High triglyceride (TG) levels and low HDL cholesterol (HDL-C) levels are risk factors for cardiovascular disease. It is unclear whether this relationship depends on glycemic dysregulation, sex, or ...LDL cholesterol (LDL-C) level.
We studied 3,216 participants (40% men, 41% with diabetes) who were free of cardiovascular disease at baseline in a community-based, prospective cohort of American Indians (median follow-up 17.7 years). Cox models estimated hazard ratios (HRs) and 95% CIs for incident ischemic stroke and coronary heart disease (CHD) in relation to combined TG and HDL-C status, where a fasting TG level ≥150 mg/dL was "high" and a fasting HDL-C level <40 mg/dL for men (<50 mg/dL for women) was "low." Models included age, sex, BMI, smoking, diabetes, fasting LDL-C level, antihypertensive medications, physical activity, estimated glomerular filtration rate, and urinary albumin-to-creatinine ratio.
Participants with high TG and low HDL levels had a 1.32-fold greater HR (95% CI 1.06-1.64) for CHD than those with normal TG and normal HDL levels. It was observed in participants with diabetes, but not in those without diabetes, that high TG plus low HDL levels were associated with a 1.54-fold greater HR (95% CI 1.15-2.06) for CHD (
value for interaction = 0.003) and a 2.13-fold greater HR (95% CI 1.06-4.29) for stroke (
value for interaction = 0.060). High TG and low HDL level was associated with CHD risk in participants with an LDL-C level of ≥130 mg/dL, but this was not observed in those participants with lower LDL-C levels. Sex did not appear to modify these associations.
Adults with both high TG and low HDL-C, particularly those with diabetes, have increased risks of incident CHD and stroke. In particular, those with an LDL-C level ≥130 mg/dL may have an increased risk of incident stroke.
Experimental studies suggest ceramides may play a role in insulin resistance. However, the relationships of circulating ceramides and related sphingolipids with plasma insulin have been underexplored ...in humans. We measured 15 ceramide and sphingomyelin species in fasting baseline samples from the Strong Heart Family Study (SHFS), a prospective cohort of American Indians. We examined sphingolipid associations with both baseline and follow-up measures of plasma insulin, HOMA of insulin resistance (HOMA-IR), and HOMA of β-cell function (HOMA-B) after adjustment for risk factors. Among the 2,086 participants without diabetes, higher levels of plasma ceramides carrying the fatty acids 16:0 (16 carbons, 0 double bond), 18:0, 20:0, or 22:0 were associated with higher plasma insulin and higher HOMA-IR at baseline and at follow-up an average of 5.4 years later. For example, a twofold higher baseline concentration of ceramide 16:0 was associated with 14% higher baseline insulin (
< 0.0001). Associations between sphingomyelin species carrying 18:0, 20:0, 22:0, or 24:0 and insulin were modified by BMI (
< 0.003): higher levels were associated with lower fasting insulin, HOMA-IR, and HOMA-B among those with normal BMI. Our study suggests lowering circulating ceramides might be a target in prediabetes and targeting circulating sphingomyelins should take into account BMI.
BACKGROUND:Cardiovascular disease (CVD) is the leading cause of death among American Indians and Alaska Natives. Over the past 50 years, the prevalence of CVD has been rising among American Indians ...and Alaska Natives. The objective of this statement is to summarize population-level risk factors and management techniques tailored for the American Indian and Alaska Native populations.
METHODS:PubMed/MEDLINE, the Centers for Disease Control and Prevention, and the annual Heart Disease and Stroke Statistics report from the American Heart Association were used to identify risk factors and interventions specific to American Indians and Alaska Natives.
RESULTS:Diabetes mellitus is a major contributor to disproportionately higher rates of coronary heart disease among American Indians and Alaska Natives compared with other racial and ethnic groups. Additional risk factors for CVD include low-density lipoprotein cholesterol levels, hypertension, renal disease, age, and sex. Smoking and exposure to toxic metals are risk factors for some subpopulations. A quarter of American Indians live below the federal poverty line, and thus, low socioeconomic status is an important social determinant of cardiovascular health. Community-based interventions have reduced CVD risk in American Indians and Alaska Natives. Underreporting of American Indian and Alaska Native race could underestimate the extent of CVD in this population.
CONCLUSIONS:Prevention and treatment of CVD in American Indians and Alaska Natives should focus on control of risk factors and community-based interventions that address social determinants of health, particularly among individuals with diabetes mellitus. Accurate reporting of race/ethnicity is encouraged to address race-specific risk factors.
