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Arterial Stiffness, Toxic Pollution, Mediterranean Diet, and DHEA

November 2017

Arterial stiffness

Coronary calcification and the risk of heart failure in the elderly: the Rotterdam Study.

OBJECTIVES: The purpose of this study was to determine the association of coronary artery calcification (CAC) with incident heart failure in the elderly and examine its independence of overt coronary heart disease (CHD). BACKGROUND: Heart failure is often observed as a first manifestation of coronary atherosclerosis rather than a sequela of overt CHD. Although numerous studies have shown that CAC, an established measure of coronary atherosclerosis, is a strong predictor of CHD, the association between CAC and future heart failure has not been studied prospectively. METHODS: In the Rotterdam Study, a population-based cohort, 1,897 asymptomatic participants (mean age, 69.9 years; 58% women) underwent CAC scoring and were followed for the occurrence of heart failure and CHD. RESULTS: During a median follow-up of 6.8 years, there were 78 cases of heart failure and 76 cases of nonfatal CHD. After adjustment for cardiovascular risk factors, increasing CAC scores were associated with heart failure (p for trend = 0.001), with a hazard ratio of 4.1 (95% confidence interval [CI]: 1.7 to 10.1) for CAC scores >400 compared with CAC scores of 0 to 10. After censoring participants for incident nonfatal CHD, increasing extent of CAC remained associated with heart failure (p for trend = 0.046), with a hazard ratio of 2.9 (95% CI: 1.1 to 7.4) for CAC scores >400. Moreover, adding CAC to cardiovascular risk factors resulted in an optimism-corrected increase in the c-statistic by 0.030 (95% CI: 0.001 to 0.050) to 0.734 (95% CI: 0.698 to 0.770) and substantially improved the risk classification of subjects (continuous net reclassification index = 34.0%). CONCLUSIONS: CAC has a clear association with the risk of heart failure, independent of overt CHD. Because heart failure is highly prevalent in the elderly, it might be worthwhile to include heart failure as an outcome in future risk assessment programs incorporating CAC.

JACC Cardiovasc Imaging. 2012 Sep;5(9):874-80.

Stroke is associated with coronary calcification as detected by electron-beam CT: the Rotterdam Coronary Calcification Study.

BACKGROUND AND PURPOSE: Coronary calcification as detected by electron-beam CT measures the atherosclerotic plaque burden and has been reported to predict coronary events. Because atherosclerosis is a generalized process, coronary calcification may also be associated with manifest atherosclerotic disease at other sites of the vascular tree. We examined whether coronary calcification as detected by electron-beam CT is related to the presence of stroke. METHODS: From 1997 onward, subjects were invited to participate in the prospective Rotterdam Coronary Calcification Study and undergo electron-beam CT to detect coronary calcification. The study was embedded in the population-based Rotterdam Study. Calcifications were quantified in a calcium score according to Agatston’s method. Calcium scores were available for 2,013 subjects (mean age [SD], 71 [5.7] years). Fifty subjects had experienced stroke before scanning. RESULTS: Subjects were 2 times more likely to have experienced stroke when their calcium score was between 101 and 500 (odds ratio [OR], 2.1; 95% CI, 0.9 to 4.7) and 3 times more likely when their calcium score was above 500 (OR, 3.3; 95% CI, 1.5 to 7.2), compared with subjects in the lowest calcium score category (0 to 100). Additional adjustment for cardiovascular risk factors did not materially alter the risk estimates. CONCLUSIONS: In this population-based study, a markedly graded association was found between coronary calcification and stroke. The results suggest that coronary calcification as detected by electron-beam CT may be useful to identify subjects at high risk of stroke.

Stroke. 2002 Feb;33(2):462-5.

Coronary artery calcification is an independent stroke predictor in the general population.

BACKGROUND AND PURPOSE: Coronary artery calcification (CAC) is a noninvasive marker of plaque load that predicts myocardial infarcts in the general population. Herein, we investigated whether CAC predicts stroke events in addition to established risk factors that are part of the Framingham risk score. METHODS: A total of 4,180 subjects from the population-based Heinz Nixdorf Recall study (45-75 years of age; 47.1% men) without previous stroke, coronary heart disease, or myocardial infarction were evaluated for stroke events over 94.9 ± 19.4 months. Cox proportional hazards regressions were used to examine CAC as stroke predictor in addition to established vascular risk factors (age, sex, systolic blood pressure, low-density lipoprotein, high-density lipoprotein, diabetes mellitus, smoking, and atrial fibrillation). RESULTS: Ninety-two incident strokes occurred (82 ischemic, 10 hemorrhagic). Subjects suffering a stroke had significantly higher CAC values at baseline than the remaining subjects (median, 104.8[Q1;Q3, 14.0;482.2] vs 11.2[0;106.2]; P<0.001). In a multivariable Cox regression, log10(CAC+1) was an independent stroke predictor (hazards ratio, 1.52 [95% confidence interval, 1.19-1.92]; P=0.001) in addition to age (1.35 per 5 years [1.15-1.59]; P<0.001), systolic blood pressure (1.25 per 10 mm Hg [1.14-1.37]; P<0.001), and smoking (1.75 [1.07-2.87]; P=0.025). CAC predicted stroke in men and women, particularly in subjects <65 years of age and independent of atrial fibrillation. CAC discriminated stroke risk specifically in participants belonging to the low (<10%) and intermediate (10%-20%) Framingham risk score categories. CONCLUSIONS: CAC is an independent stroke predictor in addition to classical risk factors in subjects at low or intermediate vascular risk.

