’ information. Participants with a self-reported history of CVD were excluded. Incident CVD events were physician adjudicated using medical records and standardised criteria. Kidney function and proteinuria measurements along with CVD risk factors were obtained at study visits.ResultsWorsening of retinopathy by two or more steps in the EDTRS retinopathy grading scale was observed in 9.8% of participants, and was associated with increased risk of incidence of any CVD in analysis adjusting for other CVD and CKD risk factors (OR 2.56, 95% CI 1.25 to 5.22, p<0.01). After imputation of missing data, these values were OR=1.66 (0.87 to 3.16), p=0.12.ConclusionProgression of retinopathy is associated with higher incidence of CVD events, and retinal-vascular pathology may be indicative of macrovascular disease even after adjustment for kidney diseases and CVD risk factors. Assessment of retinal morphology may provide important information when assessing CVD in patients with CKD.

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Western dietary pattern increases risk of cardiovascular disease in Iranian adults: a prospective population-based study

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2016-0508 ◽

2017 ◽

Vol 42 (3) ◽

pp. 326-332 ◽

Cited By ~ 9

Author(s):

Parvin Mirmiran ◽

Zahra Bahadoran ◽

Azita Zadeh Vakili ◽

Fereidoun Azizi

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Dietary Patterns ◽

Dietary Pattern ◽

Regression Models ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Western Dietary Pattern ◽

Increased Risk

Limited data are available regarding the association of major dietary patterns and risk of cardiovascular disease (CVD) in Middle Eastern countries. We aimed to evaluate the association of major dietary patterns, using factor analysis, with the risk of CVD. Participants without CVD (n = 2284) were recruited from the Tehran Lipid and Glucose Study and were followed for a mean of 4.7 years. Dietary intake of participants was assessed at baseline (2006–2008); biochemical variables were evaluated at baseline and follow-up examination. Multivariate Cox proportional hazard regression models, adjusted for potential confounders, were used to estimate risk of CVD across tertiles of dietary pattern scores. Linear regression models were used to indicate association of dietary pattern scores with changes of CVD risk factors over the study period. Two major dietary patterns, Western and traditional, were identified. During a mean 4.7 ± 1.4 years of follow-up, 57 participants experienced CVD-related events. In the fully adjusted model, we observed an increased risk of CVD-related events in the highest compared to the lowest tertile category of Western dietary pattern score (HR = 2.07, 95% CI = 1.03–4.18, P for trend = 0.01). Traditional dietary pattern was not associated with incidence of CVD or CVD risk factors. A significant association was observed between the Western dietary pattern and changes in serum insulin (β = 5.88, 95% CI = 0.34–11.4). Our findings confirm that the Western dietary pattern, characterized by higher loads of processed meats, salty snacks, sweets, and soft drinks, is a dietary risk factor for CVD in the Iranian population.

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Dietary Saturated Fat Is Associated with Larger LDL Particle Size and Reduced CVD Risk in Framingham Offspring Study (P08-128-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz044.p08-128-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Mengjie Yuan ◽

R Taylor Pickering ◽

Martha Singer ◽

Lynn Moore

Keyword(s):

