ObjectiveCarotid plaque and intima-media thickness are non-invasive arterial markers that are used as surrogate end points for cardiovascular disease. The aim was to assess the prevalence and ...severity of carotid plaque, and examine its determinant risk factors and their association to the common carotid artery intima-media thickness (CCA-IMT) in a general population.MethodsWe examined 6524 participants aged 25–69 years in the population-based REFINE (Risk Evaluation For INfarct Estimates)-Reykjavik study. Plaques at the bifurcation and internal carotid arteries were evaluated. Mean CCA-IMT was measured in the near and far walls of the common carotid arteries.ResultsThe prevalence of minimal, moderate and severe plaque was 35.0%, 8.9% and 1.1%, respectively, and the mean CCA-IMT was 0.73 (SD 0.14) mm. Age, sex, smoking and type 2 diabetes mellitus (T2DM) were the strongest risk factors associated with plaque, followed by systolic blood pressure, total cholesterol, body mass index and family history of myocardial infarct. Low educational level was also strongly and independently associated with plaque. CCA-IMT shared the same risk factors except for a non-significant association with T2DM and family history of myocardial infarction (MI). Participants with T2DM had greater plaque prevalence, 2-fold higher in those <50 years and 17–30% greater in age groups 50–54 to 60–64, and more significant plaques (moderate or severe) were the difference in prevalence was 24% in age group 50–54 and ≥60% in older age groups, compared with non-T2DM.ConclusionsCarotid plaque and CCA-IMT have mostly common determinants. However, T2DM and family history of MI were associated with plaque but not with CCA-IMT. Greater prevalence and more severe plaques in individuals with T2DM raise the concern that with increasing prevalence of T2DM we may expect an increase in atherosclerosis and its consequences.
Objectives
To compare the relative predictive power of handgrip and leg extension strength in predicting slow walking.
Design
Report of correlative analysis from two epidemiological cohort studies.
...Setting
Foundation of the National Institutes of Health Sarcopenia Project.
Participants
Men and women aged 67 to 93 (N = 6,766).
Measurements
Leg strength, handgrip strength, and gait speed were measured. Strength cutpoints associated with slow gait speed were developed using classification and regression tree analyses and compared using ordinary least squares regression models.
Results
The cutpoints of lower extremity strength associated with slow gait speed were 154.6 N‐m in men and 89.9 N‐m in women for isometric leg extension strength and 94.5 N‐m in men and 62.3 N‐m in women for isokinetic leg extension strength. Weakness defined according to handgrip strength (odds ratios (OR) = 1.99 to 4.33, c‐statistics = 0.53 to 0.67) or leg strength (ORs = 2.52 to 5.77; c‐statistics = 0.61 to 0.66) was strongly related to odds of slow gait speed. Lower extremity strength contributed 1% to 16% of the variance and handgrip strength contributed 3% to 17% of the variance in the prediction of gait speed depending on sex and mode of strength assessment.
Conclusion
Muscle weakness of the leg extensors and forearm flexors is related to slow gait speed. Leg extension strength is only a slightly better predictor of slow gait speed. Thus, handgrip and leg extension strength appear to be suitable for screening for muscle weakness in older adults.
C-reactive protein is an inflammatory marker believed to be of value in the prediction of coronary events. We report data from a large study of C-reactive protein and other circulating inflammatory ...markers, as well as updated meta-analyses, to evaluate their relevance to the prediction of coronary heart disease.
Measurements were made in samples obtained at base line from up to 2459 patients who had a nonfatal myocardial infarction or died of coronary heart disease during the study and from up to 3969 controls without a coronary heart disease event in the Reykjavik prospective study of 18,569 participants. Measurements were made in paired samples obtained an average of 12 years apart from 379 of these participants in order to quantify within-person fluctuations in inflammatory marker levels.