Stroke. 2013 Apr;44(4):1008-13.

Role of arterial stiffness in cardiovascular disease.

Propagation of the pressure wave along the arterial tree (pulse wave velocity [PWV]) is related to the intrinsic elasticity of the arterial wall. PWV is increased in stiffer arteries and, when measured over the aorta, is an independent predictor of cardiovascular morbidity and mortality. Given the predictive power of PWV, identifying strategies that prevent or reduce stiffening may be important in prevention of cardiovascular events. One view is that aortic stiffness occurs as a result of atherosclerosis along the aorta. However, there is little or no association between PWV and classical risk factors for atherosclerosis, other than age and blood pressure. Furthermore, PWV does not increase during early stages of atherosclerosis, as measured by intima-media thickness and non-calcified atheroma, but it does increase in the presence of aortic calcification that occurs within advanced atherosclerotic plaque. Age-related widening of pulse pressure is the major cause of age-related increase in prevalence of hypertension and has been attributed to arterial stiffening. This review summarizes the methods of measuring aortic stiffness in humans, the pathophysiological mechanisms leading to aortic stiffness, including its association with atherosclerosis, and the haemodynamic consequences of increased aortic stiffness.

JRSM Cardiovasc Dis. 2012 Jul 31;1(4).

Arterial stiffness and cardiovascular events: the Framingham Heart Study.

BACKGROUND: Various measures of arterial stiffness and wave reflection have been proposed as cardiovascular risk markers. Prior studies have not assessed relations of a comprehensive panel of stiffness measures to prognosis in the community. METHODS AND RESULTS: We used proportional hazards models to analyze first-onset major cardiovascular disease events (myocardial infarction, unstable angina, heart failure, or stroke) in relation to arterial stiffness (pulse wave velocity [PWV]), wave reflection (augmentation index, carotid-brachial pressure amplification), and central pulse pressure in 2,232 participants (mean age, 63 years; 58% women) in the Framingham Heart Study. During median follow-up of 7.8 (range, 0.2 to 8.9) years, 151 of 2,232 participants (6.8%) experienced an event. In multivariable models adjusted for age, sex, systolic blood pressure, use of antihypertensive therapy, total and high-density lipoprotein cholesterol concentrations, smoking, and presence of diabetes mellitus, higher aortic PWV was associated with a 48% increase in cardiovascular disease risk (95% confidence interval, 1.16 to 1.91 per SD; P=0.002). After PWV was added to a standard risk factor model, integrated discrimination improvement was 0.7% (95% confidence interval, 0.05% to 1.3%; P<0.05). In contrast, augmentation index, central pulse pressure, and pulse pressure amplification were not related to cardiovascular disease outcomes in multivariable models. CONCLUSIONS: Higher aortic stiffness assessed by PWV is associated with increased risk for a first cardiovascular event. Aortic PWV improves risk prediction when added to standard risk factors and may represent a valuable biomarker of cardiovascular disease risk in the community.

Circulation. 2010 Feb 2;121(4):505-11

Arterial stiffness as a cause of cognitive decline and dementia: a systematic review and meta-analysis.

BACKGROUND: Although arterial stiffness has recently been confirmed as a predictor of cardiovascular disease, the association between arterial stiffness and cognitive decline is less clear. AIM: We performed a systematic review and meta-analysis to examine the evidence for large artery stiffness as a cause of cognitive decline and dementia. METHOD: Electronic databases were systematically searched until September 2011 for studies reporting on the longitudinal relationship between any validated measure of large artery stiffness and cognitive decline or dementia. Meta-analysis was performed on four studies investigating the association between aortic pulse wave velocity and a decline in Mini-Mental State Examination scores. RESULTS: Six relevant longitudinal studies were located, conducted over an average of 5 years follow up. Arterial stiffness was predictive of cognitive decline in five/six studies. In meta-analysis, higher aortic stiffness predicted lower Mini-Mental State Examination scores within the sample (b=-0.03, 95% confidence interval (CI): -0.06 to 0.01, n= 3,947), although studies were not all homogeneous, and statistical heterogeneity was present (I(2) = 71.9%, P= 0.01). Removal of one study with a relatively younger cohort and lower median aortic stiffness found higher aortic stiffness to significantly predict cognitive decline (b=-0.04, 95% CI: -0.07 to -0.01, n= 3,687) without evidence of heterogeneity (I(2) = 9.5%, P= 0.33). There was little research investigating the effects of aortic stiffness on the development of dementia. CONCLUSION: Aortic stiffness was found to predict cognitive decline in both qualitative review and quantitative analysis.

