scholarly journals Lipoprotein (a) and 10-year Cardiovascular Disease Incidence in Apparently Healthy Individuals: A Sex-based Sensitivity Analysis from ATTICA Cohort Study

Angiology ◽  
2019 ◽  
Vol 70 (9) ◽  
pp. 819-829 ◽  
Author(s):  
Matina Kouvari ◽  
Demosthenes B. Panagiotakos ◽  
Christina Chrysohoou ◽  
Ekavi N. Georgousopoulou ◽  
Mary Yannakoulia ◽  
...  

The association between lipoprotein (a) (Lp(a)) and 10-year first fatal/nonfatal cardiovascular disease (CVD) risk in apparently healthy men and women was evaluated. The ATTICA prospective study was conducted during 2001-2012 and included n = 1514 men and n = 1528 women (age >18 years) from the greater Athens area, Greece. Follow-up CVD assessment (2011-2012) was achieved in n = 2020 participants (n = 317 cases); baseline Lp(a) was measured in n = 1890 participants. The recommended threshold of 50 mg/dL was used to define abnormal Lp(a) status. Ten-year CVD-event rate was 14% and 24% in participants with Lp(a) <50 and Lp(a) ≥50 mg/dL, respectively. Multivariate analysis revealed that participants with Lp(a) ≥50 mg/dL versus Lp(a) <50 mg/dL had about 2 times higher CVD risk (hazard ratio (HR) = 2.18, 95% confidence interval (CI) 1.11, 4.28). The sex-based analysis revealed that the independent Lp(a) effect was retained only in men (HR = 2.00, 95% CI 1.19, 2.56); in women, significance was lost after adjusting for lipid markers. Sensitivity analyses revealed that Lp(a) increased CVD risk only in case of abnormal high-density lipoprotein cholesterol, apolipoprotein A1, and triglycerides as well as low adherence to Mediterranean diet. Certain patient characteristics may be relevant when considering Lp(a) as a therapeutic or risk-prediction target.

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Fatemeh Koohi ◽  
Davood Khalili ◽  
Mohammad Ali Mansournia ◽  
Farzad Hadaegh ◽  
Hamid Soori

Abstract Background Understanding the distinct patterns (trajectories) of variation in blood lipid levels before diagnosing cardiovascular disease (CVD) might carry important implications for improving disease prevention or treatment. Methods We investigated 14,373 participants (45.5% men) aged 45–84 from two large US prospective cohort studies with a median of 23 years follow-up. First, we jointly estimated developmental trajectories of lipid indices, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) concentrations using group-based multi-trajectory modeling. Then, the association of identified multi-trajectories with incident CVD, heart failure, and all-cause mortality were examined using Cox proportional hazard model. Results Seven distinct multi-trajectories were identified. The majority of participants (approximately 80%) exhibited decreasing LDL-C but rising TG levels and relatively stable HDL-C levels. Compared to the individuals with healthy and stable LDL-C, HDL-C, and TG levels, those in other groups were at significant risk of incident CVD after adjusting for other conventional risk factors. Individuals with the highest but decreasing LDL-C and borderline high and rising TG levels over time were at the highest risk than those in other groups with a 2.22-fold risk of CVD. Also, those with the highest and increased triglyceride levels over time, over optimal and decreasing LDL-C levels, and the lowest HDL-C profile had a nearly 1.84 times CVD risk. Even individuals in the multi-trajectory group with the highest HDL-C, optimal LDL-C, and optimal TG levels had a significant risk (HR, 1.45; 95% CI 1.02–2.08). Furthermore, only those with the highest HDL-C profile increased the risk of heart failure by 1.5-fold (95% CI 1.07–2.06). Conclusions The trajectories and risk of CVD identified in this study demonstrated that despite a decline in LDL-C over time, a significant amount of residual risk for CVD remains. These findings suggest the impact of the increasing trend of TG on CVD risk and emphasize the importance of assessing the lipid levels at each visit and undertaking potential interventions that lower triglyceride concentrations to reduce the residual risk of CVD, even among those with the optimal LDL-C level.


