Lipoprotein(a) among normotensive patients and risk of incident hypertension.
Journal of clinical hypertension (Greenwich, Conn.)
Lipoprotein(a) has been shown to be disruptive to local endothelial cells, whose integrity is critical to blood pressure (BP) regulation. Cross-sectional analysis has shown an association between lipoprotein(a) and prevalent hypertension, though it is unclear if lipoprotein(a) increases risk of incident hypertension. To assess this, the authors measured baseline lipoprotein(a) among 5307 normotensive patients (median age 26 years (interquartile range [IQR] 12-50) and used Cox proportional hazard models to generate hazard rations (HR) with 95% confidence intervals (CI; median follow-up 10-years). The authors categorized lipoprotein(a) as <15 mg/dL, 15-<30 mg/dL, 30-50 mg/dL, >50 mg/dL, and performed subgroup analysis of adults >50 years at baseline. Incident hypertension was defined as a measured BP ≥140/90 mm Hg or a new ICD-9/10 code. After adjustment, hypertension for patients with baseline lipoprotein(a) 15-<30 mg/dL, 30-50 mg/dL, and >50 mg/dL was 0.91 (0.72-1.16), 1.05 (0.79-1.38), and 1.02 (0.83-1.26; vs. <15 mg/dL). However, among adults >50 years, lipoprotein(a) >50 mg/dL was associated with increased incident hypertension (1.62 [1.17-2.26]).
10.1111/jch.14904
Lipoprotein (a), hypertension, and cardiovascular outcomes: a prospective study of patients with stable coronary artery disease.
Liu Hui-Hui,Cao Ye-Xuan,Jin Jing-Lu,Hua Qi,Li Yan-Fang,Guo Yuan-Lin,Zhu Cheng-Gang,Wu Na-Qiong,Dong Qian,Li Jian-Jun
Hypertension research : official journal of the Japanese Society of Hypertension
Although emerging data suggest that circulating lipoprotein (a) [Lp (a)] could predict cardiovascular events (CVEs) in patients with cardiovascular disease, no study is currently available regarding the prognostic linkage of Lp (a) and hypertension in patients with coronary artery disease (CAD). This study sought to evaluate the association of Lp (a), hypertension and cardiovascular outcomes in patients with stable CAD. A total of 8668 patients with stable CAD were consecutively enrolled. Baseline Lp (a) concentrations were measured. All subjects were categorized according to Lp (a) levels of <10 (low), 10-30 (medium) and ≥30 mg/dL (high) and were further stratified by hypertension status. They were regularly followed-up for the occurrence of cardiovascular death, nonfatal myocardial infarction, and stroke. Over an average of 54.81 ± 18.60 months of follow-up, 584 (6.7%) CVEs occurred. Kaplan-Meier and multivariate Cox regression analyses showed that elevated Lp (a) levels had a significant association with CVEs in hypertensive patients, regardless of the control status of blood pressure, but not in normotensive subjects. Moreover, when analyzed by subgroups according to both Lp (a) category and hypertension status, the risk of CVEs was only significantly elevated in the high Lp (a) plus hypertension group compared with the reference group with low Lp (a) levels and normotension (hazard ratio: 1.80, 95% confidence interval: 1.11-2.91). Elevated Lp (a) was associated with an increased risk of CVEs in stable CAD patients with hypertension. Moreover, the coexistence of high Lp (a) concentrations and hypertension greatly worsened the clinical prognosis in patients with CAD, which may suggest a prognostic correlation between Lp (a) and hypertension.
10.1038/s41440-021-00668-4
Lipoprotein(a), LDL-cholesterol, and hypertension: predictors of the need for aortic valve replacement in familial hypercholesterolaemia.
European heart journal
AIMS:Familial hypercholesterolaemia (FH) and elevated lipoprotein(a) [Lp(a)] are inherited disorders associated with premature atherosclerotic cardiovascular disease (ASCVD). Aortic valve stenosis (AVS) is the most prevalent valvular heart disease and low-density lipoprotein cholesterol (LDL-C) and Lp(a) may be involved in its pathobiology. We investigated the frequency and predictors of severe AVS requiring aortic valve replacement (AVR) in molecularly defined patients with FH. METHODS AND RESULTS:SAFEHEART is a long-term prospective cohort study of a population with FH and non-affected relatives (NAR). We analysed the frequency and predictors of the need for AVR due to AVS in this cohort. Five thousand and twenty-two subjects were enrolled (3712 with FH; 1310 NAR). Fifty patients with FH (1.48%) and 3 NAR (0.27%) required AVR [odds ratio 5.71; 95% confidence interval (CI): 1.78-18.4; P = 0.003] after a mean follow-up of 7.48 (3.75) years. The incidence of AVR was significantly higher in patients with FH (log-rank 5.93; P = 0.015). Cox regression analysis demonstrated an association between FH and AVR (hazard ratio: 3.89; 95% CI: 1.20-12.63; P = 0.024), with older age, previous ASCVD, hypertension, increased LDL-CLp(a)-years, and elevated Lp(a) being independently predictive of an event. CONCLUSION:The need for AVR due to AVS is significantly increased in FH patients, particularly in those who are older and have previous ASCVD, hypertension, increased LDL-CLp(a)-years and elevated Lp(a). Reduction in LDL-C and Lp(a) together with control of hypertension could retard the progression of AVS in FH, but this needs testing in clinical trials.ClinicalTrials.gov number NCT02693548.
