24 October, 2016: 

The benefits of the Mediterranean diet in regard to cardiovascular health and metabolic risk factors in postmenopausal women are well recognized [1, 2]. Seafood is considered as one of the major components of the Mediterranean diet. So could one make a clear link between a regular consumption of fish and cardiovascular benefits? Most of us would say 'yes, certainly', but a recent publication challenges this common perception. The newest data come from a prospective cohort study of US women participating in the Women's Health Initiative from 1993 to 2014 [3]. A total of 39,876 women who were aged ≥ 45 years and free of cardiovascular disease at baseline provided dietary data on food frequency questionnaires. Analyses used Cox proportional hazards models to evaluate the association between fish and energy-adjusted omega-3 polyunsaturated fatty acid intake and the risk of major cardiovascular disease, defined as a composite outcome of myocardial infarction, stroke, and cardiovascular death. The final analytic sample included 38,392 women (mean age 55 years). During 713,559 person-years of follow-up, 1941 cases of incident major cardiovascular disease were confirmed. Tuna and dark fish (mackerel, salmon, sardines, bluefish, and swordfish) intake was not associated with the risk of incident major cardiovascular disease (p-trend > 0.05). Neither α-linolenic acid nor marine omega-3 fatty acid intake was associated with major cardiovascular disease or with individual cardiovascular outcomes (all p-trend > 0.05). There was no effect modification by age, body mass index, or baseline history of hypertension.

8 August, 2016: 

Long ago it was perceived that migraineurs have a higher risk for ischemic stroke, mainly because of short-term pro-thrombotic alterations during attacks [1, 2]. Migraine with aura confers a lifelong 2–2.5-fold elevated risk of stroke. Frequency of migraine directly correlates with higher stroke risk, but only minimal evidence supports reducing migraine frequency with medications to reduce stroke risk. Women suffering from migraine with aura who smoke have a 9-fold increased risk of stroke. There are several potential mechanisms for the increased risk of ischemic stroke in migraineurs. Migraine may increase ischemic stroke risk via vasospasm-induced cerebrovascular hypoperfusion, platelet activation, increased platelet aggregation, and increased concentrations and activity of various vascular pro-coagulant factors. Still, the absolute risk of migraine-associated stroke in women is relatively low.

18 April 2016: 

Despite the availability of effective hormonal and non-hormonal treatments for menopausal symptoms, few women with these symptoms are evaluated or treated  

Whoever can download from The New England Journal of Medicine and read the paper by Manson and Kunitz entitled 'Menopause management: getting clinical care back on track', or from the relevant commentary in Medscape must do so at their earliest convenience [1,2]. As a reminder, the authors were among the WHI study investigators, and Manson was also a Steering Committee member. Needless to detail again the consequences of the misinterpretation of the initial WHI study results, which reduced the use of postmenopausal hormone therapy (HT) by 80% or even more, just because of misunderstanding of its safety profile in recently menopausal women. Many later studies discussed the adverse outcomes of banning HT, mainly related to quality of life issues and bone health. The best would be just to bring some quotes from the article (in italics).

Despite the availability of effective hormonal and non-hormonal treatments for menopausal symptoms, few women with these symptoms are evaluated or treated. Leading medical societies devoted to the care of menopausal women agree that systemic hormone therapy is the most effective treatment currently available for these symptoms and should be recommended for women with moderate-to-severe vasomotor symptoms, in the absence of contraindications. Such criteria apply to approximately 20% of women in early menopause, most of whom remain untreated despite having symptoms that adversely affect their daily activities, sleep, and quality of life. Women's decisions regarding such therapy are now surrounded by anxiety and confusion. The WHI trial was designed to address the risks and benefits of long-term use of hormone therapy for the prevention of chronic disease in postmenopausal women who were on average 63 years of age at initiation of therapy. But the results are now being used inappropriately in making decisions about treatment for women in their 40s and 50s who have distressing vasomotor symptoms. The new generation of medical graduates and primary-care providers often lacks training and core competencies in management of menopausal symptoms and prescribing of hormonal treatments. Most primary-care residency programs in the United States don't provide adequate education in women's health in general or in menopause management in particular. Reluctance to treat menopausal symptoms has derailed and fragmented the clinical care of midlife women, creating a large and unnecessary burden of suffering.

21 March, 2016: 

Paula and colleagues in 2013 conducted a cross-sectional study to investigate the association between smoking and early onset of menopause [1]. The study included 1222 female employees on the campuses of Rio de Janeiro university. All participants were aged over 35 years. Smoking status was determined by questioning whether the participant had smoked at least 100 cigarettes during her lifetime, and whether she currently smoked. Women were classified as current smokers, former smokers or women who had never smoked. The researchers used a Cox proportional hazards model to investigate the data and the correlations between smoking status and age at the onset of menopause.