The long-term stability of C-reactive protein values (within-person correlation coefficient, 0.59; 95 percent confidence interval, 0.52 to 0.66) was similar to that of both blood pressure and total serum cholesterol. After adjustment for base-line values for established risk factors, the odds ratio for coronary heart disease was 1.45 (95 percent confidence interval, 1.25 to 1.68) in a comparison of participants in the top third of the group with respect to base-line C-reactive protein values with those in the bottom third, and similar overall findings were observed in an updated meta-analysis involving a total of 7068 patients with coronary heart disease. By comparison, the odds ratios in the Reykjavik Study for coronary heart disease were somewhat weaker for the erythrocyte sedimentation rate (1.30; 95 percent confidence interval, 1.13 to 1.51) and the von Willebrand factor concentration (1.11; 95 percent confidence interval, 0.97 to 1.27) but generally stronger for established risk factors, such as an increased total cholesterol concentration (2.35; 95 percent confidence interval, 2.03 to 2.74) and cigarette smoking (1.87; 95 percent confidence interval, 1.62 to 2.16).
C-reactive protein is a relatively moderate predictor of coronary heart disease. Recommendations regarding its use in predicting the likelihood of coronary heart disease may need to be reviewed.
Frailty is a risk factor for cardiovascular diseases (CVD), but the studies available have not considered the presence of subclinical atherosclerotic disease as potential confounders. We investigated ...the association between frailty and the onset of CVD independently of subclinical atherosclerotic disease. For this reason, a sample of 3818 older participants participating in the Age, Gene/Environment Susceptibility—Reykjavik Study without CVD at baseline was followed for a median of 8.7 years. Frailty was defined as the presence of ≥3 among five Fried's criteria (unintentional weight loss, low physical activity level, weakness, exhaustion, and slow gait speed). Incident CVD was defined as onset of coronary artery disease, heart failure, stroke, and CVD-related mortality identified using hospital, medical, and death records. Subclinical atherosclerotic disease was evaluated as the maximum value of carotid intima media thickness, presence of carotid plaque (moderate or high), and total coronary calcifications (CACs). At baseline, frail participants (
n
= 300) were more frequently obese, diabetic, and had a greater presence of metabolic syndrome than the nonfrail (
n
= 3518). Frail participants also showed a higher presence of carotid plaques and CACs. Using a Cox's regression analysis, adjusted for clinical, biochemical, and subclinical atherosclerosis estimates, frailty increased the risk of CVD (hazard ratio HR = 1.35; 95% confidence interval CI: 1.05–1.74), with results stronger for women than men (HR = 1.51,
p
= 0.006 and 1.19,
p
= 0.44, respectively). Among Fried's criteria, exhaustion was the only criterion significantly associated with the onset of new CVD events (HR = 1.30; 95% CI: 1.00–1.73). In conclusion, frailty was associated with the onset of CVD in older people even after adjusting for subclinical atherosclerotic disease.
The relevance to coronary heart disease (CHD) of cytokines that govern inflammatory cascades, such as interleukin-6 (IL-6), may be underestimated because such mediators are short acting and prone to ...fluctuations. We evaluated associations of long-term circulating IL-6 levels with CHD risk (defined as nonfatal myocardial infarction MI or fatal CHD) in two population-based cohorts, involving serial measurements to enable correction for within-person variability. We updated a systematic review to put the new findings in context.
Measurements were made in samples obtained at baseline from 2,138 patients who had a first-ever nonfatal MI or died of CHD during follow-up, and from 4,267 controls in two cohorts comprising 24,230 participants. Correction for within-person variability was made using data from repeat measurements taken several years apart in several hundred participants. The year-to-year variability of IL-6 values within individuals was relatively high (regression dilution ratios of 0.41, 95% confidence interval CI 0.28-0.53, over 4 y, and 0.35, 95% CI 0.23-0.48, over 12 y). Ignoring this variability, we found an odds ratio for CHD, adjusted for several established risk factors, of 1.46 (95% CI 1.29-1.65) per 2 standard deviation (SD) increase of baseline IL-6 values, similar to that for baseline C-reactive protein. After correction for within-person variability, the odds ratio for CHD was 2.14 (95% CI 1.45-3.15) with long-term average ("usual") IL-6, similar to those for some established risk factors. Increasing IL-6 levels were associated with progressively increasing CHD risk. An updated systematic review of electronic databases and other sources identified 15 relevant previous population-based prospective studies of IL-6 and clinical coronary outcomes (i.e., MI or coronary death). Including the two current studies, the 17 available prospective studies gave a combined odds ratio of 1.61 (95% CI 1.42-1.83) per 2 SD increase in baseline IL-6 (corresponding to an odds ratio of 3.34 95% CI 2.45-4.56 per 2 SD increase in usual long-term average IL-6 levels).