10.1093/eurheartj/ehaa1066
Association of Lp(a) (Lipoprotein[a]) and Hypertension in Primary Prevention of Cardiovascular Disease: The MESA.
Hypertension (Dallas, Tex. : 1979)
BACKGROUND:This study explored the longitudinal relationship of Lp(a) (lipoprotein[a]) and hypertension to cardiovascular outcomes in a large multiethnic cohort free of baseline cardiovascular disease. METHODS:Individuals from the MESA (Multi-Ethnic Study of Atherosclerosis; N=6674) were grouped as follows: group 1: Lp(a) <50 mg/dL and no hypertension; group 2: Lp(a) ≥50 mg/dL and no hypertension; group 3: Lp(a) <50 mg/dL and hypertension; and group 4: Lp(a) ≥50 mg/dL and hypertension. Kaplan-Meier curves and multivariable Cox proportional hazard models were used to assess the relationship of Lp(a) and hypertension with time to cardiovascular disease events. RESULTS:Mean follow-up time was 13.9 (5.0) years and 809 participants experienced a cardiovascular disease event. A statistically significant interaction was found between Log[Lp(a)] and hypertension status (=0.091). Compared with the reference group (Lp[a] <50 mg/dL and no hypertension), those with Lp[a] ≥50 mg/dL and no hypertension had no increased risk for cardiovascular disease events (hazard ratio, 1.09 [95% CI, 0.79-1.50]). However, those with Lp(a) <50 mg/dL and hypertension or Lp(a) ≥50 mg/dL and hypertension demonstrated a statistically significant increase in risk compared to the reference group (hazard ratio, 1.66 [95% CI, 1.39-1.98]) and (hazard ratio, 2.07 [95% CI, 1.63-2.62]), respectively. Among those with hypertension, Lp(a) was associated with a significant increase in cardiovascular disease risk (hazard ratio, 1.24 [95% CI, 1.01-1.53]). CONCLUSIONS:Although the major contribution to cardiovascular risk was hypertension, elevated Lp(a) significantly modified the association of hypertension with cardiovascular disease. More research is needed to understand mechanistic links among Lp(a), hypertension, and cardiovascular disease.
10.1161/HYPERTENSIONAHA.122.20189
Association between serum uric acid/high-density lipoprotein cholesterol ratio and hypertension among reproductive-aged women.
Journal of health, population, and nutrition
BACKGROUND:Uric acid/high-density lipoprotein cholesterol ratio (UHR) is a novel index of inflammation and metabolism that has been investigated in various diseases. However, association between UHR and hypertension among reproductive-aged women is unclear. METHODS:In this cross-sectional study, we investigated the association between serum UHR and hypertension among 5485 women aged 20-44 years based on the National Health and Nutrition Examination Survey (NHANES) database using various methods, including univariate and multivariate logistic regression analysis, stratified analysis, and spline regression. P < 0.05 was considered statistically significant. RESULTS:There was significant difference in UHR between the women with and without hypertension (P < 0.001). After adjusting for several covariates, UHR was positively correlated with hypertension (OR > 1, P < 0.001). In the subgroup analysis, the positive correlations still remained between UHR and hypertension in women with various age and those with BMI ≥ 30 kg/m (P < 0.05) excepted for adjusting for all covariates. We further found an inflection point of the threshold effect for UHR, and the prevalence of hypertension showed different increased trends below and above the threshold. CONCLUSION:This study indicated a positive association between serum UHR and hypertension among reproductive-aged women, indicating that UHR is a potential clinical marker of hypertension in women.
10.1186/s41043-023-00458-3
Lipoprotein (a) and Hypertension.