Among current smokers, there was an increase of 56% (hazard ratio 1.56; 95% confidence interval 1.06-2.31) in the risk of menopause, when compared with those who had never smoked (p = 0.02), while former smoking was not associated with the outcome. The results obtained from the study revealed that women who smoke are 1.8 years younger at the onset of menopause when compared to non-smoking women. There was no significant difference between the survival curves for former smokers and women who had never smoked, adding a very interesting conclusion: once a woman gives up smoking, her age at onset of menopause may be roughly equivalent to that of women who have never smoked. The results obtained from the study emphasize the importance of efforts to control cigarette smoking.

14 March, 2016: 

The effect of quitting smoking on hot flushes in women aged 45–54 years of age at baseline followed for 1–7 years was examined by Smith and his colleagues [1] in a longitudinal analysis published recently. A cohort study of hot flushes among women 45–54 years of age was conducted starting in 2006 among residents of Baltimore and its surrounding counties. Menopausal status was defined as follows: premenopausal women were those who experienced their last menstrual period within the past 3 months and reported 11 or more periods within the past year; perimenopausal women were those who experienced (1) their last menstrual period within the past year, but not within the past 3 months, or (2) their last menstrual period within the past 3 months and experienced 10 or fewer periods within the past year; postmenopausal women were those women who had not experienced a menstrual period within the past year. Participants were asked to complete a brief questionnaire during a clinic visit 3 weeks after the baseline visit, then annually after that. This questionnaire repeated all previous questions about hot flushes and smoking. Interestingly, they concluded that women who quit smoking were less likely to suffer from hot flushes, less likely to have severe hot flushes, and less likely to have frequent hot flushes than women who continued to smoke, but were more likely to suffer from any hot flushes, more severe hot flushes, and more frequent hot flushes than women who never smoked.

22 February, 2016: 

The new dietary guidelines for Americans were recently published by the US Department of Agriculture and the Department of Health and Human Services. These guidelines are updated once in 5 years, and thus the current version is for 2015–2020. The basic rationale and general principles are phrased as follows: healthy eating patterns support a healthy body weight and can help prevent and reduce the risk of chronic disease throughout periods of growth, development, and aging as well as during pregnancy. All foods consumed as part of a healthy eating pattern fit together like a puzzle to meet nutritional needs without exceeding limits, such as those for saturated fats, added sugars, sodium, and total calories. All forms of foods, including fresh, canned, dried, and frozen, can be included in healthy eating patterns. Individuals should aim to meet their nutrient needs through healthy eating patterns that include nutrient-dense foods. Foods in nutrient-dense forms contain essential vitamins and minerals and also dietary fiber and other naturally occurring substances that may have positive health effects. In some cases, fortified foods and dietary supplements may be useful in providing one or more nutrients that otherwise may be consumed in less than recommended amounts.

8 February, 2016: 

Alcohol consumption has been associated with both benefits and harms, but most studies investigated men rather than women, or analyzed data from mixed cohorts composed of males and females, with necessary adjustments for age and sex. Also, most studies focused on one alcohol-related outcome or on a single group of related diseases rather than seeing the entire spectrum of human health. Despite a wealth of information on the outcomes of drinking alcohol, there is still inconsistency on some bottom-line guiding messages related to consumption patterns (quantity, frequency, and stratified combinations), and types of alcohol consumed. Ethnicity, socio-economical features, age and gender may be factors that influence disease protection or risk.

