There is a debate on how to evaluate carotid artery intima-media thickness (IMT). We here compared IMT of the common carotid artery (CCA) and bulb with plaque area regarding incident atherosclerotic ...disease. In the PIVUS study (age 70 at baseline, 53% women, n = 856), IMT-CCA, IMT-bulb and plaque area were measured at ages 70, 75 and 80 years and these three measurements were used in updated Cox proportional hazard analysis. Over 15 years follow-up, 135 individuals experienced a first-time atherosclerotic disease (myocardial infarction or ischemic stroke). IMT-CCA was not significantly related to this composite endpoint (p = 0.10). IMT-bulb was significantly related to the endpoint (p = 0.003), but this relationship was attenuated following adjustment for CVD risk factors (p = 0.02). On the contrary, plaque area was consistently related to incident atherosclerotic disease also following adjustment for CVD risk factors (p<0.001). When added on top of traditional risk factors, both IMT-bulb and plaque area, but not IMT-CCA, improved the discrimination compared to the traditional risk factors (+5.2%, p = 0.0026 for IMT-bulb, +3.8%, p = 0.013 for plaque area and 0.0% for IMT-CCA). In elderly subjects, both IMT-bulb and plaque area improved the discrimination regarding incident atherosclerotic disease when added to traditional risk factors. This was not seen for IMT-CCA. IMT-CCA was therefore inferior compared to the other two carotid artery ultrasonographic measurements in this sample of elderly subjects.
For a couple of decades, flow-mediated vasodilation in the brachial artery (FMD) and acetylcholine-mediated vasodilation in the forearm (EDV) have been used to assess endothelium-dependent ...vasodilation. During recent years a third technique, peripheral artery tonometry (PAT) using EndoPat, has been introduced. We now aimed to investigate the relationships between these techniques, and their relation to cardiovascular risk.
In the population-based Prospective investigation of Obesity, Energy and Metabolism (POEM) study conducted in individuals all aged 50 years (50% women), EDV, FMD and the reactive hyperemia index were measured in the first 222 individuals. Cardiovascular risk was assessed by the Framingham risk score.
No significant relationships were seen between the three different tests to evaluate endothelium-dependent vasodilation. EDV (r = -0.21, P = 0.004) and FMD (r = -0.19, P = 0.004), but not PAT were significantly related to the Framingham score in an inverse way. Also sodium nitroprusside-mediated vasodilation in the forearm, reflecting endothelium-independent vasodilation (EIDV), was related to the Framingham score in an inverse way (r = -0.30, P < 0.0001).
No close relationships were seen between the three tests of endothelium-dependent vasodilation, suggesting that they each contribute with unique information on vasoreactivity. EDV, EIDV and FMD, but not PAT, were related to the Framingham score, suggesting that vasoreactivity in some vascular beds are related to cardiovascular risk in middle-aged individuals.
The first population-based cohort study in Uppsala with the aim to study cardiovascular disease was initiated in 1970 (ULSAM). This cohort of 2300 middle-aged men has since then been followed in a ...longitudinal fashion for almost 50 years. This study has been followed by the PIVUS study, investigating 1000 men and women at ages 70, 75, and 80. A very detailed examination has also been performed in 500 subjects aged 50 years, the POEM study. In recent years, a high-throughput study conducted in 13000 subjects has also been performed, named EpiHealth. Uppsala also collects data in 5,000 subjects in the nationwide SCAPIS study. Taken together, these cardiovascular-oriented studies constitute a very rich source for cardiovascular epidemiological research in Uppsala. This review summarizes the design of these studies and highlights some of the important results published based on data from these studies.
Dyslipidaemias is the leading risk factor of several major cardiovascular diseases (CVDs), but there is still a lack of sufficient evidence supporting a causal role of lipoprotein subspecies in CVDs. ...In this study, we comprehensively investigated several lipoproteins and their subspecies, as well as other metabolites, in relation to coronary heart disease (CHD), heart failure (HF) and ischemic stroke (IS) longitudinally and by Mendelian randomization (MR) leveraging NMR-measured metabolomic data from 118,012 UK Biobank participants. We found that 123, 110 and 36 analytes were longitudinally associated with myocardial infarction, HF and IS (FDR < 0.05), respectively, and 25 of those were associated with all three outcomes. MR analysis suggested that genetically predicted levels of 70, 58 and 7 analytes were associated with CHD, HF and IS (FDR < 0.05), respectively. Two analytes, ApoB/ApoA1 and M-HDL-C were associated with all three CVD outcomes in the MR analyses, and the results for M-HDL-C were concordant in both observational and MR analyses. Our results implied that the apoB/apoA1 ratio and cholesterol in medium size HDL were particularly of importance to understand the shared pathophysiology of CHD, HF and IS and thus should be further investigated for the prevention of all three CVDs.