2019 ◽  
Vol 24 (31) ◽  
pp. 3665-3671 ◽  
Author(s):  
Panagiotis Anagnostis ◽  
Pavlos Siolos ◽  
Dimitrios Krikidis ◽  
Dimitrios G. Goulis ◽  
John C. Stevenson

Background: Familial hypercholesterolaemia (FH) is a genetically determined lipid disorder, affecting 1 per 200-500 individuals in the general population. It is significantly and independently associated with an increased risk of Cardiovascular Disease (CVD), although it remains still an underrecognized and undertreated disease. Lipoprotein (a) [Lp(a)] is a low-density-lipoprotein (LDL)-like molecule, containing an additional protein, apolipoprotein (a). Objective: This review aims to present and discuss available data on the role of Lp(a) in patients with FH, in terms of its potential augmentation of CVD risk. Methods: A comprehensive search of the literature was performed to identify studies evaluating the CV effects of Lp(a) in patients with FH. Results: Lp(a) has been recognised as an independent risk factor for CVD, mainly coronary artery disease (CAD). Most, but not all, studies show increased Lp(a) concentrations in adults and children with FH. There is also evidence of an independent association between Lp(a) and CVD (mainly CAD) risk in these patients. Conclusion: Some therapeutic modalities, such as niacin, oestrogens, tibolone and proprotein convertase subtilisin/ kexin type 9 (PCSK9) inhibitors may effectively reduce Lp(a) concentrations by 25-30%, although their clinical benefit of this effect remains to be established.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Kouvari ◽  
D.B Panagiotakos ◽  
C Chrysohoou ◽  
E.N Georgousopoulou ◽  
C Pitsavos ◽  
...  

Abstract Background/Introduction Prediabetes in terms of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) are highly discussed for their aggravating effect on cardiac health and their potential inclusion in risk prediction to achieve earlier prevention. Purpose The aim of the present work was to evaluate the association between prediabetes and 10-year first fatal/non fatal cardiovascular disease (CVD) incidence in a sample without prevalent CVD, taking into account the stability of this condition or the transition to type II diabetes. Methods A prospective study was conducted during 2001–2012 studying n=1,514 males and n=1,528 females (aged &gt;18 years old) free of CVD. According to American Diabetes Association Diagnosis, prediabetes in terms of IFG was defined as fasting glucose levels 100–125 mg/dl while type 2 diabetes as fasting blood glucose &gt;125 mg/dl or the use of antidiabetic medication. Ten-year follow-up was performed in n=2,020 participants (n=317 CVD cases); the working sample here was n=1,485 (n=249 CVD cases) (without baseline diabetes and with available data on diabetes status at follow-up). Results Of the 1,485 participants, n=279 had IFG, at baseline. Ten-year CVD incidence was 19.3% in IFG subgroup and 12.3% in normoglycemic subgroup (p&lt;0.001); the IFG-to-normoglycemic CVD incidence ratio in men was 1.22 while in women 1.60. Multi-adjusted analysis revealed that IFG was an independent predictor of CVD within the decade (Hazard ratio (HR)=1.39, 95% Confidence Interval (95% CI) (1.00, 1.95)). Significant interacting effect of gender on the examined association was revealed (p for interaction=0.001); in stratified analysis, IFG was independently associated with increased CVD risk only in women (HR=1.47, 95% CI (1.10, 2.68)). Within the decade, transition to diabetes status was observed in about one out of four participants with prediabetes (25.1%) while the respective rate in normoglycemic participants was 10% (n=191 diabetes cases, in total). Interestingly, sensitivity analysis revealed that when this category (with diabetes onset within the decade) was excluded from the analysis prediabetes retained its independent aggravating –even weaker– effect on 10-year CVD risk in total sample (HR=1.18, 95% CI (1.01, 1.91)) as well as in women (HR=1.25, 95% CI (1.03, 2.97)). Conclusion Here, it was suggested that IFG independently predicted long-term CVD onset, even without transition to a more serious cardiometabolic condition (i.e. diabetes) with more evident outcomes in case of women. Considering the increasing interest for early CVD risk prediction, prediabetes condition in terms of IFG may be a useful predictor towards this perspective. Funding Acknowledgement Type of funding source: Other. Main funding source(s): This work was supported by a research grant from Hellenic Atherosclerosis Society. The ATTICA study is supported by research grants from the Hellenic Cardiology Society [HCS2002] and the Hellenic Atherosclerosis Society [HAS2003].


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Kouvari ◽  
D B Panagiotakos ◽  
C Chrysohoou ◽  
E Georgousopoulou ◽  
D Tousoulis ◽  
...  

