scholarly journals POS0678 DOES SILDENAFIL IMPROVE ENDOTHELIAL DYSFUNCTION IN RHEUMATOID ARTHRITIS? – A PILOT CLINICAL TRIAL

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 584.1-584
Author(s):  
K. Liang ◽  
D. Landsittel ◽  
Y. Li ◽  
L. Hope ◽  
L. Ruffalo ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cardiovascular Disease ◽  
Risk Factor ◽  
Endothelial Dysfunction ◽  
Adverse Events ◽  
Endothelial Function ◽  
Sample Size ◽  
Cvd Risk ◽  
Cvd Prevention ◽  
Treatment Order

Background:Rheumatoid arthritis (RA) is independently associated with an increased risk of cardiovascular disease (CVD). One of the early stages of atherosclerosis is endothelial dysfunction, which is increased in RA. Using drugs to target endothelial dysfunction is a promising novel strategy for CVD prevention in RA. Sildenafil has been shown to improve endothelial function in diabetics, who have similar increased CVD risk. Our hypothesis was that sildenafil use may be a novel primary CVD prevention strategy in RA.Objectives:To determine if sildenafil use in RA patients improves endothelial dysfunction (as measured by brachial artery flow-mediated dilation [FMD] and peripheral arterial tone [PAT]), as well as serum inflammatory and atherosclerosis biomarkers.Methods:This NIH-funded study was a phase II, randomized double-blind placebo-controlled crossover efficacy trial of 25 RA patients, with no known history of CVD, but at least one traditional CVD risk factor. Patients were randomized 1:1 to receive either sildenafil or placebo for 3 months, then after a 2-week washout, crossed over to each respective group for an additional 3 months. Vascular studies (FMD and PAT) and serum atherosclerosis biomarkers (e-Selectin, ICAM-1, VCAM-1) were performed at baseline, 3 months pre- and post-washout, and 6 months. Adverse events were collected. Given the cross-over design, analyses included a random effects model for within-subject comparisons of sildenafil versus placebo periods, adjusting for the baseline (FMD or EndoPAT) within that period and a term for treatment order. All tests were 2-sided with α=0.05.Results:A total of 233 subjects were assessed for eligibility, with 25 subjects being randomized after written informed consent. A total of 13 subjects were randomized to placebo first, and 12 to sildenafil first. Baseline characteristics were similar between those randomized to Placebo vs. Sildenafil first. Mean age was 62.0+/-10.9 years; 84% were female; and 92% were white. A total of 6 adverse events experienced in 3 subjects occurred. The primary endpoint (increase in %FMD in Sildenafil period vs. Placebo period) was not significant (p=0.19). However, note the study was powered at 80% to detect an effect size of 0.37 for change in %FMD or biomarker with a sample size of 60, not 25. However, sildenafil use was associated with a significant increase (improvement) by 0.200 units of PAT ratio (p=0.003) compared with placebo, adjusted by treatment order and baseline PAT ratio (within the given treatment period). Exploratory linear mixed models comparing e-Selectin, ICAM-1, and VCAM-1 between Sildenafil vs. Placebo periods, adjusted for treatment order and the baseline biomarker level, did not show any significant differences except for ICAM-1 (55.3 units higher in Sildenafil vs. Placebo periods, p=0.011).Conclusion:In this pilot trial of 25 RA subjects, sildenafil use was associated with a significant increase (improvement) in endothelial function as measured by PAT. However, there was no significant difference in FMD. The study is limited due to the small sample size, which was impacted by slow recruitment as well as the COVID-19 pandemic. Future larger studies are required to assess whether other PDE5 inhibitors may improve endothelial dysfunction in RA and other autoimmune disease patients at high risk of CVD.References:[1]Maradit-Kremers H, Crowson CS, Nicola PJ, et al. Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a population-based cohort study. Arthritis Rheum 2005;52:402-11.[2]Peters MJ, van Halm VP, Voskuyl AE, et al. Does rheumatoid arthritis equal diabetes mellitus as an independent risk factor for cardiovascular disease? A prospective study. Arthritis Rheum 2009;61:1571-9.[3]Deyoung L, Chung E, Kovac JR, et al. Daily use of sildenafil improves endothelial function in men with type 2 diabetes. J Andrology 2012;33:176-80.Disclosure of Interests:None declared

scholarly journals Atherosclerotic Cardiovascular Disease in Rheumatoid Arthritis: Impact of Inflammation and Antirheumatic Treatment

