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

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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Offspring birth weight and cardiovascular mortality among parents: the role of cardiovascular risk factors

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174418000065 ◽

2018 ◽

Vol 9 (3) ◽

pp. 351-357 ◽

Cited By ~ 1

Author(s):

F. Shaikh ◽

M. K. Kjøllesdal ◽

Ø. Naess

Keyword(s):

Risk Factors ◽

Blood Pressure ◽

Birth Weight ◽

Cox Proportional Hazards ◽

Inverse Association ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Birth Registry ◽

Cvd Mortality

AbstractAn inverse association between offspring birth weight (BW) and higher risk of parental cardiovascular disease (CVD) mortality and morbidity has been reported. Shared environmental, genetic and intrauterine factors may be responsible for explaining these associations. We studied the role of parental CVD risk factors in the association between offspring BW and CVD mortality among mothers and fathers. All births registered in Medical Birth Registry Norway (1967–2012) were linked to three health surveys, National Educational Registry and Cause of Death Registry. Number of births with information of parental CVD risk factors available for the analyses was 1,006,557 (520,670 for mothers and 485,887 for fathers). Cox proportional hazards regression models were used, following CVD deaths in parents from 1974 to 2012. An inverse association between offspring BW and CVD mortality was observed among both parents: hazard ratio 1.60 (1.44–1.75) for mothers and 1.16 (1.10–1.23) for fathers. Among mothers, adjustment for smoking, triglycerides and diabetes reduced the risk to 1.36 (1.25–1.52), 1.57 (1.43–1.73) and 1.58 (1.43–1.79), respectively. Adjustment for diastolic blood pressure (DBP) and systolic blood pressure (SBP) both reduced the risk to 1.53 (1.37–1.66). Among fathers, adjustments for smoking, DBP, SBP reduced the risk to 1.08 (1.02–1.15), 1.13 (1.06–1.19) and 1.14 (1.08–1.22), respectively. Triglycerides and diabetes both reduced the risk to 1.15 (1.09–1.12). Our results indicate that shared environmental factors might be important in the association. A stronger association in mothers suggest that intrauterine factors also are at play.

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Abstract 49: Consumption of Ultra-processed Foods and Beverages is Associated With Increased Risk of Cardiovascular Mortality in the Moli-sani Study Cohort

Circulation ◽

10.1161/circ.141.suppl_1.49 ◽

2020 ◽

Vol 141 (Suppl_1) ◽

Cited By ~ 1

Author(s):

Marialaura Bonaccio ◽

Augusto Filippo Di Castelnuovo ◽

Simona Costanzo ◽

Amalia De Curtis ◽

Mariarosaria Persichillo ◽

...

Keyword(s):

Risk Factors ◽

Study Cohort ◽

Processed Foods ◽

Processed Food ◽

Cvd Risk Factors ◽

Cvd Risk ◽

High Intake ◽

Saturated Fats ◽

Increased Risk ◽

Cvd Mortality

Introduction: Consumption of ultra-processed food and beverages (UPFB) is gaining growing attention due to its possible relation with increased risk of disease/mortality. To date, the possibility of such an association was only addressed in two European and one US population-based cohorts. Hypothesis: We assessed the hypothesis of a positive association between UPFB consumption and mortality risk in a large sample of the Italian population and tested whether some known cardiovascular disease (CVD) risk factors and nutrients could be on the pathway of this relation. We also separately analyzed UPFB presumed to be healthy ( e.g. , breakfast cereals, fruit juices) from nutrient-poor foods ( e.g., cakes, snacks). Methods: Longitudinal analysis on 22,810 men and women (mean age 55±12 y) recruited in the Moli-sani Study cohort between 2005-2010. Food intake was assessed using a semi-quantitative 188-item food frequency questionnaire. UPFB intake was defined by the NOVA classification according to degree of food processing and then categorized as number of servings/d. Hazard ratios with 95% confidence intervals (95% CI) were calculated using multivariable Cox-proportional hazard models. Results: Over a median follow up of 8.3 y, 1,235 deaths were ascertained. As opposed to lower intake (<2 servings/d), individuals reporting high intake of UPFB (>4 servings/d) experienced an increased risk of CVD mortality (HR=1.50; 95%CI 1.18-1.92) and of death for ischemic heart (IHD)/cerebrovascular disease (1.56; 1.13-2.14). An upward trend was found for all-cause mortality too (1.15; 1.00-1.34). Biomarkers of renal function (cystatin C and creatinine) or of lipid metabolisms were likely to be on the pathway between UPFB and CVD mortality. Among selected macronutrients, high content of sugar and saturated fats possibly drove the relation of UPFB with CVD mortality. High intake of ‘healthy’ UPFB was associated with an increased trend of risk comparable to that associated with ‘unhealthy’ UPFB. Conclusions: In a large Mediterranean cohort of Italian adults, high consumption of UPFB was associated with increased risk of CVD death and IHD/cerebrovascular mortality. This association was partly explained by established CVD risk factors and a high dietary content of sugar and saturated fats. UPFB presumed to be healthy appeared similarly linked to higher death risk. National dietary guidelines might consider discourage excessive consumption of ultra-processed food while recommending natural or minimally processed foods.