A recent study addressed the outcomes of drinking alcohol in a large cohort which included people from 12 countries in five continents with different socio-economical characteristics [1]. The PURE study included 114,970 adults, of whom 12,904 (11%) were from high-income countries, 24,408 (21%) were from upper-middle-income countries, 48,845 (43%) were from lower-middle-income countries, and 28,813 (25%) were from low-income countries. Mean age was 50 (41–58) years; median follow-up was 4.3 years (IQR 3.0–6.0). In the high- and upper-middle income countries, around 50% of the cohorts were women, but there were only 4% of women in the low-income countries. Overall, 74,685 (65%) participants were never drinkers, 4255 (4%) were former drinkers, and 36,030 (31%) were current drinkers. Of current drinkers, 26,025 (72%) had low intake, 6114 (17%) had moderate intake, and 2931 (8%) had high intake. Associations with mortality (n = 2723), cardiovascular disease (n = 2742), myocardial infarction (n = 979), stroke (n = 817), alcohol-related cancer (n = 764), injury (n = 824), admission to hospital (n = 8786), and for a composite of these outcomes (n = 11 963) were calculated. Data was adjusted for age and sex. Current drinking was associated with reduced myocardial infarction risk (HR 0.76; 95% CI 0.63–0.93), but with increased alcohol-related cancers (HR 1.51; 95% CI 1.22–1.89) and injury (HR 1.29; 95% CI 1.04–1.61). High intake was associated with increased mortality (HR 1.31; 95% CI 1.04–1.66). Compared with never drinkers, significantly reduced hazards for the composite outcome for current drinkers in high-income countries and upper-middle-income countries (HR 0.84; 95% CI 0.77–0.92), but not in lower-middle-income countries and low-income countries, for which there were no reductions in this outcome (HR 1.07; 95% CI 0.95–1.2).

Comment

Perhaps the best-known clinical bright side of alcohol consumption is cardiovascular protection, whereas the dark side is, of course, cirrhosis of the liver. The question was always how much one should drink to achieve benefits yet to avoid harms, and numerous publications have addressed this issue. The usual recommendation for healthy lifestyle encourages women to drink alcohol 'in moderation' in order to reduce the risk of cardiovascular disease. The American Heart Association guideline for the prevention of cardiovascular disease in women mentions in its Appendix that the desired quantity should be ≤ 1 serving/day, namely up to 4 oz wine, 12 oz beer, 1.5 oz of 80-proof spirits, or 1 oz of 100-proof spirits [2].

Twenty years ago, the 12-year follow-up data from the Nurses' Health Study showed that the relative risks of death in drinkers as compared with non-drinkers were 0.83 (0.74–0.93) for women who consumed 1.5–4.9 g of alcohol per day (one to three drinks per week), 0.88 (0.80–0.98) for those who consumed 5.0–29.9 g per day, and 1.19 (1.02–1.38) for those who consumed 30 g or more per day, after adjustment for other predictors of mortality [3]. Light-to-moderate drinking (1.5–29.9 g per day) was associated with a 27–43% lower risk of death from cardiovascular disease. The benefit associated with light-to-moderate drinking was most apparent among women with risk factors for coronary heart disease and those 50 years of age or older. A more recent publication on the same cohort addressed the younger women enrolled (27–44 years old at baseline) followed for 20 years [4]. The idea was to examine whether primordial prevention, defined as prevention of the development of clinical risk factors through maintenance or adoption of a healthy lifestyle, will sustain women in a low cardiovascular risk profile and reduce their future incidence of coronary heart disease. While optimal keeping of all lifestyle factors led to 92% lower risk compared to those women who did not follow any of the healthy lifestyle recommendations, the contribution of 'light drinking' (up to 14.9 g/day of alcohol intake) was in the order of 40% reduction in risk. The Women's Health Initiative Observational Study demonstrated similar results [5]. The cohort included 93,676 postmenopausal women 50–79 years of age at enrollment, followed for a median period of 10 years. Moderate alcohol use (consumption of greater than none but less than 1 drink per day) was associated with reduced incidence of cardiovascular disease [HR 0.83; 95% CI 0.72–0.95) as compared to all other non-smoking participants. This benefit was not seen in women who had more than 1 drink/day (HR 0.94; 95% CI 0.75–1.18). Another large study, the Women's Health Study, highlighted a linear association between alcohol consumption and cardiovascular disease risk [6]. Women above age 45 years (mean 55 ± 7 years, n = 26,399, mean follow-up of 12.2 years) were evaluated for different levels of alcohol intake. There were 1039 cardiovascular events and 785 deaths (153 cardiovascular deaths) during that period. Alcohol intake of 5–14.9 g/day was associated with 26%, 35%, and 51% lower risk of cardiovascular disease, total death, and cardiovascular death, respectively. Contrarily, lower (0.1–4.9 g/day), or higher (15–29.9 g/day, > 30 g/day) intakes gave non-significant benefits as confidence intervals included 1.