2021 ◽  
Vol 16 ◽  
Author(s):  
Anne Mirjam Kerola ◽  
Silvia Rollefstad ◽  
Anne Grete Semb
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Cardiovascular Disease ◽  
Systemic Inflammation ◽  
High Risk Patient ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cvd Risk ◽  
Pyrin Domain ◽  
Tnf Α ◽  
Cvd Prevention

Patients with rheumatoid arthritis (RA) are at approximately 1.5-fold risk of atherosclerotic cardiovascular disease (CVD) compared with the general population, a phenomenon resulting from combined effects of traditional CVD risk factors and systemic inflammation. Rheumatoid synovitis and unstable atherosclerotic plaques share common inflammatory mechanisms, such as expression of proinflammatory cytokines interleukin (IL)-1, tumour necrosis factor (TNF)-α and IL-6. RA patients are undertreated in terms of CVD prevention, and structured CVD prevention programmes are warranted. Alongside management of traditional risk factors, suppressing systemic inflammation with antirheumatic medication is fundamental for the reduction of CVD risk among this high-risk patient group. Many antirheumatic drugs, especially methotrexate, TNF-α-inhibitors and IL-6-inhibitors are associated with reduced risk of CVD in observational studies among RA patients, but randomised controlled trials with hard CVD endpoints are lacking. In patients without rheumatic disease, anti-inflammatory therapies targeting nucleotide-binding oligomerisation domain, leucine-rich repeat and pyrin domain-containing protein 3 inflammasome and the IL-1/IL-6 pathway arise as potential therapies after an atherosclerotic CVD event.

Influence of methylenetetrahydrofolate reductase genotype, exercise and other risk factors on endothelial function in healthy individuals

2001 ◽  
Vol 102 (1) ◽  
pp. 45-50 ◽  
Author(s):  
Catherine H. PULLIN ◽  
John F. WILSON ◽  
Pauline A.L. ASHFIELD-WATT ◽  
Zoë E. CLARK ◽  
Jenny M. WHITING ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Risk Factor ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Methylenetetrahydrofolate Reductase ◽  
Plasma Cholesterol ◽  
Hormone Replacement ◽  
Mthfr C677t ◽  
Healthy Individuals

Cardiovascular disease has a multifactorial aetiology that is influenced by both genetic and environmental factors. Endothelial dysfunction is a key event in the pathogenesis of vascular disease that occurs before structural vascular changes or clinical symptoms are evident. Conventional risk factors, for example hypertension and diabetes mellitus, are associated with endothelial dysfunction, but the influence of other putative risk factors is not clear. The methylenetetrahydrofolate reductase (MTHFR) C677T genotype, a common polymorphism that induces hyperhomocysteinaemia, has been proposed as being a genetic risk factor for cardiovascular disease. A total of 126healthy adults recruited by MTHFR C677T genotype (42 of each genotype, i.e. CC, CT and TT) underwent assessment of endothelial function. Brachial artery endothelium-dependent flow-mediated dilatation (FMD) was measured using high-resolution ultrasonic vessel ‘wall-tracking’. Using multiple regression analysis, MTHFR genotype and 21 other subject and subject-lifestyle variables were investigated as potential predictors of endothelial function. FMD was influenced positively by frequency of aerobic exercise and by hormone replacement therapy, and negatively by increases in systolic blood pressure. MTHFR C677T genotype and the associated variation in plasma homocysteine levels did not influence FMD. Additionally, other factors, including plasma cholesterol and self-supplementation with either antioxidant vitamins or cod liver oil, showed no significant relationship with FMD, although these findings are compromised by the narrow range studied for cholesterol and the small number of subjects taking supplements. These observations have implications for risk factor management in the primary prevention of cardiovascular disease in healthy individuals.