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Educational differences in cardiovascular mortality: The role of shared family factors and cardiovascular risk factors

Scandinavian Journal of Public Health ◽

10.1177/1403494816669427 ◽

2016 ◽

Vol 44 (8) ◽

pp. 744-750 ◽

Cited By ~ 5

Author(s):

M. K. R. Kjøllesdal ◽

I. Ariansen ◽

L. H. Mortensen ◽

G. Davey Smith ◽

Ø. Næss

Keyword(s):

Risk Factors ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factors ◽

Family Factors ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Educational Group ◽

Educational Differences ◽

Family Based ◽

Cvd Mortality

Aims: To explore the confounding effects of early family factors shared by siblings and cardiovascular risk factors in midlife on the educational differences in mortality from cardiovascular disease (CVD). Methods: Data from national and regional health surveys in Norway (1974–2003) were linked with data from the Norwegian Family Based Life Course Study, the National Educational Registry and the Cause of Death Registry. The study population consisted of participants with at least one full sibling among the health survey participants ( n=271,310). Data were available on CVD risk factors, including weight, height, blood pressure, total cholesterol and smoking. Results: The hazards ratio (HR) of CVD mortality was 3.44 (95% confidence interval (CI) 2.98–3.96) in the lowest educational group relative to the highest. The HRs were little altered in the within-sibship analyses. Adjusted for risk factors, the HR for CVD mortality in the cohort analyses was 2.05 (CI 1.77–2.37) in the lowest educational group relative to the highest. The respective HR in the within-sibship analyses was 2.46 (CI 1.48–2.24). Conclusions: Using a sibling design, we did not find that the association between education and CVD mortality was confounded by early life factors shared by siblings, but it was explained to a large extent by CVD risk factors. These results suggest that reducing levels of CVD risk factors could have the greatest effect on mortality in less well-educated people.

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Abstract 17: Association of Race and Sex with Cardiovascular Disease and Non-Cardiovascular Disease Mortality: The REasons for Geographic and Racial Differences in Stroke study

Circulation ◽

10.1161/circ.135.suppl_1.17 ◽

2017 ◽

Vol 135 (suppl_1) ◽

Author(s):

Gabriel S Tajeu ◽

Monika M Safford ◽

George Howard ◽

Rikki M Tanner ◽

Paul Muntner

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Racial Differences ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Cvd Risk ◽

Hazard Ratios ◽

Stroke Study ◽

Cvd Mortality

Introduction: Black Americans have higher rates of cardiovascular disease (CVD) mortality compared with whites. Differences in sociodemographic, psychosocial, CVD, and other risk factors may explain increased mortality risk. Methods: We analyzed data from 29,015 REasons for Geographic and Racial Differences in Stroke study participants to determine factors that may explain the higher hazard ratio for CVD and non-CVD mortality in blacks compared with whites. Cause of death was adjudicated by trained investigators. Within age-sex sub-groups, we used Cox proportional hazards regression with progressive adjustment to estimate black:white hazard ratios. Results: Overall, 41.0% of participants were black, and 54.9% were women. Over a mean follow-up of 7.1 years (maximum 12.3 years), 5,299 participants died (1,797 CVD and 3,502 non-CVD deaths). Among participants < 65 years of age, the age and region adjusted black:white hazard ratio for CVD mortality was 2.28 (95% CI: 1.68-3.10) and 2.32 (95% CI: 1.80-3.00) for women and men, respectively, and for participants ≥ 65 was 1.54 (95% CI: 1.30-1.82) and 1.35 (95% CI: 1.16-1.57) for women and men, respectively ( Table ). The higher black:white hazard ratios for CVD mortality were no longer statistically significant after multivariable adjustment, with the largest attenuation occurring with sociodemographic and CVD risk factor adjustment. Among participants < 65 years of age, the age and region adjusted black:white hazard ratios for non-CVD mortality were 1.51 (95% CI: 1.24-1.85) and 1.76 (95% CI: 1.46-2.13) for women and men, respectively, and for participants ≥ 65 was 1.12 (95% CI: 1.00-1.26) and 1.34 (95% CI: 1.20-1.49) for women and men, respectively. The higher black:white hazard ratios for non-CVD mortality were attenuated after adjustment for sociodemographics. Conclusions: Black:white differences are larger for CVD than non-CVD causes of death. The increased CVD mortality for blacks compared with whites is primarily explained by sociodemographic and CVD risk factors.

