There was a total of 10,081,447 registered births (51.1% men) between 1900 and 1997 (Fig. 1). Among 8,202,688 people still living in 1997, 49.6% were men. From 1997 to 2018, there was a total of 2,716,574 incident CVD events, of which 873,149 were fatal events. Correspondingly there were 463,369 incident CHD events and 340,796 deaths from CHD. Total mortality included 1,802,452 deaths (Table 1).

Fig. 1

Study population by sex ratio (males/all birth) at birth 1900–1997 in Sweden

Table 1 Study population (birth year 1900–1997) and number of cases of CHD. CVD. And fatal CHD. Fatal CVD and total mortality. 1997–2018

Almost half of the subjects lived in large cities (49.7%) and had a lower education level, 9 years or less (49.8%) (Supplementary Tables S1 and S2).

A shifting trend appeared for the cumulative rates of non-fatal CVD in men and women by sex ratio (males/all births) at birth 1900–1997 and during the follow-up 1997–2018 (Fig. 2).

Fig. 2

Cumulative rates of non-fatal CVD in men and women by sex ratio (males/all birth) at birth 1900–1997). follow-up 1997–2018 in Sweden

Risk of CVD and CHD in men in relation to sex ratio at birth

The risk of non-fatal CVD in men born in those years with the lowest SRB compared to the highest (reference) was slightly but significantly higher, HR 1.01 (95% CI: 1.01–1.02) when adjusted for age, region of residence and educational level, and remained significant HR 1.01 (1.01–1.02) when also adjusted for comorbidities, i.e. hospitalization for COPD, alcoholism, diabetes, obesity, and cancer (Table 2, supplementary Table S5). A similar risk was also noted for men in the middle SBR category after full adjustment, HR 1.01 (1.00-1.01).

A similar pattern was observed for non-fatal CHD in men in the lowest category of SRB with a HR of 1.03 (1.02–1.05) when adjusted for age, region of residence and educational level, and remained significant with a HR of 1.03 (1.02–1.04) after full adjustment for co-morbidities (Table 2, supplementary Table S6). For men in the middle SBR category, the HR was 1.02 (1.01–1.03) after full adjustment.

The risk of fatal CVD in men born in years with the lowest SRB compared to the highest was weakly but significantly higher with a HR of 1.03 (95% CI: 1.02–1.04) when adjusted for age, region of residence, and educational level, and remained significant, HR 1.03 (1.02–1.04), when also adjusted for comorbidities (Table 3, supplementary Table S3). A similar risk was noted for men in the middle SBR category after full adjustment with a HR of 1.03 (1.02–1.03).

Table 2 Association between sex ratio (males/all birth) at birth (1900–1997) and risks of non-fatal CVD and CHD, 1997–2018Table 3 Association between sex ratio (Males/all birth) at birth (1900–1997) and risks of fatal CVD. CHD and total mortality 1997–2018

The risks of fatal CHD in men born in years with the lowest or middle SBR categories after full adjustment were also modestly higher with HRs of 1.04 (1.03–1.05) and 1.03 (1.02–1.05), respectively (Table 3, supplementary Table S4).

Risk of CVD and CHD in women in relation to sex ratio at birth

The corresponding risk of non-fatal CVD in women with the lowest SRB compared to the highest (reference) was not increased with a HR of 1.00 (95% CI: 1.00–1.01) when adjusted for age, region of residence and educational level, and remained with a HR of 1.00 (1.00–1.00) when also adjusted for comorbidities (Table 2, supplementary Table S9). A similar risk was also noted for women in the middle SBR category after full adjustment, HR 1.00 (0.99-1.00).

For non-fatal CHD in women in the lowest SBR categories, the HRs were 1.03 (1.02–1.05) and 1.02 (1.01–1.04), respectively (Table 2, supplementary Table S10). The risk in women in the middle SBR category was similar after full adjustment with a HR of 1.03 (1.01–1.04).

The risk of fatal CVD in women born in years with the lowest SRB category compared to the highest was weakly but significantly higher with a HR of 1.01 (95% CI: 1.00-1.02) when adjusted for age, region of residence and educational level, and remained significant, HR 1.01 (1.00-1.02) when also adjusted for comorbidities (Table 3, supplementary Table S7). For women in the middle SBR category the risk was similar after full adjustment with a HR of 1.02 (1.01–1.03).

Weakly increased risks were also observed for fatal CHD in women in the lowest SBR category with HRs of 1.03 (1.02–1.05) and 1.03 (1.02–1.05) after full adjustment, respectively (Table 3, supplementary Table S8). For women in the middle SBR category the risk was similar after full adjustment with HR 1.04 (1.03–1.06).

Risk of all-cause mortality in men and women in relation to sex ratio at birth

Men born in years with the lowest SRB category had slightly increased total mortality compared to the highest SRB category (HR, 1.02; 95% CI, 1.01–1.03) after full adjustment, as had men born in the middle SRB category, HR 1.02 (1.01–1.02). Women born in years with the lowest or middle SRB category had almost no increased total mortality risk compared to the highest SRB category (HR, 1.00; 95% CI, 1.00-1.01; and 1.01; 1.01–1.02, respectively) (Table 3, supplementary Tables S11 and S12).

Sensitivity analyses after adjustment for maternal age at birth and family size

In a subsample based on 6,563,604 births, a further adjustment was made for family size (number of children) and maternal age at birth. The risk of non-fatal CVD in both men and women in the lowest SRB category compared to the highest was unchanged (HR, 1.01; 95% CI: 1.00-1.01). The corresponding risk for non-fatal CHD was, however, significantly lower in men (HR, 0.95; 95% CI, 0.94–0.97) and in women (0.93; 0.91–0.95) (supplementary Table S13).

For fatal CVD in men born in years with the lowest SRB compared to the highest the HR was significantly lower at 0.93 (95% CI: 0.92–0.95) and for women the HR was 0.96 (0.94–0.99). The corresponding risk for fatal CHD was lower in both men with a HR of 0.92 (0.90–0.94) and in women with a HR of 0.91 (0.87–0.95).

Finally, the corresponding risk for total mortality in men in the lowest SBR category was significantly lower with a HR of 0.98 (0.97–0.99), but non-significant in women with a HR of 1.01 (0.99–1.02) (supplementary Table S14).

Sensitivity analyses in relation to period and gender

In a further sensitivity analysis (Table S15), it was shown that cardiovascular outcomes were similar between two separate time periods comparing children born 1900–1934 with children born 1935–1980, except for total mortality, with a higher risk observed in men during the first period RR 1.12 (95% CI: 1.11–1.13) compared to the second period, RR 1.04 (1.02–1.05), (Table S16). The risk ratio for men versus women was higher for all fatal outcomes (Table S17).