In conclusion, although the exact definitions of light or moderate alcohol intake vary in different studies, it seems well validated that small amounts of alcohol have potential protective cardiac effects. However, in regard to stroke, some studies show favorable consequences, while other studies are less promising in this respect. Women consuming < 2 drinks/day in the Nurses' Health Study (to note that it included a primarily white cohort) had a 12–18% lower risk of ischemic stroke compared with non-drinkers [7]. In contrast, new data from the Atherosclerosis Risk in Communities study showed that self-reported light-to-moderate alcohol consumption at midlife was not associated with reduced stroke risk compared with abstention over 20 years of follow-up [8]. Furthermore, heavier consumption increased the risk for both ischemic and hemorrhagic stroke, as did moderate intake for intracerebral bleeding. The downside of alcohol consumption should be balanced with the benefits. In the Nurses' Health Study, heavier drinking was associated with an increased risk of death from several causes, particularly breast cancer (up to 67%) and cirrhosis (255%) [3]. The link between breast cancer and alcohol deserves more attention because of the continuously increasing incidence of both drinking and breast cancer in recent decades.

Amos Pines
Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

References

1. Smyth A, Teo KK, Rangarajan S, et al. Alcohol consumption and cardiovascular disease, cancer, injury, admission to hospital, and mortality: a prospective cohort study. Lancet 2015 Sep 17. Epub ahead of print
http://www.ncbi.nlm.nih.gov/pubmed/26386538 
2. Mosca L, Benjamin EJ, Berra K, et al. Effectiveness-based guidelines for the prevention of cardiovascular disease in women--2011 update: a guideline from the American Heart Association. J Am Coll Cardiol 2011;57:1404-23
http://www.ncbi.nlm.nih.gov/pubmed/21388771 
3. Fuchs CS, Stampfer MJ, Colditz GA, et al. Alcohol consumption and mortality among women. N Engl J Med1995;332:1245-50
http://www.ncbi.nlm.nih.gov/pubmed/7708067 
4. Chomistek AK, Chiuve SE, Eliassen AH, et al. Healthy lifestyle in the primordial prevention of cardiovascular disease among young women. J Am Coll Cardiol 2015;65:43-51
http://www.ncbi.nlm.nih.gov/pubmed/25572509 
5. Paynter NP, LaMonte MJ, Manson JE, et al. Comparison of lifestyle-based and traditional cardiovascular disease prediction in a multiethnic cohort of nonsmoking women. Circulation 2014;130:1466-73
http://www.ncbi.nlm.nih.gov/pubmed/25156990 
6. Djoussé L, Lee IM, Buring JE, Gaziano JM. Alcohol consumption and risk of cardiovascular disease and death in women: potential mediating mechanisms. Circulation 2009;120:237-44
http://www.ncbi.nlm.nih.gov/pubmed/19597054 
7. Jimenez M, Chiuve SE, Glynn RJ, et al. Alcohol consumption and risk of stroke in women. Stroke 2012;43:939–45
http://www.ncbi.nlm.nih.gov/pubmed/22403048 
8. Jones SB, Loehr L, Avery CL, et al. Midlife alcohol consumption and the risk of stroke in the Atherosclerosis Risk in Communities Study. Stroke 2015;46:3124-30
http://www.ncbi.nlm.nih.gov/pubmed/26405203 

18 January, 2016: 

To determine whether there is a risk of cardiovascular death upon withdrawal of hormone therapy (HT), Mikkola and colleagues used the Finnish National Death Registry (including 30% autopsy data) to conduct a nation-wide population study of 332,202 women who discontinued menopausal HT analyzed over 15 years with 2 million years of follow-up [1]. From 1994 to 2009, there were 3177 cardiac deaths and 1952 stroke deaths; mean HT exposure was 6.2 ± 6.0 years and mean follow-up after HT withdrawal was 5.5 ± 3.8 years. Comparing the actual death rates in the background population, the standardized mortality ratio (SMR) within the first year of HT withdrawal was elevated for cardiac and stroke death; SMR = 1.27 (95% CI 1.17–1.37) and SMR = 1.63 (95% CI 1.47–1.79), respectively. When compared to women who continued to use HT, the risk of discontinuing HT was even greater and elevated in women within as well as beyond the first year of withdrawal for both cardiac and stroke death; SMR = 2.30 (95% CI 2.12–2.50) and SMR = 2.52 (95% CI 2.28–2.77), respectively within the first year of HT withdrawal, and SMR = 1.26 (95% CI 1.21–.31) and SMR = 1.25 (95% CI 1.19–1.31), respectively beyond the first year of HT withdrawal. A similar risk pattern was shown when women were stratified by age at HT initiation or discontinuation. In women who discontinued HT at < 60 years, but not in women aged ≥ 60 years, cardiac mortality risk was elevated, SMR = 1.94 (95% CI 1.51–2.48) as was risk of stroke death, SMR = 2.87 (95% CI 2.29–3.55).