Nomograms to predict normal aortic root diameter for body surface area (BSA) in broad ranges of age have been widely used but are limited by lack of consideration of gender effects, jumps in upper ...limits of aortic diameter among age strata, and data from older teenagers. Sinus of Valsalva diameter was measured by American Society of Echocardiography convention in normal-weight, nonhypertensive, nondiabetic subjects ≥15 years old without aortic valve disease from clinical or population-based samples. Analyses of covariance and linear regression with assessment of residuals identified determinants and developed predictive models for normal aortic root diameter. In 1,207 apparently normal subjects ≥15 years old (54% women), aortic root diameter was 2.1 to 4.3 cm. Aortic root diameter was strongly related to BSA and height (r = 0.48 for the 2 comparisons), age (r = 0.36), and male gender (+2.7 mm adjusted for BSA and age, p <0.001 for all comparisons). Multivariable equations using age, gender, and BSA or height predicted aortic diameter strongly (R = 0.674 for the 2 comparisons, p <0.001) with minimal relation of residuals to age or body size: for BSA 2.423 + (age years × 0.009) + (BSA square meters × 0.461) − (gender 1 = man, 2 = woman × 0.267), SEE 0.261 cm; for height 1.519 + (age years × 0.010) + (height centimeters × 0.010) − (gender 1 = man, 2 = woman × 0.247), SEE 0.215 cm. In conclusion, aortic root diameter is larger in men and increases with body size and age. Regression models incorporating body size, age, and gender are applicable to adolescents and adults without limitations of previous nomograms.
Abstract Background Reproductive factors reflective of endogenous sex hormone exposure might have an effect on cardiac remodeling and the development of heart failure (HF). Objectives This study ...examined the association between key reproductive factors and the incidence of HF. Methods Women from a cohort of the Women's Health Initiative were systematically evaluated for the incidence of HF hospitalization from study enrollment through 2014. Reproductive factors (number of live births, age at first pregnancy, and total reproductive duration time from menarche to menopause) were self-reported at study baseline in 1993 to 1998. We employed Cox proportional hazards regression analysis in age- and multivariable-adjusted models. Results Among 28,516 women, with an average age of 62.7 ± 7.1 years at baseline, 1,494 (5.2%) had an adjudicated incident HF hospitalization during an average follow-up of 13.1 years. After adjusting for covariates, total reproductive duration in years was inversely associated with incident HF: hazard ratios (HRs) of 0.99 per year (95% confidence interval CI: 0.98 to 0.99 per year) and 0.95 per 5 years (95% CI: 0.91 to 0.99 per 5 years). Conversely, early age at first pregnancy and nulliparity were significantly associated with incident HF in age-adjusted models, but not after multivariable adjustment. Notably, nulliparity was associated with incident HF with preserved ejection fraction in the fully adjusted model (HR: 2.75; 95% CI: 1.16 to 6.52). Conclusions In post-menopausal women, shorter total reproductive duration was associated with higher risk of incident HF, and nulliparity was associated with higher risk for incident HF with preserved ejection fraction. Whether exposure to endogenous sex hormones underlies this relationship should be investigated in future studies.
Telomeres play a central role in cellular aging, and shorter telomere length has been associated with age-related disorders including diabetes. However, a causal link between telomere shortening and ...diabetes risk has not been established. In a well-characterized longitudinal cohort of American Indians participating in the Strong Heart Family Study, we examined whether leukocyte telomere length (LTL) at baseline predicts incident diabetes independent of known diabetes risk factors. Among 2,328 participants free of diabetes at baseline, 292 subjects developed diabetes during an average 5.5 years of follow-up. Compared with subjects in the highest quartile (longest) of LTL, those in the lowest quartile (shortest) had an almost twofold increased risk of incident diabetes (hazard ratio HR 1.83 95% CI 1.26-2.66), whereas the risk for those in the second (HR 0.87 95% CI 0.59-1.29) and the third (HR 0.95 95% CI 0.65-1.38) quartiles was statistically nonsignificant. These findings suggest a nonlinear association between LTL and incident diabetes and indicate that LTL could serve as a predictive marker for diabetes development in American Indians, who suffer from disproportionately high rates of diabetes.