Ward Natalie C,Nolde Janis M,Chan Justine,Carnagarin Revathy,Watts Gerald F,Schlaich Markus P
Current hypertension reports
PURPOSE OF REVIEW:To provide an overview of the associations between elevated blood pressure and lipoprotein (a) and possible causal links, as well as data on the prevalence of elevated lipoprotein (a) in a cohort of hypertensive patients. RECENT FINDINGS:Elevated lipoprotein (a) is now considered to be an independent and causal risk factor for atherosclerotic cardiovascular disease and calcific aortic valve disease. Despite this, there are limited data demonstrating an association between elevated lipoprotein (a) and hypertension. Further, there is limited mechanistic data linking lipoprotein (a) and hypertension through either renal impairment or direct effects on the vasculature. Despite the links between lipoprotein (a) and atherosclerosis, there are limited data demonstrating an association with hypertension. Evidence from our clinic suggests that ~ 30% of the patients in this at-risk, hypertensive cohort had elevated lipoprotein (a) levels and that measurement of lipoprotein (a) maybe useful in risk stratification.
10.1007/s11906-021-01161-6
Triglyceride-glucose index and triglyceride to high-density lipoprotein cholesterol ratio as potential cardiovascular disease risk factors: an analysis of UK biobank data.
Cardiovascular diabetology
BACKGROUND:The triglyceride-glucose (TyG) index and triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, two simple surrogate indicators of insulin resistance, have been demonstrated to predict cardiovascular disease (CVD). However, very few studies have investigated their associations with CVD in European populations. METHODS:A total of 403,335 participants from the UK Biobank with data for TyG index and TG/HDL-C ratio and free from CVD at baseline were included. Cox models were applied to evaluate the association between TyG index and TG/HDL-C ratio and incident CVD. Mediation analyses were performed to evaluate the contribution of prevalent diabetes, hypertension, and dyslipidemia to observed associations. RESULTS:During a median follow-up of 8.1 years, 19,754 (4.9%) individuals developed CVD, including 16,404 (4.1%) cases of CHD and 3976 (1.0%) cases of stroke. The multivariable-adjusted hazard ratios of total CVD in higher quartiles versus the lowest quartiles were 1.05, 1.05, and 1.19, respectively, for TyG index, and 1.07, 1.13, and 1.29, respectively, for TG/HDL-C ratio. There were significant trends toward an increasing risk of CVD across the quartiles of TyG index and TG/HDL-C ratio. In mediation analyses, dyslipidemia, type 2 diabetes, and hypertension explained 45.8%, 27.0%, and 15.0% of TyG index's association with CVD, respectively, and 40.0%, 11.8%, and 13.3% of TG/HDL-C ratio's association with CVD, respectively. CONCLUSIONS:Elevated baseline TyG index and TG/HDL-C ratio were associated with a higher risk of CVD after adjustment for the well-established CVD risk factors. These associations were largely mediated by greater prevalence of dyslipidemia, type 2 diabetes, and hypertension.
10.1186/s12933-023-01762-2
Lipoprotein (a): Examination of Cardiovascular Risk in a Pediatric Referral Population.
Qayum Omar,Alshami Noor,Ibezim Chizitam F,Reid Kimberly J,Noel-MacDonnell Janelle R,Raghuveer Geetha
Pediatric cardiology
Atherosclerotic cardiovascular disease (CVD), a leading cause of death globally, has origins in childhood. Major risk factors include family history of premature CVD, dyslipidemia, diabetes mellitus, and hypertension. Lipoprotein (a) [Lp(a)], an inherited lipoprotein, is associated with premature CVD, but its impact on cardiovascular health during childhood is less understood. The objective of the study was to examine the relationship between Lp(a), family history of premature CVD, dyslipidemia, and vascular function and structure in a high-risk pediatric population. This is a single-center, cross-sectional study of 257 children referred to a preventive cardiology clinic. The independent variable, Lp(a), separated children into high-Lp(a) [Lp(a) ≥ 30 mg/dL] and normal-Lp(a) groups [Lp(a) < 30 mg/dL]. Dependent variables included family history of premature CVD; dyslipidemia, defined as low-density lipoprotein cholesterol > 130 mg/dL, high-density lipoprotein cholesterol (HDL-C) < 45 mg/dL, triglycerides (TG) > 100 mg/dL; and vascular changes suggesting early atherosclerosis, as measured by carotid-femoral pulse wave velocity (PWV) and carotid artery intima-media thickness (CIMT). Of the 257 children, 110 (42.8%) had high Lp(a) and 147 (57.2%) had normal Lp(a). There was a higher prevalence of African-American children in the high-Lp(a) group (19.3%) compared to the normal-Lp(a) group (2.1%) (p < 0.001). High Lp(a) was associated with positive family history of premature CVD (p = 0.03), higher-than-optimal HDL-C (p = 0.02), and lower TG (p < 0.001). There was no difference in PWV or CIMT between groups. High Lp(a) in children is associated with family history of premature CVD and is prevalent in African-American children. In children with high Lp(a), promotion of intensive lifestyle modifications is prudent to decrease premature CVD-related morbidity.