Abstract Background : Flow-mediated vasodilation (FMD) has previously been shown to be related to cardiovascular risk factors in cross-sectional studies. The present study aims to investigate how FMD ...changes over time, and determine whether this change is paralleled by changes in cardiovascular risk factors. Methods : Of the participants in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, 750 individuals had measurements made of FMD in the brachial artery both at the ages of 70 and 75 years. In addition, the change over the 5 years in carotid artery intima-media thickness (IMT) was monitored, as well as traditional cardiovascular risk factors. Results : While no significant change in FMD occurred during the 5-year period (+0.1%, p = 0.53), large changes could be seen at the individual level. The Framingham risk score (excluding the age-variable) increased during the follow-up period (+0.54, p < 0.001). This change was inversely related to the individual change in FMD (beta −0.15, 95% CI -0.29 to −0.0059, p = 0.041). Of the eight individual CV risk factors tested, the change in FMD was only related to the change in LDL-cholesterol (inversely, p = 0.0028). The change in FMD was not related to the change in IMT seen over the 5-year period ( p = 0.41). Conclusion : While no change was seen in the mean FMD over a five-year period in elderly subjects attending both examinations despite ageing and a change in several risk factors, the individual change was mainly related to the change in LDL-cholesterol, further emphasizing the important role of lipids to determine vasoreactivity.
Abstract Background and objective Bisphenol A (BPA) levels have previously been associated with coronary heart disease (CHD). Since CHD is an atherosclerotic disease, we investigated if circulating ...levels of BPA and phthalate metabolites are related to atherosclerosis in a cross-sectional study. Methods In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (1016 subjects all aged 70), the prevalence of overt plaques and echogenectity (grey scale median, GSM) of carotid artery plaques were recorded by ultrasound in both of the carotid arteries. The thickness (IMT) and echogenicity (IM-GSM) of the intima–media complex were also measured. Bisphenol A (BPA) and 10 phthalate metabolites were analyzed in serum by a API 4000 liquid chromatograph/tandem mass spectrometer. Results Mono-methyl phthalate (MMP) was related to carotid plaques in an inverted U-shaped manner. This pattern was significant after adjustment for gender, body mass index, blood glucose, blood pressure, HDL and LDL-cholesterol, serum triglycerides, smoking, antihypertensive treatment and statin use ( p = 0.004). High levels of BPA, mono-isobutyl phthalate (MiBP) and MMP were associated with an echogenic IM-GSM and plaque GSM, while high levels of mono-2-ethylhexyl phthalate (MEHP) were associated with an echolucent IM-GSM and plaque GSM ( p < 0.0001 after adjustment). Conclusion The phthalate metabolite MMP was related to atherosclerotic plaques in an inverted U-shaped manner independently of CV risk factors. Some phthalates and BPA were also related to the echogenicity of the plaques, suggesting a role for plaque-associated chemicals in atherosclerosis.
Impaired endothelial function has been implicated as a cause of cardiovascular disease. Little is known of the relations of measures of endothelial function in resistance and conduit arteries to ...incident cardiovascular disease in the general population, and available techniques have not been compared.
In 1016 participants (70 years of age) of the population-based Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study (52% women), we measured endothelium-dependent vasodilation using the invasive forearm technique with acetylcholine given in the brachial artery, the brachial artery ultrasound technique with measurement of flow-mediated dilatation, and the pulse-wave analysis-based method with β-2-agonist terbutaline provocation. During 5 years of follow-up, 101 participants experienced a composite end point of myocardial infarction, stroke, or death, excluding the 85 persons with a history of myocardial infarction or stroke at baseline. In logistic regression models adjusted for several established and novel cardiovascular disease risk factors and medications, endothelium-dependent vasodilation by the invasive forearm technique with acetylcholine was associated with risk of the end point (odds ratio, 0.72 per SD; 95% confidence interval, 0.56 to 0.93; P=0.01). Endothelial function by the other 2 methods was not related to risk of the end point. Addition of endothelium-dependent vasodilation to the Framingham risk score improved discrimination of risk of the end point.
Endothelium-dependent vasodilation in resistance arteries, but not in the brachial conduit artery (flow-mediated dilatation), was associated with 5-year risk of a composite end point of death, myocardial infarction, or stroke independently of major cardiovascular disease risk factors. This vascular measurement improved risk discrimination when added to an established risk score in an elderly population.
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Per- and polyfluoroalkyl substances (PFAS) have been linked to immunotoxic and cardiometabolic effects in both experimental and epidemiological studies, but with conflicting results.
...The aim of the present study was to investigate potential associations between plasma PFAS levels and plasma levels of preselected proteomic biomarkers previously linked to inflammation, metabolism and cardiovascular disease.