Abstract Background/Introduction In the context of novel risk factors in cardiovascular disease (CVD) spectrum, lipoprotein (a) (Lp(a)) is a highly discussed biomarker with promising evidence. Purpose The association between Lp(a) and 10-year first fatal/non fatal CVD event in free of CVD males and females was evaluated. Methods A longitudinal prospective study was conducted during 2001–2012, studying 1,514 males and 1,528 females (aged >18 years old). Follow-up assessment of CVD (2011–2012) was achieved in n=2,020 participants (n=317 cases). Of them, baseline Lp(a) was measured in n=1,890 participants. The recommended threshold of 50mg/dL was used to define abnormal Lp(a) status (≥50mg/dL). Effect-size of Lp(a) on CVD was evaluated through Cox-regression analysis while its discrimination ability through C-statistics. Results Ten-year CVD event rate was 14% and 24% in participants with Lp(a)<50 mg/dL and Lp(a)≥50 mg/dL, respectively (p=0.05). In multivariate analysis those with Lp(a)≥50 mg/dL had two times higher risk to develop CVD compared with participants with normal Lp(a) (Hazard Ratio (HR)=2.18, 95% Confidence Interval (95% CI) 1.11, 4.28, p=0.04). Sex-based stratified analysis revealed that the independent Lp(a)-effect on CVD was retained only in males (HR=2.00, 95% CI 1.19, 2.56, p=0.05); while in females significance was lost when adjusting for low and high density lipoprotein (LDL-C, HDL-C), triglycerides and statins use (p for sex interaction=0.01). Sensitivity analyses revealed that Lp(a) significantly increased CVD risk only in case of abnormal HDL-C, apolipoprotein A1 and triglycerides; interestingly, the interaction between these lipid markers, sex and Lp(a) was significant (p for interaction=0.001) implying that this observation could be sex-mediated. C-indexes and correct classification rates of a standard model with three different levels of adjustment (i.e. Lp(a) or conventional lipid markers or combined lipid markers) were evaluated per sex. In females, the highest total correct classification rate was higher in model adjusted for conventional lipid markers (89.6%) with the rate corresponding to CVD cases being more than twice as high in Lp(a)-adjusted model (19.6% vs. 8.5%) and lower than in fully adjusted model (15.7%). A similar ranking was observed in case of C-indexes (0.831 vs. 0.820 vs. 0.829). Males presented the best total correct classification rate in fully adjusted model (96.5%). Case-related correct classification rate was about 3 times higher in Lp(a)-adjusted model compared with the respective rate in females (24.7% vs. 8.5%). C-index after Lp(a) adjustment in the model with conventional lipid markers increased by 0.01 (i.e. 0.772 vs. 0.784). Conclusion While ever increasing efforts have sought to elucidate Lp(a) as a therapeutic target or risk-prediction biomarker in CVD prevention clinical recommendations remain to be guided with appropriate conclusive evidence, mostly from a sex-centered standpoint. Acknowledgement/Funding The ATTICA study is supported by research grants from the Hellenic Cardiology Society [HCS2002] and the Hellenic Atherosclerosis Society [HAS2003].


Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1506
Author(s):  
Matina Kouvari ◽  
Demosthenes B. Panagiotakos ◽  
Christina Chrysohoou ◽  
Ekavi N. Georgousopoulou ◽  
Dimitrios Tousoulis ◽  
...  

The sex-specific effect of lipid-related biomarkers on 10-year first fatal/non fatal cardiovascular disease (CVD) incidence was evaluated. ATTICA study was conducted during 2001–2012. n = 1514 men and n = 1528 women (>18 years) from greater Athens area, Greece were recruited. Follow-up (2011–2012) was achieved in n = 2020 participants. Baseline lipid profile was measured. Overall CVD event was 15.5% (n = 317) (19.7% in men and 11.7% in women, p < 0.001). High density lipoprotein cholesterol (HDL-C) and triglycerides (TAG) were independently associated with CVD in women; per 10 mg/dL HDL-C increase, hazard ratio (HR) = 0.73, 95% confidence interval (95% CI) (0.53, 1.00); and per 10 mg/dL TAG increase, HR = 1.10, 95% CI (1.00, 1.21). Apolipoprotein A1 (ApoA1) (per 10 mg/dL increase, HR = 0.90, 95% CI (0.81, 0.99)) was inversely associated with CVD in women, while a positive association with apolipoprotein B100 (ApoB100) was observed only in men (per 10 mg/dL increase, HR = 1.10, 95% CI (1.00, 1.21)). Non-HDL-C was associated with CVD in the total sample (HR = 1.10, 95% CI (1.00, 1.21)) and in women (HR = 1.10, 95% CI (1.00, 1.21)); a steep increase in HR was observed for values >185 mg/dL in the total sample and in men, while in women, a raise in CVD risk was observed from lower values (>145 mg/dL). As for non-HDL-C/HDL-C and TC/HDL-C ratios, similar trends were observed. Beyond the common cholesterol-adjusted risk scores, reclassifying total CVD risk according to other lipid markers may contribute to early CVD prevention. Biomarkers such as HDL-C, non-HDL-C, and TAG should be more closely monitored in women.