10.1007/s00246-018-1927-3
Plasma Lipoprotein(a) Levels as Determinants of Arterial Stiffening in Hypertension.
Brosolo Gabriele,Da Porto Andrea,Bulfone Luca,Vacca Antonio,Bertin Nicole,Colussi Gianluca,Cavarape Alessandro,Sechi Leonardo A,Catena Cristiana
Biomedicines
Previous studies have shown that plasma lipoprotein(a) (Lp(a)) plays an important role in the development of hypertensive organ damage. The aim of the present study was to investigate the relationship of Lp(a) with markers of arterial stiffening in hypertension. In 138 essential hypertensive patients free of diabetes, renal failure and cardiovascular complications, we measured plasma lipids and assessed vascular stiffness through the use of pulse wave analysis and calculation of the brachial augmentation index (AIx), and measured the pulse wave velocity (PWV). Plasma Lp(a) levels were significantly and directly related to both AIx ( = 0.490; < 0.001) and PWV ( = 0.212; = 0.013). Multiple regression analysis showed that AIx was independently correlated with age, C-reactive protein, and plasma Lp(a) (beta 0.326; < 0.001), while PWV was independently and directly correlated with age, and inversely with HDL, but not with plasma Lp(a). Logistic regression indicated that plasma Lp(a) could predict an AIx value above the median for the distribution ( = 0.026). Thus, in a highly selective group of patients with hypertension, plasma Lp(a) levels were significantly and directly related to markers of vascular stiffening. Because of the relevance of vascular stiffening to cardiovascular risk, the reduction of Lp(a) levels might be beneficial for cardiovascular protection in patients with hypertension.
10.3390/biomedicines9111510
Association of Lipoprotein(a) with arterial stiffness: A Mendelian randomization study.
European journal of clinical investigation
BACKGROUND:In this study we used Mendelian randomization (MR) to investigate the potential causal association of lipoprotein (a) [Lp(a)] levels with pulse wave velocity (PWV). METHODS:Genetic variants associated with Lp(a) were retrieved from the UK Biobank GWAS (N = 290,497). A non- overlapping GWAS based on a European cohort (N = 7,000) was used to obtain genetic associations with PWV (outcome) and utilized two different measures for the same trait, brachial-ankle (baPWV) and carotid-femoral (cfPWV) PWV. We applied a two-sample MR using the inverse variance weighting method (IVW) and a series of sensitivity analyses for 170 SNPs that were selected as instrumental variables (IVs). RESULTS:Our analyses do not support a causal association between Lp(a) and PWV for neither measurement [β(baPWV) = -.0005, p = .8 and β(cfPWV) = -.006, p = .16]. The above findings were consistent across sensitivity analyses including weighted median, mode-based estimation, MR-Egger regression and MR-PRESSO. CONCLUSION:We did not find evidence indicating that Lp(a) is causally associated with PWV, the gold standard marker of arterial stiffness.
10.1111/eci.14168
Lipoprotein(a) and Arterial Stiffness Parameters.
Sorokin Alexander,Kotani Kazuhiko
Pulse (Basel, Switzerland)
BACKGROUND:Circulating lipoprotein(a) [Lp(a)] and arterial stiffness are markers associated with the atherosclerotic processes. With regard to cardiovascular outcomes, the relationship between Lp(a) and arterial stiffness has not been sufficiently summarized. The present review focuses on the existing association between Lp(a) and arterial stiffness parameters. SUMMARY:This review included human clinical studies that were published between 1980 and 2015. The metrics of arterial stiffness parameters, 'pulse wave velocity' (PWV) and 'cardio-ankle vascular index' (CAVI), were used for this search, which yielded only 4 cross-sectional studies on this topic. Of these 4 studies, 3 reports were based on the use of PWV, while 1 study was based on the use of CAVI. Three studies (including the study using CAVI) reported that high Lp(a) levels were positively associated with arterial stiffness. CONCLUSION:The present review indicates a positive association between Lp(a) and arterial stiffness, as assessed by PWV and CAVI. To definitively establish these findings, there is a need for further prospective outcome studies that simultaneously measure Lp(a) and the oxidative form of Lp(a) (as a pathological marker) as well as PWV and CAVI.
10.1159/000438733