Lipoprotein(a), family history of cardiovascular disease, and incidence of heart failure.

Lipoprotein(a) (Lp(a)) is a largely genetically determined biomarker for cardiovascular disease (CVD), while its potential interplay with family history (FHx) of CVD, a measure of both genetic and environmental exposures, remains unclear. We examined the associations of Lp(a) in terms of circulating concentration or polygenetic risk score (PRS), and FHx of CVD with risk of incident heart failure (HF). Included were 299,158 adults from the UK Biobank without known HF and CVD at baseline. Hazards ratios (HRs) and 95% Cls were estimated by Cox regression models adjusted for traditional risk factors defined by the Atherosclerosis Risk in Communities study HF risk score. During the 11.8-year follow-up, 5,502 incidents of HF occurred. Higher levels of circulating Lp(a), Lp(a) PRS, and positive FHx of CVD were associated with higher risks of HF. Compared with individuals who had lower circulating Lp(a) and no FHx, HRs (95% CIs) of HF were 1.36 (1.25, 1.49), 1.31 (1.19, 1.43), and 1.42 (1.22, 1.67) for those with higher Lp(a) and a positive history of CVD for all family members, parents, and siblings, respectively; similar results were observed by using Lp(a) PRS. The risk estimates for HF associated with elevated Lp(a) and positive FHx were attenuated after excluding those with incident myocardial infarction (MI) during follow-up. Lp(a) and FHx of CVD were independent risk factors for incident HF, and the highest risk of HF was observed among individuals with both risk factors. The association may be partly mediated by myocardial infarction.

Association of metabolic comorbidity with myocardial infarction in individuals with a family history of cardiovascular disease: a prospective cohort study.

BACKGROUND: The association between metabolic comorbidity and myocardial infarction (MI) among individuals with a family history of cardiovascular disease (CVD) is yet to be elucidated. We aimed to examine the combined effects of metabolic comorbidities, including diabetes mellitus, hypertension, and dyslipidemia, with a family history of CVD in first-degree on the risk of incident MI. METHODS: This cohort study consisted of 81,803 participants aged 40-89 years without a previous history of MI at baseline from the Korean Genome and Epidemiology Study. We performed Cox proportional hazard regression analysis to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for MI and early-onset MI risk associated with metabolic comorbidity in individuals with a family history of CVD. RESULTS: During a median follow-up of 5 years, 1,075 and 479 cases of total and early-onset MI were reported, respectively. According to the disease score, among individuals who had a positive family history of CVD, the HRs for MI were 1.92 (95% CI: 1.47-2.51) in individuals with one disease, 2.75 (95% CI: 2.09-3.61) in those with two diseases, and 3.74 (95% CI: 2.45-5.71) in those with three diseases at baseline compared to individuals without a family history of CVD and metabolic diseases. Similarly, an increase of the disease score among individuals with a positive family history of CVD was associated with an increase in early-onset MI risk. CONCLUSION: Metabolic comorbidity was significantly associated with an increased risk of MI among individuals with a family history of CVD.

Prognostic significance of positive family history in outcomes after coronary artery bypass grafting: Do we need to update our assumptions?

BACKGROUND: Recent research suggests a protective role for positive family history of premature cardiovascular disease (FHpCVD) in patients undergoing coronary artery bypass grafting. We aimed to further investigate this unlikely association. METHODS: In this registry-based cohort study, patients who underwent first-time non-emergent coronary bypass surgery at Tehran Heart Center between 2007 and 2016 were included. Patients with and without FHpCVD were compared in terms of all-cause mortality and first non-fatal cardiovascular events (CVEs) comprising non-fatal acute coronary syndrome, non-fatal stroke or transient ischemic attack, and repeat coronary revascularization. RESULTS: A total of 13,156 patients were included (mean age 60.83 ± 9.57, 74.5% male), among which 2684 (20.4%) patients had FHpCVD. Median follow-up was 77.7 months. FHpCVD was weakly associated with reduced all-cause mortality using inverse probability weight (IPW) method (hazard ratio [HR] = 0.853; 95% confidence interval [CI] 0.730-0.997; P = 0.046), and not associated with non-fatal CVEs considering death as the competing event (sub-distribution HR [SHR] = 1.124; 95% CI 0.999-1.265; P = 0.053). Within a subgroup of patients without previous myocardial infarction or revascularization (7403 cases; 56.3%), FHpCVD was associated with lower mortality (HR = 0.700; 95% CI 0.548-0.894; P = 0.004) and higher non-fatal CVEs (SHR = 1.197; 95% CI 1.019-1.405; P = 0.028), whereas among patients with previous coronary events, there was no association between FHpCVD and outcomes. CONCLUSIONS: FHpCVD was associated with lower all-cause mortality but higher non-fatal CVEs, especially in those without prior coronary events. Such discordance calls for caution in assuming a protective role for FHpCVD. The prognostic significance of FHpCVD needs further evaluation among surgical patients.

Familial factors, diet, and risk of cardiovascular disease: a cohort analysis of the UK Biobank.