2021 ◽  
Author(s):  
Yingxian Sun ◽  
Shu Zhang ◽  
Xin Fu ◽  
Zhi Du ◽  
Xiaofan Guo ◽  
...  

Abstract Background Cardiovascular disease (CVD) brings high mortality and economic burden to patients, especially in rural areas. Simple, low-cost abdominal adiposity measures may help identify individuals with increased CVD risk. It is unclear that which obesity indice is the best to predict CVD in hypertensive people. Methods NCRCHS is a prospective cohort study in a general population in Northeast China. The study examined the cardiovascular health from 2013–2015, and follow-up captured the CVD incidence in 2018. Baseline waist-to-height ratio (WHtR), body mass index (BMI),waist-to-hip(WHR)and waist circumference (WC) were calculated and analyzed in relation to the CVD incidence. Results A total of 4244 hypertensive adults without pre-existing CVD at baseline were included in this analysis (age 35–92 years; 2108 men). Over a median follow-up of 4.66 years, a total of 290 CVD cases (6.83%) were documented during the follow-up. Baseline WHtR showed a significant positive association with CVD incidence, even after adjusting for age, sex, diabetes, drinking, smoking, SBP, DBP, Triglyceride, HDL-C, LDL-C, and TC (Hazard Ratios per SD of WHtR ranging from 1.03 to 1.31, p = 0.017). Reclassification and discrimination analyses indicated WHtR addition could improve the conventional model for predicting adverse outcomes within 4 years. Moreover, WHtR predicted the CVD incidence better than other obesity indices (BMI, WC, WHR). Conclusion These findings support a positive association between WHtR and CVD incidence in CVD-free hypertensive adults. WHtR may be useful in predicting CVD incidence in hypertensive adults.


2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Ju-Sheng Zheng ◽  
Jing Yang ◽  
Tao Huang ◽  
Xiao-Jie Hu ◽  
Ming Luo ◽  
...  

Objectives. To elucidate whether consumption of two Chinese liquors, tea-flavor liquor (TFL) and traditional Chinese liquor (TCL) have protective effects on cardiovascular disease (CVD) risk factors in healthy human subjects.Methods. Forty-five healthy subjects (23 men, 22 women), aged 23–28, were recruited and randomized into two groups: TFL and TCL, and consumed 30 mL/day (45% (v/v) alcohol) of either liquor for 28 days.Results. Serum high-density lipoprotein cholesterol/low-density lipoprotein cholesterol (HDL-C/LDL-C) and apolipoprotein A1 were significantly increased, and total cholesterol (TC) and TC/HDL-C were significantly decreased after the intervention in both groups (P<0.05). Serum uric acid (P=0.004for TFL,P=0.001for TCL), glucose (P<0.001for TFL,P<0.001for TCL) and endothelial adhesion molecules (P<0.05) were significantly decreased after the intervention. ADP-induced whole blood platelet aggregation was also significantly decreased after the intervention in both TFL and TCL groups (P<0.05).Conclusions. TFL and TCL consumption had protective effects on CVD risk factors in young humans. However, the results were valid only for 28 days, and that the possibility of adverse effect (liver, kidney) of chronic alcohol consumption should be considered.


2021 ◽  
Author(s):  
Shu Zhang ◽  
Xin Fu ◽  
Zhi Du ◽  
Xiaofan Guo ◽  
Zhao Li ◽  
...  

Abstract Background Cardiovascular disease (CVD) brings high mortality and economic burden to patients, especially in rural areas. Simple, low-cost abdominal adiposity measures may help identify individuals with increased CVD risk. It is unclear that which obesity indice is the best to predict CVD in hypertensive people. Methods NCRCHS is a prospective cohort study in a general population in Northeast China. The study examined the cardiovascular health from 2013–2015, and follow-up captured the CVD incidence in 2018. Baseline waist-to-height ratio (WHtR), body mass index (BMI),waist-to-hip(WHR)and waist circumference (WC) were calculated and analyzed in relation to the CVD incidence. Results A total of 4244 hypertensive adults without pre-existing CVD at baseline were included in this analysis (age 35–92 years; 2108 men). Over a median follow-up of 4.66 years, a total of 290 CVD cases (6.83%) were documented during the follow-up. Baseline WHtR showed a significant positive association with CVD incidence, even after adjusting for age, sex, diabetes, drinking, smoking, SBP, DBP, Triglyceride, HDL-C, LDL-C, and TC (Hazard Ratios per SD of WHtR ranging from 1.03 to 1.31, p = 0.017). Reclassification and discrimination analyses indicated WHtR addition could improve the conventional model for predicting adverse outcomes within 4 years. Moreover, WHtR predicted the CVD incidence better than other obesity indices (BMI, WC, WHR). Conclusion These findings support a positive association between WHtR and CVD incidence in CVD-free hypertensive adults. WHtR may be useful in predicting CVD incidence in hypertensive adults.


