Weight change and cognitive function: findings from the Women's Health Initiative Study of Cognitive Aging

Although studies exploring relationships between obesity and cognitive impairment in the elderly are conflicting, literature suggests that overweight and obesity may be protective against cognitive impairment and dementia in older women. We examine the associations between changes in weight and waist circumference (WC) with global and domain-specific cognitive function in a large, well-defined cohort of 2,283 older, postmenopausal women (aged 65-79) prospectively followed through the Women's Health Initiative (WHI) Study of Cognitive Aging (WHISCA). We assessed the associations between changes in weight and WC collected up to 5 years before WHISCA enrollment and mean levels of global and domain-specific cognitive performance across an average of 5.4 years of subsequent follow-up. There was a lack of associations between weight and cognition in women who remained stable or gained weight. The only significant relationships observed were in association with weight loss (P ≤ 0.05), most likely signaling incipient disease. Moreover, cognition was not related to changes in WC. Relationships were largely independent of initial BMI, self-reported caloric intake or dieting. The lack of associations between weight gain and cognition in women is consistent with the existing literature.     

Calcium-channel blockers and cognitive function in elderly people: results from the Canadian Study of Health and Aging

BACKGROUND: Concern has been raised about the potential for adverse cognitive effects associated with the use of calcium-channel blockers (CCBs) in older people. This study was undertaken to examine prospectively the association between the use of these and other antihypertensive drugs and cognitive function. METHODS: The authors examined data from the Canadian Study of Health and Aging (CSHA), a population-based, prospective 5-year investigation of the epidemiology of dementia and other health problems in Canadians 65 years of age and older. The risk of cognitive decline, as indicated by a decline in performance on the Modified Mini-Mental State (3MS) examination over the 5-year period, was assessed in relation to the use of antihypertensive and diuretic drugs by 205 subjects with a history of hypertension and no evidence of dementia at baseline. RESULTS: The proportion of subjects whose cognitive performance declined over the study period was significantly higher in the group using CCBs than in the group using other antihypertensive agents (75% v. 59%). The adjusted odds ratio (OR) for a significant decline in cognitive performance (defined as a decrease in 3MS score of 10 points or more) was 2.28 (95% confidence interval [CI] 1.12-4.66) for subjects using CCBs. The adjusted ORs (and 95% CIs) for cognitive decline in subjects using selected antihypertensive agents or diuretics relative to those exposed to beta-blockers were as follows: angiotensin-converting-enzyme inhibitor, OR 1.36 (95% CI 0.41-4.55); diuretic or other antihypertensive drug, OR 1.45 (95% CI 0.51-4.14); dihydropyridine CCB (nifedipine), OR 1.94 (95% CI 0.52-7.27) and non-dihydropyridine CCB (diltiazem or verapamil), OR 3.72 (95% CI 1.22-11.36). INTERPRETATION: Older people taking CCBs were significantly more likely than those using other agents to experience cognitive decline. These findings are consistent with the results of previous cross-sectional research and emphasize the need for further trials to examine the associations between CCB use, blood pressure and cognitive impairment in elderly patients.     

Postmenopausal hormone therapy and cognitive outcomes: The Women's Health Initiative Memory Study (WHIMS)

This review discusses major findings from the Women's Health Initiative Memory Study (WHIMS). WHIMS reported hormone therapy (HT) – conjugated equine estrogen (CEE) with or without medroxyprogesterone acetate (MPA) – increased the risk for dementia (HR 1.76 [95% CI, 1.19–2.60]; P = 0.005) and global cognitive decline, with a mean decrement relative to placebo of 0.21 points on the Modified Mini Mental State Examination (3MS) (P = 0.006) in women age 65 and older.A subset of WHIMS participants joined the ancillary WHI Study of Cognitive Aging (WHISCA) trials, in which domain-specific cognitive tests and mood were measured annually. Compared with placebo, CEE + MPA had a negative impact on verbal memory over time (P = 0.01); and CEE-Alone was associated with lower spatial rotational ability (P ≤ 0.01) at the initial assessment, but the difference diminished over time.The ancillary WHIMS-MRI study measured subclinical cerebrovascular disease to possibly explain the negative cognitive findings reported by WHIMS and the increased clinical stroke in older women reported by the WHI. WHIMS-MRI reported that while CEE + MPA and CEE-Alone were not associated with increased ischemic brain lesion volume relative to placebo; both CEE + MPA and CEE-Alone were associated with lower mean brain volumes in the hippocampus (P = 0.05); frontal lobe (P = 0.004); and total brain (P = 0.07). HT-associated reductions in hippocampal volumes were greatest in women with baseline 3MS scores ≤90.     