Particle Size ◽

Fatty Acid ◽

Dietary Fat ◽

Cox Proportional Hazards ◽

Particle Sizes ◽

Food Groups ◽

Linear Regression Models ◽

Cvd Risk ◽

Ldl Particle Size ◽

Ldl Particles

Abstract Objectives Small dense LDL particles have been shown to promote atherogenic cardiovascular disease (CVD). Dietary fat type may impact LDL particle size, but few studies have examined the association between fatty acid intake and LDL particle size and CVD risk. Our goal was to examine the association of saturated fatty acid (SFA) intake with LDL particle size and CVD risk in subjects in the Framingham Offspring Study (FOS). Methods LDL particle profiles were measured by NMR spectroscopic assay during exam visit 4 in the prospective FOS. Dietary fat, carbohydrate and food groups were assessed using 3-day diet records at exams 3 and 5; intakes were adjusted for body weight using the residuals from linear regression models. Multivariable Cox proportional hazards models and generalized linear modeling (GLM) were used to adjust for sex, age, height, pack-years of smoking, fruit and non-starchy vegetable intakes, dairy, LDL particle size, and prevalent hypertension. Results Subjects were classified into 6 categories using the combined intakes of carbohydrates (<48% vs. ≥48% of calories) and weight-adjusted SFA (<20, 20-<30, ≥30 g/day). Among those with higher carbohydrate intake, increasing levels of dietary SFA were associated with reduced risk of CVD. Specifically, those with the highest SFA intake and higher energy-adjusted carbohydrate intakes had a 56% (CI: 0.24–0.82) lower risk of CVD compared with those who had both low SFA and lower carbohydrate intakes. Moreover, increasing SFA intake among those with higher carbohydrate intakes was also associated with larger LDL particle sizes (P = 0.04, highest SFA intake vs. lowest SFA intake). Among low-carbohydrate consumers, SFA intake was not associated with risk of CVD, but was still positively associated with larger LDL particle size (P = 0.0003, highest SFA intake vs. lowest SFA intake). Conclusions SFA intake was associated with larger LDL particle sizes regardless of carbohydrate intakes. However, a higher SFA intake was only associated with reduced CVD risk among those with higher carbohydrate intakes. Funding Sources National Dairy Council.

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Combined Effects of MMP-7, MMP-8 and MMP-26 on the Risk of Ischemic Stroke

Journal of Clinical Medicine ◽

10.3390/jcm8112011 ◽

2019 ◽

Vol 8 (11) ◽

pp. 2011

Author(s):

Fang-I Hsieh ◽

Hung-Yi Chiou ◽

Chaur-Jong Hu ◽

Jiann-Shing Jeng ◽

Huey-Juan Lin ◽

...

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Genetic Risk ◽

Genetic Risk Score ◽

Weighted Average ◽

Combined Effects ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Increased Risk ◽

Weighted Genetic Risk Score

Ischemic stroke (IS) is multifactorial causation combining with traditional cardiovascular disease (CVD) and genetic risk factors. Combined effects of MMP-7, MMP-8 and MMP-26 on the risk of IS remain incompletely understood. We aimed to assess individual and joint effects for IS risk by weighted genetic risk score (wGRS) from these three genes and traditional CVD risk factors. A case-control study including 500 cases with IS and 500 stroke-free healthy controls frequency-matched with cases by age and sex was conducted. The wGRS was a weighted average of the number of risk genotype across selected SNPs from MMP-7, MMP-8 and MMP-26. Multivariate logistic regression models were used to analyze the relationship between wGRS and risk of IS. A wGRS in the second tertile was associated with a 1.5-fold increased risk of IS compared with the lowest tertile after adjusting for traditional CVD risk factors. Compared to subjects with low genetic and low modifiable CVD risk, those with high genetic and high modifiable CVD risk had the highest risk of IS (adjusted-OR = 5.75). In conclusion, higher wGRS was significantly associated with an increased risk for IS. A significant interaction between genetic and traditional CVD risk factors was also found on the risk of IS.

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Birthweight in offspring and cardiovascular mortality in their parents, aunts and uncles: a family-based cohort study of 1.35 million births

International Journal of Epidemiology ◽

10.1093/ije/dyz156 ◽

2019 ◽

Vol 49 (1) ◽

pp. 205-215

Author(s):

Fareeha Shaikh ◽

Marte Karoline Kjølllesdal ◽

David Carslake ◽

Camilla Stoltenberg ◽

George Davey Smith ◽

...