2021 ◽  
Vol 10 (15) ◽  
pp. 3400
Author(s):  
Cathy Degroote ◽  
Roland von Känel ◽  
Livia Thomas ◽  
Claudia Zuccarella-Hackl ◽  
Jens C. Pruessner ◽  
...  

Hyperreactivity to stress may be one explanation for the increased risk of cardiovascular disease (CVD) in individuals with essential hypertension. We investigated blood lipid reactivity to the Montreal Imaging Stress Task (MIST), a psychosocial stressor, in hypertensive and normotensive men and tested for prospective associations with biological risk factors. Fifty-six otherwise healthy and medication-free hypertensive and normotensive men underwent the MIST. We repeatedly measured cortisol and blood lipid profiles (total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG)) immediately before and up to 1 h after stress. Lipid levels were corrected for stress hemoconcentration. Thirty-five participants completed follow-up assessment 2.9 ± 0.12 (SEM) years later. CVD risk was assessed by prospective changes in TC/HDL-C ratio, IL-6, D-dimer, and HbA1c from baseline to follow-up. The MIST induced significant changes in all parameters except TC (p-values ≤ 0.043). Compared with normotensives, hypertensives had higher TC/HDL-C-ratio and TG (p-values ≤ 0.049) stress responses. Blood lipid stress reactivity predicted future cardiovascular risk (p = 0.036) with increases in HbA1c (ß = 0.34, p = 0.046), IL-6 (ß = 0.31, p = 0.075), and D-dimer (ß = 0.33, p = 0.050). Our results suggest that the greater blood lipid reactivity to psychosocial stress in hypertensives, the greater their future biological CVD risk. This points to lipid stress reactivity as a potential mechanism through which stress might increase CVD risk in essential hypertension.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Fairbairn ◽  
P Oh ◽  
R Goeree ◽  
R.M Rogoza ◽  
M Packalen ◽  
...  

Abstract Background/Introduction Limited real-world data are available on attainment of low-density lipoprotein cholesterol (LDL-C) treatment goals in patients with atherosclerotic cardiovascular disease (ASCVD) in Canada. Purpose A retrospective observational study was conducted to describe types of ASCVD events/procedures, time between events and use of lipid lowering treatment (LLT) in patients who did not achieve LDL-C goal. Methods Patients in Ontario ≥65 years with a primary ASCVD event/procedure between 1 Apr 2005 and 31 Mar 2016, treated with an LLT and with index and follow up LDL-C values were identified from claims data at the Institute for Clinical Evaluative Sciences data repository. Patients were assessed over a 1-year follow up period for LDL-C goal attainment (&lt;2.0 mmol/L or 50% reduction from index LDL-C) and analysed by LLT and by index event type. Results Overall, 28% of 143,302 patients ≥65 years on LLT failed to attain LDL-C goal at follow up (Figure). The proportion of patients failing to achieve LDL-C goal decreased from 35% to 22% over the 11-year study period. Mean time between index and follow up LDL-C (based on lowest score &gt;2 weeks and up to 1 year after index LDL-C) was 203±97 days. When analysed by low-, moderate- or high-intensity statin, 57%, 30%, and 22% of patients failed to achieve LDL-C goal at follow up, respectively. Conclusions In this study, more than 1 in 4 patients with ASCVD in Ontario failed to achieve guideline recommended LDL-C goal despite treatment. In particular, ∼1 in 3 patients with cerebral and peripheral arterial disease were not at goal. An opportunity exists to better manage these high risk ASCVD patients with further statin intensification and additional LLTs This study made use of de-identified data from the ICES Data Repository, which is managed by the Institute for Clinical Evaluative Sciences with support from its funders and partners: Canada's Strategy for Patient-Oriented Research (SPOR), the Ontario SPOR Support Unit, the Canadian Institutes of Health Research and the Government of Ontario. The opinions, results and conclusions reported are those of the authors. No endorsement by ICES or any of its funders or partners is intended or should be inferred. Parts of this material are based on data and/or information compiled and provided by CIHI. However, the analyses, conclusions, opinions and statements expressed in the material are those of the author(s), and not necessarily those of CIHI Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen Canada Inc.


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