Intern Med J. 2012 Jul;42(7):808-15.

Arterial stiffness: detection and consequences in cognitive impairment and dementia of the elderly.

Arterial stiffness constitutes a reduction in the ability of large arteries to readily accommodate the increase in blood ejected from the heart during systole. Propagation of the pulse wave or pulse wave velocity (PWV) is a relatively simple, non-invasive, and reproducible method to determine arterial stiffness. There is mounting evidence that consistently implicates arterial stiffness in the pathogenesis of impaired cognitive function and dementia in the elderly. This paper summarizes this evidence. First, the majority (85%) of the twelve studies comprising over 6,000 individuals found a significant association between increased vascular stiffness and cognitive impairment in multivariate analysis after adjusting for age, educational level, and other factors that influence cognition. Second, higher pulse wave velocity, adjusted for age and other factors, was associated with a greater amount of white matter hyperintensities on brain imaging, indicating cerebral small-vessel disease. Third, studies consistently indicate that higher PWV is a significant predictor of subsequent cognitive decline. Fourth, some data support the proposition that arterial stiffness (PWV) increases progressively from persons with normal cognitive function to those with mild cognitive impairment, to Alzheimer’s disease, and then to vascular dementia. Fifth, there is some suggestion that antihypertensive drugs that have a more favorable effect to reduce vascular stiffness are more likely to reduce the occurrence of cognitive impairment. Taken together, these data suggest that artery stiffness may be a useful clinical tool to detect individuals at risk for cognitive impairment and dementia of the elderly.

J Alzheimers Dis. 2012;32(3):541-9.

Arterial stiffness and cognitive decline in well-functioning older adults.

BACKGROUND: Stiffness of the central arteries in aging may contribute to cerebral microvascular disease independent of hypertension and other vascular risk factors. Few studies of older adults have evaluated the association of central arterial stiffness with longitudinal cognitive decline. METHODS: We evaluated associations of aortic pulse wave velocity (centimeters per second), a measure of central arterial stiffness, with cognitive function and decline in 552 participants in the Health, Aging, and Body Composition (Health ABC) study Cognitive Vitality Substudy (mean age ± SD = 73.1 ± 2.7 years, 48% men and 42% black). Aortic pulse wave velocity was assessed at baseline via Doppler-recorded carotid and femoral pulse waveforms. Global cognitive function, verbal memory, psychomotor, and perceptual speed were evaluated over 6 years. RESULTS: After adjustment for demographics, vascular risk factors, and chronic conditions, each 1 SD higher aortic pulse wave velocity (389 cm/s) was associated with poorer cognitive function: -0.11 SD for global function (SE = 0.04, p < .01), -0.09 SD for psychomotor speed (SE = 0.04, p = .03), and -0.12 SD for perceptual speed (SE = 0.04, p < .01). Higher aortic pulse wave velocity was also associated with greater decline in psychomotor speed, defined as greater than 1 SD more than the mean change (odds ratio = 1.42 [95% confidence interval = 1.06, 1.90]) but not with verbal memory or longitudinal decline in global function, verbal memory, or perceptual speed. Results were consistent with mixed models of decline in each cognitive test. CONCLUSIONS: In well-functioning older adults, central arterial stiffness may contribute to cognitive decline independent of hypertension and other vascular risk factors.

J Gerontol A Biol Sci Med Sci. 2011 Dec;66(12):1336-42.

Role of inflammation in the pathogenesis of arterial stiffness.

Increased arterial stiffness is an independent predictor of cardiovascular disease independent from blood pressure. Recent studies have shed new light on the importance of inflammation on the pathogenesis of arterial stiffness. Arterial stiffness is associated with the increased activity of angiotensin II, which results in increased NADPH oxidase activity, reduced NO bioavailability and increased production of reactive oxygen species. Angiotensin II signaling activates matrix metalloproteinases (MMPs) which degrade TGFb precursors to produce active TGFb, which then results in increased arterial fibrosis. Angiotensin II signaling also activates cytokines, including monocyte chemoattractant protein-1, TNF-a, interleukin-1, interleukin-17 and interleukin- 6. There is also ample clinical evidence that demonstrates the association of inflammation with increased arterial stiffness. Recent studies have shown that reductions in inflammation can reduce arterial stiffness. In patients with rheumatoid arthritis, increased aortic pulse wave velocity in patients was significantly reduced by anti tumor necrosis factor-a therapy. Among the major classes of anti hypertensive drugs, drugs that block the activation of the RAS system may be more effective in reducing the progression of arterial stiffness. Thus, there is rationale for targeting specific inflammatory pathways involved in arterial stiffness in the development of future drugs. Understanding the role of inflammation in the pathogenesis of arterial stiffness is important to understanding the complex puzzle that is the pathophysiology of arterial stiffening and may be important for future development of novel treatments.

Yonsei Med J. 2012 Mar;53(2):258-61.