Volume 254 Issue November 2016
By Simona Negrini and Arnold von Eckardstein (Editor–in-Chief).
Anthropometric, biographic, and socioeconomic risk factors of cardiovascular diseases
In the prevention of cardiovascular diseases, pharmacologically modifiable risk factors play a central role both for risk assessment and treatment. The importance of anthropometric, biographic, socioeconomic, and environmental factors is generally acknowledged, but less intensively addressed by research. They are the topic of several studies and one review in the current issue of Atherosclerosis.
Infectious diseases contribute to stroke risk and are associated with the socio-economic status (SES). Palm and collaborators tested the hypothesis that the aggregate burden of infections increases the risk of ischemic stroke (IS) and partly explains the association between low SES and ischemic stroke.
In a case–control study with 470 ischemic stroke patients and 809 age- and sex-matched controls, randomly selected from the population, antibodies against the periodontal microbial agents Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, Chlamydia pneumonia, Mycoplasma pneumoniae (IgA and IgG), and CagA-positive Helicobacter pylori (IgG) were assessed.
The results showed that IgA seropositivity to two microbial agents was significantly associated with IS after adjustment for SES, but not in the fully adjusted model. By trend, cumulative IgA seropositivity was associated with stroke due to large vessel disease (LVD) after full adjustment. Disadvantageous childhood SES was associated with higher cumulative seropositivity in univariable analyses, however, its strong impact on stroke risk was not influenced by seroepidemiological data in the multivariable model. The strong association between adulthood SES and stroke was rendered non-significant when factors of dental care were adjusted for.
In conclusion, infectious burden assessed with five microbial agents does not independently contribute to ischemic stroke consistently, but may contribute to stroke due to LVD. High infectious burden may not explain the association between childhood SES and stroke risk. Lifestyle factors that include dental negligence may contribute to the association between disadvantageous adulthood SES and stroke.
Shorter stature is an established risk factor for coronary artery disease (CAD), but less is known about its association with the extent of the disease.
Bjornsson and colleagues assessed the relationship between self-reported height and angiographic findings in 7706 men and 3572 women identified from a nationwide coronary angiography registry in Iceland.
The authors found that, after adjustment for traditional cardiovascular risk factors, a standard deviation decrease in height associated with a greater likelihood of significant CAD (defined as ≥50% luminal diameter stenosis) both in men and women. In partial proportional odds logistic regression models, a standard deviation decrease in height was associated with higher odds of having greater extent of CAD in men and women. When limited to patients with significant CAD, the association was statistically significant in men but not in women.
These findings show that shorter stature is associated with greater extent of coronary atherosclerosis in a large unselected population of individuals undergoing coronary angiography. This relationship appears to be sex-dependent, with stronger effects in men than in women.
Type 2 diabetes (T2D), low-density lipoprotein-cholesterol (LDL-c), body mass index (BMI), blood pressure and smoking are established risk factors, playing a causal role in coronary artery disease (CAD). Numerous common genetic variants associated with these and other risk factors have been identified, but their association with CAD has not been comprehensively examined in a single study.
van Iperen and collaborators aimed at evaluating the association of established and emerging risk factors with CAD, using genetic variants identified in genome-wide association studies (GWAS).
The authors tested the effect of 60 traditional and putative risk factors with CAD, using summary statistics obtained in GWAS. They approximated the regression of a response variable onto an additive multi-single nucleotide polymorphism (multi-SNP) genetic risk score in the Coronary Artery DIsease Genomewide Replication And Meta-analysis (CARDIoGRAM) consortium dataset, weighed by the effect of the SNP on the risk factors.
They found that the strongest association with risk of CAD was for LDL-c SNPs. For non-established CAD risk factors, they observed significant CAD associations for coronary artery calcification (CAC), Lp(a), LP-PLA2 activity, plaque, vWF and FVIII. In the attempt to identify independent associations between risk factors and CAD, only SNPs with an effect on the target trait were included in the analysis. This lead to the identification of CAD associations for Lp(a), LDL-c, triglycerides (TG), height, CAC and carotid plaque.
These results provide further support to ongoing clinical trials on Lp(a) and TG, and suggest that CAC and plaque could be used as surrogate markers for CAD in clinical trials.
Data on the association between parity and mortality are limited by the presence of sociodemographic confounders, including cultural norms of parity.
Elajami and colleagues aimed to assess the association between parity and mortality in the Amish, a socio-economically homogenous group with a large number of children per family.
To this purpose, they conducted a population-based cohort study among 518 Old Order Amish women enrolled in a cardiovascular awareness program. The mean length of follow-up for mortality was 13.52 years. They determined the adjusted associations between parity and obesity, prevalent coronary heart disease, and mortality.
The mean number of total births per woman was 6.7 ± 3.6 with a mode of 8. No significant association was observed between parity and all-cause mortality when adjusted for age or in multivariate analysis. In addition, there was no association of parity in age or multivariable adjusted models with prevalent diabetes, hypertension or coronary heart disease. Despite the lack of effect of parity on mortality, a significant association of ten or more births was observed with higher body mass index (BMI) compared to the referent group of 8–9 total births.
In conclusion, in a highly homogeneous population with high rates of parity, no association between overall mortality and parity was observed. Ten or more births were significantly associated with a higher BMI but not with overall mortality.
In the late 1980s, several observational studies and meta-analyses suggested that hormone replacement therapy (HRT) was beneficial for prevention of osteoporosis, coronary heart disease, dementia and decreased all-cause mortality. In 1992, the American College of Physicians recommended HRT for prevention of coronary disease. In the late 1990s and early 2000s, several randomized trials in older women suggested coronary harm and that the risks, including breast cancer, outweighed any benefit. HRT stopped being prescribed at that time, even for women who had severe symptoms of menopause. Subsequently, re-analyses of the randomized trial data, using age stratification, as well as newer studies and meta-analyses, have been consistent in showing that younger women, 50–59 years or within 10 years of menopause, have decreased coronary disease and all-cause mortality, and did not have the perceived risks, including breast cancer. These newer findings are consistent with the older observational data. It has also been reported that many women who abruptly stopped HRT had more risks, including more osteoporotic fractures. The current data confirm a “timing” hypothesis for benefits and risks of HRT, showing that younger subjects have many benefits and few risks, particularly if therapy is predominantly focused on the estrogen component. In this comprehensive review, Lobo and colleagues discussed these findings and put into perspective the potential risks of treatment, suggesting that we may have come full circle regarding the use of HRT. They also propose that HRT should be considered as part of a general prevention strategy for women at the onset of menopause.