Measures of carotid atherosclerosis and fall-related hospitalization risk: The Perth Longitudinal Study of Ageing Women.

BACKGROUND AND AIMS: We and others have identified links between cardiovascular conditions and poor musculoskeletal health. However, the relationship between measures of carotid atherosclerosis such as focal carotid plaque and common carotid intima media thickness (CCA-IMT) and falls remains understudied. This study examined the association between measures of carotid atherosclerosis and fall-related hospitalization over 11.5 years in community dwelling older women. METHODS AND RESULTS: 1116 older women recruited in 1998 to a five-year randomized controlled trial to examine the effect of calcium supplementation in preventing fracture and who had undertaken B-mode ultrasound in 2001 (three years after the baseline clinical visit) were included in this study. The participants were followed for over 11.5 years as Perth Longitudinal Study of Ageing Women (PLSAW). Over the follow up period, 428 (38.4%) women experienced a fall-related hospitalization. Older women with carotid plaque had 44% a higher relative hazard for fall-related hospitalization (HR 1.44; 95%CI, 1.18 to 1.76) compared to those without carotid plaque. The association persisted after adjustment for established falls risk factors such as measures of muscle strength and physical function.Each SD increase in the mean and maximum CCA-IMT was also associated with a higher risk of fall-related hospitalizations (HR 1.10; 95%CI, 1.00 to 1.21 and HR 1.11; 95%CI, 1.01 to 1.22, respectively). CONCLUSIONS: Measures of carotid atherosclerosis are associated with a higher risk of fall-related hospitalization independent of established falls risk factors. These findings suggest the importance of vascular health when considering falls risk.

Association Between High-Sensitivity Cardiac Troponin I and Cardiac Events in Elderly Women.

BACKGROUND: Elderly women are at high risk of coronary heart disease (CHD) and heart failure. High-sensitivity assays allow detection of cardiac troponin I (hsTnI) well below diagnostic cutoffs for acute coronary syndrome. We investigated the association between these levels with future cardiac events in community-based ambulant white women aged over 70 years initially recruited for a 5-year randomized, controlled trial of calcium supplements. METHODS AND RESULTS: This was a prospective study of 1081 elderly women without clinical CHD at baseline (1998) or hsTnI above the diagnostic cutoffs for acute coronary syndrome with 14.5-year follow-up hospitalization and mortality (events). Two hundred forty-three (22%) women had CHD events, 163 (15%) myocardial infarction or CHD death (hard CHD), and 109 (10%) heart failure. In 99.6% of available serum samples, hsTnI was above the level of detection (median, 4.5 ng/L; interquartile range, 3.6-5.8). After adjusting for Framingham risk factors, each SD natural log-transformed hsTnI increase was associated with an increased hazard for CHD (hazard ratio, 1.34; 95% CI, 1.18-1.53; P<0.001) hard CHD (hazard ratio, 1.51; 95% CI, 1.29-1.76; P<0.001), and heart failure (hazard ratio, 1.65; 95% CI, 1.36-1.99; P<0.001). Step-wise increases in relative hazards were observed with increasing quartiles of hsTnI (P for trend, <0.001), whereas the addition of hsTnI to conventional risk factors modestly improved discrimination indices: Harrell's c-statistic, net reclassification, and integrated discrimination (P<0.05). CONCLUSIONS: Cardiac troponin I is independently associated with future cardiac events in elderly women without apparent clinical manifestations. The addition of cardiac troponin I to conventional risk factors may modestly improve risk prediction in this setting.

The effects of 3 years of calcium supplementation on common carotid artery intimal medial thickness and carotid atherosclerosis in older women: an ancillary study of the CAIFOS randomized controlled trial.

Calcium is an essential nutrient for skeletal health; however, it has been suggested that supplemental calcium may be associated with adverse cardiovascular effects, raising widespread concern about their use. One suggested mechanism is via increasing carotid atherosclerosis, however few randomized controlled trials (RCT) of calcium supplements have assessed these mechanisms. The calcium intake fracture outcome study (CAIFOS) was a 5-year RCT (1998 to 2003) of 1.2 g of elemental calcium in the form of calcium carbonate in 1460 elderly women. An ancillary study of 1103 women assessed common carotid artery intimal medial thickness (CCA-IMT) and carotid atherosclerosis at year 3 (2001). The effects of supplementation were studied in intention-to-treat (ITT) and per-protocol (PP) analyses before and after adjustment for baseline cardiovascular risk factors. The mean age of participants at baseline was 75.2 ± 2.7 years. In ITT analyses, women randomized to calcium supplementation had no difference in multivariable-adjusted mean CCA-IMT (calcium 0.778 ± 0.006 mm, placebo 0.783 ± 0.006 mm, p = 0.491) and maximum CCA-IMT (calcium 0.921 ± 0.007 mm, placebo 0.929 ± 0.006 mm, p = 0.404). Women randomized to calcium did not have increased carotid atherosclerosis (calcium 47.2%, placebo 52.7%, p = 0.066). However, in women taking at least 80% of the supplements, a significant reduction in carotid atherosclerosis was observed in unadjusted but not in multivariate-adjusted models (p = 0.033 and p = 0.064, respectively). Participants in the highest tertile of total calcium (diet and supplements) had reduced carotid atherosclerosis in unadjusted and multivariable-adjusted analyses compared with participants in the lowest tertile (odds ratio [OR] = 0.67 [95% confidence interval (CI) 0.50-0.90], p = 0.008, and OR = 0.70 [95% CI 0.51-0.96], p = 0.028, respectively). In conclusion, these findings do not support the hypothesis that calcium supplementation increases carotid artery intimal medial thickness or carotid atherosclerosis, and high calcium intake may reduce this surrogate cardiovascular risk factor.

