Background Elevated total cholesterol ( TC ), low-density lipoprotein cholesterol ( LDL -C), triglycerides, and non-high-density lipoprotein cholesterol (non- HDL -C) and low high-density lipoprotein ...cholesterol ( HDL -C) concentrations correlate with atherosclerotic cardiovascular disease ( ASCVD ) and mortality. Therefore, understanding how lipid trajectories throughout adulthood impact ASCVD and mortality risk is essential. Methods and Results We investigated 3875 Framingham Offspring participants (54% women, mean age 48 years) attending ≥1 examination between 1979 and 2014. We evaluated longitudinal correlates of each lipid subtype using mixed-effects models. Next, we clustered individuals into trajectories through group-based modeling. Thereafter, we assessed the prospective association of lipid trajectories with ASCVD and mortality. Male sex, greater body mass index, and smoking correlated with higher TC , LDL -C, triglycerides, non- HDL -C, and lower HDL -C concentrations. We identified 5 TC , HDL -C, and LDL -C trajectories, and 4 triglycerides and non- HDL -C trajectories. Upon follow-up (median 8.2 years; 199 ASCVD events; 256 deaths), elevated TC (>240 mg/ dL ), LDL -C (>155 mg/ dL ), or non- HDL -C (>180 mg/ dL ) concentrations conferred >2.25-fold ASCVD and mortality risk compared with concentrations <165 mg/ dL , <90 mg/ dL , and <115 mg/ dL , respectively ( TC hazard ratio ( HR )
=4.17, 95% CI 1.94-8.99; TC HR
=2.47, 95% CI 1.28-4.76 LDL -C HR
=5.09, 95% CI 1.54-16.85; LDL -C HR
=4.04, 95% CI 1.84-8.89 non- HDL -C HR
=4.60, 95% CI 1.98-10.70; LDL -C HR
=3.74, 95% CI 2.03-6.88). Consistent HDL -C concentrations <40 mg/ dL were associated with greater ASCVD and mortality risk than concentrations >70 mg/ dL (HR
=3.81, 95% CI 2.04-7.15; HR
=2.88, 95% CI 1.70-4.89). Triglycerides trajectories were unassociated with outcomes. Conclusions Using a longitudinal modeling technique, we demonstrated that unfavorable lipid trajectories over 35 years confer higher ASCVD and mortality risk later in life.
IMPORTANCE: The time course of cardiovascular disease (CVD) risk after smoking cessation is unclear. Risk calculators consider former smokers to be at risk for only 5 years. OBJECTIVE: To evaluate ...the association between years since quitting smoking and incident CVD. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of prospectively collected data from Framingham Heart Study participants without baseline CVD (original cohort: attending their fourth examination in 1954-1958; offspring cohort: attending their first examination in 1971-1975) who were followed up through December 2015. EXPOSURES: Time-updated self-reported smoking status, years since quitting, and cumulative pack-years. MAIN OUTCOMES AND MEASURES: Incident CVD (myocardial infarction, stroke, heart failure, or cardiovascular death). Primary analyses included both cohorts (pooled) and were restricted to heavy ever smokers (≥20 pack-years). RESULTS: The study population included 8770 individuals (original cohort: n = 3805; offspring cohort: n = 4965) with a mean age of 42.2 (SD, 11.8) years and 45% male. There were 5308 ever smokers with a median 17.2 (interquartile range, 7-30) baseline pack-years, including 2371 heavy ever smokers (406 17% former and 1965 83% current). Over 26.4 median follow-up years, 2435 first CVD events occurred (original cohort: n = 1612 n = 665 among heavy smokers; offspring cohort: n = 823 n = 430 among heavy smokers). In the pooled cohort, compared with current smoking, quitting within 5 years was associated with significantly lower rates of incident CVD (incidence rates per 1000 person-years: current smoking, 11.56 95% CI, 10.30-12.98; quitting within 5 years, 6.94 95% CI, 5.61-8.59; difference, −4.51 95% CI, −5.90 to −2.77) and lower risk of incident CVD (hazard ratio, 0.61; 95% CI, 0.49-0.76). Compared with never smoking, quitting smoking ceased to be significantly associated with greater CVD risk between 10 and 15 years after cessation in the pooled cohort (incidence rates per 1000 person-years: never smoking, 5.09 95% CI, 4.52-5.74; quitting within 10 to <15 years, 6.31 95% CI, 4.93-8.09; difference, 1.27 95% CI, −0.10 to 3.05; hazard ratio, 1.25 95% CI, 0.98-1.60). CONCLUSIONS AND RELEVANCE: Among heavy smokers, smoking cessation was associated with significantly lower risk of CVD within 5 years relative to current smokers. However, relative to never smokers, former smokers’ CVD risk remained significantly elevated beyond 5 years after smoking cessation.