Effect of eicosapentaenoic acid on central systolic blood pressure

Central systolic blood pressure (C-SBP) has been shown to be a better predictor of cardiovascular risk than brachial SBP. In this study, the effects of eicosapentaenoic acid (EPA) on C-SBP were compared with pravastatin. Twenty-four patients with hyperlipidemia were assigned 13 to receive 1800 mg/day EPA (EPA group) and 11 to receive 10 mg/day pravastatin (pravastatin group) for 3 months. In the EPA group, there were no changes in the LDL–cholesterol level. However, the radial augmentation index (AI) and C-SBP decreased after treatment by 5.7% (p<0.01) and 8.7% (p<0.001), respectively. Moreover, systolic and diastolic brachial BPs decreased by 7.1% and 8.0%, respectively (p<0.01 for both). In the pravastatin group, the LDL–cholesterol level decreased by 29.5% (p<0.001). However, there were no significant changes in brachial BP, AI and C-SBP between. These results suggested that EPA but not pravastatin may reduce cardiac afterload by reducing vascular reflected waves and lowering C-SBP.     

The Women's Health Initiative: The food environment, neighborhood socioeconomic status, BMI, and blood pressure

Using data (n = 60,775 women) from the Women's Health Initiative Clinical Trial (WHI CT)—a national study of postmenopausal women aged 50–79 years—we analyzed cross‐sectional associations between the availability of different types of food outlets in the 1.5 miles surrounding a woman's residence, census tract neighborhood socioeconomic status (NSES), BMI, and blood pressure (BP). We simultaneously modeled NSES and food outlets using linear and logistic regression models, adjusting for multiple sociodemographic factors, population density and random effects at the tract and metropolitan statistical area (MSA) level. We found significant associations between NSES, availability of food outlets and individual‐level measurements of BMI and BP. As grocery store/supermarket availability increased from the 10th to the 90th percentile of its distribution, controlling for confounders, BMI was lower by 0.30 kg/m². Conversely, as fast‐food outlet availability increased from the 10th to the 90th percentile, BMI was higher by 0.28 kg/m². When NSES increased from the 10th to the 90th percentile of its distribution, BMI was lower by 1.26 kg/m². As NSES increased from the 10th to the 90th percentile, systolic and diastolic BP were lower by 1.11 mm Hg and 0.40 mm Hg, respectively. As grocery store/supermarket outlet availability increased from the 10th and 90th percentiles, diastolic BP was lower by 0.31 mm Hg. In this national sample of postmenopausal women, we found important independent associations between the food and socioeconomic environments and BMI and BP. These findings suggest that changes in the neighborhood environment may contribute to efforts to control obesity and hypertension.     

A dampening effect of pulse interval variability on blood pressure variations with respect to primary variability in blood pressure during exercise

The correlation between baroreflex sensitivity (BRS) and the spectrum component at a frequency of 0.1 Hz of pulse intervals (PI) and systolic blood pressure (SBP) was studied. SBP and PI of 51 subjects were recorded beat-to-beat at rest (3 min), during exercise (0.5 W/kg of body weight, 9 min), and at rest (6 min) after exercise. BRS was determined by a spectral method (a modified alpha index technique). The subjects were divided into groups according to the spectral amplitude of SBP at a frequency of 0.1 Hz. The following limits of amplitude (in mm Hg) were used: very high > 5.4 (VH); high 5.4 > H > 3 (H); medium 3 > M > 2 (M), low < 2 (L). We analyzed the relationships between 0.1 Hz variability in PI and BRS at rest, during the exercise and during recovery in subgroups VH, H, M, L. The 0.1 Hz variability of PI increased significantly with increasing BRS in each of the groups with identical 0.1 Hz variability in SBP. This relationship was shifted to the lower values of PI variability at the same BRS with a decrease in SBP variability. The primary SBP variability increased during exercise. The interrelationship between the variability of SBP, PI and BRS was identical at rest and during exercise. A causal interrelationship between the 0.1 Hz variability of SBP and PI, and BRS was shown. During exercise, the increasing primary variability in SBP due to sympathetic activation was present, but it did not change the relationship between variability in pulse intervals and BRS.     

Variance components linkage analysis for adjusted systolic blood pressure in the Framingham Heart Study

We performed variance components linkage analysis in nuclear families from the Framingham Heart Study on nine phenotypes derived from systolic blood pressure (SBP). The phenotypes were the maximum and mean SBP, and SBP at age 40, each analyzed either uncorrected, or corrected using two subsets of epidemiological/clinical factors. Evidence for linkage to chromosome 8p was detected with all phenotypes except the uncorrected maximum SBP, suggesting this region harbors a gene contributing to variation in SBP.     

Linkage analysis of systolic blood pressure: a score statistic and computer implementation

A genome-wide linkage analysis was conducted on systolic blood pressure using a score statistic. The randomly selected Replicate 34 of the simulated data was used. The score statistic was applied to the sibships derived from the general pedigrees. An add-on R program to GENEHUNTER was developed for this analysis and is freely available.     