Long-term IL-6 levels are associated with CHD risk about as strongly as are some major established risk factors, but causality remains uncertain. These findings highlight the potential relevance of IL-6-mediated pathways to CHD.
Background
Cerebral microbleeds can confer a high risk of intracerebral hemorrhage, ischemic stroke, death and dementia, but estimated risks remain imprecise and often conflicting. We investigated ...the association between cerebral microbleeds presence and these outcomes in a large meta-analysis of all published cohorts including: ischemic stroke/TIA, memory clinic, “high risk” elderly populations, and healthy individuals in population-based studies.
Methods
Cohorts (with > 100 participants) that assessed cerebral microbleeds presence on MRI, with subsequent follow-up (≥3 months) were identified. The association between cerebral microbleeds and each of the outcomes (ischemic stroke, intracerebral hemorrhage, death, and dementia) was quantified using random effects models of (a) unadjusted crude odds ratios and (b) covariate-adjusted hazard rations.
Results
We identified 31 cohorts (n = 20,368): 19 ischemic stroke/TIA (n = 7672), 4 memory clinic (n = 1957), 3 high risk elderly (n = 1458) and 5 population-based cohorts (n = 11,722). Cerebral microbleeds were associated with an increased risk of ischemic stroke (OR: 2.14; 95% CI: 1.58–2.89 and adj-HR: 2.09; 95% CI: 1.71–2.57), but the relative increase in future intracerebral hemorrhage risk was greater (OR: 4.65; 95% CI: 2.68–8.08 and adj-HR: 3.93; 95% CI: 2.71–5.69). Cerebral microbleeds were an independent predictor of all-cause mortality (adj-HR: 1.36; 95% CI: 1.24–1.48). In three population-based studies, cerebral microbleeds were independently associated with incident dementia (adj-HR: 1.35; 95% CI: 1.00–1.82). Results were overall consistent in analyses stratified by different populations, but with different degrees of heterogeneity.
Conclusions
Our meta-analysis shows that cerebral microbleeds predict an increased risk of stroke, death, and dementia and provides up-to-date effect sizes across different clinical settings. These pooled estimates can inform clinical decisions and trials, further supporting cerebral microbleeds role as biomarkers of underlying subclinical brain pathology in research and clinical settings.
Aging is associated with increased risk of reduced mobility. However, data on muscle components in relation to subjective and objective indicators of disability is limited.
Data were from 2,725 ...participants (43% men) aged 74.8±4.7 years from the AGES-Reykjavik Study. At baseline, maximal isometric thigh strength (dynamometer chair), and midthigh muscle area and muscle fat infiltration were assessed with computed tomography. Usual 6 m gait speed and mobility disability were assessed at baseline and after 5.2±0.3 years. Incident mobility disability was defined as having much difficulty or unable to walk 500 m or climb-up 10 steps. A decrease of ≥0.1 m/s in gait speed was considered clinically relevant.
Greater strength and area were protective for mobility disability risk and gait speed decline. After adjustment for other muscle components, greater strength was independently associated with lower mobility disability risk in women odds ratios (OR) 0.78 (95% CI 0.62, 0.99), and lower decline in gait speed risk among both men OR 0.64 (0.54, 0.76), and women OR 0.72 (0.62, 0.82). Larger muscle area was independently associated with lower mobility disability risk in women OR 0.67 (0.52, 0.87) and lower decline in gait speed risk in men OR 0.74 (0.61, 0.91).
Greater muscle strength and area were independently associated with 15-30% decreased risk of mobility disability in women and gait speed decline in men. Among women, greater muscle strength was also associated with lower risk of gait speed decline. Interventions aimed at maintaining muscle strength and area in old age might delay functional decline.