BACKGROUND:The mechanism of adverse limb events associated with peripheral artery disease remains incompletely understood. We investigated whether microvascular disease is associated with amputation ...in a large cohort of veterans to determine whether microvascular disease diagnosed in any location increases the risk of amputation alone and in concert with peripheral artery disease.
METHODS:Participants in the Veterans Aging Cohort Study were recruited from April 1, 2003 through December 31, 2014. We excluded participants with known prior lower limb amputation. Using time-updated Cox proportional hazards regression, we analyzed the effect of prevalent microvascular disease (retinopathy, neuropathy, and nephropathy) and peripheral artery disease status on the risk of incident amputation events after adjusting for demographics and cardiovascular risk factors.
RESULTS:Among 125 674 veterans without evidence of prior amputation at baseline, the rate of incident amputation over a median of 9.3 years of follow-up was 1.16 per 1000 person-years, yielding a total of 1185 amputations. In time-updated multivariable-adjusted analyses, compared with those without peripheral artery disease or microvascular disease, microvascular disease alone was associated with a 3.7-fold (95% CI, 3.0–4.6) increased risk of amputation; peripheral artery disease alone conferred a 13.9-fold (95% CI, 11.3–17.1) elevated risk of amputation; and the combination of peripheral artery disease and microvascular disease was associated with a 22.7-fold (95% CI, 18.3–28.1) increased risk of amputation.
CONCLUSIONS:Independent of traditional risk factors, the presence of microvascular disease increases the risk of amputation alone and synergistically increases risk in patients with peripheral artery disease. Further research is needed to understand the mechanisms by which this occurs.
Androgen deprivation therapy is a cornerstone of prostate cancer treatment. Pharmacological androgen deprivation includes gonadotropin-releasing hormone agonism and antagonism, androgen receptor ...inhibition, and CYP17 (cytochrome P450 17A1) inhibition. Studies in the past decade have raised concerns about the potential for androgen deprivation therapy to increase the risk of adverse cardiovascular events such as myocardial infarction, stroke, and cardiovascular mortality, possibly by exacerbating cardiovascular risk factors. In this review, we summarize existing data on the cardiovascular effects of androgen deprivation therapy. Among the therapies, abiraterone stands out for increasing risk of cardiac events in meta-analyses of both randomized controlled trials and observational studies. We find a divergence between observational studies, which show consistent positive associations between androgen deprivation therapy use and cardiovascular disease, and randomized controlled trials, which do not show these associations reproducibly.
Background
Recent studies suggest that circulating concentrations of specific ceramide species may be associated with coronary risk and mortality. We sought to determine the relations between the ...most abundant plasma ceramide species of differing acyl chain lengths and the risk of coronary heart disease (CHD) and mortality in community‐based samples.
Methods and Results
We developed a liquid chromatography/mass spectrometry assay to quantify plasma C24:0, C22:0, and C16:0 ceramides and ratios of these very–long‐chain/long‐chain ceramides in 2642 FHS (Framingham Heart Study) participants and in 3134 SHIP (Study of Health in Pomerania) participants. Over a mean follow‐up of 6 years in FHS, there were 88 CHD and 90 heart failure (HF) events and 239 deaths. Over a median follow‐up time in SHIP of 5.75 years for CHD and HF and 8.24 years for mortality, there were 209 CHD and 146 HF events and 377 deaths. In meta‐analysis of the 2 cohorts and adjusting for standard CHD risk factors, C24:0/C16:0 ceramide ratios were inversely associated with incident CHD (hazard ratio per average SD increment, 0.79; 95% confidence interval, 0.71–0.89; P<0.0001) and inversely associated with incident HF (hazard ratio, 0.78; 95% confidence interval, 0.61–1.00; P=0.046). Moreover, the C24:0/C16:0 and C22:0/C16:0 ceramide ratios were inversely associated with all‐cause mortality (C24:0/C16:0: hazard ratio, 0.60; 95% confidence interval, 0.56–0.65; P<0.0001; C22:0/C16:0: hazard ratio, 0.65; 95% confidence interval, 0.60–0.70; P<0.0001).
