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Interestingly, relations between microvascular function, aortic stiffness, and pressure pulsatility have been reported. In the Framingham Heart Study offspring cohort increased aortic stiffness was associated with higher forearm vascular resistance at baseline and during reactive hyperemia, and with blunted flow reserve during hyperemia. 51 Moreover, aortic stiffening is accompanied by microcirculatory structural or functional remodeling beyond that which is explained by contemporaneously measured cardiovascular risk factors. One interpretation is that microvascular damage may result from increased aortic stiffness and elevated forward wave amplitude or from increased transmission of a given forward wave into the microcirculation. Consistent with this hypothesis, prior studies in animal models have shown that locally induced isolated alterations in pressure pulsatility have major effects on microvascular structure and function. 52,53 Another interpretation is that abnormalities in the microcirculation and, therefore, in peripheral vascular resistance, lead to the perturbations in aortic stiffness. Recent careful observations by Christensen and Mulvany Maison Margiela Chunky heel mules l6R8bUEb9
have confirmed that pulsatility penetrates much deeper in the microvasculature than was previously supposed. It has, therefore, been hypothesized that structural alterations (rarefaction) leading to changes in the architectural design of the distal vascular tree influence pulse pressure and the augmentation index beyond the Windkessel (compliance, resistance) paradigm. 55 The biophysical basis of this influence is still poorly explored, although recent studies suggest a possible role for microvascular branching angles and related geometric parameters in hypertension-related cardiovascular disease. 56

The pathophysiological basis of the metabolic syndrome is multiple and complex. There is increasing evidence that microvascular function is a potential factor explaining the clustering of several components of the metabolic syndrome such as hypertension, obesity, and insulin resistance ( Figure 3 ). Also, microvascular defects play an important role in the end-organ damage associated with the metabolic syndrome and may contribute to macrovascular dysfunction, although further studies will have to elucidate the physiological mechanisms underlying relationships between these two segments of the circulation. Thus, the microcirculation may present a promising future therapeutic and preventative target in the metabolic syndrome. Hence, clarification of pathophysiological pathways that contribute to microvascular dysfunction is essential. This review discusses the potential role for defects in intracellular insulin signaling and obesity-related endocrine signaling therein. These pathways are worth more detailed studies in the future to develop targeted interventions for microvascular dysfunction.

Focus on the few emails that are actually high priority. What counts as an important email? I’ll suggest that the truly essential ones are client communication and inquiries about potential new engagements. Using that metric, only 10.5% of the messages I received over the two-week period qualified.

Focus on the few emails that are actually high priority.

The answer, then, is to avoid getting lost in the endless stream and instead to focus on the small percentage of messages that matter most, from clients and potential clients. Even in the darkest days of email overwhelm, if you force yourself to put a “star” on high priority messages, you can often successfully tackle that handful.

Despite the rise of technologies like Slack, for the foreseeable future, email will always be with us – and indeed, some predict the number of messages we receive will continue to grow at a compounded annual rate of 15% . Spending more time fielding messages – time away from our own priorities – isn’t a sustainable answer. And asking people to take you off of mailing lists or leave you off of “reply all” threads is a losing battle. (Just save your time and don’t respond.)

Instead, by understanding the signal to noise ratio of our inboxes, and recognizing how easy it is for others to make (often onerous) requests for our time, we can make smarter choices about where to focus our attention.

Dorie Clark is a marketing strategist and professional speaker who teaches at Duke University’s Fuqua School of Business. She is the author of and . You can receive her free self-assessment .

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9 COMMENTS

Thanks Dorie. I will share in my management and leadership development seminars. Sounds like there is quite a bit that a bot can respond to, particularly the requests for interviews or headshot or similar. perhaps leading people to a webpage with downloadables. My friend Jim Cathcart has over the years figured all requests and laid the files and downloadables up on his website for easy access but you're right we're so overwhelmed by it all. I have used unroll.me as well. Happy Friday.

The exceptions to treatment in the context of absolute CHD risk are severe hypertension (systolic > 160 mm Hg and/or diastolic > 100 mm Hg), familial hypercholesterolaemia or other inherited dyslipidaemia, or patients with diabetes mellitus with associated target organ damage.

The proportions of men and women (excluding patients with reported CHD or other atherosclerotic disease) who are potentially eligible for treatment at different levels of absolute CHD risk (table 1 ) in England and Scotland has been estimated by applying the Framingham risk function to the Health Survey for England (1994) and the Scottish Health Survey. The Health Survey for England did not measure HDL cholesterol and this has been estimated from the Scottish data. The Scottish survey is based on people aged 30−64 whereas in England the population 30−75 years was surveyed. For the age group 64−75 in England the average HDL cholesterol at age 64 years in Scotland was used.

View this table:
Table 1

Percentage of men and women in England and Scotland at different levels of CHD risk

Priority should be given to lifestyle. Indeed, for many patients whose absolute CHD risk is not sufficiently high to justify pharmacotherapy at their present age, lifestyle intervention will be the only approach offered for primary prevention. All cigarette smokers should be encouraged to stop smoking. Men and women who do so experience a rapid decline in the risk of CHD, by as much as half after one year, but up to 10 years may be needed to reach the risk level of those people who never smoked. 110-115 Physician advice and encouragement given repeatedly over time to healthy high risk men has been shown in randomised controlled trials to reduce smoking by 21%. All forms of nicotine replacement therapy are effective aids for nicotine dependent smokers, particularly for those who seek help in stopping smoking. 24 Nicotine gum (2 mg) and patch reduced smoking by 11% and 13%, respectively, in trials of self referred smokers compared to placebo. However, in unselected smokers nicotine gum and patch only reduced smoking by 3% and 4%, respectively. Nicotine gum (4 mg) was more useful in the more dependent smokers. Many individuals will require dietary advice, including weight reduction, 32 and would also benefit from increased physical activity. 116 Physical activity, either at work or in leisure time, is associated with a lower risk of CHD in both men and women. 117-121 The largest reduction in risk is seen between sedentary and moderately active individuals and the additional reduction in risk between moderately and vigorously active individuals is more modest. Protection is lost when people stop exercising and, conversely, inactive people who take up exercise acquire a lower risk of CHD. Although any activity appears to be of benefit, those which are more active such as brisk walking or heavy gardening appear to be more protective. However, where the absolute risk of CHD is sufficiently high to justify more intensive intervention, or when the level of any one risk factor is already associated with target organ damage, lifestyle measures alone are not sufficient and drugs should also be used. 122 123

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