Comment

These newest findings by Mikkola and colleagues are the largest and most robust data to date confirming that both cardiac and stroke mortality are potentially increased after discontinuing HT [1]. Although these data were derived from an observational study, rates of fatal cardiac and stroke events were unlikely influenced by biases. The data from Mikkola and colleagues are consistent with studies showing increased health hazards after stopping HT that have substantial mortality such as hip fractures [2].

 desirable levels of vitamin D and supplementation

21 December, 2015: 

In a recent article in JAMA, Hansen and colleagues presented a randomized clinical trial of treatment of vitamin D insufficiency in postmenopausal women [1]. The trial compared the effects of placebo, low-dose cholecalciferol, and high-dose cholecalciferol on 1-year changes in total fractional calcium absorption, bone mineral density (BMD), timed-up-and-go and five sit-to-stand tests, and muscle mass in postmenopausal women with vitamin D insufficiency. This randomized, double-blind, placebo-controlled trial studied a total of 230 postmenopausal women 75 years or younger with baseline levels of 25-hydroxyvitamin D or 25(OH)D of 14–27 ng/ml and no osteoporosis. Outcome measures were 1-year change in total fractional calcium absorption using two stable isotopes, BMD and muscle mass, using dual-energy X-ray absorptiometry. After baseline absorption was controlled for, calcium absorption increased by 1% (10 mg/day) in the high-dose arm but decreased by 2% in the low-dose arm (p = 0.005 vs. high-dose arm) and 1.3% in the placebo arm (p = 0.03 vs. high-dose arm). We found no between-arm changes in spine, mean total hip, mean femoral neck, or total body BMD, trabecular bone score, muscle mass, and timed-up-and-go or five sit-to-stand test scores. Likewise, we found no between-arm differences for number of falls, number of fallers, physical activity, or functional status.

High-dose cholecalciferol therapy increased calcium absorption, but the effect was small and did not translate into beneficial effects on BMD, muscle function, muscle mass, or falls. We found no data to support experts’ recommendations to maintain serum 25(OH)D levels of 30 ng/ml or higher in postmenopausal women. Instead, we found that low- and high-dose cholecalciferol were equivalent to placebo in their effects on bone and muscle outcomes in this cohort of postmenopausal women with 25(OH)D levels less than 30 ng/ml.

Comment

In the US National Library of Medicine [2], we can read that vitamin D includes both cholecalciferol and ergocalciferol. Vitamin D is a hormone since it is formed in the skin by action of ultraviolet rays upon the precursors, 7-dehydrocholesterol and ergosterol, and acts on vitamin D receptors to regulate calcium in opposition to parathyroid hormone (PTH). But, because in our times, exposure to sunlight is so difficult, vitamin D is really a vitamin, as we need take vitamin D with meals; however, we have another problem: a diet does not usually contain a sufficient amount of vitamin D, as it is present in very few foods.

14 December, 2015: 

Obesity is a well-known major risk factor for many disease situations as well as for mortality. This risk is easily identified by a simple measurement of weight or of body mass index (BMI). However, there are several additional related parameters, namely lean body mass, total body fat, visceral fat, body composition and distribution of body fat, which have been investigated in light of their potential prognostic values. A recent study presented data from the Women's Health Initiative on associations between BMI, body composition, and incident mortality [1]. About 10,500 postmenopausal women, who underwent dual-energy X-ray absorptiometry scans (DXA) for estimation of total body fat and lean body mass, were followed for 13.6 (± 4.6) years. Their baseline characteristics were: age 63 (± 7) years; age at menopause 47 (± 7) years; weight 74 kg (± 16) kg; BMI 28 (± 6) kg/m2; total lean body mass 53% (± 7%); total fat body mass 44% (± 7%). Overall, BMI 35 kg/m2 was associated with increased mortality (adjusted HR 1.45, 95% CI 1.16–1.82), while total body fat and lean body fat were not. Among women aged 50–59 years, higher % total body fat increased risk of death (HR 2.44, 95% CI 1.38–4.34) and higher % lean body mass decreased risk of death (HR 0.41, 95% CI 0.23–0.74), despite broad-ranging BMIs. However, the relationships were reversed among women aged 70–79 years (p < 0.05). When the results were stratified by waist circumference, the protective association of higher lean body mass in younger women (age < 60 years) was seen only among those with low waist circumference (< 88 cm) and not those with larger waists (≥ 88 cm). Furthermore, the increased mortality risk among older women (ages 60–69 and ≥ 70 years) with higher lean body mass was seen only among those with a high waist circumference.

Comment

Body weight and BMI give pretty good correlations with many metabolic, cardiovascular and neoplastic diseases.