Conclusions
The ratio of C24:0/C16:0 ceramides in blood may be a valuable new biomarker of CHD risk, HF risk, and all‐cause mortality in the community.
BACKGROUND:The effect of human immunodeficiency virus (HIV) on the development of peripheral artery disease (PAD) remains unclear. We investigated whether HIV infection is associated with an ...increased risk of PAD after adjustment for traditional atherosclerotic risk factors in a large cohort of HIV-infected (HIV+) and demographically similar HIV-uninfected veterans.
METHODS:We studied participants in the Veterans Aging Cohort Study from April 1, 2003 through December 31, 2014. We excluded participants with known prior PAD or prevalent cardiovascular disease (myocardial infarction, stroke, coronary heart disease, and congestive heart failure) and analyzed the effect of HIV status on the risk of incident PAD events after adjusting for demographics, PAD risk factors, substance use, CD4 cell count, HIV-1 ribonucleic acid, and antiretroviral therapy. The primary outcome is incident peripheral artery disease events. Secondary outcomes include mortality and amputation in subjects with incident PAD events by HIV infection status, viral load, and CD4 count.
RESULTS:Among 91 953 participants, over a median follow up of 9.0 years, there were 7708 incident PAD events. Rates of incident PAD events per 1000 person-years were higher among HIV+ (11.9; 95% confidence interval CI, 11.5–12.4) than uninfected veterans (9.9; 95% CI, 9.6–10.1). After adjustment for demographics, PAD risk factors, and other covariates, HIV+ veterans had an increased risk of incident PAD events compared with uninfected veterans (hazard ratio HR, 1.19; 95% CI, 1.13–1.25). This risk was highest among those with time-updated HIV viral load >500 copies/mL (HR, 1.51; 95% CI, 1.38–1.65) and CD4 cell counts <200 cells/mm (HR, 1.91; 95% CI, 1.71–2.13). In contrast, HIV+ veterans with time updated CD4 cell count ≥500 cells/mm had no increased risk of PAD (HR, 1.03; 95% CI, 0.96–1.11). Mortality rates after incident PAD events are high regardless of HIV status. HIV infection did not affect rates of amputation after incident PAD events.
CONCLUSIONS:Infection with HIV is associated with a 19% increased risk of PAD beyond that explained by traditional atherosclerotic risk factors. However, for those with sustained CD4 cell counts <200 cells/mm, the risk of incident PAD events is nearly 2-fold higher whereas for those with sustained CD4 cell counts ≥500 cells/mm there is no excess risk of incident PAD events compared with uninfected people.
Circulating levels of the endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), are positively associated with the prevalence of metabolic syndrome (MetS) in ...cross-sectional investigations. It is unclear if circulating ADMA and other methylarginines are associated with incident MetS prospectively.
We related circulating ADMA, symmetric dimethylarginine (SDMA), L-arginine (ARG) concentrations (measured with a validated tandem mass spectrometry assay) and the ARG/ADMA ratio to MetS and its components in 2914 (cross-sectional analysis, logistic regression; mean age 58 years, 55% women) and 1656 (prospective analysis, Cox regression; mean age 56 years, 59% women) individuals from the Framingham Offspring Study who attended a routine examination.
Adjusting for age, sex, smoking, and eGFR, we observed significant associations of ADMA (direct) and ARG/ADMA (inverse) with odds of MetS (N = 1461 prevalent cases; Odds Ratio OR per SD increment 1.13, 95%CI 1.04-1.22; and 0.89, 95%CI 0.82-0.97 for ADMA and ARG/ADMA, respectively). Upon further adjustment for waist circumference, systolic and diastolic blood pressure, glucose, high-density lipoprotein cholesterol, and triglycerides, we observed a positive relation between SDMA and MetS (OR per SD increment 1.15, 95% CI 1.01-1.30) but the other associations were rendered statistically non-significant. We did not observe statistically significant associations between any of the methylarginines and the risk of new-onset MetS (752 incident events) over a median follow-up of 11 years.