Risk Factor Profiles for Atherosclerotic Cardiovascular Disease in Black and Other Africans with Established Rheumatoid Arthritis

2010 ◽  
Vol 37 (5) ◽  
pp. 953-960 ◽  
Author(s):  
AHMED SOLOMON ◽  
BERENICE F. CHRISTIAN ◽  
GAVIN R. NORTON ◽  
ANGELA J. WOODIWISS ◽  
PATRICK H. DESSEIN
Keyword(s):  
Rheumatoid Arthritis ◽  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Risk Factor ◽  
Arterial Stiffness ◽  
Atherosclerotic Cardiovascular Disease ◽  
Established Rheumatoid Arthritis ◽  
Cvd Risk ◽  
Markers Of Inflammation ◽  
Black Patients

Objective.Black Africans reportedly experience a distinctly low risk for atherosclerotic cardiovascular disease (CVD). We investigated whether this protection was present among Africans with established rheumatoid arthritis (RA).Methods.We determined disparities in CVD risk factor profiles (major conventional: hypertension, dyslipidemia, smoking, and diabetes; other conventional: underweight, obesity, metabolic syndrome, chronic kidney disease, alcohol consumption, tension, depression, and body height; nonconventional: rheumatoid factor status and markers of inflammation) and arterial stiffness (brachial pulse pressure) between 291 black and 335 other (229 white, 64 Asian, and 42 mixed ancestry) consecutive Africans with RA in multivariable regression models.Results.After adjusting for demographic characteristics and healthcare sector attendance, black Africans had more prevalent hypertension (OR 1.76, p = 0.01) and diabetes (OR 1.90, p = 0.07), smoked less frequently (OR 0.12, p < 0.0001), and had concurrent lower total and high-density lipoprotein cholesterol concentrations that resulted in unaltered atherogenic indices (p = 0.2) than the other participants in the study. These findings translated into global scores for major conventional risk factor-mediated future CVD event rates that were not reduced in black patients. Proportions of individual metabolic syndrome components differed between black and other patients but their total numbers of metabolic risk factors (p = 0.4) and metabolic syndrome frequencies (OR 1.44, p = 0.1) were similar. Black ethnicity did not independently associate with rheumatoid factor status, markers of inflammation, and brachial pulse pressures.Conclusion.The overall conventional and nonconventional atherosclerotic CVD risk burdens and arterial stiffness were not reduced in black patients with RA. CVD risk should be assessed and managed independent of ethnic origin and epidemiological transition stage in RA.

scholarly journals Cardiovascular Disease in Rheumatoid Arthritis: Risk Factors, Autoantibodies, and the Effect of Antirheumatic Therapies

2021 ◽  
Vol 14 ◽  
pp. 117954412110287
Author(s):  
Mir Sohail Fazeli ◽  
Vadim Khaychuk ◽  
Keith Wittstock ◽  
Boris Breznen ◽  
Grace Crocket ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Cardiovascular Disease ◽  
Literature Review ◽  
Rheumatoid Factor ◽  
Qualitative Evidence Synthesis ◽  
Cvd Risk ◽  
Rheumatoid Arthritis Risk ◽  
Published Evidence ◽  
Increased Risk

Objective: To scope the current published evidence on cardiovascular risk factors in rheumatoid arthritis (RA) focusing on the role of autoantibodies and the effect of antirheumatic agents. Methods: Two reviews were conducted in parallel: A targeted literature review (TLR) describing the risk factors associated with cardiovascular disease (CVD) in RA patients; and a systematic literature review (SLR) identifying and characterizing the association between autoantibody status and CVD risk in RA. A narrative synthesis of the evidence was carried out. Results: A total of 69 publications (49 in the TLR and 20 in the SLR) were included in the qualitative evidence synthesis. The most prevalent topic related to CVD risks in RA was inflammation as a shared mechanism behind both RA morbidity and atherosclerotic processes. Published evidence indicated that most of RA patients already had significant CV pathologies at the time of diagnosis, suggesting subclinical CVD may be developing before patients become symptomatic. Four types of autoantibodies (rheumatoid factor, anti-citrullinated peptide antibodies, anti-phospholipid autoantibodies, anti-lipoprotein autoantibodies) showed increased risk of specific cardiovascular events, such as higher risk of cardiovascular death in rheumatoid factor positive patients and higher risk of thrombosis in anti-phospholipid autoantibody positive patients. Conclusion: Autoantibodies appear to increase CVD risk; however, the magnitude of the increase and the types of CVD outcomes affected are still unclear. Prospective studies with larger populations are required to further understand and quantify the association, including the causal pathway, between specific risk factors and CVD outcomes in RA patients.