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Do Women with Diabetes Need More Intensive Action for Cardiovascular Reduction than Men with Diabetes?

Current Diabetes Reports ◽

10.1007/s11892-020-01348-2 ◽

2020 ◽

Vol 20 (11) ◽

Author(s):

Jürgen Harreiter ◽

Helena Fadl ◽

Alexandra Kautzky-Willer ◽

David Simmons

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Meta Analysis ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Risk Factor Management ◽

High Risk Women ◽

Background Population ◽

Cvd Mortality

Abstract Purpose of Review This narrative review makes the case for greater efforts to reduce cardiovascular disease (CVD) risk in women with diabetes. Recent Findings In a recent meta-analysis including five CVOTs of diabetes medications with 46,606 subjects, women (vs men) with type 2 diabetes had a higher relative risk for stroke (RR 1.28; 95% CI 1.09, 1.50) and heart failure (1.30; 1.21, 1.40). Prior studies found higher “within-gender” RR for CVD mortality in women with diabetes although men have an absolute higher risk. Women with prior gestational diabetes mellitus (GDM) have a 2-fold higher CVD risk than the background population. Worse CVD and CVD risk factor management in women, as well as lower female therapy adherence, contribute further to these disparities. Summary The mechanism behind this excess risk includes biological, hormonal, socioeconomic, clinical, and behavioral factors that still require further investigation. The need for more intensive CVD reduction in women now includes more attention to screening for both incident diabetes and CVD risk factors among high-risk women.

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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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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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Differences in Cardiovascular Mortality Risk among African Americans in the Minnesota Heart Survey: 1985-2015 vs The Atherosclerosis Risk in Communities Study Cohort: 1987-2015

Ethnicity & Disease ◽

10.18865/ed.29.1.47 ◽

2019 ◽

Vol 29 (1) ◽

pp. 47-52 ◽

Cited By ~ 3

Author(s):

Kristen M. George ◽

Aaron R. Folsom ◽

Lyn M. Steffen ◽

Lynne E. Wagenknecht ◽

Thomas H. Mosley

Keyword(s):

Risk Factors ◽

Risk Factor ◽

African Americans ◽

Population Based ◽

Study Cohort ◽

Cvd Risk ◽

Atherosclerosis Risk In Communities ◽

Hazard Ratios ◽

Atherosclerosis Risk ◽

Cvd Mortality

Geographic differences in cardiovascular disease (CVD) mortality among African Americans (AAs) are well-established, but not well-characterized. Using the Minnesota Heart Survey (MHS) and Atherosclerosis Risk in Communities (ARIC) Study, we aimed to assess whether CVD risk factors drive geographic disparities in CVD mortality among AAs.ARIC risk factors were measured between1987-1989 from a population-based sample of AAs, aged 45 to 64 years, living in Jackson, MS and Forsyth County, NC. Similar measures were made at MHS baseline, 1985, in AAs from Minneapolis-St. Paul, MN. CVD mortality was identified using ICD codes for underlying cause of death. We compared MHS and ARIC on CVD death rates using Poisson regression, risk factor prevalences, and hazard ratios using Cox regression.After CVD risk factor adjustment, AA men in MHS had 3.4 (95% CI: 2.1, 4.7) CVD deaths per 1000 person-years vs 9.9 (95% CI: 8.7, 11.1) in ARIC. AA women in MHS had 2.7 (95% CI: 1.8, 3.6) CVD deaths per 1000 person-years vs 6.7 (95% CI: 6.0, 7.4) in ARIC. A 2-fold higher CVD mortality rate remained in ARIC vs MHS after additional adjustment for education and income. ARIC had higher total cholesterol, hypertension, diabetes, and BMI, as well as less education and income than MHS. Risk factor hazard ratios of CVD death did not differ.The CVD death rate was lower in AAs in Minnesota (MHS) than AAs in the Southeast (ARIC). While our findings support maintaining low risk for CVD prevention, differences in CVD mortality reflect unidentified geographic variation.Ethn Dis. 2019;29(1):47-52; doi:10.18865/ ed.29.1.47

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