Long and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights ...into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP traits (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure) across five ancestry groups in two stages using 2 degree of freedom (df) joint test followed by 1df test of interaction effects. Primary multi-ancestry analysis in 62,969 individuals in stage 1 identified three novel gene by sleep interactions that were replicated in an additional 59,296 individuals in stage 2 (stage 1 + 2 P
< 5 × 10
), including rs7955964 (FIGNL2/ANKRD33) that increases BP among long sleepers, and rs73493041 (SNORA26/C9orf170) and rs10406644 (KCTD15/LSM14A) that increase BP among short sleepers (P
< 5 × 10
). Secondary ancestry-specific analysis identified another novel gene by long sleep interaction at rs111887471 (TRPC3/KIAA1109) in individuals of African ancestry (P
= 2 × 10
). Combined stage 1 and 2 analyses additionally identified significant gene by long sleep interactions at 10 loci including MKLN1 and RGL3/ELAVL3 previously associated with BP, and significant gene by short sleep interactions at 10 loci including C2orf43 previously associated with BP (P
< 10
). 2df test also identified novel loci for BP after modeling sleep that has known functions in sleep-wake regulation, nervous and cardiometabolic systems. This study indicates that sleep and primary mechanisms regulating BP may interact to elevate BP level, suggesting novel insights into sleep-related BP regulation.
The
promoter polymorphism (rs35705950) has been associated with interstitial lung abnormalities (ILA) in white participants from the general population; whether these findings are replicated and ...influenced by the ILA subtype is not known. We evaluated the associations between the
genotype and ILA in cohorts with extensive imaging characterisation.We performed ILA phenotyping and
promoter genotyping in 5308 and 9292 participants from the AGES-Reykjavik and COPDGene cohorts, respectively.We found that ILA was present in 7% of participants from the AGES-Reykjavik, 8% of non-Hispanic white participants from COPDGene and 7% of African-American participants from COPDGene. Although the
genotype was strongly associated (after correction for multiple testing) with ILA (OR 2.1, 95% CI 1.8-2.4, p=1×10
), there was evidence of significant heterogeneity between cohorts (I
=81%). When narrowed to specific radiologic subtypes, (
subpleural ILA), the
genotype remained strongly associated (OR 2.6, 95% CI 2.2-3.1, p=1×10
) with minimal heterogeneity (I
=0%). Although there was no evidence that the
genotype influenced survival, there was evidence that
genotype improved risk prediction for possible usual interstitial pneumonia (UIP) or a UIP pattern in non-Hispanic white populations.The
promoter polymorphism is strongly associated with ILA and specific radiologic subtypes of ILA, with varying degrees of heterogeneity in the underlying populations.
Associations between circulating markers of dysglycaemia and coronary heart disease (CHD) risk in people without diabetes have not been reliably characterised. We report new data from a prospective ...study and a systematic review to help quantify these associations.
Fasting and post-load glucose levels were measured in 18,569 participants in the population-based Reykjavik study, yielding 4,664 incident CHD outcomes during 23.5 y of mean follow-up. In people with no known history of diabetes at the baseline survey, the hazard ratio (HR) for CHD, adjusted for several conventional risk factors, was 2.37 (95% CI 1.79-3.14) in individuals with fasting glucose > or = 7.0 mmol/l compared to those < 7 mmol/l. At fasting glucose values below 7 mmol/l, adjusted HRs were 0.95 (0.89-1.01) per 1 mmol/l higher fasting glucose and 1.03 (1.01-1.05) per 1 mmol/l higher post-load glucose. HRs for CHD risk were generally modest and nonsignificant across tenths of glucose values below 7 mmol/l. We did a meta-analysis of 26 additional relevant prospective studies identified in a systematic review of Western cohort studies that recorded fasting glucose, post-load glucose, or glycated haemoglobin (HbA(1c)) levels. In this combined analysis, in which participants with a self-reported history of diabetes and/or fasting blood glucose > or = 7 mmol/l at baseline were excluded, relative risks for CHD, adjusted for several conventional risk factors, were: 1.06 (1.00-1.12) per 1 mmol/l higher fasting glucose (23 cohorts, 10,808 cases, 255,171 participants); 1.05 (1.03-1.07) per 1 mmol/l higher post-load glucose (15 cohorts, 12,652 cases, 102,382 participants); and 1.20 (1.10-1.31) per 1% higher HbA(1c) (9 cohorts, 1639 cases, 49,099 participants).
In the Reykjavik Study and a meta-analysis of other Western prospective studies, fasting and post-load glucose levels were modestly associated with CHD risk in people without diabetes. The meta-analysis suggested a somewhat stronger association between HbA(1c) levels and CHD risk.
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