It is unclear whether dimethylarginines play an important role in the incidence of cardiometabolic risk in the community, notwithstanding cross-sectional associations. Further studies of larger samples are needed to replicate our findings.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Adverse childhood experiences (ACEs) are an independent risk factor for chronic disease, including obesity and metabolic syndrome. Therefore, we sought to determine the association of ACEs with BMI ...and plasma metabolic biomarkers affecting a multiracial cohort. Total ACE score was calculated in 38,353 non‐Hispanic Black and White men and women who participated in the second follow‐up of the Southern Community Cohort Study (2012‐2015). We used regression analyses to assess whether total ACE score or individual ACE components were associated with BMI and included interaction terms to evaluate if the association differed by sex or race, and for female participants, we accounted for menopause status. Total ACE score was associated with BMI (non‐linear p‐value=0.0026) and differed by sex and race (interaction p‐value<0.0001), but not menopause status. BMI steadily increased with cumulative ACEs among Black women. Among White women, BMI sharply increased from 0 to 1 ACEs, and steadily increased thereafter. In White men, BMI increased as ACEs increased from 0 to 3 and remained relatively stable among individuals with >4 ACEs. In Black men, BMI decreased with cumulative ACEs. Among Black women, emotional and sexual abuse were associated with higher BMI (p<0.05). Including both Black women and men, having an incarcerated family member was associated with lower BMI. Physical abuse was associated with increased BMI in Black and White men, while emotional neglect was associated with increased BMI in White women (p<0.05). In addition, regression analysis revealed an association between total ACE score and waist circumference, total
cholesterol, the ratio of leptin to adiponectin, HbA1c, and insulin. Furthermore, with increasing number of ACEs, Black men were the most affected in waist circumference, showing a 6 cm overall increase; however, they showed reduced BMI. This data indicates increased visceral fat deposition which is an indicator of metabolic syndrome and insulin resistance. Using a mouse model of postnatal neglect, and in line with this data, we have found that female mice, and not male mice, develop exacerbated adiposity. Specifically, female mice display increased whitening of adipose tissue via the actions of the mineralocorticoid receptor on lipid storage and adipocyte differentiation. Overall, ACEs are associated with BMI, but each ACE component has a unique contribution to this effect that varies based on sex and race. Future pre‐clinical studies should aim to model sex‐ and race‐specific effect of ACE on the development of obesity to provide insights on potential personalized therapies for people undergoing these health disparities.
The epidemiology and prognostic impact of increased pulmonary pressure among HIV-infected individuals in the antiretroviral therapy era is not well described.
To examine the prevalence, clinical ...features, and outcomes of increased echocardiographic pulmonary pressure in HIV-infected and -uninfected individuals.
This study evaluated 8,296 veterans referred for echocardiography with reported pulmonary artery systolic pressure (PASP) estimates from the Veterans Aging Cohort study, an observational cohort of HIV-infected and -uninfected veterans matched by age, sex, race/ethnicity, and clinical site. The primary outcome was adjusted mortality by HIV status.
PASP was reported in 2,831 HIV-infected and 5,465 HIV-uninfected veterans (follow-up mean ± SD, 3.8 ± 2.6 yr). As compared with uninfected veterans, HIV-infected veterans with HIV viral load greater than 500 copies/ml (odds ratio, 1.27; 95% confidence interval CI, 1.05-1.54) and those with CD4 cell count less than 200 cells/μl (odds ratio, 1.28; 95% CI, 1.02-1.60) had a higher prevalence of PASP greater than or equal to 40 mm Hg. As compared with uninfected veterans with a PASP less than 40 mm Hg, HIV-infected veterans with a PASP greater than or equal to 40 mm Hg had an increased risk of death (adjusted hazard ratio, 1.78; 95% CI, 1.57-2.01). This risk persisted even among participants without prevalent comorbidities (adjusted hazard ratio, 3.61; 95% CI, 2.17-6.01). The adjusted risk of mortality in HIV-infected veterans was higher at all PASP values than in uninfected veterans, including at values currently considered to be normal.
HIV-infected people with high HIV viral loads or low CD4 cell counts have a higher prevalence of increased PASP than uninfected people. Mortality risk in HIV-infected veterans increases at lower values of PASP than previously recognized and is present even among those without prevalent comorbidities. These findings may inform clinical decision-making regarding screening and surveillance of pulmonary hypertension in HIV-infected individuals.
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