Abstract P400: The Association Between Cross-sex Hormone Therapy and Cardiovascular Disease Risk Factors Among Male-to-female Transgender Persons in Chiang Mai, Thailand

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Rebecca L Molinsky ◽  
Kanokwan Kulprachakarn ◽  
Sakaewan Ounjaijean ◽  
Ryan Demmer ◽  
Kittipan Rerkasem
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Risk Factor ◽  
Hormone Therapy ◽  
Sex Hormone ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Transgender Persons ◽  
The Relationship ◽  
Male To Female

Background: Cross-sex hormone therapy (CSHT) is prescribed to transition secondary sexual characteristics among individuals undergoing male-to-female (MtF) transitions (age range 18-41, mean age=24). Limited data exist to inform the cardiovascular disease (CVD) risk factor profile associated with CSHT. We investigated the relationship between CSHT and cardiovascular risk factors in MtF transgender persons and hypothesize that CSHT will be associated with adverse CVD risk factor profiles. Methods: A cross-sectional study was conducted from October 1 st , 2018 to November 30 th , 2018 in 100 MtF transgender people not receiving CSHT vs. 100 receiving CSHT. CSHT use was defined by self-report use of up to 23 medications. Serum testosterone and 17-beta estradiol were assessed to validate CSHT use. Systolic and diastolic blood pressure was measured. Lipid profiles, fasting plasma glucose (FPG), C-reactive protein, cardiac troponin I and pro b-type natriuretic peptide (proBNP) were assessed from fasting blood. Non-invasive arterial examinations included: carotid intima-media thickness (CIMT), ankle-brachial index (ABI), cardio-ankle vascular index (CAVI), and pulse wave velocity (PWV). Multivariable linear regression models, regressed CVD risk factors on CSHT status. Among the subgroup of CSHT users, we assessed the relationship between duration of use and CVD risk factors. Multivariable models included age, gender, education, income, drinking, smoking, exercise, and BMI. Results: Participant mean age was 24±0.38 years and did not differ by CSHT use. Mean±SE values of testosterone were in the CSHT vs. control group were 4.8±0.3 vs. 5.8±0.3 ng/ml, p=0.06 and 17-beta estradiol levels were 45.6±14.9 vs. 34.7±14.8, p=0.7). CIMT was modestly lower among CSHT vs. controls (0.35±0.01 vs. 0.38±0.01, p=0.09). The average duration of CSHT use was 6.65±0.522 years. Among CSHT users, for every 1-year increase in duration of CSHT use total cholesterol decreased by -2.360 ± 1.096, p=0.0341 mg/dL, LDL-cholesterol decreased by -3.076 ± 1.182, p=0.0109 mg/dL, ABI decreased by -0.006 ± 0.002, p=0.0087 while FPG increased by 2.558 ± 0.899 mg/dL, p=0.0055. Conclusion: Among MtF transgender persons, using CSHT was not associated with increased CVD risk factors levels.

Abstract 14592: Pregnancy Loss and Cardiovascular Disease Risk Factors in Early Adulthood: Preliminary Findings From Add Health

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Yamnia I Cortes ◽  
Shuo Zhang ◽  
Diane C Berry ◽  
Jon Hussey
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Risk Factor ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Early Adulthood ◽  
Add Health ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Live Births