Keyword(s):

Risk Factors ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Birth Registry ◽

Nuclear Families ◽

Hazard Ratios ◽

Increased Risk ◽

Paternal Aunt ◽

Family Based ◽

Cvd Mortality

Abstract Background A link between suboptimal fetal growth and higher risk of cardiovascular disease (CVD) is well documented. It has been difficult to assess the contribution of environmental versus genetic factors to the association, as these factors are closely connected in nuclear families. We investigated the association between offspring birthweight and CVD mortality in parents, aunts and uncles, and examined whether these associations are explained by CVD risk factors. Methods We linked Norwegian data from the Medical Birth Registry, the Cause of Death Registry and cardiovascular surveys. A total of 1 353 956 births (1967–2012) were linked to parents and one maternal and one paternal aunt/uncle. Offspring birthweight and CVD mortality association among all relationships was assessed by hazard ratios (HR) from Cox regressions. The influence of CVD risk factors on the associations was examined in a subgroup. Results Offspring birthweight was inversely associated with CVD mortality among parents and aunts/uncles. HR of CVD mortality for one standard deviation (SD) increase in offspring birthweight was 0.72 (0.69–0.75) in mothers and 0.89 (0.86–0.92) in fathers. In aunts/uncles, the HRs were between 0.90 (0.86–0.95) and 0.93 (0.91–0.95). Adjustment for CVD risk factors in a subgroup attenuated all the associations. Conclusions Birthweight was associated with increased risk of CVD in parents and in aunts/uncles. These associations were largely explained by CVD risk factors. Our findings suggest that associations between offspring birthweight and CVD in adult relatives involve both behavioural variables (especially smoking) and shared genetics relating to established CVD risk factors.

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Maternal cardiovascular disease risk factors as predictors of preterm birth in California: a case–control study

BMJ Open ◽

10.1136/bmjopen-2019-034145 ◽

2020 ◽

Vol 10 (6) ◽

pp. e034145

Author(s):

Anne B. Rohlfing ◽

Gregory Nah ◽

Kelli K. Ryckman ◽

Brittney D. Snyder ◽

Deborah Kasarek ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Preterm Birth ◽

Disease Risk ◽

Case Control ◽

Chronic Hypertension ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Increased Risk ◽

Early Preterm Birth

ObjectiveTo determine whether maternal cardiovascular disease (CVD) risk factors predict preterm birth.DesignCase control.SettingCalifornia hospitals.Participants868 mothers with linked demographic information and biospecimens who delivered singleton births from July 2009 to December 2010.MethodsLogistic regression analysis was employed to calculate odds ratios for the associations between maternal CVD risk factors before and during pregnancy (including diabetes, hypertensive disorders and cholesterol levels) and preterm birth outcomes.Primary outcomePreterm delivery status.ResultsAdjusting for the other maternal CVD risk factors of interest, all categories of hypertension led to increased odds of preterm birth, with the strongest magnitude observed in the pre-eclampsia group (adjusted OR (aOR), 13.49; 95% CI 6.01 to 30.27 for preterm birth; aOR, 10.62; 95% CI 4.58 to 24.60 for late preterm birth; aOR, 17.98; 95% CI 7.55 to 42.82 for early preterm birth) and chronic hypertension alone for early preterm birth (aOR, 4.58; 95% CI 1.40 to 15.05). Diabetes (types 1 and 2 and gestational) was also associated with threefold increased risk for preterm birth (aOR, 3.06; 95% CI 1.12 to 8.41). A significant and linear dose response was found between total and low-density lipoprotein (LDL) cholesterol and aORs for late and early preterm birth, with increasing cholesterol values associated with increased risk (likelihood χ2 differences of 8.422 and 8.019 for total cholesterol for late and early, and 9.169 and 10.896 for LDL for late and early, respectively). Receiver operating characteristic curves using these risk factors to predict late and early preterm birth produced C statistics of 0.601 and 0.686.ConclusionTraditional CVD risk factors are significantly associated with an increased risk of preterm birth; these findings reinforce the clinical importance of integrating obstetric and cardiovascular risk assessment across the healthcare continuum in women.

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Chronic Inflammatory Diseases and Atherosclerotic Cardiovascular Disease: Innocent Bystanders or Partners in Crime?