The sex-specific impact of systolic hypertension and systolic blood pressure on arterial-ventricular coupling at rest and during exercise

In healthy subjects the arterial system and the left ventricle (LV) are tightly coupled at rest to optimize cardiac performance. Systolic hypertension (SH) is a major risk factor for heart failure and is associated with structural and functional alterations in the arteries and the LV. The effects of SH and resting systolic blood pressure (SBP) on arterial-ventricular coupling (E(a)I/E(LV)I) at rest, at peak exercise, and during recovery are not well described. We noninvasively characterized E(a)I/E(LV)I as end-systolic volume index/stroke volume index in subjects who were normotensive (NT, n = 203) or had SH (brachial SBP > or =140 mmHg, n = 79). Cardiac volumes were measured at rest and throughout exhaustive upright cycle exercise with gated blood pool scans. E(a)I/E(LV)I reserve was calculated by subtracting peak from resting E(a)I/E(LV)I. At rest, E(a)I/E(LV)I did not differ between SH and NT men but was 23% (P = 0.001) lower in SH vs. NT women. E(a)I/E(LV)I did not differ between SH and NT men or women at peak exercise or during recovery. Nevertheless, E(a)I/E(LV)I reserve was 61% (P < 0.001) lower in SH vs. NT women. Similarly, resting SBP (as a continuous variable) was not associated with E(a)I/E(LV)I in men (beta = -0.12, P = 0.17) but was inversely associated with E(a)I/E(LV)I in women (beta = -0.47, P < 0.001). SH and a higher resting brachial SBP are associated with a lower E(a)I/E(LV)I at rest in women but not in men, and SH women have an attenuated E(a)I/E(LV)I reserve. Whether a smaller E(a)I/E(LV)I reserve leads to functional limitations warrants further examination.     

Evidence of a rare gene for low systolic blood pressure in the Framingham Heart Study

A major risk factor for coronary heart disease in both men and women is elevated systolic blood pressure (SBP). We performed segregation analysis on age, sex-adjusted, and transformed systolic blood pressure data on 1,141 families from the Framingham cohort-offspring study using the segregation analysis program POINTER. The results of hypothesis testing revealed: (1) these data are consistent with familial transmission; (2) there is evidence for the transmission of a rare, major gene for low SBP with a gene frequency of q = 0.02; and (3) most of the transmissible component to SBP can be attributed to the polygenic background with H = 0.31.     

Short-term variability of pulse pressure and systolic and diastolic time in heart transplant recipients

In heart transplant recipients (HTR), short-term systolic blood pressure variability is preserved, whereas heart rate variability is almost abolished. Heart period is the sum of left ventricular ejection time (LVET) and diastolic time (DT). In the present time-domain prospective study, we tested the hypothesis that short-term fluctuations in aortic pulse pressure (PP) in HTR were related to fluctuations in LVET. Seventeen male HTR (age 48 +/- 6 yr) were studied 16 +/- 11 mo after transplantation. Aortic root pressure was obtained over a 15-s period using a micromanometer both at rest (n = 17) and following the cold pressor test (CPT, n = 14). There was a strong positive linear relationship between beat-to-beat LVET and beat-to-beat PP in all patients at rest and in 13 of 14 patients following CPT (each P < 0.01). The slope of this relationship showed little scatter both at rest (0.34 +/- 0.07 mmHg/ms) and following CPT (0.35 +/- 0.09 mmHg/ms, P = not significant). Given the essentially fixed heart period, DT varied inversely with LVET. As a result, in 13 of 17 HTR at rest and in 12 of 14 HTR following CPT, there was a negative linear relationship between beat-to-beat PP and DT. In conclusion, our short-term time-domain study demonstrated a strong positive linear relationship between LVET and blood pressure variability in male HTR. We also identified a subgroup of HTR in whom there was a mismatch between PP and DT.     

Thermal stress elevates the systolic blood pressure of spontaneously hypertensive rats

The effect of thermal stress on the systolic blood pressure of spontaneously hypertensive rats (SHR) and normotensive rats (WKY) of the Wistar/Kyoto strain was compared using our newly-developed indirect method which does not require heating of the animal to measure its blood pressure. The blood pressure of SHR increased significantly at 30°C and reached a maximum increase of about 20% at 32°C in 16 minutes in spite of the fact that the heart rate was decreased. In contrast to SHR, the systolic pressure of WKY did not change significantly after 30 minutes at 34°C or 36°C.     

Dynamics of blood pressure, pulse wave transit time and systolic timei intervals during acute gravity changes induced by parabolic flight

To investigate cardiovascular adaptation to transient microgravity (Microgravity), we measured RR intervals (RRI), arterial blood pressure (BP), pulse wave transit time (PTT) and systolic time intervals (STI) during parabolic flight. Our results demonstrate that during microgram RRI, BP and PTT are subject to a rapid adaptation likely mediated by the baroreflex whereas STI changes with microgravity but does not present further adaptation.