Three PFAS (perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and perfluorohexane sulfonic acid (PFHxS)) were measured by non-targeted metabolomics and 249 proteomic biomarkers were measured by the proximity extension assay (PEA) in plasma from 2,342 individuals within the Epidemiology for Health (EpiHealth) study from Sweden (45–75 years old, 50.6 % men).
After adjustment for age and sex, 92% of the significant associations between PFOS concentrations and proteins were inverse (p < 0.0002, Bonferroni-adjusted). The results were not as clear for PFOA and PFHxS, but still with 80% and 64 % of the significant associations with proteins being inverse. After adjustment for age, sex, smoking, education, exercise habits and alcohol consumption, levels of epidermal growth factor receptor (EGFR), and paraoxonase type 3 (PON3) remained positively associated with all three PFAS, while resistin (RETN) and urokinase plasminogen activator surface receptor (uPAR) showed inverse associations with all three PFAS.
Our findings imply that PFAS exposure is cross-sectionally linked to altered levels of proteins previously linked to inflammation, metabolism and cardiovascular disease in middle-aged humans.
•PFAS have been linked to increased cholesterol levels and cardiovascular disease (CVD).•Incident CVD and PFAS levels were analyzed in two independent cohorts (n=2,278 and n=1,016 at baseline).•In ...addition, a meta-analysis was performed including five prospective studies.•No overall associations, but a sex interaction for PFOS and an inverse association could be seen in middle-aged men.•The meta-analysis showed a risk ratio of 0.80 (CI: 0.66, 0.94) when high levels were compared to low levels.•No increased risk of incident CVD with moderately elevated PFAS levels.
Per- and polyfluoroalkyl substances (PFAS) are persistent chemicals that have been linked to increased cholesterol levels and thus may have a role in the development of cardiovascular disease (CVD).
To investigate associations between PFAS exposure and incident CVD (a combined CVD end-point consisting of myocardial infarction, ischemic stroke, or heart failure) in two independent population-based cohorts in Sweden. In addition, we performed a meta-analysis also including results from previous studies.
In 2,278 subjects aged 45–75 years from the EpiHealth study, the risk of incident CVD in relation to relative plasma levels of perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) was investigated. Associations between plasma levels of six PFAS and incident CVD were also examined in the PIVUS-study (n=1,016, all aged 70 years). In addition, a meta-analysis was performed including three previous prospective studies, together with the results from the present study.
There were no overall statistically significant associations between levels of the different PFAS and incident CVD, neither in EpiHealth nor in PIVUS. However, there was a significant sex interaction for PFOS in EpiHealth (p=0.008), and an inverse association could be seen only in men (Men, HR: 0.68, 95 % CI: 0.52, 0.89) (Women, HR: 1.13, 95 % CI: 0.82, 1.55). A meta-analysis of five independent studies regarding PFOA and incident CVD showed a risk ratio (RR) of 0.80 (CI: 0.66, 0.94) when high levels were compared to low levels.
This longitudinal study using data from two population-based cohort studies in Sweden did not indicate any increased risk of incident CVD for moderately elevated PFAS levels. A meta-analysis of five independent cohort studies rather indicated a modest inverse association between PFOA levels and incident CVD, further supporting that increasing PFAS levels are not linked to an increased risk of CVD.
Self-reported leisure-time physical activity (PA) has previously been linked to risk of cardiovascular disease (CVD). We now aim to investigate the strength of associations between PA and different ...CVDs and how the risk varies with age.
PA and traditional CV risk factors assessed by a questionnaire on a four-level scale in 2,175 men at age 50 years in the ULSAM study. Examinations were thereafter repeated at ages 60, 70, and 77.
During 40 years follow-up, 883 individuals experienced a CVD (myocardial infarction, stroke, or heart failure). Using data from all four examinations, a graded reduction in risk of incident CVD was seen with increasing PA (HR 0.84, 95%CI; 0.77-0.93, p = 0.001 for trend test). PA was related to myocardial infarction (HR 0.84, 95%CI; 0.74-0.95, 490 cases), heart failure (HR 0.79, 95%CI; 0.68-0.91, 356 cases), but only of borderline significance vs ischemic stroke (HR 0.85, 95%CI; 0.73-1.00, 315 cases) when the CVDs were analyzed separately. Adjusting for traditional CV risk factors attenuated all relationships between PA and incident CVD, and PA did not improve discrimination of CVD when added on top of risk factors. When 10-year risk was calculated from each examination, age 70 was the time-point when PA was most closely related to incident CVD.
Leisure-time physical activity is related to future CVD. This was most evident at 70 years of age. If a causal relationship between self-reported PA and CVD exists, this relationship might to a major degree be mediated by traditional risk factors.
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