Current Pharmaceutical Design ◽

10.2174/1381612824666180110102341 ◽

2018 ◽

Vol 24 (3) ◽

pp. 281-290 ◽

Cited By ~ 4

Author(s):

Peter Riis Hansen

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Inflammatory Diseases ◽

Atherosclerotic Cardiovascular Disease ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Chronic Inflammatory Diseases ◽

Increased Risk ◽

Shared Risk

Inflammation plays a significant role in atherosclerosis and cardiovascular disease (CVD). Patients with chronic inflammatory diseases are at increased risk of CVD, but it is debated whether this association is causal or dependent on shared risk factors, other exposures, genes, and/or inflammatory pathways. The current review summarizes epidemiological, clinical, and experimental data supporting the role of shared inflammatory mechanisms between atherosclerotic CVD and rheumatoid arthritis, psoriasis, inflammatory bowel disease, and periodontitis, respectively, and provides insights to future prospects in this area of research. Awareness of the role of inflammation in CVD in patients with chronic inflammatory diseases and the potential for anti-inflammatory therapy, e.g., with tumor necrosis factor-α inhibitors, to also reduce atherosclerotic CVD has evolved into guideline- based recommendations. These include regular CVD risk assessment, aggressive treatment of traditional CVD risk factors, and recognition of reduced CVD as an added benefit of strict inflammatory disease control. At present, chronic inflammatory diseases would appear to qualify as partners in crime and not merely innocent bystanders to CVD. However, definite incremental contributions of inflammation versus effects of the complex interplay with other CVD risk factors may never be fully elucidated and for the foreseeable future, inflammation is posed to maintain its current position as both a marker and a maker of CVD, with clinical utility both for identification of patient at risk of CVD and as target for therapy to reduce CVD.

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Abstract 14731: Glyc A, a Novel Marker of Inflammation, Predicts Cardiovascular Events in HIV-Positive Patients: Results of SMART Study

Circulation ◽

10.1161/circ.130.suppl_2.14731 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Daniel Duprez ◽

Jacqueline Neuhaus ◽

James Otvos ◽

James D Neaton ◽

Jens D Lundgren

Keyword(s):

Risk Factors ◽

Acute Phase ◽

Acute Phase Proteins ◽

Lipid Lowering ◽

Hiv Positive ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Hiv Patients ◽

Smart Study ◽

Increased Risk

Background: Cardiovascular disease (CVD) is increasing in HIV-infected patients. Glyc A is a novel nuclear magnetic resonance (NMR) spectroscopy signal in plasma arising from the glycosylation of circulating acute phase proteins. The acute phase proteins have been independently associated with CVD in HIV patients, but the association of Glyc A and CVD has not been studied. We aimed to quantify the risk of CVD associated with Glyc A at baseline in HIV-positive patients enrolled in the Strategies for Management of Anti-Retroviral Therapy (SMART) study. Methods: In a nested case-control study, Glyc A was measured using NMR at baseline in 246 HIV positive patients [median age, interquartile range (IQR): 49 (44,56) years, 81 % male], who experienced a CVD event (defined as coronary heart disease (CHD), myocardial infarction, coronary artery disease requiring revascularization, atherosclerotic non-CHD (stroke and peripheral arterial disease), congestive heart failure and CVD or unwitnessed death) over an average of 2.8 years of follow-up and 472 matched controls. Odds ratios (ORs) associated with baseline levels of Glyc A for CVD were estimated using conditional logistic regression unadjusted and after adjustment for BMI, race, HIV-RNA and antiretroviral therapy status, smoking, prior CVD, diabetes, total/high-density lipoprotein cholesterol ratio, use of blood pressure and lipid-lowering drugs, hepatitis co-infection, CD4+ and major baseline ECG abnormalities. Results: At baseline median Glyc A (IQR) was 383 (333, 442) μmol/L in patients who developed a CVD event and 368 (322, 419) μmol/L in controls (P < 0.001 for difference). The unadjusted OR for CVD (highest versus lowest quartile) was 2.18 (with 95% confidence interval (CI) 1.38-3.44, P < 0.001). After adjustment for baseline covariates and CVD risk factors, OR was 2.20 (95% CI, 1.29-3.76, P = 0.004). Conclusion: Higher levels of Glyc A are associated with increased risk of CVD in HIV patients after considering established CVD risk factors.

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