BACKGROUND: Both diet and familial factors have a major role in the development of cardiovascular disease (CVD). However, it remains unclear whether familial predisposition to CVD modifies the association between dietary factors and CVD. OBJECTIVES: The aim was to assess whether the association between diet and CVD varies with familial predisposition to CVD. METHODS: In this prospective cohort of the UK Biobank, 462,155 CVD-free participants were included in 2006-2010 and followed for CVD incidence until 2020. Food intake was measured using a short food-frequency questionnaire. Familial predisposition was measured by self-reported family history of CVD and by polygenic risk score (PRS) for CVD based on summary statistics of independent genome-wide association studies. RESULTS: During a median follow-up of 11.2 y, 46,164 incident CVD cases were identified. A moderately higher risk of CVD was associated with more frequent processed-meat consumption, with an adjusted HR of 1.07 (95% CI: 1.03, 1.11; highest vs. lowest level). Conversely, intakes of fish, cheese, vegetables, and fruit were each associated with reduced CVD risk [HR (95% CI): 0.92 (0.89, 0.96), 0.90 (0.86, 0.94), 0.98 (0.95, 1.00), and 0.93 (0.89, 0.96), respectively]. Stratification analyses by family history of CVD and by PRS for CVD revealed an inverse association between CVD and intakes of fish and cheese, for both subgroups with and without a familial predisposition to CVD. Notably, while the association between processed-meat intake and CVD was restricted to individuals with a familial predisposition to CVD [e.g., HR: 1.11 (1.05, 1.16) and 1.03 (0.97, 1.10) for with and without a family history, respectively, P-interaction < 0.001], the risk reduction of CVD associated with vegetable and fruit intake was only noted among participants without a CVD familial predisposition [e.g., HR for fruit consumption: 1.00 (0.97, 1.03) and 0.91 (0.87, 0.95), respectively, P < 0.001]. CONCLUSIONS: Familial factors modify the association between diet and CVD, underscoring the need for personalized dietary guidelines for CVD prevention.

Dyslipidemia and cardiovascular disease risk factors in patients with type 1 diabetes: A single-center experience.

BACKGROUND: Type 1 diabetes (T1D) contributes to altered lipid profiles and increases the risk of cardiovascular disease (CVD). Youth with T1D may have additional CVD risk factors within the first decade of diagnosis. AIM: To examine risk factors for dyslipidemia in young subjects with T1D. METHODS: Longitudinal and cross-sectional retrospective study of 170 young subjects with T1D (86 males; baseline mean age 12.2 ± 5.6 years and hemoglobin A1c 8.4% ± 1.4%) were followed in a single tertiary diabetes center for a median duration of 15 years. Predictors for outcomes of lipid profiles at last visit (total cholesterol [TC], triglycerides [TGs], low-density lipoprotein-cholesterol [LDL-c], and high-density lipoprotein-cholesterol [HDL-c]) were analyzed by stepwise linear regression models. RESULTS: At baseline, 79.5% of the patients had at least one additional CVD risk factor (borderline dyslipidemia/dyslipidemia [37.5%], pre-hypertension/hypertension [27.6%], and overweight/obesity [16.5%]) and 41.6% had multiple (≥ 2) CVD risk factors. A positive family history of at least one CVD risk factor in a first-degree relative was reported in 54.1% of the cohort. Predictors of elevated TC: family history of CVD (ß[SE] = 23.1[8.3], P = 0.006); of elevated LDL-c: baseline diastolic blood pressure (DBP) (ß[SE] = 11.4[4.7], P = 0.003) and family history of CVD (ß[SE] = 20.7[6.8], P = 0.017); of elevated TGs: baseline DBP (ß[SE] = 23.8[9.1], P = 0.010) and family history of CVD (ß[SE] = 31.0[13.1], P = 0.020); and of low HDL-c levels: baseline DBP (ß[SE] = 4.8[2.1], P = 0.022]). CONCLUSION: Our findings suggest that elevated lipid profiles are associated with DBP and a positive family history of CVD. It is of utmost importance to prevent and control modifiable risk factors such as these, as early as childhood, given that inadequate glycemic control and elevation in blood pressure intensify the risk of dyslipidemia.

Combined Effects of Family History of Cardiovascular Disease and Serum C-reactive Protein Level on the Risk of Stroke: A 9.2-year Prospective Study among Mongolians in China.

OBJECTIVE: We aimed to evaluate the combined effect of a family history of cardiovascular disease (CVD) and high serum C-reactive protein (CRP) on the stroke incidence in an Inner Mongolian population in China. METHODS: A prospective cohort study was conducted from June 2002 to July 2012, with 2,544 participants aged 20 years and over from Inner Mongolia, China. We categorized participants into four groups based on the family history of CVD and CRP levels. RESULTS: We adjusted for age; sex; smoking; drinking; hypertension; body mass index; waist circumference; and blood glucose, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels. Compared with the group with no family history of CVD/low CRP levels, the group with family history of CVD/high CRP levels had a hazard ratio (HR) of 1.78 [95% confidence interval (CI), 1.03-3.07; P = 0.039] of stroke, and an HR of 2.14 (95% CI, 1.09-4.20; P = 0.027) of ischemic stroke. The HRs of hemorrhagic stroke for the other three groups were not statistically significant (all P > 0.05). CONCLUSION: Participants with both a family history of CVD and high CRP levels had the highest stroke incidence, suggesting that high CRP levels may increase stroke risk, especially of ischemic stroke, among individuals with a family history of CVD.