Effect of colchicine (0.5 mg twice daily) on high-sensitivity C-reactive protein independent of aspirin and atorvastatin in patients with stable coronary artery disease.

In patients with stable coronary artery disease, elevated levels of biomarkers of inflammation, including high-sensitivity C-reactive protein (hs-CRP) > or = 2.0 mg/L, are predictors of future vascular events. Because long-term low-dose colchicine is a safe and effective means of dampening inflammation, we conducted an open-label pilot study to determine whether it could significantly lower hs-CRP in patients with stable coronary artery disease in whom hs-CRP was > or = 2.0 mg/L despite taking both aspirin and high-dose atorvastatin therapy. Plasma hs-CRP was measured in 200 patients with clinically stable coronary artery disease who were taking aspirin and atorvastatin. In 64 patients, hs-CRP was > or = 2.0 mg/L. In 20 of these patients, hs-CRP was measured again at 2 weeks (no treatment group), and in 44 patients, hs-CRP was measured again after 4 weeks of open-label colchicine 0.5 mg twice daily (treatment group). In the no treatment group, mean baseline hs-CRP did not decrease significantly, measuring 4.28 +/- 2.03 mg/L at baseline and 3.70 +/- 2.30 mg/L after repeated measurement (mean change 11.0%, 95% confidence interval [CI] -30% to +9%, p = NS). In contrast, hs-CRP decreased in all patients administered colchicine, with mean baseline hs-CRP decreasing from 4.58 +/- 2.05 to 1.78 +/- 1.38 mg/L (p <0.001), an absolute decrease of 2.80 mg/L (95% CI 2.40 to 3.65 mg/L) and a relative decrease of 60% (95% CI 54% to 67%). In 28 patients (64%) in this group, the decrease in hs-CRP was >50% from baseline, and in 31 patients (70%), hs-CRP decreased to <2.0 mg/L. No significant side effects were reported. In conclusion, low-dose colchicine (0.5 mg twice daily) can effectively decrease hs-CRP in patients with clinically stable coronary artery disease and increased hs-CRP independent of aspirin and atorvastatin use. Additional controlled studies are warranted to confirm this observation and determine whether long-term use of low-dose colchicine can improve clinical outcomes in patients with advanced vascular disease.

Effects of intensive versus moderate lipid-lowering therapy on myocardial ischemia in older patients with coronary heart disease: results of the Study Assessing Goals in the Elderly (SAGE).

BACKGROUND: Clinical trials have demonstrated that, compared with placebo, intensive statin therapy reduces ischemia in patients with acute coronary syndromes and in patients with stable coronary artery disease. However, no studies to date have assessed intensive versus moderate statin therapy in older patients with stable coronary syndromes. METHODS AND RESULTS: A total of 893 ambulatory coronary artery disease patients (30% women) 65 to 85 years of age with > or = 1 episode of myocardial ischemia that lasted > or = 3 minutes during 48-hour ambulatory ECG at screening were randomized to atorvastatin 80 mg/d or pravastatin 40 mg/d and followed up for 12 months. The primary efficacy parameter (absolute change from baseline in total duration of ischemia at month 12) was significantly reduced in both groups at month 3 and month 12 (both P<0.001 for each treatment group) with no significant difference between the treatment groups. Atorvastatin-treated patients experienced greater low-density lipoprotein cholesterol reductions than did pravastatin-treated patients, a trend toward fewer major acute cardiovascular events (hazard ratio, 0.71; 95% confidence interval, 0.46, 1.09; P=0.114), and a significantly greater reduction in all-cause death (hazard ratio, 0.33; 95% confidence interval, 0.13, 0.83; P=0.014). CONCLUSIONS: Compared with moderate pravastatin therapy, intensive atorvastatin therapy was associated with reductions in cholesterol, major acute cardiovascular events, and death in addition to the reductions in ischemia observed with both therapies. The contrast between the therapies' differing efficacy for major acute cardiovascular events and death and their nonsignificant difference in efficacy for reduction of ischemia suggests that low-density lipoprotein cholesterol-lowering thresholds for ischemia and major acute cardiovascular events may differ. The Study Assessing Goals in the Elderly (SAGE) demonstrates that older men and women with coronary artery disease benefit from intensive statin therapy.

Folic acid does not improve endothelial function in healthy hyperhomocysteinaemic subjects.

Folic acid supplementation lowers total plasma homocysteine (tHcy) and improves endothelial function in individuals with coronary artery disease (CAD) and in those with additional CAD risk factors. In the present study, we assessed whether endothelial function is impaired in healthy subjects with hyperhomocysteinaemia but without other CAD risk factors and whether folic acid supplementation improves endothelial function in these subjects. Flow-mediated dilatation (FMD) of the brachial artery was performed on 26 healthy subjects, age 49 +/- 2 years (mean +/- S.E.M.), with high tHcy (15.6 +/- 1.5 micromol/l) and 16 healthy age-matched subjects with low tHcy (7.9 +/- 0.6 micromol/l; P < 0.001). Subjects with high tHcy were then randomized to receive 5 mg/day of folic acid or placebo for 8 weeks in a double-blind cross-over trial with a 4-week washout. FMD was not associated with tHcy and was not different between high and low tHcy groups (7.0 +/- 0.6% compared with 6.6 +/- 1.2%, P = 0.76). Treatment with folic acid decreased tHcy by 34% in hyperhomocysteinaemic subjects ( P = 0.02 compared with placebo), but had no effect on FMD (+ 0.5 +/- 0.6% compared with -0.7 +/- 0.5%; P = 0.17 compared with placebo). In healthy subjects with hyperhomocysteinaemia, but without additional cardiovascular risk, endothelial function is unimpaired and folic acid supplementation has no additional effect.