Introduction: Pregnancy loss, including miscarriage and stillbirth, affect 15-20% of pregnancies in the United States annually. Accumulating evidence suggests that pregnancy loss is associated with greater cardiovascular disease (CVD) burden later in life. However, associations between pregnancy loss and CVD risk factors in early adulthood (age<35 years) have not been assessed. Objective: To examine associations between pregnancy loss and CVD risk factors in early adulthood. Methods: We conducted a secondary data analysis using the public-use data set for Wave IV (2007-2009) of the National Longitudinal Study of Adolescent to Adult Health (Add Health). Our sample consisted of women, ages 24-32 years, with a previous pregnancy who completed biological data collection (n=2,968). Pregnancy loss was assessed as any history of miscarriage or stillbirth; and as none, one, or recurrent (≥2) pregnancy loss. Dependent variables included physical measures and blood specimens: body mass index (BMI), blood pressure, diabetes status, and dyslipidemia. Associations between pregnancy loss and each CVD risk factor were tested using linear (for BMI) and logistic regression adjusting for sociodemographic factors, parity, pre-pregnancy BMI, smoking during pregnancy, and depression. Results: Six hundred and ninety-three women (23%) reported a pregnancy loss, of which 21% reported recurrent pregnancy loss. Women with all live births were more likely to identify as non-Hispanic White (73%) and report a higher annual income. After adjusting for sociodemographics (age, race/ethnicity, education, income), pregnancy loss was associated with a greater BMI (ß=0.90; SE,0.39). In fully-adjusted models, women with recurrent pregnancy loss were more likely to have hypertension (AOR, 2.50; 95%CI, 1.04-5.96) and prediabetes (AOR, 1.93; 95%CI. 1.11-3.37) than women with all live births; the association was non-significant for women with one pregnancy loss. Conclusions: Pregnancy loss is associated with a more adverse CVD risk factor profile in early adulthood. Findings suggest the need for CVD risk assessment in young women with a prior pregnancy loss. Further research is necessary to identify underlying risk factors of pregnancy loss that may predispose women to CVD.

Diabetic dyslipidaemia

2011 ◽  
pp. 1963-1969
Author(s):  
John Betteridge
Keyword(s):  
Cardiovascular Disease ◽  
Practical Approach ◽  
Cvd Risk ◽  
Diagnosis And Management ◽  
Cvd Prevention ◽  
Multifactorial Approach ◽  
Lipoprotein Disorders

Management of dyslipidaemia is an integral part of the multifactorial approach to cardiovascular disease (CVD) prevention in people with diabetes. In this chapter the pathogenesis of lipid and lipoprotein disorders in diabetes and their relationship to CVD risk will be discussed together with a practical approach to diagnosis and management.

Sleep deprivation and endothelial function: reconciling seminal evidence with recent perspectives

2021 ◽  
Vol 320 (1) ◽  
pp. H29-H35
Author(s):  
Joshua M. Cherubini ◽  
Jem L. Cheng ◽  
Jennifer S. Williams ◽  
Maureen J. MacDonald
Keyword(s):  
Cardiovascular Disease ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Sleep Deprivation ◽  
Vascular Function ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Health Concern ◽  
Short Sleep ◽  
Inadequate Sleep

Sleep is critical for the maintenance of physiological homeostasis and, as such, inadequate sleep beckons a myriad of pathologies. Sleep deprivation is a growing health concern in contemporary society since short sleep durations are associated with increased cardiovascular disease risk and atherosclerotic plaque development. Vascular endothelial dysfunction is an antecedent to atherosclerosis and cardiovascular disease. Herein, we review seminal literature indicating that short sleep durations attenuate endothelial function and explore more recent evidence indicating that sleep deprivation perturbs autonomic balance and the circadian rhythmicity of peripheral vascular clock components. We further examine literature that indicates a mechanistic link between short sleep duration and endothelial dysfunction and subsequent morbidity. Understanding the mechanisms that regulate endothelial function in the context of sleep deprivation facilitates the development and optimization of interventions, such as exercise, that mitigate the ramifications of inadequate sleep on vascular function and cardiovascular health. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/sleep-deprivation-and-endothelial-function/

scholarly journals Diurnal patterns of sedentary time in rheumatoid arthritis: associations with cardiovascular disease risk

RMD Open ◽  
2020 ◽  
Vol 6 (2) ◽  
pp. e001216
Author(s):  
Sally A M Fenton ◽  
Nikos Ntoumanis ◽  
Joan L Duda ◽  
George S Metsios ◽  
Peter C Rouse ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cardiovascular Disease ◽  
Light Intensity ◽  
Sedentary Behaviour ◽  
Sedentary Time ◽  
Cvd Risk ◽  
Diurnal Patterns ◽  
Hourly Data ◽  
Vigorous Intensity ◽  
Time Periods