Recent studies suggest that the type of saturated fatty acid bound to sphingolipids influences the biological activity of those sphingolipids. However, it is unknown whether associations of ...sphingolipids with diabetes may differ by the identity of bound lipid species. Here, we investigated associations of 15 ceramide (Cer) and SM species (i.e., all sphingolipids, measured with coefficient of variation less than 20%) with incident type 2 diabetes in the Cardiovascular Health Study (n = 3,645), a large cohort study of cardiovascular disease among elderly adults who were followed from 1989 to 2015. Diabetes incidence was defined as fasting glucose ≥126 mg/dl or nonfasting glucose ≥200 mg/dl; reported use of insulin or oral hypoglycemic medication; or documentation of diabetes diagnosis through the Centers for Medicare and Medicaid Services records. Associations of each sphingolipid with incident diabetes were assessed using a Cox proportional hazards regression model. We found that higher circulating levels of Cer with acylated palmitic acid (Cer-16), stearic acid containing Cer (Cer-18), arachidic acid containing Cer (Cer-20), and behenic acid containing Cer (Cer-22) were each associated with a higher risk of diabetes. The hazard ratios for incident diabetes per 1 SD higher log levels of each Cer species were as follows: 1.21 (95% CI: 1.09–1.34) for Cer-16, 1.23 (95% CI: 1.10–1.37) for Cer-18, 1.14 (95% CI: 1.02–1.26) for Cer-20, and 1.18 (95% CI: 1.06–1.32) for Cer-22. In conclusion, higher levels of Cer-16, Cer-18, Cer-20, and Cer-22 were associated with a higher risk of diabetes.
IMPORTANCE: Health outcomes from the Women’s Health Initiative Estrogen Plus Progestin and Estrogen-Alone Trials have been reported, but previous publications have generally not focused on all-cause ...and cause-specific mortality. OBJECTIVE: To examine total and cause-specific cumulative mortality, including during the intervention and extended postintervention follow-up, of the 2 Women’s Health Initiative hormone therapy trials. DESIGN, SETTING, AND PARTICIPANTS: Observational follow-up of US multiethnic postmenopausal women aged 50 to 79 years enrolled in 2 randomized clinical trials between 1993 and 1998 and followed up through December 31, 2014. INTERVENTIONS: Conjugated equine estrogens (CEE, 0.625 mg/d) plus medroxyprogesterone acetate (MPA, 2.5 mg/d) (n = 8506) vs placebo (n = 8102) for 5.6 years (median) or CEE alone (n = 5310) vs placebo (n = 5429) for 7.2 years (median). MAIN OUTCOMES AND MEASURES: All-cause mortality (primary outcome) and cause-specific mortality (cardiovascular disease mortality, cancer mortality, and other major causes of mortality) in the 2 trials pooled and in each trial individually, with prespecified analyses by 10-year age group based on age at time of randomization. RESULTS: Among 27 347 women who were randomized (baseline mean SD age, 63.4 7.2 years; 80.6% white), mortality follow-up was available for more than 98%. During the cumulative 18-year follow-up, 7489 deaths occurred (1088 deaths during the intervention phase and 6401 deaths during postintervention follow-up). All-cause mortality was 27.1% in the hormone therapy group vs 27.6% in the placebo group (hazard ratio HR, 0.99 95% CI, 0.94-1.03) in the overall pooled cohort; with CEE plus MPA, the HR was 1.02 (95% CI, 0.96-1.08); and with CEE alone, the HR was 0.94 (95% CI, 0.88-1.01). In the pooled cohort for cardiovascular mortality, the HR was 1.00 (95% CI, 0.92-1.08 8.9 % with hormone therapy vs 9.0% with placebo); for total cancer mortality, the HR was 1.03 (95% CI, 0.95-1.12 8.2 % with hormone therapy vs 8.0% with placebo); and for other causes, the HR was 0.95 (95% CI, 0.88-1.02 10.0% with hormone therapy vs 10.7% with placebo), and results did not differ significantly between trials. When examined by 10-year age groups comparing younger women (aged 50-59 years) to older women (aged 70-79 years) in the pooled cohort, the ratio of nominal HRs for all-cause mortality was 0.61 (95% CI, 0.43-0.87) during the intervention phase and the ratio was 0.87 (95% CI, 0.76-1.00) during cumulative 18-year follow-up, without significant heterogeneity between trials. CONCLUSIONS AND RELEVANCE: Among postmenopausal women, hormone therapy with CEE plus MPA for a median of 5.6 years or with CEE alone for a median of 7.2 years was not associated with risk of all-cause, cardiovascular, or cancer mortality during a cumulative follow-up of 18 years. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000611
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