ObjectivesResearch demonstrates that sedentary behaviour may contribute towards cardiovascular disease (CVD) risk in rheumatoid arthritis (RA). This study explored diurnal patterns of sedentary time and physical activity (PA) in RA and examined associations with long-term CVD risk.Methods97 RA patients wore an accelerometer for 7 days to assess sedentary time, light-intensity and moderate-to-vigorous-intensity PA. Estimated 10-year CVD risk was determined via QRISK score. Hourly estimates of sedentary time and PA (min/hour) were computed for valid-wear hours (ie, valid-wear = 60 min/hour of activity data, ≥3 days). Hourly data were averaged across time periods to represent morning (08:00–11:59), afternoon (12:00–17:59) and evening (18:00–22:59) behaviour. Participants providing data for ≥2 complete time periods/day (eg, morning/evening, or morning/afternoon) were used in the main analysis (n = 41). Mixed linear modelling explored the associations between 10-year CVD risk and within-person (time: morning, afternoon, evening) changes in sedentary time and PA.ResultsSedentary time was higher, and light-intensity and moderate-to-vigorous-intensity PA lower in the evening, compared to morning and afternoon. Significant interactions revealed individuals with higher CVD risk were more sedentary and did less light-intensity PA during the afternoon and evening. Findings remained significant after adjustment for disease duration, functional ability and erythrocyte sedimentation rate.ConclusionResults suggest that the evening time period may offer a significant window of opportunity for interventions to reduce sedentary behaviour in RA and contribute to associated improvements in CVD risk. Due to inverse patterns of engagement, replacing sedentary time with light-intensity PA may offer an effective approach for intervention.

scholarly journals Lipoprotein(a) Is an Independent Risk Factor for Cardiovascular Disease in Heterozygous Familial Hypercholesterolemia

2005 ◽  
Vol 51 (11) ◽  
pp. 2067-2073 ◽  
Author(s):  
Daniel T Holmes ◽  
Brian A Schick ◽  
Karin H Humphries ◽  
Jiri Frohlich
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Risk Factor ◽  
Familial Hypercholesterolemia ◽  
Independent Risk Factor ◽  
Independent Predictor ◽  
Cvd Risk ◽  
Lipoprotein A ◽  
Heterozygous Familial Hypercholesterolemia ◽  
Lipid Clinic

Abstract Background: The role of lipoprotein(a) [Lp(a)] as a predictor of cardiovascular disease (CVD) in patients with heterozygous familial hypercholesterolemia (HFH) is unclear. We sought to examine the utility of this lipoprotein as a predictor of CVD outcomes in the HFH population at our lipid clinic. Methods: This was a retrospective analysis of clinical and laboratory data from a large multiethnic cohort of HFH patients at a single, large lipid clinic in Vancouver, Canada. Three hundred and eighty-eight patients were diagnosed with possible, probable, or definite HFH by strict clinical diagnostic criteria. Multivariate Cox regression analysis was used to study the relationship between several established CVD risk factors, Lp(a), and the age of first hard CVD event. Results: An Lp(a) concentration of 800 units/L (560 mg/L) or higher was a significant independent risk factor for CVD outcomes [hazard ratio (HR) = 2.59; 95% confidence interval (CI), 1.53–4.39; P &lt;0.001]. Other significant risk factors were male sex [HR = 3.19 (1.79–5.69); P &lt;0.001] and ratio of total to HDL-cholesterol [1.18 (1.07–1.30); P = 0.001]. A previous history of smoking or hypertension each produced HRs consistent with increased CVD risk [HR = 1.55 (0.92–2.61) and 1.57 (0.90–2.74), respectively], but neither reached statistical significance (both P = 0.10). LDL-cholesterol was not an independent predictor of CVD risk [HR = 0.85 (0.0.71–1.01); P = 0.07], nor was survival affected by the subcategory of HFH diagnosis (i.e., possible vs probable vs definite HFH). Conclusion: Lp(a) is an independent predictor of CVD risk in a multiethnic HFH population.

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